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Objective Visual electrophysiology and optical correlation tomography angiography （OCTA） were used to investigate differences in preoperative retinal function in patients with type 2 diabetic cataract （DC） without obvious retinopathy （NDR） and to determine the clinical application of whole-process blood glucose management （WBGM） for improving postoperative vision in DC patients. Methods This study investigated the preoperative and postoperative visual electrophysiology （N75, P100, photopic FERG, and scotopic FERG）, peripapillary retinal nerve fiber layer （pRNFL） and peripapillary capillary vessel density （ppVD） data, as well as trends in these data changes during blood glucose management intervention. Results As the course of T2DM progressed, FBG and HbA1c increased, the N75 and P100 lategraduancy periods of patients gradually lengthened, and the photopic FERG, scotopic FERG, pRNFL, and ppVD values decreased at each postoperative time point. At the same time, the best corrected visual acuity （BCVA） of patients after surgery gradually decreased （P < 0.05）. Compared with that at 1 week after surgery, the BCVA of Group A （without whole-process blood glucose management） gradually increased at 1 month and 3 months after surgery but showed a downward trend at 1 year after surgery. The BCVA of Group B （with whole-process blood glucose management） gradually stabilized at 1 month after surgery, and at all time points after surgery, the BCVA of Group B was better than that of Group A. The results showed that N75 and P100 in Group A were greater than those in Group B, while the photopic and scotopic FERG, pRNFL, and ppVD （%） in Group A were lower than those in Group B. In addition, N75 and P100 in Group A showed a gradual prolongation trend at various time points after surgery, while photopic FERG, scotopic FERG, pRNFL, and ppVD （%） showed a gradually decreasing trend. However, the above data in Group B gradually stabilized at 3 months after DC surgery, approaching the preoperative level of the group （P < 0.05）. In the state of whole blood glucose management, although N75 and P100 both reached their longest durations at 1 week after surgery, N75, P100, photopic FERG, scotopic FERG, and pRNFL showed a gradually decreasing trend at 1 month and 3 months after surgery, while ppVD （%） gradually increased （P < 0.05）. At various time points from 3 months to 1 year after surgery, the overall trend of the above indicators remained stable and close to the preoperative values （P > 0.05）. Conclusion According to the results of the quantitative analysis of visual electrophysiology and OCTA, in DC patients without obvious retinopathy and with the worsening of diabetes, retinal function decreased, but whole-process blood glucose management effectively restored retinal function and improved visual quality after surgery. [ABSTRACT FROM AUTHOR]

Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity. This study addresses the critical gap in our understanding of modifiable lifestyle factors, such as physical exercise, that may mitigate retinal aging and its related pathologies. We investigated the effects of different exercise regimens—voluntary (recreational-type) and forced (high-intensity)—on the retinal health of aging Wistar rats (18-month-old), serving as a model for studying the translational potential of exercise interventions in humans. Male Wistar rats were divided into four groups: a young control (3-month-old) for baseline comparison, an aged sedentary control, an aged group engaging in voluntary exercise via a running wheel in their cage, and an aged group subjected to forced exercise on a treadmill for six sessions of 20 min each per week. After a 6-month experimental period, we assessed retinal function via electroretinography (ERG), measured retinal thickness histologically, and analyzed protein expression changes relevant to oxidative stress, inflammation, and anti-aging mechanisms. Our findings reveal that voluntary exercise positively impacts retinal function and morphology, reducing oxidative stress and inflammation markers while enhancing anti-aging protein expression. In contrast, forced exercise showed diminished benefits. These insights underscore the importance of exercise intensity and preference in preserving retinal health during aging. The study highlights the potential of recreational physical activity as a non-invasive strategy to counteract retinal aging, advocating for further research into exercise regimens as preventative therapies for age-related ocular degenerations. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the potential protective effect of Qiju Granule in a rat model of age-related macular degeneration (AMD) and investigate the underlying mechanisms involved. Methods: Rats were injected intravenously with 40 mg/kg of sodium iodate (SI) to induce a dry AMD model. The rats in the treatment group received three different doses of Qiju Granule once a day via gavage, while the rats in the control group were given an equal volume of physiological saline. On day 14 and day 28 following the intervention, various methods were employed to evaluate retinal function and structure, including electroretinography (ERG), optical coherence tomography (OCT), and histological examination. The expression of glial fibrillary acidic protein (GFAP), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) was assessed via immunofluorescence. Beyond immunofluorescence, the mRNA levels of bFGF, BDNF, and CNTF were quantitatively determined using real-time polymerase chain reaction (qRT-PCR). Results: Rats treated with Qiju Granule exhibited significant improvements in both retinal function and structure compared to the model group. The most noteworthy effects were observed at a high dose of Qiju Granule. Furthermore, the expression levels of bFGF, BDNF, and CNTF were significantly unregulated in the treated groups compared to the model group. Conclusions: Qiju Granule demonstrated a protective effect on the retina in the SI-induced rat model of AMD. The protective mechanism may be attributed to the upregulation of retinal neurotrophic factors expression.

Although AMD is a complex disease, oxidative stress is a crucial contributor to its development, especially in view of the higher oxygen demand of the retina. Paraoxonase 2 (PON2) is a ubiquitously and constitutively expressed antioxidant protein that is found intracellularly associated with mitochondrial membranes and modulates mitochondrial ROS production and function. The contribution of PON2 to AMD has not been studied to date. In this study, we examined the role of PON2 in AMD utilizing both in vitro and in vivo models of AMD with emphasis on mitochondrial function. Mitochondrial localization and regulation of PON2 following oxidative stress were determined in human primary cultured retinal pigment epithelium (hRPE) cells. PON2 was knocked down in RPE cells using siRNA and mitochondrial bioenergetics were measured. To investigate the function of PON2 in the retina, WT and PON2-deficient mice were administered NaIO3 (20 mg/kg) intravenously; fundus imaging, optical coherence tomography (OCT), electroretinography (ERG) were conducted; and retinal thickness and cell death were measured and quantified. In hRPE, mitochondrial localization of PON2 increased markedly with stress. Moreover, a time-dependent regulation of PON2 was observed following oxidative stress, with an initial significant increase in expression followed by a significant decrease. Mitochondrial bioenergetic parameters (basal respiration, ATP production, spare respiratory capacity, and maximal respiration) showed a significant decrease with oxidative stress, which was further exacerbated in the absence of PON2. NaIO3 treatment caused significant retinal degeneration, retinal thinning, and reduced rod and cone function in PON2-deficient mice when compared to WT mice. The apoptotic cells and active caspase 3 significantly increased in PON2-deficient mice treated with NaIO3, when compared to WT mice. Our investigation demonstrates that deficiency of PON2 results in RPE mitochondrial dysfunction and a decline in retinal function. These findings imply that PON2 may have a beneficial role in retinal pathophysiology and is worthy of further investigation.

Lipid peroxidation from oxidative stress is considered a major contributor to age-related macular degeneration (AMD). The retina is abundant with circulating low-density lipoproteins (LDL), which are taken up by LDL receptor (LDLR) in the RPE and Müller cells. The purpose of this study is to investigate the role of LDLR in the NaIO3-induced model of dry AMD. Confluent primary human RPE (hRPE) and LDLR-silenced ARPE-19 cells were stressed with 150 µM tert-butyl hydroperoxide (tBH) and caspase 3/7 activation was determined. WT and Ldlr-/- mice were administered NaIO3 (20 mg/kg) intravenously. On day 7, fundus imaging, OCT, ERG, and retinal thickness were measured. Histology, TUNEL, cleaved caspase 3 and lipid accumulation were assessed. Treatment of hRPE with tBH markedly decreased LDLR expression. Caspase 3/7 activation was significantly increased in LDLR-silenced ARPE-19 cells treated with tBH. In Ldlr-/- mice, NaIO3 administration resulted in significant (a) retinal thinning, (b) compromised photoreceptor function, (c) increased percentage of cleaved caspase 3 positive and apoptotic cells, and (d) increased lipid droplet accumulation in the RPE, Bruch membrane, choroid, and sclera, compared to WT mice. Our findings imply that LDLR loss leads to lipid accumulation and impaired retinal function, which may contribute to the development of AMD.

Lipid processing by the retinal pigment epithelium (RPE) is necessary to maintain retinal health and function. Dysregulation of retinal lipid homeostasis due to normal aging or age-related disease triggers lipid accumulation within the RPE, on Bruch's membrane (BrM), and in the subretinal space. In its role as a hub for lipid trafficking into and out of the neural retina, the RPE packages a significant amount of lipid into lipid droplets for storage and into apolipoprotein B (APOB)-containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the MTTP gene, is essential for Blp assembly. Herein we test the hypothesis that MTP expression in the RPE is essential to maintain lipid balance and retinal function using the newly generated RPEΔMttp mouse model. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic depletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor-associated cholesterol deposits, and photoreceptor cell death, and loss of rod but not cone function. RPE-specific reduction in Mttp had no significant effect on plasma lipids and lipoproteins. While APOB was decreased in the RPE, most ocular retinoids remained unchanged, with the exception of the storage form of retinoid, retinyl ester. Thus suggesting that RPE MTP is critical for Blp synthesis and assembly but is not directly involved in plasma lipoprotein metabolism. These studies demonstrate that RPE-specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function. [ABSTRACT FROM AUTHOR]

IntroductionThis study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes.MethodsWe measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM).ResultsSignificant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not.DiscussionOur data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Glaucoma is characterized by cupping of the optic disc, apoptotic degeneration of retinal ganglion cells (RGCs) and their axons, and thinning of the retinal nerve fiber layer, with patchy loss of vision. Elevated intraocular pressure (IOP) is a major risk factor for hypertensive glaucoma and the only modifiable one. There is a need to find novel compounds that counteract other risk factors contributing to RGC degeneration. The oil derived from the wild olive tree (Olea europaea var. sylvestris), also called Acebuche (ACE), shows powerful anti-inflammatory, antioxidant and retinoprotective effects. We evaluated whether ACE oil could counteract glaucoma-related detrimental effects. To this aim, we fed mice either a regular or an ACE oil-enriched diet and then induced IOP elevation through intraocular injection of methylcellulose. An ACE oil-enriched diet suppressed glaucoma-dependent retinal glia reactivity and inflammation. The redox status of the glaucomatous retinas was restored to a control-like situation, and ischemia was alleviated by an ACE oil-enriched diet. Notably, retinal apoptosis was suppressed in the glaucomatous animals fed ACE oil. Furthermore, as shown by electroretinogram analyses, RGC electrophysiological functions were almost completely preserved by the ACE oil-enriched diet. These ameliorative effects were IOP-independent and might depend on ACE oil's peculiar composition. Although additional studies are needed, nutritional supplementation with ACE oil might represent an adjuvant in the management of glaucoma. [ABSTRACT FROM AUTHOR]

Background: With the clinical advances in the field of gene therapy, the development of objective measures of visual function of patients with inherited retinal dystrophies (IRDs) is of utmost importance. Here, we propose one such measure. Methods: We retrospectively analyzed data from a cohort of 194 eyes of 97 genetically diagnosed patients with retinitis pigmentosa (RP), the most common IRD, followed at the UPMC Vision Institute. The analyzed data included the reflectivity ratio (RR) of the retinal nerve fiber layer (RNFL) to that of the entire retina, visual acuity (VA) and the thickness of the retinal outer nuclear layer (ONL) and the RNFL. Results: There was a strong positive correlation between the RR and VA. Both VA and the RR were negatively correlated with disease duration; VA, but not the RR, was negatively correlated with age. The RR correlated with the ONL but not with the RNFL thickness or the intraocular pressure. Age, RR, disease duration and ONL thickness were found to be independent predictors of VA by multivariate analysis. Conclusion: The OCT RR could serve as an independent predictor of visual acuity, and by extension of retinal function, in genetically diagnosed RP patients. Such objective measures can be of great value in patient selection for therapeutic trials. [ABSTRACT FROM AUTHOR]

This article provides a commentary on a review of retinal electrophysiology in central nervous system (CNS) disorders, focusing on human and mouse studies. The authors discuss the variations in retinal function observed in patients with CNS disorders such as autism, ADHD, bipolar disorder, schizophrenia, depression, Parkinson's disease, and Alzheimer's disease. They suggest that analyzing electroretinography (ERG) signals could help understand neurotransmitter anomalies and the classification and progression of CNS disorders. Specifically, they highlight the potential of using ERG as a marker for therapeutic response in patients with major depressive disorder (MDD) who are treated with antidepressants or light therapy. The authors propose conducting further studies to develop ERG biomarkers for monitoring antidepressant responses in MDD patients. [Extracted from the article]

Purpose: Exposure to blue light is thought to be harmful to the retina. The purpose of this study was to determine the effects of long-term exposure to narrowband blue light on retinal function in rhesus monkeys. Methods: Young rhesus monkeys were reared under short-wavelength "blue" light (n = 7; 465 nm, 183 ± 28 lx) on a 12-h light/dark cycle starting at 26 ± 2 days of age. Age-matched control monkeys were reared under broadband "white" light (n = 8; 504 ± 168 lx). Light- and dark-adapted full-field flash electroretinograms (ERGs) were recorded at 330 ± 9 days of age. Photopic stimuli were brief red flashes (0.044–5.68 cd.s/m2) on a rod-saturating blue background and the International Society for Clinical Electrophysiology of Vision (ISCEV) standard 3.0 white flash on a 30 cd/m2 white background. Monkeys were dark adapted for 20 min and scotopic stimuli were ISCEV standard white flashes of 0.01, 3.0, and 10 cd.s/m2. A-wave, b-wave, and photopic negative response (PhNR) amplitudes were measured. Light-adapted ERGs in young monkeys were compared to ERGs in adult monkeys reared in white light (n = 10; 4.91 ± 0.88 years of age). Results: For red flashes on a blue background, there were no significant differences in a-wave (P = 0.46), b-wave (P = 0.75), and PhNR amplitudes (P = 0.94) between white light and blue light reared monkeys for all stimulus energies. ISCEV standard light- and dark-adapted a- and b-wave amplitudes were not significantly different between groups (P > 0.05 for all). There were no significant differences in a- and b-wave implicit times between groups for all ISCEV standard stimuli (P > 0.05 for all). PhNR amplitudes of young monkeys were significantly smaller compared to adult monkeys for all stimulus energies (P < 0.05 for all). There were no significant differences in a-wave (P = 0.19) and b-wave (P = 0.17) amplitudes between young and adult white light reared monkeys. Conclusions: Long-term exposure to narrowband blue light did not affect photopic or scotopic ERG responses in young monkeys. Findings suggest that exposure to 12 h of daily blue light for approximately 10 months does not result in altered retinal function. [ABSTRACT FROM AUTHOR]

Objective To study the effect of strong visible light on the structure and function of the rat retina and its mechanism. Methods Self-made light box. Adult Sprague-Dawley (SD) rats were randomly divided into normal control and experimental groups. Normal control group rats were raised in a normal environment of 12 h light / 12 h dark cycle. Rats in the experimental group were first darkly adapted for 24 h, then were irradiated with 5 000 lx strong visible light for 48 h, followed by a dark adaption of another 24 h. All the rats were anesthetized for about 30 minutes. Firstly, the retinal function of the rats were detected by retinal electrophysiology (ERG); Secondly, rats' eyeballs were removed and fixed in fixative solution or 4% polyoxymethylene before paraffin or frozen sections were made for HE staining and TUNEL staining respectively. Paraffin sections with HE staining were used to observe the change of retinal tissue structures under light microscope, and frozen sections with TUNEL staining were observed under confocol microscope. qRT-PCR and Western blot (WB) were used to detect tumor necrosis factor-α (TNF-α) content in the photo damaged retinas. Results HE staining showed that retinal outer nuclear layer was significantly thinner than normal after light exposure, and the temporal side was more severely damaged than the nasal side; TUNEL staining showed that the number of retinal apoptotic cells increased significantly after photo damage; qRT-PCR and WB revealed that TNF-α increased in the photo damaged retinas；and ERG demonstrated that the retinal function of photo damaged rats was significantly reduced. All the results above were statistically different（P<0.05）. Conclusions The damage of outer nuclear layer (ONL) after light exposure is one of the reasons for the impairment of retinal function, and the retinal damage may be related to the increased expression of TNF-α. [ABSTRACT FROM AUTHOR]

Background: Retinal ischaemia is present to a greater or lesser extent in all eyes with diabetic retinopathy (DR). Nonetheless, our understanding of its pathogenic mechanisms, risk factors, as well as other characteristics of retinal ischaemia in DR is very limited. To date, there is no treatment to revascularise ischaemic retina. Methods: Review of the literature highlighting the current knowledge on the topic of retinal ischaemia in DR, important observations made, and underlying gaps for which research is needed. Results: A very scarce number of clinical studies, mostly cross-sectional, have evaluated specifically retinal ischaemia in DR. Interindividual variability on its natural course and consequences, including the development of its major complications, namely diabetic macular ischaemia and proliferative diabetic retinopathy, have not been investigated. The in situ, surrounding, and distance effect of retinal ischaemia on retinal function and structure and its change over time remains also to be elucidated. Treatments to prevent the development of retinal ischaemia and, importantly, to achieve retinal reperfusion once capillary drop out has ensued, are very much needed and remain to be developed. Conclusion: Research into retinal ischaemia in diabetes should be a priority to save sight. [ABSTRACT FROM AUTHOR]

Glaucoma is characterized by cupping of the optic disc, apoptotic degeneration of retinal ganglion cells (RGCs) and their axons, and thinning of the retinal nerve fiber layer, with patchy loss of vision. Elevated intraocular pressure (IOP) is a major risk factor for hypertensive glaucoma and the only modifiable one. There is a need to find novel compounds that counteract other risk factors contributing to RGC degeneration. The oil derived from the wild olive tree (Olea europaea var. sylvestris), also called Acebuche (ACE), shows powerful anti-inflammatory, antioxidant and retinoprotective effects. We evaluated whether ACE oil could counteract glaucoma-related detrimental effects. To this aim, we fed mice either a regular or an ACE oil-enriched diet and then induced IOP elevation through intraocular injection of methylcellulose. An ACE oil-enriched diet suppressed glaucoma-dependent retinal glia reactivity and inflammation. The redox status of the glaucomatous retinas was restored to a control-like situation, and ischemia was alleviated by an ACE oil-enriched diet. Notably, retinal apoptosis was suppressed in the glaucomatous animals fed ACE oil. Furthermore, as shown by electroretinogram analyses, RGC electrophysiological functions were almost completely preserved by the ACE oil-enriched diet. These ameliorative effects were IOP-independent and might depend on ACE oil’s peculiar composition. Although additional studies are needed, nutritional supplementation with ACE oil might represent an adjuvant in the management of glaucoma.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration.

Introduction: Wistar Han rats are a preferred strain of rodents for general toxicology and safety pharmacology studies in drug development. In some of these studies, visual functional tests that assess for retinal toxicity are included as an additional endpoint. Although the influence of gender on human retinal function has been documented for more than 6 decades, preclinically it is still uncertain if there are differences in retinal function between naïve male and female Wistar Han rats.Methods: In this study, sex-related differences in the retinal function were quantified by analyzing electroretinography (ERG) in 7-9-week-old (n = 52 males and 51 females) and 21–23-week-old Wistar Han rats (n = 48 males and 51 females). Optokinetic tracking response, brainstem auditory evoked potential, ultrasonic vocalization and histology were tested and evaluated in a subset of animals to investigate the potential compensation mechanisms of spontaneous blindness.Results/Discussion: Absence of scotopic and photopic ERG responses was found in 13% of 7-9-week-old (7/52) and 19% of 21–23-week-old males (9/48), but none of female rats (0/51). The averaged amplitudes of rod- and cone-mediated ERG b-wave responses obtained from males were significantly smaller than the amplitudes of the same responses from age-matched females (−43% and −26%, respectively) at 7–9 weeks of age. There was no difference in the retinal and brain morphology, brainstem auditory responses, or ultrasonic vocalizations between the animals with normal and abnormal ERGs at 21–23 weeks of age. In summary, male Wistar Han rats had altered retinal responses, including a complete lack of responses to test flash stimuli (i.e., blindness), when compared with female rats at 7–9 and 21–23 weeks of age. Therefore, sex differences should be considered when using Wistar Han rats in toxicity and safety pharmacology studies with regards to data interpretation of retinal functional assessments.

Aim of the study: Investigation of pattern electroretinography in individuals with major depression (MD). Material and methods: In 25 untreated individuals with MD (mean age 46.8 years) and in 25 of age- and sex-matched healthy controls (mean age 46.9 years) the following examinations were performed: visual acuity (Snellen), intraocular pressure, biomicroscopy of anterior and posterior segment of eye, macular structure (SD-OCTZeiss) and pattern electroretinogram (PERG-ISCEV standards). An analysis of correlation between the parameters of PERG and depression severity (the Hamilton Scale) was performed. To estimate the diagnostic power of the PERG test a receiver operating characteristics (ROC) curve was used. Obtained data were used to analyze the significance level p < 0.05. Results: In both groups the clinical results and macular structure were normal. In the PERG test in the MD group a significant decrease of amplitudes of P50 (AP50) and N95 (AN95) waves (p < 0.001) was detected. The most frequent abnormality was the reduction of AN95 (32.0%). The Hamilton Scale correlated negatively and significantly with AN95 (p = 0.036). The analysis of ROC curve revealed that in the case of AP50 the cut-off point was 6.75 with sensitivity 0.960 and specificity 0.840. The area under the curve (AUC) was 0.931 (p < 0.001). In the case of AN95, the cut-off point was 9.0, with sensitivity 0.920 and specificity 0.920. The AUC was 0.923 (p < 0.001). Conclusions: In major depression, a dysfunction of the ganglion cells in the macular region is present with the ability to be registered by PERG recording. The abnormalities in function of the ganglion cells detected in PERG examination have the potential to be an objective marker of MD [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to determine the morphological and functional retinal changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal bevacizumab 1.25 mg.Methods: This was a prospective, nonrandomized, interventional study. Eighteen eyes of 18 subjects with nAMD were treated with intravitreal bevacizumab (1.25 mg) injection. Subjects underwent complete ophthalmic evaluation which included visual acuity, slitlamp examination, tonometry, binocular ophthalmoscopy, optical coherence tomography (OCT), and MP1 microperimetry before the intravitreal injection and the follow-up at 1 and 3 months. Test of significance such as Chi-squared test, paired ttest and oneway analysis of variance (ANOVA) linear trend were used to compare the pre- and post-anti-VEGF outcomes. Intraclass correlation was done to assess the intra observer variability.Results: Mean retinal sensitivity had increased from 3.77 ± 3.13 dB at baseline to 4.93 ± 2.42 dB at 3 months (P = 0.05). Visual acuity improved from 0.62 ± 0.36 at baseline to 0.52 ± 0.36 at 1 month and 0.48 ± 0.34 at 3-month followup, but overall change was not significant (P = 0.40). There was a significant reduction in central foveal thickness (CFT) from 274.61 ± 117.95 at baseline to 179.83 ± 84.18 at 1 month and 179.00 ± 126.55 at 3-month follow-up (P = 0.013).Conclusion: Intravitreal bevacizumab (1.25 mg) injection in nAMD improves retinal function, quantified by retinal sensitivity, scotoma characteristics, fixation stability by MP 1 microperimetry and morphological parameters quantified by CFT in SDOCT. These changes show the effectiveness of treatment with intravitreal bevacizumab in nAMD. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the potential protective effect of Qiju Granule in a rat model of age-related macular degeneration (AMD) and investigate the underlying mechanisms involved. Rats were injected intravenously with 40 mg/kg of sodium iodate (SI) to induce a dry AMD model. The rats in the treatment group received three different doses of Qiju Granule once a day via gavage, while the rats in the control group were given an equal volume of physiological saline. On day 14 and day 28 following the intervention, various methods were employed to evaluate retinal function and structure, including electroretinography (ERG), optical coherence tomography (OCT), and histological examination. The expression of glial fibrillary acidic protein (GFAP), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) was assessed via immunofluorescence. Beyond immunofluorescence, the mRNA levels of bFGF, BDNF, and CNTF were quantitatively determined using real-time polymerase chain reaction (qRT-PCR). Rats treated with Qiju Granule exhibited significant improvements in both retinal function and structure compared to the model group. The most noteworthy effects were observed at a high dose of Qiju Granule. Furthermore, the expression levels of bFGF, BDNF, and CNTF were significantly unregulated in the treated groups compared to the model group. Qiju Granule demonstrated a protective effect on the retina in the SI-induced rat model of AMD. The protective mechanism may be attributed to the upregulation of retinal neurotrophic factors expression. • The etiology of age-related macular degeneration (AMD) is multifactorial, involving both genetic and environmental components. • Currently, there are no effective preventive measures or treatments available for dry AMD. • This study assesses the protective effects of Qiju Granule in a rat model of dry AMD and finds significant improvements in retinal function and structure, especially at higher doses. • The protective mechanism is associated with the upregulation of neurotrophic factors, including bFGF, BDNF, and CNTF, as demonstrated by immunofluorescence and qRT-PCR analyses. • These findings provide valuable insights into potential therapeutic approaches and highlight the importance of targeting these neurotrophic factors to enhance the treatment of AMD. [ABSTRACT FROM AUTHOR]

Birds are highly dependent on their vision for orientation and navigation. The avian eye differs from the mammalian eye as the retina is avascular, leaving the inner, highly metabolically active layers with a very long diffusion distance to the oxygen supply. During flight at high altitudes, birds face a decrease in environmental oxygen partial pressure, which leads to a decrease in arterial oxygen levels. Since oxygen perfusion to the retina is already limited in birds, we hypothesize that visual function is impaired by low oxygen availability. However, the visual performance of birds exposed to hypoxia has not been evaluated before. Here, we assess the optomotor response (OMR) in zebra finches under simulated high-altitude hypoxia (10%) and show that the OMR is largely maintained under hypoxia with only a modest reduction in OMR, demonstrating that birds can largely maintain visual function at high altitudes. The method of our study does not provide insight into the mechanisms involved, but our findings suggest that birds have evolved physiological mechanisms for retinal function at low tissue oxygen levels. • New optomotor response test tracks bird vision under simulated high-altitude hypoxia. • Finches do not lose vision when exposed to high-altitude hypoxia. • Birds must possess mechanisms for maintaining retinal function at high altitudes. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is characterized by at least one major depressive episode. It requires medical attention typically involving the prescription of antidepressants. Remission in MDD patients is often difficult to achieve because of the limited effectiveness of these drugs. Nowadays, numerous patients undergo various antidepressant treatments, with subjective changes in their personal experiences being regularly monitored. Therefore, it is essential to find clinical and objective tools that offer a more tailored approach to antidepressant selection. The neurochemistry of the retina being similar to the brain, one promising approach would be to use ElectroRetinoGraphy (ERG) measurements on MDD patients requiring antidepressant treatment. Thus, the aim of this scoping review is to highlight effects of different classes of antidepressants on retinal function evaluated by full-field ERG (ffERG), Pattern ERG (PERG) and multifocal ERG (mfERG) waveforms in MDD patients. These ERG measurements could serve as pivotal indicators in defining patient profiles, facilitating a more objective and personalized approach to therapeutic interventions, thereby advancing precision psychiatry. • A normalization of electroretinographic (ERG) parameters occurs when antidepressants reduces depressive symptoms. • Each class of antidepressants influence differently ERG measurements in major depressive disorder (MDD) patients. • Antidepressants influence on ERG results can be explained by variations of monoamine rates. • ERG would enable to discriminate MDD patients responding or not to antidepressants, and thus improving their care management. [ABSTRACT FROM AUTHOR]

Background: With the clinical advances in the field of gene therapy, the development of objective measures of visual function of patients with inherited retinal dystrophies (IRDs) is of utmost importance. Here, we propose one such measure. Methods: We retrospectively analyzed data from a cohort of 194 eyes of 97 genetically diagnosed patients with retinitis pigmentosa (RP), the most common IRD, followed at the UPMC Vision Institute. The analyzed data included the reflectivity ratio (RR) of the retinal nerve fiber layer (RNFL) to that of the entire retina, visual acuity (VA) and the thickness of the retinal outer nuclear layer (ONL) and the RNFL. Results: There was a strong positive correlation between the RR and VA. Both VA and the RR were negatively correlated with disease duration; VA, but not the RR, was negatively correlated with age. The RR correlated with the ONL but not with the RNFL thickness or the intraocular pressure. Age, RR, disease duration and ONL thickness were found to be independent predictors of VA by multivariate analysis. Conclusion: The OCT RR could serve as an independent predictor of visual acuity, and by extension of retinal function, in genetically diagnosed RP patients. Such objective measures can be of great value in patient selection for therapeutic trials.

Although AMD is a complex disease, oxidative stress is a crucial contributor to its development, especially in view of the higher oxygen demand of the retina. Paraoxonase 2 (PON2) is a ubiquitously and constitutively expressed antioxidant protein that is found intracellularly associated with mitochondrial membranes and modulates mitochondrial ROS production and function. The contribution of PON2 to AMD has not been studied to date. In this study, we examined the role of PON2 in AMD utilizing both in vitro and in vivo models of AMD with emphasis on mitochondrial function. Mitochondrial localization and regulation of PON2 following oxidative stress were determined in human primary cultured retinal pigment epithelium (hRPE) cells. PON2 was knocked down in RPE cells using siRNA and mitochondrial bioenergetics were measured. To investigate the function of PON2 in the retina, WT and PON2-deficient mice were administered NaIO3 (20 mg/kg) intravenously; fundus imaging, optical coherence tomography (OCT), electroretinography (ERG) were conducted; and retinal thickness and cell death were measured and quantified. In hRPE, mitochondrial localization of PON2 increased markedly with stress. Moreover, a time-dependent regulation of PON2 was observed following oxidative stress, with an initial significant increase in expression followed by a significant decrease. Mitochondrial bioenergetic parameters (basal respiration, ATP production, spare respiratory capacity, and maximal respiration) showed a significant decrease with oxidative stress, which was further exacerbated in the absence of PON2. NaIO3 treatment caused significant retinal degeneration, retinal thinning, and reduced rod and cone function in PON2-deficient mice when compared to WT mice. The apoptotic cells and active caspase 3 significantly increased in PON2-deficient mice treated with NaIO3, when compared to WT mice. Our investigation demonstrates that deficiency of PON2 results in RPE mitochondrial dysfunction and a decline in retinal function. These findings imply that PON2 may have a beneficial role in retinal pathophysiology and is worthy of further investigation.

Purpose: This study was conducted to determine the morphological and functional retinal changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal bevacizumab 1.25 mg. Methods: This was a prospective, nonrandomized, interventional study. Eighteen eyes of 18 subjects with nAMD were treated with intravitreal bevacizumab (1.25 mg) injection. Subjects underwent complete ophthalmic evaluation which included visual acuity, slitlamp examination, tonometry, binocular ophthalmoscopy, optical coherence tomography (OCT), and MP1 microperimetry before the intravitreal injection and the follow-up at 1 and 3 months. Test of significance such as Chi-squared test, paired ttest and oneway analysis of variance (ANOVA) linear trend were used to compare the pre- and post-anti-VEGF outcomes. Intraclass correlation was done to assess the intra observer variability. Results: Mean retinal sensitivity had increased from 3.77 ± 3.13 dB at baseline to 4.93 ± 2.42 dB at 3 months (P = 0.05). Visual acuity improved from 0.62 ± 0.36 at baseline to 0.52 ± 0.36 at 1 month and 0.48 ± 0.34 at 3-month followup, but overall change was not significant (P = 0.40). There was a significant reduction in central foveal thickness (CFT) from 274.61 ± 117.95 at baseline to 179.83 ± 84.18 at 1 month and 179.00 ± 126.55 at 3-month follow-up (P = 0.013). Conclusion: Intravitreal bevacizumab (1.25 mg) injection in nAMD improves retinal function, quantified by retinal sensitivity, scotoma characteristics, fixation stability by MP 1 microperimetry and morphological parameters quantified by CFT in SDOCT. These changes show the effectiveness of treatment with intravitreal bevacizumab in nAMD.

The impact of regular cannabis use on retinal function has already been studied using flash (fERG) and pattern (PERG) electroretinogram. Delayed ganglion and bipolar cells responses were observed as showed by increased peak time of PERG N95 and fERG b-wave recorded in photopic condition. Hypoactivity of amacrine cells was also showed by decreased amplitudes of oscillatory potentials (OPs). However, it is unknown how these retinal anomalies evolve according to the level of cannabis use in cannabis users. The aim of this study was to longitudinally assess the retinal function during a treatment aiming to reduce cannabis use. We recorded PERG and fERG in 40 regular cannabis users receiving either an 8 weeks mindfulness-based relapse prevention program or an 8 weeks treatment-as-usual therapy. ERGs were recorded before treatment, at the end of it, and 4 weeks afterward. We found reduced peak times in PERG N95 and fERG b-wave (p = 0.032 and p = 0.024: Dunn's post-hoc test) recorded at week 8 and increased amplitudes in OP2 and OP3 (p = 0.012 and p = 0.030: Dunn's post-hoc test) recorded at week 12 in users with decreased cannabis use. These results support variations of retinal anomalies with the level of cannabis use, implying that reduction of cannabis use could restore retinal function in regular users. [ABSTRACT FROM AUTHOR]

AIM: To assess the retinal function in patients with dense cataracts in resource poor settings in Kinshasa, DR Congo. METHODS: In a tertiary eye care center, the Purkinje entoptic test was performed as part of the ophthalmological examination in 98 eyes in patients with cataract, using a penlight. Totally 92 cataract patients including 86 patients suffered from unilateral and 6 from bilateral cataracts were included in the study. The investigator asked the patients about their perception of the vascular pattern most commonly described as a leafless or dead tree. Visual acuity≥6/60 was considered an indication of good visual function and visual acuity

The impact of regular cannabis use on retinal function has already been studied using flash (fERG) and pattern (PERG) electroretinogram. Delayed ganglion and bipolar cells responses were observed as showed by increased peak time of PERG N95 and fERG b-wave recorded in photopic condition. Hypoactivity of amacrine cells was also showed by decreased amplitudes of oscillatory potentials (OPs). However, it is unknown how these retinal anomalies evolve according to the level of cannabis use in cannabis users. The aim of this study was to longitudinally assess the retinal function during a treatment aiming to reduce cannabis use. We recorded PERG and fERG in 40 regular cannabis users receiving either an 8 weeks mindfulness-based relapse prevention program or an 8 weeks treatment-as-usual therapy. ERGs were recorded before treatment, at the end of it, and 4 weeks afterward. We found reduced peak times in PERG N95 and fERG b-wave (p = 0.032 and p = 0.024: Dunn’s post-hoc test) recorded at week 8 and increased amplitudes in OP2 and OP3 (p = 0.012 and p = 0.030: Dunn’s post-hoc test) recorded at week 12 in users with decreased cannabis use. These results support variations of retinal anomalies with the level of cannabis use, implying that reduction of cannabis use could restore retinal function in regular users.

Purpose: The NLRP3 inflammasome, a cytoplasmic signal transduction complex that regulates inflammation, has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of visual impairment in industrialized countries. We tested the therapeutic effect of anti-inflammatory gene therapy, delivered preventively, in Liver-X-Receptor alpha knockout (LXRα-/-) mice, which exhibit features of dry AMD. Methods:LXRα-/- mice were treated with an adeno-associated virus (AAV) vector that delivers a secretable and cell-penetrating form of the caspase activation and recruitment domain (CARD). A sGFP-FCS-TatCARD-AAV or sGFP-FCS (control) vector was delivered intravitreally to 3-5 month-old, LXRα-/- mice, who were then aged to 15-18 months (12-13 month treatment). Retinal function and morphology were assessed pre- and post-treatment. Results: TatCARD treated LXRα-/- mice did not show improvement in rod and cone photoreceptor function, measured by dark adapted a- and b-wave amplitudes, and rod-saturated b-wave amplitudes. We found a sex-dependent, significant therapeutic effect in c-wave amplitudes in the TatCARD treated mice, which exhibited maintenance of amplitudes in comparison to the significant decline recorded in the control treated group, indicating a therapeutic effect mediated in part through retinal pigment epithelial (RPE) cells. Additionally, the retinas of the TatCARD treated mice exhibited a significant decline in the concentration of interleukin-1 beta (IL-1β) concomitant with modulation of several inflammatory cytokines in the retina and RPE-choroid tissues, as measured by ELISA and cytokine array, respectively. Conclusion: Collectively, these results support that anti-inflammatory gene constructs such as AAV-TatCARD may be considered for the treatment of inflammation in AMD and other ocular diseases of the posterior pole in which inflammation may play a role. Furthermore, our findings emphasize the need to carefully consider potential sex-different responses when assessing potential therapies in pre-clinical models. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether primary open-angle glaucoma (POAG) is associated with changes in fixation stability parameters assessed by microperimetry (MP) and whether the severity of glaucoma is related to a deterioration in these indicators. This study analyzed fixation stability using MP macular analyzer integrity assessment (MAIA) in patients with mild and moderate/severe POAG and healthy controls. The resulting fixation indices were correlated with parameters used to assess retinal function with MP and standard automated perimetry (SAP) and retinal structure with optical coherence tomography (OCT) and OCT angiography (OCTA). We enrolled 54 eyes in the POAG groups (32 eyes with mild POAG and 22 eyes with moderate/severe POAG) and 24 eyes in the healthy group. It was shown that fixation stability in POAG eyes deteriorated with increasing disease severity, and significant differences in bivariate contour ellipse area (BCEA) including 95% of fixation points were observed among groups (p = 0.042). Quantitative analysis of structural and functional retinal parameters also showed significant deterioration with the progression of glaucoma (p < 0.001). Correlations among fixation parameters and abnormalities in the retinal structure and function were confirmed. We concluded that POAG is associated with disturbances in the fixation pattern, which worsen as the disease progresses and can be effectively assessed by performing a MP test. [ABSTRACT FROM AUTHOR]

The electroretinogram (ERG) is a noninvasive, objective technique to evaluate retinal function that has become increasingly important in the study of diabetic retinopathy. We summarize the principles and rationale of the ERG, present findings from recent clinical studies that have used the full-field ERG, multifocal ERG, and pattern ERG to evaluate neural dysfunction in patients with diabetes, and weigh the strengths and limitations of the technique as it applies to clinical studies and management of patients with diabetic retinopathy. Taken together, ERG studies have provided convincing evidence for dysfunction of the neural retina in patients with diabetes, including those who have no clinically-apparent retinal vascular abnormalities. Recent full-field ERG findings have pointed to the intriguing possibility that photoreceptor function is abnormal in early-stage disease. Pattern ERG data, in conjunction with recently developed photopic negative response analyses, indicate inner retina dysfunction. In addition, multifocal ERG studies have shown spatially localized neural abnormalities that can predict the location of future microaneurysms. Given the insights provided by the ERG, it is likely to play a growing role in understanding the natural history of neural dysfunction in diabetes, as well as providing an attractive outcome measure for future clinical trials that target neural preservation in diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Preclinical studies of optic nerve injury models have led to significant insight into the mechanism underlying retinal ganglion cell neurodegeneration. During the process of ganglion cell injury, morphological changes can occur prior to gross structural changes and cell death. Similarly, following injury, functional changes can occur in the absence of substantive structural changes. These more subtle effects can often be detected using functional tools such as the electroretinogram. Moreover, the electroretinogram is a sensitive and complementary means to quantify treatment efficacy. Here, we describe in vivo electroretinography for assessing ganglion cell injury in rodent models., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Developing easy-to-access biomarkers is crucial in Major Depressive Disorder. The retina has already been suggested as relevant. However, there is a need for a global and local assessment of whole retinal function using a reproducible, standardized protocol allowing for comparison across studies. Our aim is to assess whole retinal function in patients with actual unipolar Major Depressive Episode (MDE) using pattern, flash and multifocal electroretinogram (ERG) according to the International Society for Clinical Electrophysiology of Vision standardized protocols.Methods: We assessed retinal function in 14 males and females with MDE, diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, and in age- and sex-matched healthy controls.Results: Comparing the patients with the controls, we observed the following using multifocal ERG: a significant increase in N1 peak time in ring 3 and a decrease in P1 amplitude in ring 2; using pattern ERG: a significant increase in P50 peak time; using flash ERG: a decrease in a- and b-wave peak time and an increase in the b-wave amplitude in dark-adapted 3.0, a decrease in a- and b-wave peak time and an increase in both wave amplitudes in light-adapted 3.0, and a decrease in the b-wave peak time in light-adapted flicker.Limitations: Sample size. Contribution of pharmacological treatments to the outcomes cannot be formally excluded.Conclusions: Patients with MDE exhibit delayed signaling in the central retina and hyperreactivity to light in the periphery. Central retinal function may be a marker of psychomotor retardation and cognitive impairment in MDE. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between ophthalmic structure/function measures and five standardized quality of life (QoL) instruments, in patients with advanced age-related macular degeneration (AMD). Methods: We examined 20 AMD patients (ages 66–93 years) recruited from the Canberra Hospital Ophthalmology Department. Visual function measures included low and high contrast visual acuity (LCVA and HCVA) and measures from 10–2 Matrix visual fields (VF). Optical coherence tomography (OCT) quantified central retinal thickness (CRT), average macular thickness (AT), and retinal nerve fibre layer thickness (RNFL). The QoL instruments were the macular degeneration-related quality of life (MacDQoL), the National Eye Institute Visual Functioning Questionnaire (VFQ), its two face-recognition questions (A6 and 11), and the Geriatric Depression Scale (GDS). Pearson correlations, Canonical Correlation Analysis (CCA), and cross-validated stepwise-regression were used to examine the relationships between structure/function measures and the QoL instruments. Results: The selected models for the five instruments had R2 ranging from 0.65 ± 0.12 to 0.90 ± 0.05 (mean ± SD) and median F-statistics > 188. HCVA was strongly associated with all QoL except the GDS, for which CRT, AT and RNFL figured highly. RNFL was most important for MacDQoL, and 2nd for VFQ question-A6. Centrally weighted VF measures were rarely selected but global VF measures were common, especially for the overall NEI-VFQ questionnaire. CCA revealed that the structure/function measures and QoL instruments contained 2 statistically independent mechanisms. Conclusions: In patients with advanced AMD, CRT and HCVA were strong determinants of QoL instruments in AMD patients. [ABSTRACT FROM AUTHOR]

Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes., Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM)., Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not., Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations., Competing Interests: LS is listed as an inventor on National Aeronautics and Space Administration patents that cover some of the methods used in this paper but is not involved in any commercialization activities. Furthermore, none of NASA’s commercial licensees had any involvement in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 United States Government as represented by the Administrator of the National Aeronautics and Space Administration and Mr. Berneshawi, Dr. Goel, Mr. Anderson, Dr. Akay, Dr. Akay, and Dr. Leung. At least a portion of this work is authored by Ms. Seyedmadani, Mr. Tyson and Dr. Stone on behalf of the U.S government and, as regards Ms. Seyedmadani, Mr. Tyson and Dr. Stone, U.S. copyright protection does not attach to separable portions of a Work authored solely by U.S. Government employees as part of their official duties. The U.S. Government is the owner of foreign copyrights in such separable portions of the Work and is a joint owner (with any non-U.S. Government author) of U.S. and foreign copyrights that may be asserted in inseparable portions the Work. The U.S. Government retains the right to use, reproduce, distribute, create derivative works, perform, and display portions of the Work authored solely or co-authored by a U.S. Government employee. Non-U. S copyrights also apply.)

Purpose: To demonstrate an organic (retinal) amblyogenic defect in functional amblyopes not responding to treatment. Methods: Twenty-four children (Mean age: 5.9 ± 1.8 years; range: 4–10 years) with functional amblyopia were recruited for this study. All these children underwent complete ophthalmic and orthoptic evaluation. In addition, Kinetic Goldman Visual Fields (KGVF), Spectral Domain Optical Coherence Tomography (SD-OCT), full field flash electroretinograms (ffERG) and multifocal electroretinograms (mfERG) were also performed. Ratios were subsequently derived by comparing the amplitudes obtained from the amblyopic eye (AE) to the good eye (GE) for the a- and b-waves of the ffERG, as well as for the ring analysis of the mfERG. Results: KGVF showed a central scotoma of varying size (3°–7°) and density (absolute to relative), with increasing target size in 14/24 patients whose best post-treatment vision in the AE ranged from 20/100 to 20/40. The scotoma decreased in size and density with improving vision until a plateau of recovery was reached. The remaining 10/24 patients with a vision ≥ 20/30 showed no scotoma. SD-OCT showed no significant difference between the AE and GE. ffERG and mfERG were obtained in 18/24 patients. The ffERG AE/GE ratio was abnormal in 7 patients, 5 of which had large scotomas on KGVF. The mfERG ring 1 AE/GE ratio was significantly (p <.05) attenuated in 9/18 patients out of which 3 were no longer amblyopic. However, there was no significant difference (p >.05) in ring 1 AE/GE amplitude ratio between those who achieved 20/50–20/40 (.81 ±.26) and those with ≥ 20/25(.86 ±.25). Conclusions: The combined findings of central scotoma on KGVF and mfERG anomalies in patients who did not achieve optimal vision with treatment suggest an underlying organic defect impairing macular function. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate whether treatment with fingolimod (FTY) may induce functional changes on the macular pre-ganglionic retinal elements in patients affected by relapsing–remitting multiple sclerosis (RR-MS) without optic neuritis (ON). Methods: This case–control observational and retrospective study assessed multifocal electroretinogram (mfERG) responses from 35 healthy controls (mean age 43.58 ± 5.76 years), 41 patients with RR-MS without ON (mean age 40.64 ± 4.83 years, MS-noFTY group), and from 21 patients with RR-MS without ON (mean age 42.38 ± 12.34 years) and treated with fingolimod (Gilenya®, Novartis Europharm, 0.5 mg/day) (MS-FTY group). MfERG N1 and P1 implicit times (ITs), and N1–P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), 20–25° (R5). We considered R1 and R2 as "central macular areas" and R3, R4 and R5 as "more eccentric retinal areas". In the MS-FTY group, mfERG recordings were performed between 6 and 12 months (mean 7.2 ± 1.5 months) from the start of FTY. Results: In the MS-FTY group, the mean values of mfERG N1 and P1 ITs and RADs detected in both central macular areas (R1 and R2) and in more eccentric retinal areas (R3, R4 and R5) were not significantly different (p > 0.01) with respect to those of control and MS-noFTY groups. Conclusions: Our mfERG results suggest that the chronic use of FTY does not induce a dysfunction of pre-ganglionic retinal elements located in the 0–25° of central retina. Since FTY does not cause any retinal functional abnormality, we suggest that FTY treatment could not produce any toxic effect on pre-ganglionic retinal elements even in the absence of macular oedema. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is associated with cognitive impairment and dementia. The detection of cognitive impairment is important because this population is at higher risk of experiencing difficulties in the self-management of diabetes. Mild cognitive impairment (MCI) often remains undiagnosed due to lack of simple tools for screening at large scale. This represents an important gap in the patients' management because subjects with diabetes and MCI are at high risk of progressing to dementia. Due to its developmental origin as a brain-derived tissue, the retina has been proposed as a potential means of non-invasive and readily accessible exploration of brain pathology. Recent evidence showed that retinal imaging and/or functional tests are correlated with the cognitive function and brain changes in T2D. Simple retinal functional tests (i.e. retinal microperimetry) have proven to be useful as reliable tool for the cognitive evaluation and monitoring in patients with T2D>65 years. This review gives an overall update on the usefulness of retinal imaging in identifying patients with T2D at risk of developing dementia. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) and nanoplastics (NPs) are widely spreading in our living environment, accumulating in the human body and potentially threating human health. The retina, which is a terminally differentiated extension of the central nervous system, is essential for the visual system. However, the effects and molecular mechanisms of MPs/NPs on retina development and function are still unclear. Here, we investigated the effects and modes of action of polystyrene NPs (PS-NPs) on the retina using mice as a mammalian model species. Maternal PS-NP exposure (100 nm) at an environmentally realistic concentration of 10 mg L−1 (or 2.07 *1010 particles mL−1) via drinking water from the first day of pregnancy till the end of lactation (21 days after birth) caused defective neural retinal development in the neonatal mice, by depositing in the retinal tissue and reducing the number of retinal ganglion cells and bipolar cells. Exposure to PS-NPs retarded retinal vascular development, while abnormal electroretinogram (ERG) responses and an increased level of oxidative stress were also observed in the retina of the progeny mice after maternal PS-NP exposure. Metabolomics showed significant dysregulation of amino acids that are pivotal to neuron retinal function, such as glutamate, aspartate, alanine, glycine, serine, threonine, taurine, and serotonin. Transcriptomics identified significantly dysregulated genes, which were enriched in processes of angiogenesis, visual system development and lens development. Regulatory analysis showed that Fos gene mediated pathways could be a potential key target for PS-NP exposure in retinal development and function. Our study revealed that maternal exposure to PS-NPs generated detrimental effects on retinal development and function in progeny mice, offering new insights into the visual toxicity of PS-NPs. [Display omitted] • Maternal PS-NP exposure delayed retinal vessel development in progeny mice. • Maternal PS-NP exposure caused abnormal ERG responses in progeny mice. • Neurotransmitters related metabolites were significantly disturbed in retinas. • Fos gene mediated pathways could be a potential key target for PS-NP in retina. [ABSTRACT FROM AUTHOR]

The key to reducing the individual and societal burden of age-related macular degeneration (AMD)-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

Abstract Background A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer’s disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age. Methods Electroretinogram (ERG) and optical coherence tomography (OCT) was performed in APP/PS1 and wild type (WT) control mice every 3 months from 3 to 12 months of age. For functional assessment, the a- and b-wave of the ERG, amplitude of oscillatory potentials (OP) and the positive scotopic threshold response (pSTR) were quantified at each time point. For structural assessment, the inner and outer retinal thickness was segmented and measured from OCT scans. Episodic memory was evaluated at 6, 9 and 12 months of age using the novel object recognition test. Amyloid beta (Aβ) distribution in the hippocampus and the retina were visualised at 3, 6 and 12 months of age. Inter- and intra- group analysis was performed to study rate of change for each parameter between the two groups. Results Inter-group analysis revealed a significant difference in b-wave and OPs of APP/PS1 compared to WT controls starting from 3 months (p

Gernot Roessler, Michael Vobig, Peter Walter, Babac AE Mazinani Department of Ophthalmology, RWTH Aachen University, D-52057 Aachen, Germany Purpose: To determine ocular side effects of vardenafil with special regard to color vision and retinal function. Methods: This was a single center, randomized, double-blind, placebo-controlled, twofold crossover study with an administration of a single oral dose of two 20 mg tablets of BAY 38–9456 (vardenafil hydrochloride) or corresponding placebo in 24 healthy male subjects. Ocular investigations included Farnsworth–Munsell D100 color vision test, electroretinogram, and basic ophthalmological examinations like visual acuity, visual field, and slit-lamp of anterior segment and fundus. Results: Compared to placebo, administration of vardenafil hydrochloride lead to a temporary significant increase of Farnsworth–Munsell D100 total error score after 1 and 6 hours as well as in error lines 3 and 4 after 1 hour. Twenty-four hours after administration there was no significant alteration of total error score or of any error line. While latency of electroretinogram b-wave remained unaffected, amplitudes showed a significant decrease compared to placebo 1 hour following administration. While other ocular examinations did not reveal any differences in general some mild to moderate but no serious adverse events have been reported. Conclusion: Despite temporary changes in retinal function our study reports good tolerability of vardenafil in regard to ocular side effects. Keywords: phosophodiesterase-5 inhibitor, retinal function, color vision, electroretinogram, adverse events, placebo-controlled

Purpose: Using a quick electroretinography (ERG) protocol for rapid assessment of the retinal function of wild giant pandas (Ailuropoda melanoleuca) performed in field conditions to demonstrate the range of ERG recordings in giant pandas of unknown retinal status. Animals studied: Nine free range giant pandas. Procedure: All the giant pandas were anesthetized using an intramuscular dexMTZ injection, which is a combination of dexmedetomidine and tiletamine‐zolazepam. After 20 mins of dark adaptation, scotopic ERGs were obtained by using three flash intensities: −25 dB (0.0087 cd·s/m2), 0 dB (2.75 cd·s/m2), and +5 dB (8.7 cd·s/m2). Next, photopic ERGs were acquired using a single flash protocol with a flash intensity of 3.0 cd·s/m2 after 10 minutes of light adaptation. Results: In scotopic ERG at 0.0087 cd·s/m2, mean b‐wave amplitude and peak time were 82.26 µV (SD ± 16.65 and 95% CI 68.33‐96.18) and 66.97 ms (SD ± 10.86 and 95% CI 57.90‐76.05), respectively. This flash intensity was below a‐wave threshold and resulted in b waves with greater peak times compared to those with higher intensities. At 2.75 cd·s/m2, the mean a‐wave amplitude and peak time were 53.95 µV (SD ± 11.63 and 95% CI 44.23‐63.67) and 16.13 ms (SD ± 2.62 and 95% CI 13.94‐18.31), and mean b‐wave amplitude and peak time were 119.57 µV (SD ± 15.54 and 95% CI 106.57‐132.56) and 32.00 ms (SD ± 6.47 and 95% CI 26.59‐37.41). At 8.7 cd·s/m2, the mean a‐wave amplitude and peak time were 58.85 µV (SD ± 14.90 and 95% CI 46.39‐71.31) and 15.59 ms (SD ± 2.63 and 95% CI 13.40‐17.79), and the mean b‐wave amplitude and peak time were 132.97 µV (SD ± 22.11 and 95% CI 114.48‐151.46) and 32.66 ms (SD ± 6.87 and 95% CI 26.91‐38.40). In photopic ERG at 2.75 cd·s/m2, the mean a‐wave amplitude and peak time were 62.08 µV (SD ± 16.61 and 95% CI 48.19‐75.97) and 16.28 ms (SD ± 0.90 and 95% CI 15.53‐17.03), and the mean b‐wave amplitude and peak time were 214.93 µV (SD ± 70.41 and 95% CI 156.07‐273.80) and 33.09 ms (SD ± 1.27 and 95% CI 32.03‐34.15). Conclusion: Using a portable ERG system with a brief ERG protocol to perform electroretinographies in wild giant pandas is a practical, useful, and reliable method for the rapid assessment of their retinal function. [ABSTRACT FROM AUTHOR]

To investigate whether 17β-estradiol (βE2) can activate the NF-E2-related factor 2 (Nrf2) pathway to resist the downregulation of retinal function induced by light damage. Methods Two weeks after female SD rats were castrated, they were divided into the following six groups: control group (control), lightdamage group (LD), saline group, saline light-damage group (saline-LD), βE2 group, and βE2 light-damage group (βE2-LD). Rats in the light-damage were exposed to 8000-lux fluorescence for 12h after 18h of dark adaptation. Then electroretinogram (ERG), immunofluorescence, Real-time PCR and immunohistochemical detection were performed after one day of dark recovery. Results The results of ERG showed that ERG was lower in LD group than in control group (P<0.05). After light damage, ROS was increased and the mRNA expressions of antioxidant genes, such as Sod1, Sod2, Cat, Glrx1, Glrx2, Txn1, and Txn2 were decreased (all P<0.05). After βE2 administration, compared with those in saline-LD, ROS level was decreased, the levels of Nrf2 protein and antioxidant genes were increased, and ERG was recovered to a certain extent in βE2-LD (P<0.05). Conclusion βE2 can restore the function of rat retina, and its mechanism might be related to the upregulation of Nrf2 and antioxidant genes [ABSTRACT FROM AUTHOR]

Cdr1as is the abundant circular RNA (circRNA) in human and vertebrate retinas. However, the role of Cdr1as in the retina remains unknown. In this study, we aimed to generate a Cdr1as knockout (KO) mouse model and investigate the retinal consequences of Cdr1as loss of function. Through in situ hybridization (ISH), we demonstrated that Cdr1as is mainly expressed in the inner retina. Using CRISPR/Cas9 targeting Cdr1as, we successfully generated KO mice. We carried out ocular examinations in the KO mice until postnatal day 500. Compared with the age-matched wild-type (WT) siblings, the KO mice displayed increased b-wave amplitude of photopic electrophysiological response and reduced vision contrast sensitivity. Through small RNA profiling of the retinas, we determined that miR-7 was downregulated, while its target genes were upregulated. Taken together, our results demonstrated for the first time that Cdr1as ablation led to a mild retinal consequence in mice, indicating that Cdr1as abundance is not indispensable for retinal development and maintenance.

IntroductionMicroRNAs (miRNAs) are small, non-coding RNA molecules that have powerful regulatory properties, with the ability to regulate multiple messenger RNAs (mRNAs) and biological pathways. MicroRNA-223-3p (miR-223) is known to be a critical regulator of the innate immune response, and its dysregulation is thought to play a role in inflammatory disease progression. Despite miR-223 upregulation in numerous neurodegenerative conditions, largely in cells of the myeloid lineage, the role of miR-223 in the retina is relatively unexplored. Here, we investigated miR-223 in the healthy retina and in response to retinal degeneration.MethodsmiR-223-null mice were investigated in control and photo-oxidative damage-induced degeneration conditions. Encapsulated miR-223 mimics were intravitreally and intravenously injected into C57BL/6J wild-type mice. Retinal functional responses were measured using electroretinography (ERG), while extracted retinas were investigated by retinal histology (TUNEL and immunohistochemistry) and molecular analysis (qPCR and FACS).ResultsRetinal function in miR-223–/– mice was adversely affected, indicating that miR-223 may be critical in regulating the retinal response. In degeneration, miR-223 was elevated in the retina, circulating serum, and retinal extracellular vesicles. Conversely, retinal microglia and macrophages displayed a downregulation of miR-223. Further, isolated CD11b+ inflammatory cells from the retinas and circulation of miR-223-null mice showed an upregulation of pro-inflammatory genes that are critically linked to retinal inflammation and progressive photoreceptor loss. Finally, both local and systemic delivery of miR-223 mimics improved retinal function in mice undergoing retinal degeneration.ConclusionmiR-223 is required for maintaining normal retinal function, as well as regulating inflammation in microglia and macrophages. Further investigations are required to determine the targets of miR-223 and their key biological pathways and interactions that are relevant to retinal diseases. Future studies should investigate whether sustained delivery of miR-223 into the retina is sufficient to target these pathways and protect the retina from progressive degeneration.