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Purpose: To evaluate the effect of prophylactic anti-malarial chloroquine treatment, and its cessation, on electroretinographic (ERG) responses of captive African penguins., Methods: A brief ERG protocol ("QuickRetCheck") was recorded under mesopic conditions with manual restraint and no sedation or pupil dilation. Birds were recorded on two separate occasions, first while being treated with a daily chloroquine dose of 10 mg/kg for 12 days (n = 15, treatment group) and second after 4 months without chloroquine treatment (n = 6, off-treatment group). Three birds were recorded on both occasions. Three other birds from the flock that died were studied histopathologically., Results: Scotopic responses were unmeasurable in either recording and therefore were not analyzed. Mean a- and b-wave amplitudes of the mixed rod-cone responses to standard (3 cd·s/m 2 ) and high (10 cd·s/m 2 ) intensity flashes were higher in the off-treatment group. No difference in implicit times was observed. Sex, age, and number of previous chloroquine treatments did not affect ERG responses. Histopathology revealed Plasmodium spp.in the lungs, liver, and brain, but not in the eyes, of the necropsied birds, and there were no signs of retinitis or retinopathy., Conclusions: Daily chloroquine treatment was associated with attenuated ERG responses in penguins, which improve following cessation of treatment. Further work is warranted to establish a chloroquine dose that is efficacious yet has minimal adverse effects. Our results suggest that ERG responses of captive penguins undergoing ERG for any indication (such as prior to cataract surgery), must be evaluated in light of the birds' anti-malaria treatment status., (© 2021 American College of Veterinary Ophthalmologists.)

Gene augmentation therapy based on subretinal delivery of adeno-associated viral (AAV) vectors is proving to be highly efficient in treating several inherited retinal degenerations. However, due to potential complications and drawbacks posed by subretinal injections, there is a great impetus to find alternative methods of delivering the desired genetic inserts to the retina. One such method is an intravitreal delivery of the vector. Our aim was to evaluate the efficacy of two capsid-modified vectors that are less susceptible to cellular degradation, AAV8 (doubleY-F) and AAV2 (quadY-F+T-V), as well as a third, chimeric vector AAV[max], to transduce photoreceptor cells following intravitreal injection in sheep. We further tested whether saturation of inner limiting membrane (ILM) viral binding sites using a nonmodified vector, before the intravitreal injection, would enhance the efficacy of photoreceptor transduction. Only AAV[max] resulted in moderate photoreceptor transduction following intravitreal injection. Intravitreal injection of the two other vectors did not result in photoreceptor transduction nor did the saturation of the ILM before the intravitreal injection. However, two of the vectors efficiently transduced photoreceptor cells following subretinal injection in positive control eyes. Previous trials with the same vectors in both murine and canine models resulted in robust and moderate transduction efficacy, respectively, of photoreceptors following intravitreal delivery, demonstrating the importance of utilizing as many animal models as possible when evaluating new strategies for retinal gene therapy. The successful photoreceptor transduction of AAV[max] injected intravitreally makes it a potential candidate for intravitreal delivery, but further trials are warranted to determine whether the transduction efficacy is sufficient for a clinical outcome.

Objective: Our aim was to generate baseline optical coherence tomography (OCT) measurements of retinal thickness in female Beagles and to determine how these are affected by meridian, eccentricity, and age., Methods: Twenty-three female Beagles, including six puppies (<6 months old), six mature (1.8-8.2 years old), and 11 elderly dogs (>11 years old) were studied. Both retinas of each dog were scanned (in 4 principal meridians) using the Heidelberg Spectralis following ophthalmic examination, refraction, and sedation. In each eye and each meridian, total retinal, outer retinal, and nerve fiber layer (NFL) thickness were measured from the disc rim up to 6 mm peripherally., Results: The canine retina is thickest dorsally and thinnest ventrally. Total retinal, outer retinal, and NFL thickness decrease progressively and significantly as a function of eccentricity. The greatest eccentricity-dependent thinning occurs dorsally. This thinning is due mostly to NFL tapering, while the eccentricity-dependent change in outer retinal thickness is more moderate, especially in the lateral meridian, possibly due to the presence of the visual streak. The retina is thickest in puppies, but there were no significant differences between mature and elderly dogs., Conclusions: Our results provide normative values for total, outer, and inner retinal thickness in female dogs and may facilitate OCT use in the diagnosis of canine glaucoma and inherited retinopathies., (© 2019 American College of Veterinary Ophthalmologists.)

Purpose: To establish whether there is cone contribution to retinal function and structure in chinchillas (Chinchilla lanigera), in view of the prevailing notion that this species possesses a pure rod retina., Methods: Photopic electroretinography (ERG) responses to high-intensity flashes (10 and 25 cd*s/m 2 ) were recorded unilaterally in six pigmented chinchillas following 10 minutes of light adaptation (30 cd/m 2 ). Retinas of two animals were studied histologically, and immunohistochemistry (IHC) was conducted to detect the presence of short and medium/long wavelength cone photoreceptors., Results: ERG recordings revealed photopic responses, albeit of low amplitudes. Histopathology demonstrated presumptive cone inner segments in the photoreceptor layer. Presence of cone photoreceptors was confirmed by IHC. Cone density was higher in the central retina, and red/green cones outnumbered blue cones., Conclusions: Our results provide convincing evidence for the presence of functioning cone photoreceptors in the chinchilla retina, disproving the established belief that the species has a pure rod retina., (© 2018 American College of Veterinary Ophthalmologists.)

Purpose: Our aim was to compare the electroretinographic (ERG) responses of two eyes obtained by consecutive unilateral recordings to those obtained by a simultaneous bilateral recording in sheep., Methods: Eight sheep underwent two full-field ERG recordings, using two recording strategies of the standard ISCEV protocol: consecutive unilateral recordings of one eye after the other, and simultaneous bilateral recording of both eyes. The order of recording strategy within an animal (unilateral/bilateral), eye recording sequence in the unilateral session (OD/OS), and amplifier channel assignment for each eye were all randomized. To test whether duration of dark adaptation and/or anesthesia affect the results, the ISCEV protocol was recorded bilaterally in six additional eyes following 38 min of patched dark adaptation, as was done for the second eye recorded in the consecutive unilateral recordings., Results: The second recorded eye in the unilateral session had significantly higher scotopic b-wave amplitudes compared to the first recorded eye and to the bilaterally recorded eyes. A-wave amplitudes of the dark-adapted mixed rod-cone responses to a high-intensity flash were also significantly higher in the second eye compared to the first eye recorded unilaterally and to the bilaterally recorded eyes. Light-adapted responses were unaffected by the recording strategy. When the ISCEV protocol was recorded after 38 min of dark adaptation, the scotopic responses were higher than in the first eyes, and similar to those of the second eyes recorded unilaterally, suggesting that indeed the longer duration of anesthesia and dark adaptation are responsible for the increased scotopic responses of the second eye., Conclusions: Consecutive unilateral ERG recordings of two eyes result in higher amplitudes of the dark-adapted responses of the eye recorded second, compared to the eye recorded first and to bilaterally recorded eyes. The differences in scotopic responses can be attributed to different duration of dark adaptation and/or anesthesia of the two consecutively recorded eyes. Photopic responses are not affected. Therefore, simultaneous bilateral ERG responses should be recorded when possible, especially for evaluation of scotopic responses.

Recombinant adeno associated viruses (AAV) are the most commonly used vectors in animal model studies of gene therapy for retinal diseases. The ability of a vector to localize and remain in the target tissue, and in this manner to avoid off-target effects beyond the site of delivery, is critical to the efficacy and safety of the treatment. The in vivo imaging system (IVIS) is a non-invasive imaging tool used for detection and quantification of bioluminescence activity in rodents. Our aim was to investigate whether IVIS can detect localization and biodistribution of AAV5 vector in mice following subretinal (SR) and intravitreal (IVT) injections. AAV5 carrying firefly luciferase DNA under control of the ubiquitous cytomegalovirus (CMV) promoter was injected unilaterally IVT or SR (in the central or peripheral retina) of forty-one mice. Luciferase activity was tracked for up to 60 weeks in the longest surviving animals, using repeated (up to 12 times) IVIS bioluminescence imaging. Luciferase presence was also confirmed immunohistochemically (IHC) and by PCR in representative animals. In the SR group, IVIS readings demonstrated luciferase activity in all (32/32) eyes, and luciferase presence was confirmed by IHC (4/4 eyes) and PCR (12/12 eyes). In the IVT group, IVIS readings demonstrated luciferase activity in 7/9 eyes, and luciferase presence was confirmed by PCR in 5/5 eyes and by IHC (2/2 eyes). In two SR-injected animals (one each from the central and peripheral injection sites), PCR detected luciferase presence in the ipsilateral optic nerves, a finding that was not detected by IVIS or IHC. Our results show that when evaluating SR delivery, IVIS has a sensitivity and specificity of 100% compared with the gold standard PCR. When evaluating IVT delivery, IVIS has a sensitivity of 78% and specificity of 100%. These finding confirm the ability of IVIS to detect in-vivo localized expression of AAV following SR delivery in the retina up to 60 weeks post-treatment, using repeated imaging for longitudinal evaluation, without fading of the biological signal, thereby replacing the need for post mortem processing in order to confirm vector expression. However, IVIS is probably not sensitive enough, compared with genome detection, to demonstrate biodistribution to the optic nerve, as it could not detect luciferase activity in ipsilateral optic nerves following SR delivery in mice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To study retinal morphology and function in the collared peccary, an ungulate species distantly related to the domestic pig., Animal Studies: Twenty captive peccaries anesthetized for routine health examinations. Procedures No abnormalities were noted on a complete ophthalmic examination. Fundi were examined ophthalmoscopically and photographed. The eyes of an individual that died of unrelated, nonocular reasons were studied histologically and by immunohistochemistry. Scotopic, mixed rod-cone, and photopic electroretinography (ERG) responses were recorded using the 'QuickRetCheck' (n = 6) and 'Dog diagnostic' (n = 5) protocols of the Handheld Multispecies ERG (HMsERG)., Results: The fundus of the peccary is atapetal, with varying amounts of pigmentation seen ophthalmoscopically, and histologically in the retinal pigment epithelium (RPE) and choroid. The retina is holangiotic with dichotomously branching vessels. These cross, and apparently loop on, the optic disk surface, but no venous circle was seen. Immunohistochemistry suggests a high concentration of cone photoreceptors with red/green cones being more abundant than blue cones. Rod ERG responses were very low with no evident dark adaptation. Mixed rod-cone and cone ERG response amplitudes were low compared to those of domestic pigs, but quite similar to those of minipigs., Conclusions: To the best of our knowledge, this study describes the collared peccary's retinal features for the first time. A comparison of our findings with data from other ungulate species shows some similarities between the peccary and pig retinas. Further studies are warranted to determine whether the peccary can be used alongside the pig as an animal model in retinal studies., (© 2017 American College of Veterinary Ophthalmologists.)

Purpose: The aim of this study was to evaluate an innovative approach for closing retinal tears using DuraSeal™ (DS) hydrogel sealant in a rabbit model., Methods: Retinal detachment with a small tear was performed on 20 New Zealand rabbits. Thereafter, rabbits were divided into two groups; the experimental group received a transscleral injection of 0.1 ml DS into the subretinal space whereas the control group received sham injection of saline. Eyes were clinically evaluated using indirect ophthalmoscopy, retinal function was recorded in ten rabbits by electroretinography and the sealant's toxicity was evaluated histopathologically., Results: We found that the DS hydrogel was easily injected transsclerally into the subretinal space of the detached retinas with no major complications. Retinal reattachment was seen in both groups within 2 weeks with no toxicity to the sensory retina. There were no significant differences in retinal function between groups., Conclusion: Subretinal injection of hydrogel through a transscleral route is easy to perform and may open a new avenue in the treatment of retinal detachment. However, the efficacy of the DS as a tamponade for sealing retinal tear is yet to be definite. Long-term clinical, functional, and toxicological studies are needed to evaluate its full potential for clinical applications.

The transcription factor Sip1 (Zeb2) plays multiple roles during CNS development from early acquisition of neural fate to cortical neurogenesis and gliogenesis. In humans, SIP1 (ZEB2) haploinsufficiency leads to Mowat-Wilson syndrome, a complex congenital anomaly including intellectual disability, epilepsy and Hirschsprung disease. Here we uncover the role of Sip1 in retinogenesis. Somatic deletion of Sip1 from mouse retinal progenitors primarily affects the generation of inner nuclear layer cell types, resulting in complete loss of horizontal cells and reduced numbers of amacrine and bipolar cells, while the number of Muller glia is increased. Molecular analysis places Sip1 downstream of the eye field transcription factor Pax6 and upstream of Ptf1a in the gene network required for generating the horizontal and amacrine lineages. Intriguingly, characterization of differentiation dynamics reveals that Sip1 has a role in promoting the timely differentiation of retinal interneurons, assuring generation of the proper number of the diverse neuronal and glial cell subtypes that constitute the functional retina in mammals., Competing Interests: The authors declare no competing or financial interests., (© 2016. Published by The Company of Biologists Ltd.)

Achromatopsia is a hereditary form of day blindness caused by cone photoreceptor dysfunction. Affected patients suffer from congenital color blindness, photosensitivity, and low visual acuity. Mutations in the CNGA3 gene are a major cause of achromatopsia, and a sheep model of this disease was recently characterized by our group. Here, we report that unilateral subretinal delivery of an adeno-associated virus serotype 5 (AAV5) vector carrying either the mouse or the human intact CNGA3 gene under the control of the red/green opsin promoter results in long-term recovery of visual function in CNGA3-mutant sheep. Treated animals demonstrated shorter maze passage times and a reduced number of collisions with obstacles compared with their pretreatment status, with values close to those of unaffected sheep. This effect was abolished when the treated eye was patched. Electroretinography (ERG) showed marked improvement in cone function. Retinal expression of the transfected human and mouse CNGA3 genes at the mRNA level was shown by polymerase chain reaction (PCR), and cone-specific expression of CNGA3 protein was demonstrated by immunohistochemisrty. The rescue effect has so far been maintained for over 3 years in the first-treated animals, with no obvious ocular or systemic side effects. The results support future application of subretinal AAV5-mediated gene-augmentation therapy in CNGA3 achromatopsia patients.

The vertebrate retina, which is part of the central nervous system, is a window into the brain. The present study investigated the extent to which the retina can be used as a model for studying the pathological effects of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD). Immunohistochemical studies of retinas from young (4 months old) apoE4-targeted replacement mice and from corresponding mice which express the AD benign apoE3 allele, revealed that the density of the perikarya of the different classes of retinal neurons was not affected by apoE4. In contrast, the synaptic density of the retinal synaptic layers, which was assessed immunohistochemically and by immunoblot experiments, was significantly lower in the apoE4 than in the apoE3 mice. This was associated with reduced levels of the presynaptic vesicular glutamatergic transporter, VGluT1, but not of either the GABAergic vesicular transporter, VGaT, or the cholinergic vesicular transporter, VAChT, suggesting that the glutamatergic nerve terminals are preferentially affected by apoE4. In contrast, the post synaptic scaffold proteins PSD-95 and Gephyrin, which reside in excitatory and inhibitory synapses, respectively, were both elevated, and their ratio was not affected by apoE4. Electroretinogram (ERG) recordings revealed significant attenuation of mixed rod-cone responses in dark-adapted eyes of apoE4 mice. These findings suggest that the reduced ERG response in the apoE4 mice may be related to the observed decrease in the retinal nerve terminals and that the retina could be used as a novel model for non-invasive monitoring of the effects of apoE4 on the CNS.

Purpose: Age-related changes in retinal ganglion cell (RGC) activity may impact results of long-term functional studies of disease progression and drug efficacy in humans and animal models. Though these changes can be evaluated using the pattern electroretinogram (PERG), longitudinal studies suffer from failure of follow-up from birth to senescence. Our aim was to perform a long-term, longitudinal study evaluating age-related changes in the rat PERG, by conducting repeated, serial recordings in the same animals. Additionally, we tested the hypothesis that neuroprotective treatment using glatiramer acetate (COP-1) immunization may delay age-related decline in function., Methods: PERG was recorded from six untreated and seven Cop-1-immunized Lewis rats. Recordings were conducted at 2- to 4-week intervals from age 5 to 59 weeks., Results: PERG amplitudes significantly increased between 5 to 7 weeks of age, and decreased from age 30 weeks onward (P = 0.016 and 0.0002, respectively). Amplitudes fluctuated insignificantly in weeks 7 to 30, with peak amplitudes reached at age 18 weeks in most spatial frequencies tested. N2 implicit times were shortened, mainly during weeks 5 to 18 and 40 to 59 (P < 0.001). PERG amplitudes of Cop-1-treated rats were similar to controls (P = 0.137) but peaked later (22-26 weeks)., Conclusions: This 14-month-long study provided accurate measurement of developmental and aging changes of rat RGC function using repeated testing of individual animals. We found functional development to extend beyond the reported period of structural changes. Cop-1-immunized rats were not protected against age-related decline in inner retinal function, although their PERG maturation dynamics were altered.

Background: In recent years, the rat has become a commonly-used animal model for the study of retinal diseases. Similar to other tissues, the retina undergoes significant functional changes during maturation. Aiming to gain knowledge on additional aspects of retinal maturation, we performed gene expression and histological analyses of the rat retina during maturation., Methods: Rat retinas were dissected at three time points. Histological examination of the samples was performed, and the expression levels of retinal genes were evaluated using the rat whole-genome microarray system. Quantitative real-time PCR analysis was used to validate selected expression patterns. Various statistical and bioinformatic tools were used to identify differentially expressed genes., Results: The microarray analysis revealed a relatively high number of highly expressed non-annotated genes. We identified 603 differentially expressed genes, which were grouped into six clusters based on changes in expression levels during the first 20 weeks of life. A bioinformatic analysis of these clusters revealed sets of genes encoding proteins with functions that are likely to be relevant to retinal maturation (potassium, sodium, calcium, and chloride channels, synaptic vesicle transport, and axonogenesis). The histological analysis revealed a significant reduction of outer nuclear layer thickness and retinal ganglion cell number during maturation., Conclusions: These data, taken together with our previously reported electrophysiological data, contribute to our understanding of the retinal maturation processes of this widely-used animal model.

Background and Objectives: To functionally evaluate the efficacy of glatiramer acetate (Cop-1) as a neuroprotective treatment for laser-induced retinal injuries in rats., Study Design/materials and Methods: Using standard lasering and flash ERG techniques, we evaluated the effect of photocoagulation and of Cop-1 treatment on retinal function 3, 20, and 60 days after covering one-half of the retina with of 23 rats with argon laser lesions., Results: Significant neuroprotective effects of Cop-1 treatment on functional recovery were observed 20 and 60 days after retinal photocoagulation. Two months post-lasering, the amplitude of electroretinographic signals in lasered eyes (mean+/-SEM) was 99.5+/-10.2% of that of intact eyes in the Cop-1-treated group and 85.8+/-5.5% in the untreated lasered control group (P<0.05)., Conclusions: Cop-1 immunization in rats is neuroprotective against laser-induced injuries to the outer retina and improves functional recovery of the injured retina. Studies have documented effective neuroprotective treatment after laser damage to myelinated neurons, but this is the first report of neuroprotection of nonmyelinated neurons., ((c) 2008 Wiley-Liss, Inc.)

Purpose: The retina of some avian species contains two macular regions, making it an excellent model for retinal, and especially macular, development. Previous studies have provided evidence of the involvement of Pax6 in macular development. The purpose was to perform a comprehensive expression analysis of Pax6 isoforms in different regions of the pigeon retina., Methods: The different mRNA transcripts were amplified by RT-PCR and characterized by sequencing analysis. Semiquantitative PCR and quantitative real-time PCR analyses were used to study the level of expression of each transcript. Western blot analysis was performed on both the cytosolic and nuclear cell fractions., Results: An evolutionary analysis of all human-chicken retinal homologues revealed that Pax6 is one of the most conserved retinal genes. By alternative splicing and alternative initiation of transcription, Pax6 produces 41 different mRNA transcripts, encoding 17 protein isoforms in the pigeon retina, five of which are paired-less cytosolic proteins. Semiquantitative expression analysis revealed that the short, paired-less, transcripts have a relatively high level of expression. Quantitative real-time PCR analysis of the central macula, red area, and peripheral retina revealed a spatial and temporal expression profile indicating that many Pax6 transcripts take a part in macular development., Conclusions: These data suggest that Pax6, a highly conserved gene, can maintain evolutionarily conserved variability at the protein level by alternative splicing and initiation mechanisms, allowing it to perform multiple functions. The variability in the length of the paired domain suggests that the different Pax6 isoforms activate different sets of genes.

Though the rat is increasingly used as an animal model in ophthalmic research, including the study of glaucoma, little is known about age-related changes in its inner retinal function. The aim of this study was to evaluate these changes in the rat during the first 18 weeks of life. The pattern electroretinogram (PERG) was used to monitor inner retinal activity in 16 developing rats. In each animal, recordings were conducted at ages 3, 5, 7, 11, 14 and 18 weeks to assess age-related changes in function. Signals were evoked by five stimuli of progressively increasing check width (subtending 82-1312 arc minutes of visual angle) that were projected directly onto the fundus through a specially modified ophthalmoscope which allowed visual and manual control of stimulus quality. Poor signal:noise ratio prevented signal analysis at age 3 weeks. Subsequently, PERG amplitude increased significantly, up to 242% (depending on stimulus check width), during weeks 5-11. After peaking at 11 weeks, signal amplitude declined moderately. Signal latency mirrored that of amplitude, decreasing during the first 11 weeks, and then increasing steadily. Latency was not affected by stimulus check width. Age was highly correlated with P1 latency (R(2)=0.80) and moderately correlated with N2 latency (R(2)=0.52). Therefore, we propose that studies of inner retinal diseases (such as glaucoma) in the rat model should use age-matched controls, as electrophysiological results may be confounded by age-related changes. The rat PERG undergoes many of the age-related changes that have been reported in humans, and thus may serve as an animal model to study development of inner retinal function.

Background and Objectives: To determine the threshold for electrophysiological detection of functional changes after laser photocoagulation in rats, and to correlate the functional damage with retinal morphology., Study Design/materials and Methods: Argon-laser lesions, covering a quarter or half of the retina, were produced in the right eyes of 25 rats. Eyes were evaluated by flash electroretinography (ERG) and histologically at 3, 21, and 60 days after lasering., Results: Lasering of half the retina, but not of a quarter, produced a significant decrease in signals at all time points. Some functional recovery was evident 60 days after injury, and was consistent with concurrent morphological healing., Conclusions: In rats, lasering of half the retina, but not a quarter, leads to significant deficits in outer retinal functions over a 2-month period. Thereafter some recovery occurs, presumably as a result of migration of photoreceptors from undamaged areas and their retinal remodeling., (Copyright 2006 Wiley-Liss, Inc.)

Much work remains to be done to establish the clinical usefulness of the RFI for early diagnosis and treatment guidance. The discoveries obtained by functional optical imaging of the neocortex in the last 15 years and the recent RFI studies of the eyes of normal subjects and patients with diabetic retinopathy, glaucoma, and age-related macular degeneration suggest that functional optical imaging of the retina is likely to become a multi-modality powerful clinical tool.

Purpose: To investigate the cellular sources underlying the functional damage observed by multifocal electroretinography (mfERG) responses of glaucomatous eyes of monkeys., Methods: First- and second-order (K1 and K2, respectively) mfERG responses of three normal and three experimentally induced glaucomatous eyes of cynomolgus monkeys were measured at two different levels of luminance. Retinal contributors to the responses were isolated by intravitreal injections of pharmacological agents that suppress specific retinal cells. gamma-Aminobutyric acid (GABA) and glycine were administered to block inner retinal function, followed by 2-amino-4-phosphonobutyric acid (APB), to block ON-bipolar cells., Results: An inner retinal component removed by GABA and glycine was found in both the normal and glaucomatous eyes. However, it was attenuated in the latter, correlating with changes observed in the baseline K1 responses. Delays in the latency of outer retinal components were found in the responses of the glaucomatous eyes. K2 responses were dominated by an inner retinal contribution and were diminished in the responses of glaucomatous eyes. The outer retina responded to increased luminance with a shorter implicit time. A distinct wave part of the inner retinal component responded to increased luminance with increased amplitudes., Conclusions: The integration of the retinal sources forming the mfERG response was compared between normal and glaucomatous monkey eyes. Both inner and outer retinal functions were aberrant in the responses of the glaucomatous eyes, with the attenuation of the inner retinal function more conspicuous. Nevertheless, glaucomatous eyes retained certain inner retinal activity, despite the advanced stage of disease. K2 responses were more sensitive to glaucomatous changes than were K1 responses.

Purpose: To evaluate the effect of contrast and luminance attenuation on the multifocal electroretinogram (mfERG) responses of normal and glaucomatous eyes of cynomolgus monkeys., Methods: Nine adult male cynomolgus monkeys with unilateral experimentally induced glaucoma were used. Hypertension-induced damage was confirmed by tomography of the optic disc. mfERGs were recorded with five different stimulus contrasts and/or luminance settings. The first-order and the first slice of second-order responses were analyzed., Results: Waveforms of normal and glaucomatous eyes differed in shape and amplitude. Second-order responses contributed to first-order responses of the signals in the normal eyes, but made a negligible contribution to the signals in the glaucomatous eyes. Contrast and luminance attenuation affected both first- and second-order responses. The differences between signals in normal and glaucomatous eyes were sufficiently large for an unsupervised clustering algorithm to achieve accurate segregation., Conclusions: The observations in this study indicate that outer and inner retinal generators participate in first-order mfERG responses and that both inner and outer retinal contributors respond to contrast and luminance changes in stimulus. The hypertension-induced changes in the mfERG furthermore suggest damage to both inner and outer retina.

Purpose: Review octopus ocular anatomy and describe the histopathologic findings in three octopuses diagnosed with phakitis and retinitis. Animals: Two common octopuses (Octopus vulgaris) and one giant Pacific octopus (Enteroctopus dofleini) with a history of ophthalmic disease. Methods: A literature search was performed for the ocular anatomy section. Both eyes from all three octopuses, and two control eyes, were submitted for histopathologic evaluation. Hematoxylin and eosin stain was used for standard histopathologic evaluation; GMS stain was used to screen for fungi, gram stain for bacteria; and Fite's acid fast stain for acid fast bacteria. Results: Anatomically, the anterior chamber of the octopus has direct contact with ambient water due to an opening in the dorsal aspect of a pseudocornea. The octopus lens is divided into anterior and posterior segments. The anterior half is exposed to the environment through the opening into the anterior chamber. Neither part of the lens has a lens capsule. The retina is everted, unlike the inverted vertebrate retina, and consists of just two layers. Histopathology revealed inflammatory phakitis and retinitis of varying severity in all six eyes of the study animals. No intraocular infectious organisms were recognized but one common octopus eye had clusters of coccidian parasites, identified as Aggregata sp., in extraocular tissues and blood vessels. Conclusion: We describe inflammatory phakitis and retinitis in two species of octopuses. The underlying cause for the severe intraocular response may be direct intraocular infection, water quality, an ocular manifestation of a systemic disease, or natural senescence. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine whether pre‐operative electroretinography (ERG) predicts postoperative vision in dogs undergoing retinal reattachment surgery (RRS). Methods: This 18‐month prospective study recorded signalment, duration, cause, and extent of retinal detachment and pre‐operative vision status. Rod and mixed rod‐cone ERG responses were recorded prior to RRS. Referring veterinary ophthalmologists assessed vision 2 months postoperatively. Results: Thirty dogs (40 affected eyes) aged 4 months to 12.1 years were included. The detachment extent was 150°–320° in 15 of 40 eyes, 360° in 24 of 40 eyes, and not recorded in one eye. Most dogs had a genetic predisposition for retinal detachment. Eight eyes of seven dogs had previous cataract surgery. Mean estimated duration of detachment prior to surgery was 24.5 ± 19.6 days. Pre‐operatively, 34 of 40 eyes were blind, two of 40 eyes were sighted, and four of 40 eyes had severely diminished vision. Compared to normative ERG values in our clinics, pre‐operative ERGs were classified as “normal” in five of 40 eyes, “attenuated” in seven of 40 eyes, and “flat” in 28 of 40 eyes. Following RRS, the retina was fully reattached in all operated eyes. Two‐month postoperatively, 30 of 40 eyes had “normal” vision as defined by referring veterinary ophthalmologists, six of 40 eyes had “limited” or “diminished” vision and four of 40 eyes were blind. Normal vision was regained in 12 of 12 (100%) of eyes with normal or attenuated pre‐operative ERG's, but only in 18 of 28 (64%) of eyes with flat pre‐operative ERG ‘s (Linear‐by‐linear test, P = 0.029). Conclusions: A recordable pre‐operative ERG, even if attenuated, is associated with return of vision in canine RRS patients, and is a favorable prognostic indicator. [ABSTRACT FROM AUTHOR]

Abstract: With the increasing use of the rat as an animal model for glaucoma and for the evaluation of neuroprotective treatments, there is a need for a sensitive test of retinal ganglion cell (RGC) function in this species. The aims of this study were to detect functional abnormalities of the inner retina in a rat model of high intraocular pressure (IOP) using the pattern electroretinogram (PERG), and to correlate them with morphometric analysis of RGC survival and the functional integrity of the inner retina. Unilateral ocular hypertension was induced in 17 Lewis rats through laser photocoagulation. Pattern ERGs were recorded prior to lasering and 3 weeks later, using a series of shifting patterns of decreasing spatial frequency projected directly onto the animals'' fundus. IOP was measured at the same intervals, and the number of surviving RGCs estimated. Low amplitude PERG signals could be recorded in response to a narrow grating of 0·368 cycles per degree (cpd), and increased with stimulus size. Lasering caused mean (±s.d.) IOP to increase significantly from 18·3±4·5 (baseline) to 29·8±8·8mmHg within 3 weeks (p&#60;0·0001). At this time, PERG amplitudes were significantly reduced (p&#60;0·05), declining an average of 45% compared to the normotensive, control eyes. No outer retinal damage was observed, but the mean number of RGCs decreased significantly (p&#60;0·001), from 2 525·0±372·4 to 1 542·8±333·8cells per mm2.This decrease in RGC number was significantly (p=0·03) correlated the decrease in PERG amplitude. The correlation between functional integrity of the inner retina and the rat PERG was further demonstrated by intravitreal tetrodotoxin injections, which temporarily abolished the PERG but did not affect outer retinal activity, reflected in the flash ERG. The evidence for early functional deficits, combined with tonometry and documentation of correlated ganglion cells loss, confirms the sensitivity of this diagnostic tool and the validity and importance of this animal model in glaucoma research. [Copyright &y& Elsevier]