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Purpose: HM-3, an RGD-modified endostatin-derived polypeptide, is a potent angiogenesis inhibitor synthesized in our laboratory. This study investigated the HM-3 pharmacokinetics of intravitreally administered in mice eyes as an anti-angiogenesis drug for age-related macular degeneration. Materials and methods: A total of 288 C57BL/6J mice were evaluated and divided into four groups. Each mouse in different groups received single bilateral intravitreal injection with HM-3. The concentrations of HM-3 in choroid/sclera, retina and serum were determined by indirect competitive enzyme-linked immunosorbent assay. Results: After intravitreal administration of doses of 0, 10, 20 and 40 μg/eye HM-3, the observed maximum concentration ( Cmax) was 12.98 ± 1.42, 27.87 ± 3.64 and 55.96 ± 11.94 ng/mg, respectively; and the total area under the curve (AUCtot) was 739.23 ± 190.32, 1171.74 ± 528.75 and 1777.71 ± 511.64 h ng/mg; the elimination half-life ( T1/2) in retina was 104.85 ± 36.90, 107.42 ± 35.25 and 101.12 ± 15.82 h; the mean residence time (MRT) was 172.46 ± 63.80, 164.70 ± 52.72 and 181.32 ± 26.01 h, respectively. In choroid/sclera, the Cmax was 5.29 ± 0.34, 6.29 ± 1.87 and 8.14 ± 0.71 ng/mg, respectively; AUCtot was 579.03 ± 56.50, 762.20 ± 201.09 and 720.91 ±243.87 h ng/mg; T1/2 was 54.04 ± 25.99, 59.33 ± 24.46 and 47.10 ± 10.00 h, respectively; MRT was 139.98 ± 23.93, 155.43 ± 17.81 and 136.45 ± 18.17 h, respectively. But in serum, the Cmax was 482.00 ± 38.97, 493.94 ± 97.64 and 1033.10 ± 276.33 ng/ml, respectively; AUCtot was 21128.55 ± 4683.68, 53444.57 ± 16963.99 and 53164.84 ±1535.06 h ng/ml; T1/2 was 48.39 ± 14.89, 47.96 ± 12.97 and 49.98 ± 30.07 h, respectively; MRT was 108.6 ± 47.17, 159.76 ± 18.82 and 125.33 ± 21.41 h, respectively. Conclusions: The pharmacokinetic profiles of intravitreal administration HM-3 provide the basis for the development of reasonable dosing regimens of clinical choroidal neovascularization (CNV) treatment. However, the vitreous and blood retinal barrier might be barriers to drug distribution and diffusion. In addition, fluid flow for the anterior transport and choroidal blood circulation might play important roles for multiple peaking. Carrying out the research into pharmacokinetics of HM-3 provides the information for laying down drug delivery scheme in mice model of CNV. [ABSTRACT FROM AUTHOR]

Using the paradigm of in vitro differentiation of hESCs/iPSCs into retinal pigment epithelial (RPE) cells, we have recently profiled mRNA and miRNA transcriptomes to define a set of RPE mRNA and miRNA signature genes implicated in directed RPE differentiation. In this study, in order to understand the role of DNA methylation in RPE differentiation, we profiled genome-scale DNA methylation patterns using the method of reduced representation bisulfite sequencing (RRBS). We found dynamic waves of de novo methylation and demethylation in four stages of RPE differentiation. Integrated analysis of DNA methylation and RPE transcriptomes revealed a reverse-correlation between levels of DNA methylation and expression of a subset of miRNA and mRNA genes that are important for RPE differentiation and function. Gene Ontology (GO) analysis suggested that genes undergoing dynamic methylation changes were related to RPE differentiation and maturation. We further compared methylation patterns among human ESC- and iPSC-derived RPE as well as primary fetal RPE (fRPE) cells, and discovered that specific DNA methylation pattern is useful to classify each of the three types of RPE cells. Our results demonstrate that DNA methylation may serve as biomarkers to characterize the cell differentiation process during the conversion of human pluripotent stem cells into functional RPE cells. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we study the following Linear Complementarity problem: f : R n →R n , find x ≥0, such that f(x)≥0, x T f (x)=0.We use Poineare-Bohn''s homotopy invariance theorem of degree to derive an alternative theorem, and give a new exceptional families. Based on this result, for the nonlinear complementarity problems with a quasi- P * -mapping or a P(τ, α, β) -mapping or a semi-monotone mapping, a sufficiently condition is established to assure the existence and boundedness of solution curve [Copyright &y& Elsevier]

Transfer RNA‐derived fragments (tRFs) represent a novel class of non‐coding RNA transcripts that possess specific biological functions. However, the involvement of tRFs in retinal microvascular diseases remains poorly understood. In this study, we aimed to reveal whether modulation of tRF‐30 expression could attenuate pathological retinal neovascular diseases. Our findings demonstrate a significant upregulation of tRF‐30 expression levels in both in vivo models of diabetic retinopathy (DR) and in vitro endothelial sprouting models. Conversely, inhibition of tRF‐30 expression suppressed the formation of abnormal neovascularization in the retina in vivo, while reducing the proliferation and migration activity of retinal vascular endothelial cells in vitro. We also found that tRF‐30 modulates retinal neovascularization through the tRF‐30/TRIB3/signal transducer and activated transcription 3 signaling pathway. Furthermore, we validated a significant upregulation of tRF‐30 expression levels in the vitreous humor of DR patients, with high levels of both validity and specificity in diagnostic testing. Collectively, our findings highlight a pro‐angiogenic role for tRF‐30 in DR. Intervening in the tRF‐30 signaling pathway may represent a promising prevention and treatment strategy for retinal angiogenesis. [ABSTRACT FROM AUTHOR]

This cross-sectional study aims to investigate the prevalence and causes of visual impairment (VI) and blindness in Jiangsu Province, China in 2022 during the COVID-19 pandemic. Participants (n = 13,208, aged 18–93) underwent comprehensive ocular examinations. The prevalence and causes of binocular VI (presenting visual acuity [VA] ≥ 20/400 and < 20/63 in the better eye) and blindness (presenting VA < 20/400 in the better eye) were assessed according to the World Health Organization (WHO) criteria. The estimation of refractive error prevalence was conducted using the following classification: myopia ≤ − 0.50 diopters (D), high myopia ≤ − 6.00 D, hyperopia ≥ 0.50 D, and anisometropia ≥ 1.00 D. The overall prevalence of binocular VI and blindness was 21.04% (95% confidence interval [CI] 20.35–21.74%) and 0.47% (95% CI 0.37–0.60%). The highest prevalence of binocular VI was in the population aged 18–24 years old (46.29%, [95% CI 44.30–48.28%]), those with education at university and above (43.47%, [95% CI 41.93–45.02%]), students (54.96%, [95% CI 52.73–57.17%]). Uncorrected refractive error (URE) was the leading cause of presenting binocular VI (93.40%) and blindness (50.79%). The prevalence of myopia was 54.75% (95% CI 53.90–55.60%). Actions are needed to control URE and myopia within the adult Chinese population, with a particular emphasis on the younger, well-educated demographic. [ABSTRACT FROM AUTHOR]

Pathologic microvasculature plays a crucial role in innumerable diseases causing death and major organ impairment. A major clinical challenge is the development of selective therapies to remove these diseased microvessels without damaging surrounding tissue. This report describes our development of novel photo-mediated ultrasound therapy (PUT) technology for precisely removing choroidal blood vessels in the eye. PUT selectively removes microvessels by concurrently applying nanosecond laser pulses with ultrasound bursts. In PUT experiments on rabbit eyes in vivo, we applied 55-75 mJ/cm2 of light fluence at the retinochoroidal surface at 532-nm and 0.5 MPa of ultrasound pressure at 0.5 MHz. PUT resulted in significantly reduced blood perfusion in the choroidal layer which persisted to four weeks without causing collateral tissue damage, demonstrating that PUT is capable of removing choroidal microvasculature safely and effectively. With its unique advantages, PUT holds potential for the clinical management of eye diseases associated with microvessels and neovascularization. [ABSTRACT FROM AUTHOR]

Background: High cataract incidence and low cataract surgical rate are serious public health problems in China, despite the fact that efficient day care cataract surgery has been implemented in some public Tertiary A hospitals in China. In this study, we compared not only clinical outcomes, hospitalization time and total costs but also payment manners between day care and inpatient procedures for cataract surgery in a Jiangsu public Tertiary A hospital to put forward several instructional suggestions for the improvement of government medical policies.Methods: In total, 4151 day care cases and 2509 inpatient cases underwent the same cataract surgery in the day care ward and ordinary ward respectively, and were defined as two groups. General information, complications, postoperative best corrected visual acuity (BCVA), hospitalization time, total costs and especially payment method were analyzed to compare day care versus inpatient.Results: The general data display no significant differences (P > 0.05), and no significant difference between complications and postoperative BCVA were observed between the two groups (P > 0.05). The period of stay in hospital was significantly different (P < 0.001). The total costs were lower for day care than for inpatients (P < 0.001). To avoid sampling error, we analyzed the data of payment manner for each patient among this period. Day care patients tended to pay for the procedure using the Urban Employees Basic Medical Insurance (UEBMI) method, while inpatients tended to use the Out-of-Pocket Medical Treatment (OMT) payment method (P < 0.001).Conclusion: Day surgery of cataract is more cost-effective and efficient than inpatient surgery with equivalent clinical outcomes. As an efficient therapeutic regimen, day care surgery should be further promoted and supported by the government policies. [ABSTRACT FROM AUTHOR]

Background: Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy presenting remarkable genetic heterogeneity. Genetic annotations would help with better clinical assessments and benefit gene therapy, and therefore should be recommended for RP patients. This report reveals the disease causing mutations in two RP pedigrees with confusing inheritance patterns using whole exome sequencing (WES).Methods: Twenty-five participants including eight patients from two families were recruited and received comprehensive ophthalmic evaluations. WES was applied for mutation identification. Bioinformatics annotations, intrafamilial co-segregation tests, and in silico analyses were subsequently conducted for mutation verification.Results: All patients were clinically diagnosed with RP. The first family included two siblings born to parents with consanguineous marriage; however, no potential pathogenic variant was found shared by both patients. Further analysis revealed that the female patient carried a recurrent homozygous C8ORF37 p.W185*, while the male patient had hemizygous OFD1 p.T120A. The second family was found to segregate mutations in two genes, TULP1 and RP1. Two patients born to consanguineous marriage carried homozygous TULP1 p.R419W, while a recurrent heterozygous RP1 p.L762Yfs*17 was found in another four patients presenting an autosomal dominant inheritance pattern. Crystal structural analysis further indicated that the substitution from arginine to tryptophan at the highly conserved residue 419 of TULP1 could lead to the elimination of two hydrogen bonds between residue 419 and residues V488 and S534. All four genes, including C8ORF37, OFD1, TULP1 and RP1, have been previously implicated in RP etiology.Conclusions: Our study demonstrates the coexistence of diverse inheritance modes and mutations affecting distinct disease causing genes in two RP families with consanguineous marriage. Our data provide novel insights into assessments of complicated pedigrees, reinforce the genetic complexity of RP, and highlight the need for extensive molecular evaluations in such challenging families with diverse inheritance modes and mutations. [ABSTRACT FROM AUTHOR]

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)‐derived exosomes (Lec‐exo) is largely unknown. Thus, we aimed to investigate whether Lec‐exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen‐induced retinopathy and laser‐induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec‐exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high‐throughput miRNAs sequencing analysis detected that miR‐146a‐5p was enriched in Lec‐exo. Mechanistically, exosomal miR‐146a‐5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec‐exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is currently one of the common causes of vision loss in working-age adults. It is clinically diagnosed and classified according to the vascular changes in the fundus. However, the activation of immune cells occurs before these vascular changes become detectable. These, together with molecular studies and the positive clinical outcomes of anti-inflammatory treatment, highlight the pivotal involvement of the immune system. The role of innate immunity in DR pathophysiology has been studied in depth, but the contribution of adaptive immunity remains largely elusive. This review aims to summarize our current understanding of the activation mechanism of adaptive immunity in DR microenvironments and to discuss the relationship between adaptive immunity and local vascular units or innate immunity, which opens new avenues for clinical applications in DR treatment. [ABSTRACT FROM AUTHOR]

• MiRNA sequencing for exosomes. • Some selective exosomal miRNAs from retinal pigment epithelial cells expressed by oxidative stress. • Potential functions and targets of the differentially expressed exosomal miRNAs. The function of exosomal miRNAs (miRs) in retinal degeneration is largely unclear. We were aimed to investigate the functions of exosomes as well as their miRs derived from retinal pigment epithelial (RPE) cells following exposure to oxidative stress (OS). After the OS by lipopolysaccharide and rotenone on RPE cells, interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) were upregulated, along with the decreased mitochondrial membrane potential and upregulated oxidative damage marker 8-OH-dG in RPE cells. RPE-derived exosomes were then isolated, identified, injected into the subretinal space in mice. After subretinal injection, RPE-exosomes after OS not only induced higher ROS level and apoptotic retinal cells, but also elevated IL-1β, IL-6 alongside TNF-α expressions among retina/RPE/choroidal complex. Next, miRs inside the exosomes were sequenced by the next generation sequencing (NGS) technology. NGS revealed that certain miRs were abundant in exosomes, while others were selectively kept by RPE cells. Further, downregulated miRs, like miR-125b-5p, miR-125a-5p, alongside miR-128-3p, and upregulated miR, such as miR-7-5p were validated byRT-qPCR. Finally, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to find the possible target genes of those selective exosomal miRs. Our results proved that the RPE-derived exosomes after OS selectively express certain miRs, providing novel insights into the pathogenesis of age-related macular degeneration (AMD) in future. [ABSTRACT FROM AUTHOR]

Objectives: Stem cell‐derived photoreceptor replacement therapy is a promising strategy for the treatment of retinal degenerative disease. The development of 3D retinal organoids has permitted the production of photoreceptors. However, there is no strategy to enrich a specific photoreceptor subtype due to inadequate knowledge of the molecular mechanism underlying the photoreceptor fate determination. Hence, our aim is to explore the uncharacterized function of somatostatin signalling in human pluripotent stem cell‐derived photoreceptor differentiation. Materials and Methods: 3D retinal organoids were achieved from human embryonic stem cell. The published single‐cell RNA‐sequencing datasets of human retinal development were utilized to further investigate the transcriptional regulation of photoreceptor differentiation. The assays of immunofluorescence staining, lentivirus transfection, real‐time quantitative polymerase chain reaction and western blotting were performed. Results: We identified that the somatostatin receptor 2 (SSTR2)‐mediated signalling was essential for rod photoreceptor differentiation at the precursor stage. The addition of the cognate ligand somatostatin in human 3D retinal organoids promoted rod photoreceptor differentiation and inhibited cone photoreceptor production. Furthermore, we found that the genesis of rod photoreceptors was modulated by endogenous somatostatin specifically secreted by developing retinal ganglion cells. Conclusions: Our study identified SSTR2 signalling as a novel extrinsic regulator for rod photoreceptor fate determination in photoreceptor precursors, which expands the repertoire of functional signalling pathways in photoreceptor development and sheds light on the optimization of the photoreceptor enrichment strategy. [ABSTRACT FROM AUTHOR]

Vitreous fibrovascular membranes (FVMs), the hallmark of proliferative diabetic retinopathy (PDR), cause retinal hemorrhage, detachment, and eventually blindness. However, little is known about the pathophysiology of FVM. In this study, we used single-cell RNA sequencing on surgically harvested PDR-FVMs and generated a comprehensive cell atlas of FVM. Eight cellular compositions were identified, with microglia as the major cell population. We identified a GPNMB+ subpopulation of microglia, which presented both profibrotic and fibrogenic properties. Pseudotime analysis further revealed the profibrotic microglia was uniquely differentiated from retina-resident microglia and expanded in the PDR setting. Ligand-receptor interactions between the profibrotic microglia and cytokines upregulated in PDR vitreous implicated the involvement of several pathways, including CCR5, IFNGR1, and CD44 signaling, in the microglial activation within the PDR microenvironment. Collectively, our description of the novel microglia phenotypes in PDR-FVM may offer new insight into the cellular and molecular mechanism underlying the pathogenesis of DR, as well as potential signaling pathways amenable to disease-specific intervention. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR), a most common microangiopathy of diabetes, causes vision loss and even blindness. The mechanisms of exosomal lncRNA remain unclear in the development of DR. Here, we first identifed the pro-angiogenic effect of exosomes derived from vitreous humor of proliferative diabetic retinopathy patients, where lncRNA-MIAT was enriched inside. Secondly, lncRNA-MIAT was demonstrated significantly increased in exosomes from high glucose induced human retinal vascular endothelial cell, and can regulate tube formation, migration and proliferation ability to promote angiogenesis in vitro and in vivo. Mechanistically, the pro-angiogenic effect of lncRNA-MIAT was via the lncRNA-MIAT/miR-133a-3p/MMP-X1 axis. The reduced level of lncRNA-MIAT in this axis mitigated the generation of retinal neovascular in mouse model of oxygen-induced retinopathy (OIR), providing crucial evidence for lncRNA-MIAT as a potential clinical target. These findings enhance our understanding of the role of exosomal lncRNA-MIAT in retinal angiogenesis, and propose a promising therapeutic strategy against diabetic retinopathy. [Display omitted] • LncRNAs may serve as interventional targets in management of DR. • The exosomes from vitreous humor (VH) of PDR patients (exo-PDR) exhibited a pro-angiogenic property. • LncRNA-MIAT modulated MMP-X1 expression through sponging miR-133a-3p. • The role of exosomal lncRNA-MIAT in retinal angiogenesis may propose a promising therapeutic strategy against DR. [ABSTRACT FROM AUTHOR]

The lens is an avascular tissue, where epithelial cells (LECs) are the primary living cells. The role of LECs-derived exosomes (LEC-exos) is largely unknown. In our study, we determined the anti-angiogenic role of LEC-exos, manifested as regressed retinal neovascularization (NV) using the oxygen-induced retinopathy (OIR), and reduced choroidal NV size and pathological vascular leakage using the laser-induced choroidal neovascularization (laser-induced CNV). Furthermore, the activation and accumulation of microglia were also restricted by LEC-exos. Based on Luminex multiplex assays, the expressions of chemokines such as SCYB16/CXCL16, MCP-1/CCL2, I-TAC/CXCL11, and MIP 3beta/CCL19 were decreased after treatment with LEC-exos. Transwell assays showed that LEC-exos restricted the migration of the mouse microglia cell line (BV2 cells). After incubation with LEC-exos-treated BV2 cells, human umbilical vein endothelial cells (hUVECs) were collected for further evaluation using tube formation, Transwell assays, and 5-ethynyl-2′-deoxyuridine (EDU) assays. Using in vitro experiments, the pro-angiogenic effect of microglia was restricted by LEC-exos. Hence, it was investigated that LEC-exos attenuated ocular NV, which might attribute to the inhibition of microglial activation and accumulation. • LEC-exos play a pivotal role in the non-vascularized state of the lens. • Microglia stimulated with hypoxia or inflammation promote the ocular angiogenesis. • LEC-exos suppressed the activation and accumulation of microglia. • After pretreated with LEC-exos, BV2 cells display less pro-angiogenic effect. [ABSTRACT FROM AUTHOR]

Optical coherence tomography angiography (OCTA) is a novel imaging modality that has been widely utilized in ophthalmology and neuroscience studies to observe retinal vessels and microvascular systems. However, publicly available OCTA datasets remain scarce. In this paper, we introduce the largest and most comprehensive OCTA dataset dubbed OCTA-500, which contains OCTA imaging under two fields of view (FOVs) from 500 subjects. The dataset provides rich images and annotations including two modalities (OCT/OCTA volumes), six types of projections, four types of text labels (age/gender/eye/disease) and seven types of segmentation labels (large vessel/capillary/artery/vein/2D FAZ/3D FAZ/retinal layers). Then, we propose a multi-object segmentation task called CAVF, which integrates capillary segmentation, artery segmentation, vein segmentation, and FAZ segmentation under a unified framework. In addition, we optimize the 3D-to-2D image projection network (IPN) to IPN-V2 to serve as one of the segmentation baselines. Experimental results demonstrate that IPN-V2 achieves an about 10% mIoU improvement over IPN on CAVF task. Finally, we further study the impact of several dataset characteristics: the training set size, the model input (OCT/OCTA, 3D volume/2D projection), the baseline networks, and the diseases. The dataset and code are publicly available at: https://ieee-dataport.org/open-access/octa-500. • Proposed OCTA-500, which is the largest and comprehensive OCTA dataset. • The OCTA-500 includes OCTA imaging from 500 subjects and rich annotation information. • Proposed a CAVF task, which integrates multiple key segmentation tasks. • Optimized the IPN to IPN-V2 to serve as one of the competitive baselines. • The OCTA-500 dataset has great potential to promote other researches in OCTA. [ABSTRACT FROM AUTHOR]

Purpose: To robustly segment retinal layers that are affected by complex variety of retinal diseases for optical coherence tomography angiography (OCTA) en face projection generation. Methods: In this paper, we propose a robust retinal layer segmentation model to reduce the impact of multifarious abnormalities on model performance. OCTA vascular distribution that is regarded as the supplements of spectral domain optical coherence tomography (SD‐OCT) structural information is introduced to improve the robustness of layer region encoding. To further reduce the sensitivity of region encoding to retinal abnormalities, we propose a multitask layer‐wise refinement (MLR) module that can refine the initial layer region segmentation results layer‐by‐layer. Finally, we design a region‐to‐surface transformation (RtST) module without additional training parameters to convert the encoding layer regions to their corresponding layer surfaces. This transformation from layer regions to layer surfaces can remove the inaccurate segmentation regions, and the layer surfaces are easier to be used to protect the retinal layer natures than layer regions. Results: Experimental data includes 273 eyes, where 95 eyes are normal and 178 eyes contain complex retinal diseases, including age‐related macular degeneration (AMD), diabetic retinopathy (DR), central serous chorioretinopathy (CSC), choroidal neovascularization (CNV), and so forth. The dice similarity coefficient (DSC: %) of superficial, deep and outer retina achieves 98.92, 97.48, and 98.87 on normal eyes and 98.35, 95.33, and 98.17 on abnormal eyes. Compared with other commonly used layer segmentation models, our model achieves the state‐of‐the‐art layer segmentation performance. Conclusions: The final results prove that our proposed model obtains outstanding performance and has enough ability to resist retinal abnormalities. Besides, OCTA modality is helpful for retinal layer segmentation. [ABSTRACT FROM AUTHOR]

The performance of supervised deep learning significantly relies on the volume of training samples. However, the vast majority of medical images lacks manual expert annotations. Compared to natural image annotation, the cost of medical image annotation is more expensive as it requires professional medical knowledge guidance. To tackle the predicament, semi-supervised learning and self-supervised learning are very effective technologies. In this paper, we present a twin self-supervision based semi-supervised learning (TS-SSL) approach that embeds two types of self-supervised strategies (namely generative self-supervised learning and discriminative self-supervised learning) into semi-supervised framework to simultaneously learn from few-shot labeled images and vast unlabeled images. TS-SSL is an end-to-end classification model, in which semi-supervision and self-supervision can be jointly trained. The proposed TS-SSL is applied to perform retinal anomaly classification based on spectral-domain optical coherence tomography (SD-OCT) images. The experiments demonstrate that TS-SSL yields the good classification performance on one public SD-OCT dataset and two private SD-OCT datasets with only 10% labels. We also claim that TS-SSL can be transferred to other medical imaging modalities. The code is available at https://github.com/ZhangYH0502/TS-SSL. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the preoperative neovascular change pattern on the fibrovascular membrane (FVM) within 7 days after intravitreal injection of conbercept (IVC) using optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR). Methods: Prospective, observational study of PDR patients with visible FVM receiving or not receiving IVC. Neovascular changes were assessed by OCTA pre-IVC and 1, 3, 5, and 7 days post-IVC. Vessel skeleton density (SD) and vessel density (VD) were quantified by an intensity-based optical microangiography algorithm. The interclass correlation coefficient (ICC) was calculated to assess the agreement between measurements. The SD and VD were compared between follow-ups using repeated-measures analysis in the IVC group. Results: The ICC was 0.992 (95% confidence interval [CI]: 0.982–0.996) for SD and 0.926 (95% CI: 0.838–0.912) for VD of neovascularization. The neovascularization on FVM significantly regressed in the IVC group (n = 16) compared with no IVC (n = 8) (p = 0.001 for SD and p < 0.001 for VD). The comparisons between consecutive follow-ups showed a statistically significant reduction in SD and VD at 1 and 3 days post-IVC. However, from day 3 onward, the SD and VD remained unchanged. There was no development or progression of tractional retinal detachment within the 7-day period after IVC. Conclusion: OCTA–based quantification of the neovascularization on FVM in PDR is feasible, with high inter-reader agreement. The regression of neovascularization reaches a plateau 3 days after IVC. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR-IPR-17014160). [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a multifactorial disease resulting in the gradual loss of retinal pigment epithelium (RPE) and the permanent visual damage. Various risk factors, including oxidative stress, form a complex network at the confluence of inflammation. Mesenchymal stem cell (MSC) is a well-studied population of adult stem cell with strong neuroprotective and immunoregulatory properties. Here, we reported the protective effect of MSC on sodium iodate (NaIO3)-triggered RPE degeneration. Sodium iodate (NaIO3)-induced RPE cell death was remarkably reduced when cocultured with MSC. Inhibition of several cell death pathways mediated by mitochondrial instability and its subsequent caspase-1/3/8 activation was implicated in this process. In addition, NLRP3 inflammasome, the upstream of caspase-1 activation, was also found downregulated via suppressing its priming signal NF-κB pathway. Taken together, MSC protected against NaIO3-triggered RPE death via deactivating NF-κB-mediated NLRP3 inflammasome and maintaining mitochondrial integrity. This study highlights the significant role of MSC in modulating the proinflammatory environment of AMD, and suggests the clinical value of MSC in treating AMD as well as RPE replacement therapy. [ABSTRACT FROM AUTHOR]

Background and Objective The measurement of choroidal volume is more related with eye diseases than choroidal thickness, because the choroidal volume can reflect the diseases comprehensively. The purpose is to automatically segment choroid for three-dimensional (3D) spectral domain optical coherence tomography (SD-OCT) images. Methods We present a novel choroid segmentation strategy for SD-OCT images by incorporating the enhanced depth imaging OCT (EDI-OCT) images. The down boundary of the choroid, namely choroid-sclera junction (CSJ), is almost invisible in SD-OCT images, while visible in EDI-OCT images. During the SD-OCT imaging, the EDI-OCT images can be generated for the same eye. Thus, we present an EDI-OCT-driven choroid segmentation method for SD-OCT images, where the choroid segmentation results of the EDI-OCT images are used to estimate the average choroidal thickness and to improve the construction of the CSJ feature space of the SD-OCT images. We also present a whole registration method between EDI-OCT and SD-OCT images based on retinal thickness and Bruch's Membrane (BM) position. The CSJ surface is obtained with a 3D graph search in the CSJ feature space. Results Experimental results with 768 images (6 cubes, 128 B-scan images for each cube) from 2 healthy persons, 2 age-related macular degeneration (AMD) and 2 diabetic retinopathy (DR) patients, and 210 B-scan images from other 8 healthy persons and 21 patients demonstrate that our method can achieve high segmentation accuracy. The mean choroid volume difference and overlap ratio for 6 cubes between our proposed method and outlines drawn by experts were −1.96µm3 and 88.56%, respectively. Conclusions Our method is effective for the 3D choroid segmentation of SD-OCT images because the segmentation accuracy and stability are compared with the manual segmentation. [ABSTRACT FROM AUTHOR]

Aims Proliferative diabetic retinopathy (PDR), characterized by angiogenesis, can cause serve vision loss and even blindness. Recent studies have suggested a pivotal role of vasohibin-2 (VASH2) in the promotion of angiogenesis in tumor tissues. Here we further investigated the role of VASH2 in the proliferation and migration of retinal endothelial cells. Main methods The expression of VASH2 in vascular endothelial cells of epiretinal fibrovascular membranes (FVMs) from PDR patients were detected by immunofluorescence. VASH2 gene interfering lentiviral vectors ( VASH2 -shRNA) and miR-200b/c were constructed for the evaluation of the VASH2 effect on high glucose induced human retinal microvascular endothelial cell line (HRMECs). Cell proliferation, cell cycle and cell migration were carried out subsequently. The relationship between VASH2 and miR-200b/c was determined by luciferase reporter gene assays. Key findings A positive expression of VASH2 was identified in vascular endothelial cells of FVMs from PDR patients. In HRMECs, cells transfected with shRNA or miR-200b/c mimics showed a significantly reduced VASH2 expression compared with negative control group by real time-polymerase chain reaction and western-blot analysis. Inhibition of VASH2 was demonstrated to suppress cell proliferation and migration from Day 2 to Day 4. The luciferase reporter gene assays confirmed the post-transcriptional regulation of VASH2 by miR-200b/c in HRMECs. Significance The present study suggests a protective effect of miR-200b/c on high glucose induced HRMECs dysfunction by inhibiting VASH2. It could be a potential therapeutic strategy to inhibit angiogenesis for the treatment of retinal vascular disease. [ABSTRACT FROM AUTHOR]

In this study we described a new model of subretinal edema induced by single intraocular injection of DL-alpha-aminoadipic acid (DLAAA) that can be employed to study the mechanism of retinal edema and test the efficacy or potential toxicity of treatments. The progression of subretinal edema was evaluated by fundus photography, fluorescein angiography and optical coherence tomography for up to 4 weeks following DLAAA injection. The VEGF, IL-6, TNF-α, Occludin, ZO-1, AQP4, Kir4.1, GFAP and GS levels were examined in DLAAA models by immunostaining, immumohistochemical staining and Western blot. Additionally, bulk RNA-seq was used to detect the mechanism involved in DLAAA-induced retinal Müller cellular injuries. In vivo and vitro assays were further conducted to confirm the sequencing results. Subretinal edema was successfully induced by DLAAA in New Zealand White rabbits (1.29 mg/eye) and C57BL/6 mice (50 or 100 μg/eye). Our results demonstrated that the disruption of blood-retinal-barrier, including vascular hyperpermeability, inflammation, and Müller cell dysfunction of fluid clearance, was involved in subretinal edema formation in the model. Bulk RNA-seq and in vitro studies indicated the activation of p38 MAPK signaling pathway in DLAAA models. This DLAAA-induced subretinal edema model can be used for mechanistic studies or drug screening. [Display omitted] • The first report of a novel model of subretinal edema induced by DL-alpha aminoadipic acid (DLAAA) • The disruption of blood-retinal-barrier, including vascular hyperpermeability, inflammation, and Müller cell dysfunction of fluid clearance, was involved in subretinal edema formation in DLAAA models • DLAAA-induced dysfunction of Müller cells is partly via the activation of p38 MAPK signaling pathway [ABSTRACT FROM AUTHOR]

Purpose To evaluate the impact of postoperative posturing with or without face-down on the anatomical and functional outcomes of macular hole surgery. Methods A literature-based meta-analysis was conducted to identify studies relevant to posturing following macular hole surgery ( MHS). PubMed and Web of Science databases were used to retrieve articles up to 1 June 2015. The primary measures included MH closure and ideal vision acuity improvement. Pooled odds ratios ( ORs) and 95% confidence intervals ( CIs) were estimated in Review Manager. Results Four randomized control trials ( RCTs) comprising 251 cases were included in the final meta-analysis. No face-down posturing ( FDP) after MHS revealed lower anatomic success rate compared to face-down posturing ( OR = 0.33, 95% CI [0.13, 0.81], p = 0.02). For holes smaller than 400 μm in size, the subgroup meta-analysis indicated no significant effect of FDP on successful hole closure ( OR = 0.29, 95% CI [0.01, 7.34], p = 0.45). However, when holes were larger than 400 μm, it seemed less effective on MH closure following surgery in no FDP group ( OR = 0.23, 95% CI [0.07, 0.71]), and this was statistically significant (p = 0.01). Conclusions Our work found that no FDP was not inferior to its face-down counterpart for the success of MHS when macular holes were smaller than 400 μm in size. For macular holes larger than 400 μm, statistical analysis proved that FDP might be necessary. More well-conducted randomized control trials are needed to verify our findings. [ABSTRACT FROM AUTHOR]

Objective: Oxidative stress-induced retinal neurodegenerative changes are among the pathological alterations observed in diabetic retinopathy. Resveratrol (RSV), a polyphenolic compound with diverse pharmacological effects, has shown preventive qualities in several neurodegenerative illnesses, including anti-inflammatory, anti-aging, and antioxidant benefits. However, its therapeutic efficacy in diabetic retinal neurodegeneration has not yet been thoroughly elucidated. Our study aimed to explore the protective mechanisms and therapeutic benefits of RSV on diabetic retinal neurodegeneration alterations., Materials and Methods: Using streptozotocin, we created a diabetic mouse model and conducted visual electrophysiological examinations on mice from the normal group, diabetic group, and diabetic group treated with RSV. Retinas were harvested for histological staining. Additionally, primary retinal ganglion cells cultured in high glucose conditions were used to assess malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels upon siRNA-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) interference. Protein levels of Nrf-2, heme oxygenase-1 (HO-1), and transcriptional levels of them were also measured., Results: We demonstrated that RSV significantly improved the retinal morphology and function in the diabetic retinopathy model mice. The treated mice exhibited notable improvements in visual electrophysiology, with a significant reduction in retinal ganglion cell apoptosis. Following RSV treatment, the high glucose-cultured ganglion cells demonstrated a considerable rise in SOD levels and a substantial drop in MOD. Moreover, the protein expression of solute carrier family 7 member 11 (SLC7A11) and Nrf2 significantly increased. RT-PCR and Western blot results indicated a significant attenuation of RSV's therapeutic effects upon Nrf2 inhibition., Conclusion: Our findings suggest that RSV may reduce oxidative stress levels in the retina and inhibit retinal ganglion cell apoptosis via reducing the Nrf2/HO-1 pathway, which lessens the harm that excessive glucose causes to the retina., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The inadequate knowledge of RPE pathology is hindered by a lack of patient RPE datasets, especially at the single-cell resolution. In this study, we delved into a large-scale single-cell resource of AMD donors in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both in vivo and in vitro models revealed that carboxypeptidase X, M14 family member 2 (CPXM2) was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrate that CPXM2 plays a crucial role in regulating atrophic AMD and may serve as a potential therapeutic target for atrophic AMD.

Ocular angiogenic diseases, such as proliferative diabetic retinopathy (PDR), are often characterized by pathological new vessels and fibrosis formation. Anti-vascular endothelial growth factor (VEGF) therapy, despite of its efficiency to inhibit new vessels, has limitations, including drug resistance and retinal fibrosis. Here, we identified that Gremlin1, a novel angiogenesis and fibrosis inducer, was secreted from Müller glial cells, and its expression increased in the vitreous fluid from patients with PDR. Mechanistically, Gremlin1 triggered angiogenesis by promoting endothelial-mesenchymal transition via the EGFR/RhoA/ROCK pathway. In addition, Gremlin1 activated microglia to present profibrotic and fibrogenic properties. Further, anti-Gremlin1 antibody inhibited ocular angiogenesis and microglia fibrosis in mouse models. Collectively, Gremlin1 could be a potential therapeutic target in the treatment of ocular angiogenic diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: This study aimed to identify an initial screening tool for congenital ectopia lentis (CEL) by comparing ocular biological parameters in children with myopia., Methods: A retrospective case-control study was conducted at one tertiary referral centre, from October 2020 to June 2022. Axial length (AL), corneal curvature (CC), refractive astigmatism (RA), corneal astigmatism (CA), internal astigmatism (IA), the difference between the axis of RA and CA [AXIS(RA-CA)], white-to-white corneal diameter (WTW), and axial length-corneal radius ratio (AL/CR) were compared in 28 eyes of CEL patients, and 60 eyes of myopic patients matched for age and refraction. The spherical equivalent of each eye was < -3.00 D. Area under the curve (AUC) of the receiver operating characteristic curves were calculated., Results: The differences in RA, AL, mean keratometry (Kmed), maximum keratometry (Kmax), minimum keratometry (Kmin), CA, IA, AXIS(RA-CA), WTW, and AL/CR between the CEL and myopic groups were statistically significant (p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001; p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). In logistic regression analysis RA, IA, AXIS(RA-CA), and AL/CR were significantly associated with CEL (p < 0.05). AUCs for RA, IA, AXIS(RA-CA), and AL/CR were 0.694, 0.853, 0.814, and 0.960, respectively. AUCs for AL/CR in SE< -6.00 D subgroup was 0.970, and 0.990 in -6.00 D ≤ SE < -3.00 D group. An AL/CR < 3.024 was the optimal cut-off point differentiating the CEL and control groups (sensitivity, 92.9%; specificity, 88.30%)., Conclusions: A smaller AL/CR could identify CEL in children with myopia. An AL/CR cut-off value of 3.024 may be the most sensitive and specific parameter for the differential diagnosis of CEL in patients with mild to high myopia., (© 2023. The Author(s).)

Diabetic retinopathy (DR), one of the most common microangiopathic complications in diabetes, causes severe visual damage among working-age populations. Retinal vascular endothelial cells, the key cell type in DR pathogenesis, are responsible for abnormal retinal angiogenesis in advanced stages of DR. The roles of exosomes in DR have been largely unknown. In this study, we report the first evidence that exosomes derived from the vitreous humor of patients with proliferative DR (PDR-exo) promote proliferation, migration, and tube formation of human retinal vascular endothelial cells (HRVECs). We identified long noncoding RNA (lncRNA) LOC100132249 enrichment in PDR-exo via high-throughput sequencing. This lncRNA, also mainly derived from HRVECs, promoted angiogenesis both in vitro and in vivo. Mechanistically, LOC100132249 acted as a competing endogenous sponge of miRNA-199a-5p (miR-199a-5p), thus regulating the endothelial-mesenchymal transition promoter SNAI1 via activation of the Wnt/β-catenin pathway and ultimately resulting in endothelial dysfunction. In conclusion, our findings underscored the pathogenic role of endothelial-derived exosomes via the LOC100132249/miR-199a-5p/SNAI1 axis in DR angiogenesis and may shed light on new therapeutic strategies for future treatment of DR., Article Highlights: This study provides the first evidence that exosomes derived from vitreous humor from patients with proliferative diabetic retinopathy participate in angiogenesis. The findings demonstrate an unreported long noncoding RNA (lncRNA), LOC100132249, by exosomal sequencing of vitreous humor. The newly found lncRNA LOC100132249, mainly derived from endothelial cells, promotes angiogenesis via an miRNA-199a-5p/SNAI1/Wnt/β-catenin axis in a pro-endothelial-mesenchymal transition manner., (© 2023 by the American Diabetes Association.)

Retinal development is initiated by multipotent retinal progenitor cells, which undergo several rounds of cell divisions and subsequently terminal differentiation. Retinal regeneration is usually considered as the recapitulation of retinal development, which share common mechanisms underlying the cell cycle re-entry of adult retinal stem cells and the differentiation of retinal neurons. However, how proliferative retinal progenitor cells perform a precise transition to postmitotic retinal cell types during the process of development and regeneration remains elusive. It is proposed that both the intrinsic and extrinsic programming are involved in the transcriptional regulation of the spatio-temporal fate commitment. Epigenetic modifications and the regulatory mechanisms at both DNA and chromatin levels are also postulated to play an important role in the timing of differentiation of specific retinal cells. In the present review, we have summarized recent knowledge of epigenetic regulation that underlies the commitment of retinal progenitor cells in the settings of retinal development and regeneration., Competing Interests: Declaration of competing interest The 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., (Copyright © 2023. Published by Elsevier B.V.)

Age-related macular degeneration (AMD) causes irreversible blindness in people aged over 50 worldwide. The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD. In the current study, we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database. We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis. Peroxisome and tumor necrosis factor-α (TNF-α) signaling and nuclear factor kappa B (NF-κB) were among the top 10 pathways, and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs (circRNAs). We then constructed a competing endogenous RNA network, which is related to differentially expressed circRNAs. This network included seven circRNAs, 15 microRNAs, and 82 mRNAs. The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was a common downstream event. The results of the current study may provide insights into the pathological processes of atrophic AMD.

Introduction: Fixed-combination bimatoprost 0.03%/timolol 0.5% ophthalmic solution (FCBT; Ganfort ® , Allergan, an AbbVie company) effectively reduces intraocular pressure (IOP) via complementary mechanisms of action of the agents, but long-term (> 12 weeks) safety evaluations of FCBT remain limited. FCBT safety is evaluated herein, with particular focus on hyperemia and eyelash growth, at 24 weeks in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT)., Methods: In this multicenter, open-label, noncomparative, phase 4 study conducted in China, patients diagnosed with OAG or OHT having insufficient response to β-blocker- or prostaglandin analogue/prostamide (PGA)-based IOP-lowering monotherapy in one or both eyes were switched from their current IOP-lowering treatment to FCBT (one drop per eye every evening) without prior washout. Assessment visits were scheduled at baseline and weeks 4, 12, and 24 (or study exit). The primary outcome measure was adverse event (AE) incidence through 24 weeks., Results: Of 725 patients enrolled, 632 (87.2%) completed the study; 93 (12.8%) patients discontinued, including 29 (4.0%) due to AEs. Of 1326 FCBT-treated eyes (total), 594 (44.8%) experienced ≥ 1 ocular treatment-related AE during the study. Conjunctival hyperemia (the most common AE overall) and eyelash growth were reported in 269 (20.3%) and 54 (4.1%) FCBT-treated eyes, respectively. The incidence of other known PGA-related AEs (including blepharal pigmentation and erythema of eyelid) was < 10% each. Most conjunctival hyperemia reports were mild in severity (214/259; 82.6%) and only 1/259 (0.4%) was severe. Similarly, most cases of eyelash growth were mild (46/52; 88.5%); none were severe. One (< 0.1%) FCBT-treated eye had a serious ocular AE (OAG) considered FCBT-related., Conclusions: The frequency and severity of FCBT-related AEs, including conjunctival hyperemia and eyelash growth, are consistent with previously published findings. No new safety concerns were raised. This prospective study reaffirms that once-daily FCBT is a safe and well-tolerated therapy for OAG and OHT., Gov Identifier: NCT02571712., (© 2022. The Author(s).)

Introduction: The aim of this study was to assess the effects of preoperative intravitreal aflibercept (IVA) injection on the incidence of postoperative vitreous hemorrhage (VH) after vitrectomy for proliferative diabetic retinopathy (PDR)., Methods: This study involved a prospective, randomized clinical trial. One hundred twenty-eight eyes of 128 patients of PDR who underwent pars plana vitrectomy (PPV) were enrolled. Sixty-four eyes were assigned randomly to either the IVA group (IVA injection 1 to 5 days before PPV) or the control group (no IVA injection). The primary outcome was the incidence of VH at 1 month after PPV. Secondary outcome measures were best-corrected visual acuity (BCVA) changes from baseline to at 1 week, 1 month, 2 months, and 3 months after surgery., Results: The VH incidences in the IVA group and the control group were 14.8 and 39.3% at week 1, 8.6 and 31.7% at month 1, 11.7 and 30.5% at month 2, and 8.6 and 30.5% at month 3, respectively. Intergroup differences showed a significantly decreased VH rate in the IVA group compared with that in the control group at week 1, month 1, and month 3 ( p = 0.021, 0.006, and 0.047, respectively). Compared to the baseline, neither the mean BCVA nor the BCVA change in the Logarithm of the Minimum Angle of Resolution (logMAR) scale did differ significantly between the two groups at each visit point. There are a greater number of eyes with BCVA improvement of more than 2 logMAR in the IVA group than in the control group at week 1 (8 vs. 2, p = 0.048)., Conclusions: This study found that the adjunctive use of preoperative IVA reduces early and late postoperative VH in vitrectomy for PDR., Competing Interests: The 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., (Copyright © 2023 Qu, Chen, Liu, Wang, Li, Zhou, Yao and Li.)

Purpose: Cone and rod photoreceptors in the retina convert light to electrical signals which are transmitted to the visual cortex of the brain. Abnormal photoreceptor development and degeneration results in blindness. So far, the mechanism that controls photoreceptor specification and its subsequent fate bifurcation remain elusive., Methods: To trace and enrich the human photoreceptor lineage, we first engineered H9 human embryonic stem cell (hESC) reporter line by fusing EGFP to endogenous BLIMP1 using CRISPR/CAS9 gene-editing technology, and then used the cell line to generate 3D retinal organoids. Following EGFP-based cell sorting, single-cell RNA-sequencing was conducted via 10x Genomics Chromium system, and the data were analyzed using Seurat. Immunofluorescence combined with lentivirus-mediated knockdown and overexpression experiments were used as validation approaches., Results: Single-cell transcriptomic profiling revealed that retinal progenitor cells were temporally programmed to differentiate to cone and rod sequentially. We identified PHLDA1 as a novel regulator of photoreceptor specification. PHLDA1 mediated the effects of IGF1 through IGF1R, and inhibited AKT phosphorylation during photoreceptor development., Conclusions: Our data established a transcriptomic cell atlas of the human photoreceptor lineage, and identified IGF1-PHLDA1 axis to regulate human photoreceptor development.

Accumulating evidence has suggested the significant role of long noncoding RNAs (lncRNA) in regulating ferroptosis, while its regulatory mechanism in diabetic retinopathy (DR) remains unelucidated. In this work, we first demonstrated that lncRNA zinc finger antisense 1 (ZFAS1) is upregulated in high glucose-cultured human retinal endothelial cells (hRECs) and ZFAS1 inhibition attenuated high glucose- (HG-) induced ferroptosis, which was evidenced by cell viability, total iron and ferrous iron levels, reactive oxygen species (ROS) level, and Glutathione Peroxidase 4 (GP X 4) expression detection. Mechanistically, we validated that ZFAS1 may act as a competing endogenous RNA by competitively binding with microRNA-7-5p (miR-7-5p) and modulating the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4), which is now identified as a classic driver gene of ferroptosis process. In conclusion, our results demonstrate that HG-induced ZFAS1 elevation activates ferroptosis in hRECs and the ZFAS1/miR-7-5p/ACSL4 axis may serve as a therapeutic target for endothelial dysfunction in DR., Competing Interests: All authors declare no competing interests., (Copyright © 2022 Yu Liu et al.)

Objectives: The relationship between renal function and diabetic retinopathy has been controversial. This study is to investigate the influence of renal function on the complex and surgical outcomes of proliferative diabetic retinopathy (PDR)., Methods: This was a post hoc analysis of the CONCEPT clinical trial. A total of 45 eyes with PDR underwent vitrectomy were included. Based on the estimated glomerular filtration rate (eGFR), they were divided into abnormal renal function group ( ARF group ) and normal renal function group ( NRG group ). Baseline PDR complex, intraoperative outcomes (Intraoperative bleeding, frequency of endodiathermy, surgical time, iatrogenic hole, and tamponade) and postoperative outcomes (logMAR best-corrected visual acuity, vitreous re-hemorrhage, and macular edema, follow up at postoperative 1 month and 3 months) were estimated. Vitreous, aqueous humor and serum were collected at the vitrectomy day and Vascular endothelia growth factor-A levels were quantified for all included patients using liquid chip method., Results: There was no significant difference in baseline PDR complex, intraoperative and postoperative outcomes between ARF group and NRG group (all P > 0.05). At the vitrectomy day, there was also no difference of Vascular endothelia growth factor-A levels in vitreous, aqueous humor and serum between the two groups (all P > 0.05)., Conclusion: Our results showed that the renal function seems not parallel to the severity of PDR, neither to the surgical outcomes. This might be interpreted by the similar Vascular endothelia growth factor-A levels in vitreous, aqueous humor and serum between the two groups., Competing Interests: The 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., (Copyright © 2022 Liu, Zhang, Xie, Yuan, Jiang, Liu and Hu.)