Investigative ophthalmology & visual science最新文献

{"title":"Artificial Intelligence Versus Rules-Based Approach for Segmenting NonPerfusion Area in a DRCR Retina Network Optical Coherence Tomography Angiography Dataset.","authors":"Tristan T Hormel, Wesley T Beaulieu, Jie Wang, Jennifer K Sun, Yali Jia","doi":"10.1167/iovs.66.3.22","DOIUrl":"10.1167/iovs.66.3.22","url":null,"abstract":"<p><strong>Purpose: </strong>Loss of retinal perfusion is associated with both onset and worsening of diabetic retinopathy (DR). Optical coherence tomography angiography is a noninvasive method for measuring the nonperfusion area (NPA) and has promise as a scalable screening tool. This study compares two optical coherence tomography angiography algorithms for quantifying NPA.</p><p><strong>Methods: </strong>Adults with (N = 101) and without (N = 274) DR were recruited from 20 U.S. sites. We collected 3 × 3-mm macular scans using an Optovue RTVue-XR. Rules-based (RB) and deep-learning-based artificial intelligence (AI) algorithms were used to segment the NPA into four anatomical slabs. For comparison, a subset of scans (n = 50) NPA was graded manually.</p><p><strong>Results: </strong>The AI method outperformed the RB method in intersection over union, recall, and F1 score, but the RB method has better precision relative to manual grading in all anatomical slabs (all P ≤ 0.001). The AI method had a stronger rank correlation with Early Treatment of Diabetic Retinopathy Study DR severity than the RB method in all slabs (all P < 0.001). NPAs graded using the AI method had a greater area under the receiver operating characteristic curve for diagnosing referable DR than the RB method in the superficial vascular complex, intermediate capillary plexus, and combined inner retina (all P ≤ 0.001), but not in the deep capillary plexus (P = 0.92).</p><p><strong>Conclusions: </strong>Our results indicate that output from the AI-based method agrees better with manual grading and can better distinguish between clinically relevant DR severity levels than a RB approach using most plexuses.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"22"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological Comparison of Astrocytes in the Lamina Cribrosa and Glial Lamina.","authors":"Susannah Waxman, Hannah Schilpp, Ashley Linton, Tatjana C Jakobs, Ian A Sigal","doi":"10.1167/iovs.66.3.1","DOIUrl":"10.1167/iovs.66.3.1","url":null,"abstract":"<p><strong>Purpose: </strong>Although the mechanisms underlying glaucomatous neurodegeneration are not yet well understood, cellular and small animal models suggest that lamina cribrosa (LC) astrocytes undergo early morphologic and functional changes, indicating their role as early responders to glaucomatous stress. These models, however, lack the LC found in larger animals and humans, leaving the in situ morphology of LC astrocytes and their role in glaucoma initiation underexplored. In this work, we aimed to characterize the morphology of LC astrocytes in situ and determine differences and similarities with astrocytes in the mouse glial lamina (GL), the analogous structure in a prominent glaucoma model.</p><p><strong>Methods: </strong>Astrocytes in the LCs of 22 eyes from goats, sheep, and pigs were stochastically labeled via Multicolor DiOlistics and imaged in situ using confocal microscopy. The 3D models of DiOlistically labeled LC astrocytes and hGFAPpr-GFP mouse GL astrocytes were constructed to quantify morphological features related to astrocyte functions. LC and GL astrocyte cross-pore contacts, branching complexity, branch tortuosity, and cell and branch span were compared.</p><p><strong>Results: </strong>LC astrocytes displayed distinct spatial relationships with collagen, greater branching complexity, and higher branch tortuosity compared to GL astrocytes. Despite substantial differences in their anatomic environments, LC and GL astrocytes had similar cell and branch spans.</p><p><strong>Conclusions: </strong>Astrocyte morphology in the LC was characterized through multicolor DiOlistic labeling. LC and GL astrocytes have both distinct and shared morphological features. Further research is needed to understand the potentially unique roles of LC astrocytes in glaucoma initiation and progression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Secreted Ly6/uPAR-Related Protein-1 (SLURP1) Protects the Cornea From Oxidative Stress.","authors":"Satinder Kaur, Peri Sohnen, Simran Kumar, Mehak Vohra, Sudha Swamynathan, Shivalingappa Swamynathan","doi":"10.1167/iovs.66.3.30","DOIUrl":"10.1167/iovs.66.3.30","url":null,"abstract":"<p><strong>Purpose: </strong>Previously, we reported that the secreted Ly6/uPAR-related protein-1 (SLURP1), abundantly expressed by the corneal epithelium (CE) and secreted into the tear fluid, suppresses NF-κB signaling in healthy corneas and is downregulated in response to a variety of stressors, allowing helpful inflammation to progress. Here we investigate whether SLURP1 manifests its broad protective effects by promoting corneal redox homeostasis.</p><p><strong>Methods: </strong>Oxidative stress was induced in the wild-type (WT) and Slurp1-null (Slurp1X-/-) mouse corneas using 1350 J/m2 UV-B, and in human corneal limbal epithelial (HCLE) and SLURP1-overexpressing HCLE-SLURP1 cells with 100 J/m2 UV-B, 0.4 µg/mL mitomycin-C, or 0-100 µM H2O2. We evaluated their (i) redox status (GSH:GSSG ratio) using O-phthalaldehyde; (ii) reactive oxygen species (ROS) accumulation using 2',7'-dichlorodihydrofluorescein diacetate; (iii) antioxidants GPX4, CAT, and SOD2 expression by qRTPCR; (iv) lipid peroxidation by staining for 4-hydroxynonenol, malondialdehyde, and BODIPY-C11; and (v) DNA damage and NF-κB activation by immunostaining for γH2AX, 8-OHdG, NF-κB, and IκB.</p><p><strong>Results: </strong>Slurp1 was significantly downregulated in the UV-B-irradiated WT corneas. Oxidatively stressed HCLE-SLURP1 cells displayed relatively less ROS accumulation, lipid peroxidation, DNA damage and NF-κB activation, and a higher GSH/GSSG ratio and antioxidant gene expression than the similarly treated control HCLE cells. UV-B-irradiated Slurp1X-/- corneas displayed relatively more ROS accumulation, DNA damage and less GPX4 expression than the similarly treated WT corneas.</p><p><strong>Conclusions: </strong>Collectively, these results elucidate that SLURP1 serves as an insult-agnostic immunomodulator that upregulates antioxidants and suppresses ROS accumulation to promote redox homeostasis in corneal epithelial cells and protect them from diverse genotoxic stressors.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"30"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evodiamine Promotes Autophagy and Alleviates Oxidative Stress in Dry Eye Disease Through the p53/mTOR Pathway.","authors":"Boda Li, Junpeng Liu, Di Zhang, Yiran Chu, Zeying Chen, Jiaruei Tsao, Taige Chen, Jiaxuan Jiang, Kai Hu","doi":"10.1167/iovs.66.3.44","DOIUrl":"10.1167/iovs.66.3.44","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the therapeutic efficacy of evodiamine (EVO) in the treatment of dry eye disease (DED).</p><p><strong>Methods: </strong>Mouse models of DED was developed using benzalkonium chloride eye drops and subcutaneous atropine injections. Corneal epithelial defects were assessed by fluorescein sodium staining, and tear secretion was measured with the phenol red thread test. For the in vitro model, human corneal epithelial cells were cultured in a sodium chloride-enriched medium. Phenotypic and mechanistic analyses were conducted using real-time quantitative PCR, Western blotting, flow cytometry, and immunofluorescence staining.</p><p><strong>Results: </strong>The administration of EVO eye drops significantly enhanced tear secretion in mice, ameliorated ocular surface damage, decreased the expression of corneal inflammatory factors, and increased the density of conjunctival goblet cells. Furthermore, EVO reduced oxidative stress by promoting autophagy. Mechanistically, EVO-induced autophagy was mediated via the p53/mammalian target of rapamycin pathway.</p><p><strong>Conclusions: </strong>These findings suggest that EVO is a potential therapeutic agent for the treatment of DED, with its beneficial effects attributed to the activation of autophagy through the p53/mammalian target of rapamycin pathway.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"44"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lens Thickness-to-Anterior Chamber Depth Ratio: A Biometric Determinant of Chamber Angle Width in Han Chinese Cataract Patients.","authors":"Ao Miao, Fan Yang, Tianhui Chen, Dongjin Qian, Yongxiang Jiang, Jie Xu, Tianyu Zheng","doi":"10.1167/iovs.66.3.42","DOIUrl":"10.1167/iovs.66.3.42","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to individuate a novel ocular biometric index, the lens thickness-to-anterior chamber depth (LT/ACD) ratio, and identify its role in explaining anterior chamber angle width (ACAW) in Han Chinese patients with cataract.</p><p><strong>Methods: </strong>We enrolled 400 patients with cataract with phakic eyes. According to the axial length (AL), the eyes were divided into short eyes (AL < 22 mm, n = 100), medium eyes (22 ≤ AL < 24 mm, n = 100), medium‒long eyes (24 ≤ AL < 26 mm, n = 100), and long eyes (AL ≥ 26 mm, n = 100). We used a Pentacam HR to determine ACAW and an IOLMaster 700 to measure ACD and LT. A narrow chamber angle was defined as an ACAW < 20 degrees.</p><p><strong>Results: </strong>Using a multivariable linear model, which included the LT/ACD ratio, age, sex, AL, white-to-white, keratometry, central corneal thickness, and pupil diameter, the LT/ACD ratio was the strongest determinant of ACAW in the total group (standardized regression coefficient [β] = -0.71), short eyes (β = -0.71), medium eyes (β = -0.69), medium-long eyes (β = -0.72), and long eyes (β = -0.63). The LT/ACD ratio remained the strongest determinant of ACAW in eyes with an ACD < 3.0 mm (β = -0.51) or an LT ≥ 5.0 mm (β = -0.64). Multivariable logistic analysis revealed a significant association between a greater LT/ACD ratio and the presence of angle narrowness in the total group (odds ratio = 156.7, 95% confidence interval [CI] = 10.8-2270.4). An LT/ACD ratio of 1.8 could indicate angle narrowness (area under the curve = 0.94).</p><p><strong>Conclusions: </strong>In Han Chinese patients with cataract, the LT/ACD ratio can be used as an ocular biometric determinant of ACAW. An LT/ACD ratio exceeding 1.8 could effectively identify the presence of angle narrowness.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"42"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Proteomic Profiling of Exfoliation Glaucoma Via Mass Spectrometry Reveals SVEP1 as a Potential Biomarker.","authors":"Jiayong Li, Yuncheng Ma, Lingling Xie, Kaichen Zhuo, Yuxian He, Xin Ma, Shufen Zheng, Shicheng Guo, Yizhen Tang, Guzainuer Muhetaer, Mireayi Aizezi, Dan Zhang, Aizezi Wumaier, Xu Zhang, Chao Tang, Wei Wang, Wenyong Huang, Xinbo Gao","doi":"10.1167/iovs.66.3.19","DOIUrl":"10.1167/iovs.66.3.19","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the proteomic landscape of exfoliation glaucoma to find potential biomarkers.</p><p><strong>Methods: </strong>The study enrolled 34 patients diagnosed with either exfoliation syndrome with/without glaucoma or age-related cataract. Plasma proteins were analyzed through mass spectrometry and Mendelian randomization (MR) based on data from deCODE, FinnGen, Atherosclerosis Risk in Communities (ARIC), eQTLGen, and UK Biobank (UKB) cohorts to infer relationships.</p><p><strong>Results: </strong>Among 2025 plasma proteins analyzed, 130 were differentially expressed in the exfoliation glaucoma group, which exhibited elevated intraocular pressure. Our proteomics data suggested that infection, immune responses including intestinal immune network, endocrine hormones, and complement and coagulation cascades are involved in the development of exfoliation glaucoma. Notably, there was a significant correlation between SVEP1 and exfoliation glaucoma (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.10 to 1.31, P = 0.0000428), with findings corroborated in an independent cohort. Further analysis predicted a protective role of LOXL1-AS1 in exfoliation glaucoma through its regulation of SVEP1 expression. In MR phenome-wide association studies, SVEP1 was associated with complications of exfoliation glaucoma. After multiple testing corrections, there was a tendency for SVEP1 to be associated with glaucoma (OR = 1.14, 95% CI = 1.11 to 1.16, P = 0.0000003) and type 2 diabetes (OR = 1.07, 95% CI = 1.05 to 1.08, P = 0.0000067).</p><p><strong>Conclusions: </strong>Plasma proteomic analysis reveals that high expression of SVEP1 is a risk factor for exfoliation glaucoma, which potentially affects diabetes and is affected by estradiol or LOXL1-AS1. However, further research is needed to establish causality.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"19"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal Biomechanics Are Associated With FBN1 Mutations in Patients With Marfan Syndrome and Ectopia Lentis.","authors":"Qiu-Yi Huo, Rui-Zheng Zhang, Wan-Nan Jia, Ya-Lei Wang, Xin Shen, Xin-Yao Chen, Tian-Hui Chen, Yan Liu, Ling-Hao Song, Xinyue Wang, Yong Lv, Ze-Xu Chen, Yong-Xiang Jiang","doi":"10.1167/iovs.66.3.23","DOIUrl":"10.1167/iovs.66.3.23","url":null,"abstract":"<p><strong>Background: </strong>We investigated the corneal biomechanical properties and their genotype-phenotype correlation correlations in patients with Marfan syndrome (MFS) and ectopia lentis (EL).</p><p><strong>Methods: </strong>Patients with MFS with EL underwent panel-based next-generation sequencing in this retrospective cohort study. The FBN1 genotypes were categorized into the dominant-negative (DN) group and the haploinsufficiency (HI) group. The DN variants were further subclassified based on the affected residues and their locations. Corneal biomechanical parameters were measured using dynamic Scheimpflug-based biomechanical analysis (CorVis ST). The correlations between corneal biomechanical properties and FBN1 genotype or nongenetic factors were analyzed. The differences between patients with MFS and normal control were also evaluated after matching confounding factors.</p><p><strong>Results: </strong>One hundred one consecutive MFS probands participated in this study, with a median age of 6 years. Patients with HI and DN variants affecting critical residues, namely the DN (-Cys + CaB) variants, exhibited significantly higher deformation amplitude ratios (P = 0.029) and lower stress-strain index values (P = 0.007) compared with those in the DN (others) group, indicating lower corneal stiffness in the former group. DN variants in the FUN-EGF3 region were associated with lower deformation amplitude ratios (P = 0.011) and higher stress-strain index values (P = 0.002), whereas those in the DN-CD region exhibited the opposite pattern. Compromised corneal stiffness was significantly associated with HI and DN (-Cys + CaB) variants (b = -0.184; P = 0.01) and variants located outside the FUN-EGF3 region (b = 0.256; P = 0.001), after adjusting for confounding factors. Compared with matched controls, patients with MFS demonstrated significantly higher deformation amplitude ratios (P = 0.023), further confirming decreased corneal stiffness in this population.</p><p><strong>Conclusions: </strong>The FBN1 genotype impacts the corneal biomechanical properties of patients with MFS and EL. Corneal biomechanics provide a novel platform to study the genotype-phenotype correlation of MFS.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"23"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Butyrate Ameliorates Graves' Orbitopathy Through Regulating Orbital Fibroblast Phenotypes and Gut Microbiota.","authors":"Pingbo Ouyang, Jia Qi, Boding Tong, Yunping Li, Jiamin Cao, Lujue Wang, Tongxin Niu, Xin Qi","doi":"10.1167/iovs.66.3.5","DOIUrl":"10.1167/iovs.66.3.5","url":null,"abstract":"<p><strong>Purpose: </strong>Graves' orbitopathy (GO), the common extrathyroidal complication of Graves' disease (GD), is characterized by orbital fibroblast stimulation, adipogenesis, and hyaluronan production. Recently, gut microbiota and its metabolites have garnered attention for their possible involvement in GO.</p><p><strong>Methods: </strong>This study utilized an animal model of GO and examined the effects of butyrate treatment on orbital fibroblast cells and gut microbiota. Ex vivo experiments were performed using orbital fibroblasts derived from healthy patients' and patients' with GO orbital tissue to evaluate vitality, activation, and adipogenesis in response to butyrate treatment. Gut microbiota diversity was also analyzed in butyrate-treated and untreated GO mice.</p><p><strong>Results: </strong>In human orbital fibroblasts, butyrate treatment dramatically decreased the vitality of GO-derived fibroblasts without harming normal fibroblasts. Butyrate prevented activation and fibrotic processes induced by transforming growth factor beta 1 (TGF-β1) in GO and normal fibroblasts. Additionally, butyrate reduced lipid droplet formation and downregulated lipogenic markers in GO and normal orbital fibroblasts, inhibiting adipogenesis. In the GO mouse model, butyrate therapy improved orbital histological abnormalities and normalized serum thyroid hormone and antibody levels. The intestinal microbiome of butyrate-treated GO mice also changed significantly, with a reduction in certain bacteria (Bifidobacterium, GCA-900066575, and Parabacteroides) and an increase in others (Bacteroides and Rikenellaceae_RC9).</p><p><strong>Conclusions: </strong>Butyrate ameliorates several of the symptoms of GO, lowering GO orbital fibroblast viability, adipogenesis, and TGF-β1-induced fibrosis without damaging normal fibroblasts. Butyrate normalizes thyroid function in a GO mouse model, improves histopathological alterations, and transforms gut microbiota populations, proving its potential in treating GO through the gut-thyroid axis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Ocular Gene-Set Expression Library for Heritability Partition and Cell Line Enrichment Analyses.","authors":"Pirro G Hysi, Christopher J Hammond","doi":"10.1167/iovs.66.3.11","DOIUrl":"10.1167/iovs.66.3.11","url":null,"abstract":"<p><strong>Purpose: </strong>Use of genome-wide association studies (GWASs) in combination with transcriptomic arrays of different tissues or cell lines can reveal relevant cellular profiles and significantly improve understanding of the mechanisms of diseases. However, due to difficulty of access, few ocular transcriptomics datasets are available. This work aimed to create and make available an expression library platform that can be used with popular and versatile tools such as the linkage disequilibrium score (LDSC) regression techniques to identify specific cell lines enriched in ocular diseases.</p><p><strong>Methods: </strong>We used transcriptome information from six publicly available single-cell and single-nucleus RNA sequence datasets to obtain matrices of normalized gene expression and estimated enrichment of the 10% most expressed transcripts in each cell line. We tested for type 1 error using simulated GWAS datasets and then used LDSC regression analyses to study the enrichment in different eye diseases.</p><p><strong>Results: </strong>Gene expression databases for over 197 ocular cell lines were generated. Simulations of 1000 random GWASs of varying sample sizes showed no genomic inflation. Cell line-specific analyses of GWAS results found that genes near single nucleotide polymorphisms (SNPs) associated with refractive error were significantly enriched in cones (P = 0.008), rods (P = 0.002) and peripheral retina Müller cells (P = 0.002), juxtacanalicular cribriform cells (P = 0.0017), stromal keratocytes (P = 0.0018), and one beam-cell subpopulation (P = 0.0028) in primary open-angle glaucoma, emphasizing the importance of intraocular pressure in its etiology.</p><p><strong>Conclusions: </strong>We have built a structured ocular transcriptomics library to estimate cell line enrichment among association signals from genome-wide association studies that may be extended by incorporating other datasets. We identified cells that appear important in the genetics of common eye diseases.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"11"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Roles of Macrophages and Microglia in Subretinal Fibrosis Secondary to Neovascular Age-Related Macular Degeneration.","authors":"Manon Szczepan, María Llorián-Salvador, Caijiao Yi, David Hughes, Matthias Mack, Mei Chen, Heping Xu","doi":"10.1167/iovs.66.3.41","DOIUrl":"10.1167/iovs.66.3.41","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the differential role of infiltrating CCR2+ macrophages and CX3CR1+ microglia in neovascular AMD (nAMD)-mediated subretinal fibrosis.</p><p><strong>Methods: </strong>Subretinal fibrosis was induced using the two-stage laser protocol in C57BL/6J or CX3CR1gfp/+ mice. The fibrotic lesion was detected using collagen-1 staining in retinal pigment epithelial /choroidal flatmounts. Infiltrating macrophages and microglial were identified using F4/80, CCR2, and CX3CR1 markers at one, three, six, and 10 days after the second laser. Circulating CCR2+ monocytes were depleted using the MC-21 antibody, whereas CX3CR1+ microglia were depleted using PLX5622. BV2 microglia were treated with TGF-β1 for 96 hours, and their profibrotic potential was examined by quantitative PCR and immunocytochemistry.</p><p><strong>Results: </strong>Subretinal fibrosis lesions developed three days after the second laser, accompanied by persistent CCR2+F4/80+ macrophage and CX3CR1+ cell infiltration. Inflammation in the first three days after the second laser was dominated by filtrating CX3CR1+ cells, and the number increased until day (D) 10 post-second laser. Depletion of CCR2+ monocytes from D5-10 significantly reduced the vascular and fibrotic components of the lesion, while CX3CR1+ cell depletion reduced Isolectin B4+ but not collagen-1+ lesion size. Bone marrow-derived macrophages from D6 and D10 mice expressed significantly higher levels of α-smooth muscle actin (α-SMA) and collagen-1 compared to cells from D1 and D3. TGFβ1 treatment increased TMEM119, CX3CR1, IL1b and iNOS gene expression but did not affect Acta2 and Col1a1 gene expression in BV2 cells.</p><p><strong>Conclusions: </strong>CCR2+ monocytes, but not CX3CR1+ microglia, critically contribute to the development of subretinal fibrosis in nAMD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"41"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}