Investigative ophthalmology & visual science最新文献

{"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":"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":"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}

{"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":"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":"Prevalence of HSV Genomic Signatures Among Acanthamoeba Hosts and Contaminated Lens Cases: A Molecular and Clinical Study.","authors":"Juan-Carlos Navia, Alexander Alfonso, Darlene Miller, Jorge Maestre-Mesa, Heather Durkee, Paula A Sepulveda-Beltran, Felipe Echeverri-Tribin, Salomon Merikansky, Jaime D Martinez, Harry W Flynn, Eduardo C Alfonso, Jean-Marie Parel, Guillermo Amescua","doi":"10.1167/iovs.66.2.4","DOIUrl":"10.1167/iovs.66.2.4","url":null,"abstract":"<p><strong>Purpose: </strong>To document the presence of herpes simplex virus (HSV) genomic signatures among Acanthamoeba hosts recovered from patients with Acanthamoeba keratitis (AK) and in contaminated lens cases.</p><p><strong>Methods: </strong>We used a combination of PCR sequencing and shotgun metagenomics to detect and confirm the presence of HSV genomic signatures in Acanthamoeba hosts and lens cases. Clinical outcomes were correlated with the prevalence of host HSV signatures.</p><p><strong>Results: </strong>HSV genomic signatures were detected in 26% (n = 6) of Acanthamoeba hosts recovered from patients with culture confirmed AK. HSV-1 and HSV-2 or both were identified in 33%, 50%, and 17% of isolates, respectively. Fifty-two percent of patients (12/23) were misdiagnosed initially as presenting with HSV keratitis. Patients with HSV-positive Acanthamoeba isolates had a mean best-corrected visual acuity of 1.43 LogMAR at diagnosis and 0.53 LogMAR at follow-up, compared with 1.85 and 0.92 LogMAR, respectively, in HSV-negative cases. Contact lens use was identified as a risk factor in 83% of 18 patients. We detected 46,597 viral signatures in 5 of 14 contaminated lens cases (35.7%). Distribution included 33% bacteriophages, 8.2% giant viruses, 4.1% nonhuman Herpesviridae, and 0.39% human Herpesviridae. Among the 184 human Herpesviridae genomic signatures, HSV types 1 or 2 or both were documented in 5.7%, VZV in 39.7%, HHV7 in 38.6%, HHV6 in 15.0%, and Epstein-Barr virus in 0.5%.</p><p><strong>Conclusions: </strong>This study is the first to identify HSV-positive genomic signatures in clinical AK isolates and/or contact lens cases. Taken together, the high prevalence of HSV genomic signatures in both amebic hosts and lens cases, might signal an unrecognized Acanthamoeba-HSV association and the need for reassessing current management.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079954","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":"Oridonin Preserves Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates Choroidal Neovascularization.","authors":"Juming Zhu, Dongmei Ding, Tao Sun, Yuting Zhang, Huizi Miao, Yunjie Gu, Ming Dai, Manhui Zhu","doi":"10.1167/iovs.66.2.56","DOIUrl":"10.1167/iovs.66.2.56","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the role and mechanism of oridonin (ORI), a bioactive diterpenoid extracted from the Chinese herbal medicine Rabdosia rubescens, on the integrity of outer blood-retinal barrier (oBRB) during choroidal neovascularization (CNV).</p><p><strong>Methods: </strong>ARPE-19 cells were exposed to hypoxia and treated with ORI. The expression of ZO-1 and occludin in the axis of TGFβR/SUV39H1/KLF11 was detected by WB, chromatin immunoprecipitation, luciferin report activity assay, and immunofluorescence assay (IF), and the effect of ORI on the barrier properties of ARPE-19 cells was studied. A laser-induced mouse CNV model was constructed, and ORI was administrated by oral gavage. IF on mouse choroid flat mounts was done to confirm the effect of ORI on BRB integrity. Indocyanine green angiography and IF on mouse retina-RPE-choroid flat mounts were performed to determine the effect of ORI on CNV formation and retinal function. Hematoxylin and eosin staining and TUNEL staining were carried out to appraise ocular and systemic cytotoxicity caused by ORI.</p><p><strong>Results: </strong>ORI protected ARPE-19 cells from hypoxia-induced destruction of barrier properties and promoted the expression of ZO-1 and occludin by the TGFβR/SUV39H1/KLF11 axis, maintaining barrier properties of ARPE-19 cells with hypoxia. ORI improved BRB integrity during laser-induced CNV in mice and mitigated laser-induced CNV formation in mice without any ocular or systemic cytotoxicity (n = 4-5 in each group).</p><p><strong>Conclusions: </strong>ORI ameliorates BRB integrity and subsequent formation of CNV via regulating the TGFβR/SUV39H1/KLF11 pathway in RPE cells.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"56"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11855140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468014","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":"Characterization, Enrichment, and Computational Modeling of Cross-Linked Actin Networks in Transformed Trabecular Meshwork Cells.","authors":"Haiyan Li, Devon H Harvey, Jiannong Dai, Steven P Swingle, Anthony M Compton, Chenna Kesavulu Sugali, Kamesh Dhamodaran, Jing Yao, Tsai-Yu Lin, Todd Sulchek, Taeyoon Kim, C Ross Ethier, Weiming Mao","doi":"10.1167/iovs.66.2.65","DOIUrl":"10.1167/iovs.66.2.65","url":null,"abstract":"<p><strong>Purpose: </strong>Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM). We previously developed the GTM3L cell line, which spontaneously forms fluorescently labeled CLANs, by transducing GTM3, a transformed glaucomatous TM cell line, with a lentivirus expressing the LifeAct-GFP fusion protein. Here, we determined if LifeAct-GFP viral copy numbers are associated with CLANs, developed approaches to increase CLAN incidence, and computationally studied the biomechanical properties of CLAN-containing GTM3L cells.</p><p><strong>Methods: </strong>GTM3L cells were fluorescently sorted for viral copy number analysis to determine whether increased CLAN incidence was associated with copy number. CLAN incidence was increased by combining (1) differential adhesion sorting, (2) cell deswelling, and (3) cell stiffness selection. GTM3L cells were cultured on glass or soft hydrogels for stiffness measurement by atomic force microscopy. Computational models studied the biomechanical properties of CLANs.</p><p><strong>Results: </strong>GTM3L cells had one LifeAct-GFP viral copy/cell on average, and viral copy number or LifeAct-GFP expression level did not associate with CLAN incidence rate. However, CLAN rate was increased from -0.28% to -50% by combining the three enrichment methods noted above. Further, GTM3L cells formed more CLANs on a stiff versus a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus.</p><p><strong>Conclusions: </strong>It is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the biomechanics, mechanobiology, and etiology of CLANs in the TM.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"65"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501383","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":"Retinal Responses to Short- and Longer-Term Predominant ON or OFF Stimulation in Emmetropes and Myopes.","authors":"Sandra Wagner, Annemarie Settele, Torsten Strasser","doi":"10.1167/iovs.66.2.66","DOIUrl":"10.1167/iovs.66.2.66","url":null,"abstract":"<p><strong>Purpose: </strong>The link between nearwork and myopia is controversially discussed. Features of the viewing target may stimulate eye growth, for example, black-on-white text was found to stimulate retinal OFF pathways and promote choroidal thinning, whereas inverted text led to ON pathway stimulation and thicker choroids. We used electroretinograms (ERGs) to compare retinal activity for both stimuli in the parafovea in emmetropes and myopes and studied the effects of adaptation.</p><p><strong>Methods: </strong>ERGs were recorded in 42 subjects (18-30 years) during 200 ms-flashes on a CRT monitor, superimposed with an annulus or circles filled with gray or inverted or standard text. Ganzfeld ERGs (500 ms) were taken before and after 30 minutes of reading standard or inverted text at 25 cm to determine adaptation effects. The ON- (b-wave) and OFF-responses (d-wave) were analyzed using linear mixed effects models and pointwise t-testing.</p><p><strong>Results: </strong>(1) Stimulus size affected retinal ON-responses of both groups (p < 0.001), with larger responses to a 6 to 12 degrees annulus than to a 12-degree circle. (2) Myopes displayed larger ON-responses to inverted text contrast than emmetropes within 6 to 12 degrees. (3) After adaptation to text, ON-responses were reduced (p = 0.010) irrespective of refraction and contrast. (4) Emmetropes showed reduced ON- and OFF-responses to inverted text contrast. (5) Only emmetropes had reduced ON- and larger OFF-responses after adapting to standard text.</p><p><strong>Conclusions: </strong>Myopes had largest ON-responses with inverted contrast in the perifovea. Emmetropes displayed larger adaptive changes after ON/OFF stimulation. In both groups, inverted contrast still reduced ON-responses, suggesting that efficient activation of retinal ON channels to inhibit myopia might require additional OFF channel suppression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"66"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501385","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":"Depth and Strain-Dependent Structural Responses of Mouse Lens Fiber Cells During Whole Lens Shape Changes.","authors":"Sepideh Cheheltani, Mahbubul H Shihan, Justin Parreno, Sondip K Biswas, Woo-Kuen Lo, Velia M Fowler","doi":"10.1167/iovs.66.2.53","DOIUrl":"10.1167/iovs.66.2.53","url":null,"abstract":"<p><strong>Purpose: </strong>To study the relationship between whole lens shape changes and fiber cell responses to externally applied loads.</p><p><strong>Methods: </strong>Freshly dissected mouse lenses were compressed by applying glass coverslips to the lens anterior, followed by fixation to preserve lens shape, and preparation for scanning electron microscopy (SEM). SEM images were collected from the outer cortex to the nucleus, and fiber cell end-to-end curvature and membrane paddle dimensions were measured using ImageJ.</p><p><strong>Results: </strong>At 23% and 29% axial strain, cortical fiber bundle curvature increased significantly compared to control uncompressed lenses, whereas nuclear fiber bundle curvature was unaffected. Outer cortical fiber cell membrane paddles and protrusions were dramatically distorted in a radial direction, with loss of paddle-associated small protrusions in compressed lenses compared to controls, but nuclear fiber cell morphologies were unchanged. The compression-induced increases in cortical fiber cell curvature and distortion of membrane paddles were reversible, with fiber cell morphologies returning to those of control lenses after the release of load.</p><p><strong>Conclusions: </strong>Whole lens shape changes due to an increase in axial strain result in increased fiber cell curvature and distorted membrane morphologies in cortical but not nuclear fiber cells, indicating that mechanical strain dissipates with depth. The recovery of normal cortical fiber cell curvature and membrane morphologies after the removal of load and lens rounding back to its original shape suggests elastic properties of the young and mature fiber cells and their membrane paddles.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"53"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457938","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}