Investigative ophthalmology & visual science最新文献

{"title":"Predicting the Structure-Function Relationship in Glaucoma Using a Physiological Model.","authors":"Chris Bradley, Jithin Yohannan","doi":"10.1167/iovs.66.11.75","DOIUrl":"10.1167/iovs.66.11.75","url":null,"abstract":"<p><strong>Purpose: </strong>Determine how well a physiological model-the retina-V1 (RV1) model of target detection-predicts the structure-function relationship in glaucoma.</p><p><strong>Methods: </strong>Unlike curve-fitting models, the RV1 model includes a map of retinal ganglion cell (RGC) receptive fields across the visual field (VF), enabling simulation of different patterns of RGC loss. Predicted mean sensitivity for different patterns of simulated RGC loss and predictions of different curve-fitting models were compared to 12,917 paired SITA-Standard 24-2 VFs and optical coherence tomography measurements of average retinal nerve fiber layer thickness from 4432 eyes of 2418 patients with glaucoma between 1997 and 2023. Except for one free parameter, all RV1 model parameters were fixed from a previous study that fit the model to an unrelated data set of contrast sensitivities for 43 localized achromatic stimuli.</p><p><strong>Results: </strong>Different structure-function relationships were predicted by the RV1 model for different patterns of RGC loss. Random RGC loss resulted in a mean absolute error of 2.99 dB, which was marginally but significantly smaller than 3.01 dB for ninth-degree polynomial regression-the highest degree polynomial whose coefficients could be estimated. Other patterns of simulated RGC loss, including periphery-to-fovea loss typical in glaucoma, accounted for much of the observed variance in the structure-function data. Unlike curve-fitting models, the RV1 model correctly predicted higher variance at lower dB/micron levels.</p><p><strong>Conclusions: </strong>A physiological model can account for much of the observed variance in structure-function data for glaucoma by simulating different patterns of RGC loss-this is currently not possible with curve-fitting models.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"75"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954537","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 Role of Retinal Antigen-Presenting Cells in Spontaneous Retinal Autoimmunity.","authors":"Joe Sherman, Laura Burgstaler, Yunan Li, Heidi Roehrich, Dale S Gregerson, Scott W McPherson","doi":"10.1167/iovs.66.11.26","DOIUrl":"10.1167/iovs.66.11.26","url":null,"abstract":"<p><strong>Purpose: </strong>We reported earlier that induction of spontaneous autoimmune uveoretinitis (SAU) correlated with the recruitment of circulating antigen-presenting cells (APCs) into the retina. Here, we investigated the role of resident retinal APCs on the course of SAU.</p><p><strong>Methods: </strong>R161H+/- mice (B10.RIII), which spontaneously and rapidly develop severe autoimmune uveoretinitis, were crossed with CD11cDTR/GFP mice (B6/J). R161H+/- mice on the B6/J background develop slower, less severe SAU than R161H+/--B10.RIII mice, allowing assessment of disease development relative to the depletion or activation of retinal or systemic APCs. The course of SAU was established in a cohort of control R161H+/- × CD11cDTR/GFP F1 mice and then reanalyzed in test cohorts following treatment with diphtheria toxin or stimulation by optic nerve crush (ONC) injury. Analysis was done by retinal imaging, flow cytometry, and histology.</p><p><strong>Results: </strong>Systemic depletion of APCs halted the progression of SAU in R161H+/- × CD11cDTR/GFP F1 mice and, if commenced early in the disease process, would reduce SAU severity. However, following depletion of APCs specifically from the retina, SAU in R161H+/- × CD11cDTR/GFP F1 mice progressed in a manner similar to that of control mice. In contrast, SAU in R161H+/- × CD11cDTR/GFP F1 mice was exacerbated following the activation of retinal APCs by ONC.</p><p><strong>Conclusions: </strong>Our observations that local depletion of retinal APCs failed to inhibit SAU progression and that depletion of circulating APCs not only limited SAU progression but also, under defined circumstances, reduced clinical SAU support the idea that circulating APCs are crucial for the induction and progression of SAU.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"26"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816655","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":"Human Omental Mesothelial Cells Exhibit a Corneal Endothelial-Like Cell Phenotype for Tissue Engineering of a Corneal Endothelium Biomimetic.","authors":"Jorge L Alió, Benoit R Gauthier, Juan C Gómez Rosado, Jorge L Alió Del Barrio, Alejandra E Rodríguez, Francisco J Díaz Corrales, Luis C Capitán Morales, Bernat Soria, Christian C Lachaud","doi":"10.1167/iovs.66.11.7","DOIUrl":"10.1167/iovs.66.11.7","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether cultured human omental mesothelial cells (OMC) exhibit phenotypic and functional similarities to human corneal endothelial cells (CEC) and whether they can adhere to the corneal stroma and form a biomimetic corneal endothelium when grown on a human anterior lens capsule (HALC).</p><p><strong>Methods: </strong>Human OMC were isolated from the greater omentum. Human B4G12 CEC were used as a reference for native and functional CEC phenotype whereas human mesenchymal stromal cells (MSC) served as a phenotypically distinct control group. OMC, CEC and MSC were compared using flow cytometry, immunofluorescence and qRT-PCR for lineage-specific markers, as well as through a transepithelial permeability assay. The adhesion capacity of OMC was also evaluated on both mouse corneal stroma and a decellularized HALC.</p><p><strong>Results: </strong>Several cell-surface markers commonly expressed at high levels in MSC (CD13, CD105, CD73 and CD44) were detected at markedly lower levels in OMC and CEC. OMC and CEC, but not MSC, also shared a similar expression profile of key structural markers (pan cytokeratin, ZO-1, β-catenin, N-cadherin, COL4A2, COL8A2) and functional corneal endothelium markers (AQP1, ATP1A1, SLC4A11, CLCN-3). In addition, OMC demonstrated transepithelial permeability values comparable to those of CEC monolayers supporting their barrier-forming capacity. Both CEC and OMC formed cobblestone-like monolayers on mouse corneal stroma and OMC seeded onto HALC generated a bioconstruct that reproduced the key morphological and ultra-structural features of native corneal endothelium.</p><p><strong>Conclusions: </strong>Overall, our findings show that cultured human OMC exhibit phenotypic and functional similarities to CEC. The ability of OMC to adhere to the corneal stroma and to generate a biomimetic corneal endothelium when combined with HALC highlights their potential use in corneal endothelial regeneration.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"7"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12347251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784328","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":"Foveal Identification and Development in Prematurity-Implications on Zone Localization and Nutritional Supplementation.","authors":"Sarthak V Shah, Arthur R Brant, Akwasi Ahmed, Naana A Wireko Brobby, Cindy S Zhao, Ashna Ahya, Geoffrey C Tabin, Darius M Moshfeghi","doi":"10.1167/iovs.66.11.17","DOIUrl":"10.1167/iovs.66.11.17","url":null,"abstract":"<p><strong>Purpose: </strong>Accurate identification of retinal Zone I in retinopathy of prematurity (ROP) is critical for treatment decisions and prognosis. Current definitions rely on identifying the macular center, limited by absence of the foveal light reflex (FLR) early in screening. Understanding factors influencing FLR development could improve zone localization and guide nutritional interventions. We sought to determine whether absolute infant weight gain independently predicts FLR development in premature infants, beyond postmenstrual age (PMA).</p><p><strong>Methods: </strong>Prospective observational cohort study conducted from November 2024 to March 2025 within a multicenter telemedicine-based ROP screening program (GHANAROP). Premature infants meeting ROP screening criteria, screened before 37 weeks PMA, who subsequently developed FLR identifiable on wide-field digital retinal imaging were included. Logistic regression assessed associations between FLR presence, PMA, and infant weight. Multivariate logistic regression with elastic net regularization evaluated combined predictive value of PMA and weight.</p><p><strong>Results: </strong>Among 318 eyes, FLR was first identified at mean PMA of 35 0/7 weeks (low risk ROP) and 35 2/7 weeks (more than low risk ROP), and mean weight of 1723g (low risk) and 1565g (more than low risk). Univariate modeling found that each additional week of PMA increased odds of FLR presence by 44.6% (OR = 1.446; 95% CI, 1.371-1.524) and that each 200g increase in weight increased odds by 23.1% (OR = 1.231; 95% CI, 1.113-1.360). Multivariate modeling demonstrated PMA and weight as predictors of FLR development, achieving 84.8% predictive accuracy (Nagelkerke R² = 0.2783).</p><p><strong>Conclusions: </strong>Absolute infant weight independently predicts FLR development beyond PMA alone, highlighting opportunities for nutritional interventions to accelerate foveal maturation and potentially enhance visual outcomes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"17"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12347157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794456","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":"Contribution and Compensation Effects of Refracting Components to Ocular Aberrations in Keratoconus.","authors":"Satish K Gupta, Andrew Carkeet, Scott A Read, Stephen J Vincent, David A Atchison","doi":"10.1167/iovs.66.11.64","DOIUrl":"https://doi.org/10.1167/iovs.66.11.64","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to determine the (i) contributions of refracting components to ocular aberrations and (ii) compensation effects exhibited by these components in keratoconus.</p><p><strong>Methods: </strong>Right eyes of 14 keratoconus and 20 control participants were analyzed using 5 mm pupils. Ocular aberrations were measured with a Hartmann-Shack aberrometer. Corneas were imaged with a Scheimpflug tomographer. Three-dimensional models of the total cornea and anterior cornea were created. Raytracing included correct object-image conjugates and corneal decentration relative to the aberrometer pupillary center to determine the total corneal and anterior corneal aberrations. Posterior corneal and lenticular aberrations were computed. Compensation effects (%) were calculated: 100 (anterior corneal-total corneal aberration)/anterior corneal aberration, and 100 (total corneal-ocular aberration)/total corneal aberration.</p><p><strong>Results: </strong>Considering coefficients for the total cornea with absolute values >0.05 µm, for both corneal surfaces, keratoconus had higher magnitudes than controls for C(2,-2), C(3,-3), C(3,-1), C(4,-2), total root mean square (RMS), higher-order RMS (HORMS), and J45. Both surfaces' RMS aberrations were approximately 2 to 5 times higher in keratoconus than in controls. Anterior corneal RMS aberrations were approximately 5 times (keratoconus) and approximately 3 to 4 times (controls) higher than those of the posterior cornea. Posterior corneal compensations for anterior corneal aberrations were higher in keratoconus than in controls for C(3,-3) (21%, decompensation of -14%), C(3,-1) (21%, -33%), C(4,-2) (27%, -10%), C(4,+2) (22%, 10%), HORMS (20%, 2%), and J0 (68%, 66%), as were lenticular compensations for total corneal aberrations for C(2,-2) (40%, -64%), C(2,+2) (70%, 60%), total RMS (21%, 20%), and J0 (642%, -55%).</p><p><strong>Conclusions: </strong>Keratoconic eyes exhibited higher anterior and posterior corneal aberrations than control eyes. The posterior cornea and lens compensated partly for the anterior cornea and total cornea, respectively, with greater percentage compensations in keratoconus.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"64"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954438","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":"Mathematical Models of Topically and Intravitreally Applied Ranibizumab.","authors":"Paul A Roberts, Chloe N Thomas, Gabriel Bellamy Plaice, James A Roberts, Marie-Christine Jones, James W Andrews, Lisa J Hill","doi":"10.1167/iovs.66.11.45","DOIUrl":"https://doi.org/10.1167/iovs.66.11.45","url":null,"abstract":"<p><strong>Purpose: </strong>Wet age-related macular degeneration (AMD) causes vision loss when vascular endothelial growth factor (VEGF) stimulates blood vessel growth into the light-sensitive retina. Anti-VEGF treatments such as ranibizumab are currently administered to treat wet AMD via intravitreal injections, which are unpleasant, expensive, and risk complications. We explored the efficacy of topically administered ranibizumab, with cell-penetrating peptides (CPPs).</p><p><strong>Methods: </strong>Ex vivo pig eyes were divided into three groups and treated with (1) topical or (2) intravitreal ranibizumab and CPP, or (3) intravitreal ranibizumab. ELISAs measured ranibizumab and VEGF concentrations in the aqueous and vitreous at 20 min, 40 min, 1 h, and 3.5 h (n = 3, per group). An ordinary differential equation model was formulated to describe the evolving concentrations of ranibizumab, VEGF, and their compounds in the tear, aqueous, and vitreal compartments.</p><p><strong>Results: </strong>Experimental-Topical: aqueous ranibizumab levels increased significantly, coincident with a significant drop in aqueous VEGF. Vitreal ranibizumab increased significantly, while vitreal VEGF remained constant. Intravitreal (with and without CPP): vitreal ranibizumab reached high concentrations, coincident with a significant drop in vitreal VEGF. Mathematical-topical treatment may provide sustained, moderate suppression of vitreal VEGF levels, while intravitreal treatment provides strong suppression, which lessens between treatments.</p><p><strong>Conclusions: </strong>CPP allows topical ranibizumab to penetrate the cornea. Combined intravitreal/topical treatment presents a promising approach; topical treatment suppresses vitreal VEGF levels between injections and thereby potentially reduces the frequency of injections. Treatment efficacy would be enhanced if ranibizumab's rate of binding to VEGF or tear residence time could be increased.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"45"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954559","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 Importance of Matching Optical Coherence Tomography Angiography Metrics to Diabetic Retinopathy Severity for Detecting Progression.","authors":"Shinji Kakihara, Kallista Zhuang, Mohamed AbdelSalam, Taffeta Chingning Yamaguchi, Amani A Fawzi","doi":"10.1167/iovs.66.11.49","DOIUrl":"https://doi.org/10.1167/iovs.66.11.49","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to determine which macular optical coherence tomography angiography (OCTA) metric best captures early progression of capillary non-perfusion across diabetic retinopathy (DR) severities.</p><p><strong>Methods: </strong>In this prospective, 1-year observational study, 208 patients with diabetes (320 eyes) underwent 3 × 3 mm macular OCTA at baseline, 6 months, and 12 months. Registered, averaged images yielded geometric perfusion deficits (GPDs), vessel density (VD), vessel length density (VLD) in the superficial and deep capillary plexuses (SCP and DCP), and foveal avascular zone area. Eyes were graded as non-referable or referable. Linear mixed models adjusted for age, sex, diabetes duration, hemoglobin A1c, and hypertension were conducted. Post hoc Dunnett's tests compared follow-ups with baseline within each severity group.</p><p><strong>Results: </strong>A total of 709 eye visits were analyzed by OCTA. Across the cohort, referable DR, longer diabetes duration, and hypertension were independently associated with higher GPD values. In referable eyes, GPD-DCP increased at 6 months (P = 0.036) and 1 year (P = 0.016), whereas no other OCTA metric changed significantly at 6 months. In non-referable eyes, the only significant change was a decrease in VD-SCP at 1 year (P = 0.004).</p><p><strong>Conclusions: </strong>Microvascular progression follows distinct, layer-specific patterns. In non-referable DR, capillary ischemia progresses more slowly and is more prominent in the SCP. In referable DR, GPD-DCP detected the earliest signs of microvascular progression and may serve as a promising biomarker, preceding vessel-based metrics. These findings suggest that the most informative OCTA metric should be tailored not only to the study question or timeline, but also to DR severity.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"49"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954512","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":"Revisiting the Trans-Ancestry Genetic Correlation of Refractive Error.","authors":"Rosie Clark, Xi He, Thu Nga Nguyen, Thanh Huyen Bui, Hannah Noor, Cathy Williams, Louise Terry, Jeremy A Guggenheim","doi":"10.1167/iovs.66.11.60","DOIUrl":"https://doi.org/10.1167/iovs.66.11.60","url":null,"abstract":"<p><strong>Purpose: </strong>The prevalence of myopia varies significantly across the globe. This may be a consequence of differences in exposure to lifestyle risk factors or differences in genetic susceptibility across ancestry groups. \"Trans-ancestry genetic correlation\" quantifies the similarity in genetic predisposition to a trait or disease between different populations. We estimated the trans-ancestry genetic correlation of refractive error across Europeans, South Asians, East Asians, and Africans using recently developed approaches.</p><p><strong>Methods: </strong>Two methods were applied: (1) trans-ancestry genetic correlation with unbalanced data resources (TAGC-UDR) and (2) trans-ancestry bivariate genomic-relatedness-based restricted maximum-likelihood (TAB-GREML). TAGC-UDR analyses were carried out for UK Biobank participants of European (n = 3500), East Asian (n = 972), South Asian (n = 4303), and African (n = 3877) ancestry. TAB-GREML analyses were carried out for participants of European (n = 10,000), South Asian (n = 4303), and African (n = 3877) ancestry.</p><p><strong>Results: </strong>TAGC-UDR analyses suggested the trans-ancestry genetic correlation of refractive error was in the range 0.7-1.0 for the European versus African, European versus East Asian, and European versus South Asian ancestry pairs. The TAB-GREML estimates were consistent with the TAGC-UDR findings. Precision of the estimates was limited, reflecting the modest sample sizes of the non-European samples.</p><p><strong>Conclusions: </strong>These results support and extend previous work suggesting that genetic susceptibility to refractive error is largely shared across Europeans, Africans, and South Asians. This suggests geographical differences in myopia prevalence are mostly driven by lifestyle factors or rare genetic variants not considered in the current work.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"60"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954580","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":"Hyperglycemia-Reduced Platelet-Derived Growth Factor-BB Expression Impairs Corneal Wound Healing in Diabetic Mice.","authors":"Yangyang Zhang, Rui Wang, Ya Li, Wei Zhu, Yanling Liu, Zhenzhen Zhang, Xia Qi, Huabo Chen, Qingjun Zhou, Lixin Xie","doi":"10.1167/iovs.66.11.61","DOIUrl":"https://doi.org/10.1167/iovs.66.11.61","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the role and primary mechanisms of platelet-derived growth factor-BB (PDGF-BB) in regulating corneal epithelial injury repair and nerve regeneration under diabetic conditions.</p><p><strong>Methods: </strong>Type 1 diabetes was induced in C57BL/6 mice via streptozotocin injection. Platelet depletion was achieved using an anti-mouse GPIbα antibody. Platelet levels were quantified in intra- and extravascular compartments of the corneal limbus. Concentrations of growth factors released by activated platelets were measured in human and murine diabetic and nondiabetic samples. Diabetic mice with corneal epithelial wounds received PDGF-BB eye drops alone or combined with ERK1/2 or AKT inhibitors. Platelet-depleted mice were treated with PDGF-BB eye drops, while wild-type C57BL/6 mice received subconjunctival anti-PDGF-BB antibody injections. Human primary corneal limbal epithelial stem cells (HLECs) from diabetic and nondiabetic donors were treated with anti-PDGF-BB antibodies or PDGF-BB small interfering RNA.</p><p><strong>Results: </strong>Diabetic individuals exhibited reduced peripheral blood platelet counts and diminished PDGF-BB expression following platelet activation. Both platelet depletion and hyperglycemia impaired corneal epithelial repair and nerve regeneration, correlating with reduced PDGF-BB levels. Inhibiting PDGF-BB signaling significantly delayed corneal epithelial healing and nerve regeneration in wild-type mice. In vitro, PDGF-BB enhanced HLEC migration and proliferation. PDGF-BB promoted corneal epithelial repair and nerve regeneration in diabetic mice via ERK1/2 and AKT pathway activation.</p><p><strong>Conclusions: </strong>Hyperglycemia suppresses PDGF-BB expression, impairing corneal epithelial wound healing and nerve regeneration by inhibiting ERK1/2 and AKT signaling. PDGF-BB may represent a potential therapeutic strategy for diabetic keratopathy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"61"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954569","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":"Yes-Associated Protein (YAP) Is Associated With Disease Severity and Visual Prognosis in Epiretinal Membrane.","authors":"Hyun Seung Yang, Yong-Ha Jo, Dongwoo Kim, Suho Choi, Byung Gil Moon, Youngseop Lee, Minji Kim, Donghoon Koo, Jeongmin Kim","doi":"10.1167/iovs.66.11.39","DOIUrl":"10.1167/iovs.66.11.39","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether Yes-associated protein (YAP), a key mechanotransduction effector, is associated with disease severity, surgical difficulty, and postoperative outcomes in epiretinal membrane (ERM) and to explore its prognostic relevance.</p><p><strong>Methods: </strong>This prospective study enrolled patients undergoing vitrectomy for ERM. Pre- and postoperative best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including ERM stage, central subfield thickness (CST), inner retinal irregularity index (IRII), and ellipsoid zone disruption (EZD), were evaluated. Surgical grading of internal limiting membrane (ILM) adherence (SGIA) was applied to assess ILM adhesion and surgical difficulty. ERMs were analyzed by immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR), and vitreous cytokines were also analyzed.</p><p><strong>Results: </strong>Among 152 patients with ERM stages ≥ 2, 26.3% were classified as stage 2, 42.1% as stage 3, and 31.6% as stage 4. Advancing ERM stage was significantly associated with poorer BCVA, higher SGIA grade, and worsening OCT parameters. YAP expression (by qPCR and IHC) and vitreous TGF-β1 levels progressively increased with ERM stage. YAP on IHC showed stronger associations with postoperative CST, postoperative IRII, and both pre- and postoperative EZD, whereas TGF-β1 was more strongly linked to preoperative CST and IRII. YAP also correlated independently with SGIA grade. Multivariate analysis identified YAP expression and SGIA grade as independent predictors of postoperative BCVA and visual improvement.</p><p><strong>Conclusions: </strong>ILM adhesion and surgical difficulty increase with ERM progression. YAP expression reflects ERM stage, ILM adhesion-related surgical complexity, postoperative retinal remodeling, and visual outcomes, independent of TGF-β pathways. These findings highlight YAP-mediated mechanotransduction as a key contributor to ERM pathophysiology and prognosis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"39"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873196","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}