Investigative ophthalmology & visual science最新文献

{"title":"Circadian Rhythms in Murine Ocular Tissues Including Sclera Are Affected by Neurobasal A Medium Preincubation and Mouse Strain, but Not Sex.","authors":"Nemanja Milicevic, Cristina Sandu, Etienne Challet, Teemu O Ihalainen, Soile Nymark, Marie-Paule Felder-Schmittbuhl","doi":"10.1167/iovs.66.6.62","DOIUrl":"10.1167/iovs.66.6.62","url":null,"abstract":"<p><strong>Purpose: </strong>Our understanding of ocular clocks has been profoundly advanced by the development of real-time recording of bioluminescence of PER2-luciferase (PER2::LUC) knock-in mouse explants. However, the effect of sex, mouse strain, and culturing conditions on ocular clocks remains unknown. Here, we studied the role these variables play on PER2::LUC bioluminescence rhythms of ocular tissues: retinas, corneas, and posterior eye cups (PECs). We also tested the hypothesis that the sclera contains a circadian oscillator by using scraped PECs as a proxy.</p><p><strong>Methods: </strong>Retinas, corneas, and intact and scraped PECs were obtained from male and female PER2::LUC knock-in mice maintained on either a pigmented C57BL/6J or albino RjOrl:SWISS background. PER2::LUC bioluminescence rhythms in ocular tissues were measured using a Lumicycle.</p><p><strong>Results: </strong>We compared PER2::LUC bioluminescence rhythms between ocular tissues and found that all ocular tissues oscillated, including the scraped PECs, which were previously not known to oscillate. The rhythms in scraped PECs had lower amplitudes, longer periods, and distinct acrophases compared with other ocular tissues. Immunolabeling revealed the presence of the protein product of the clock gene BMAL1 in the sclera. Ocular tissues of RjOrl:SWISS mice oscillated with higher amplitudes compared with the ones of C57BL/6J, with corneal rhythms being most affected by mouse strain. A 24-hour preincubation with Neurobasal A medium affected rhythms of ocular tissues, whereas sex differences were not detected for these rhythms.</p><p><strong>Conclusions: </strong>We discovered a novel oscillator in the sclera. PER2::LUC bioluminescence rhythms in murine ocular tissues are affected by Neurobasal A medium preincubation mouse strain but not sex.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"62"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333131","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":"Erratum in: Dysregulation of Autophagy Occurs During Congenital Cataract Development in βA3ΔG91 Mice.","authors":"","doi":"10.1167/iovs.66.6.75","DOIUrl":"https://doi.org/10.1167/iovs.66.6.75","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"75"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Retinal Features Using a Self-Configuring CNN for Clinical Intervention.","authors":"Daniel S Kermany, Wesley Poon, Anaya Bawiskar, Natasha Nehra, Orhun Davarci, Glori Das, Matthew Vasquez, Shlomit Schaal, Raksha Raghunathan, Stephen T C Wong","doi":"10.1167/iovs.66.6.55","DOIUrl":"10.1167/iovs.66.6.55","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal diseases are leading causes of blindness worldwide, necessitating accurate diagnosis and timely treatment. Optical coherence tomography (OCT) has become a universal imaging modality of the retina in the past 2 decades, aiding in the diagnosis of various retinal conditions. However, the scarcity of comprehensive, annotated OCT datasets, that are labor-intensive to assemble, has hindered the advancement of artificial intelligence (AI)-based diagnostic tools.</p><p><strong>Methods: </strong>To address the lack of annotated OCT segmentation datasets, we introduce OCTAVE, an extensive 3D OCT dataset with high-quality, pixel-level annotations for anatomic and pathological structures. Additionally, we provide similar annotations for four independent public 3D OCT datasets, enabling their use as external validation sets. To demonstrate the potential of this resource, we train a deep learning segmentation model using the self-configuring no-new-U-Net (nnU-Net) framework and evaluate its performance across all four external validation sets.</p><p><strong>Results: </strong>The OCTAVE dataset collected consists of 198 OCT volumes (3762 B-scans) used for training and 221 OCT volumes (4109 B-scans) for external validation. The trained deep learning model demonstrates clinically significant performance across all retinal structures and pathological features.</p><p><strong>Conclusions: </strong>We demonstrate robust segmentation performance and generalizability across independently collected datasets. OCTAVE bridges the gap in publicly available datasets, supporting the development of AI tools for precise disease detection, monitoring, and treatment guidance. This resource has the potential to improve clinical outcomes and advance AI-driven retinal disease management.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"55"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316929","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":"BCAT1 Activation Reprograms Branched-Chain Amino Acid Metabolism and Epigenetically Promotes Inflammation in Diabetic Retinopathy.","authors":"Jingyi Wang, Zihan Yin, Jingxiao Yang, Sijun Sun, Xiaofang Tang, Shengjie Zhang, Yi-Ping Wang, Haiyan Wang","doi":"10.1167/iovs.66.6.59","DOIUrl":"10.1167/iovs.66.6.59","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate how branched-chain amino acid (BCAA) metabolism is remodeled and to determine its contribution to diabetic retinopathy progression.</p><p><strong>Methods: </strong>We analyzed Bcat1 and Bcat2 expression in the retina using single-cell sequencing data and immunofluorescence. Bcat1-mediated remodeling of BCAA metabolism was assessed via targeted metabolomics in Müller cells. We performed chromatin immunoprecipitation (ChIP) to examine histone methylation at inflammatory gene promoters. Additionally, we utilized RNA sequencing and kinase screening assays to delineate phosphorylation regulation of Bcat1 activity. In vivo, we established diabetic mouse models and treated them with Bcat1-specific inhibitor to evaluate retinal inflammation and vascular leakage.</p><p><strong>Results: </strong>Bcat1 was predominantly expressed in Müller cells and exhibited increased activity under diabetic conditions, leading to a remodeling of BCAA catabolism and upregulation of inflammatory genes (interleukin 6 [Il6] and tumor necrosis factor-α [Tnf-α]). Bcat1 activity was negatively regulated by polo-like kinase 4 (Plk4)-mediated phosphorylation at threonine 333. In high glucose-treated Müller cells, elevated Bcat1 activity reduced α-ketoglutarate (α-KG), a critical substrate for histone demethylation reactions, resulting in higher histone H3 lysine 4 trimethylation (H3K4me3) levels at inflammatory gene promoters, and further boosted retinal inflammation. Treatment with chemical Bcat1 inhibitors (BAY-069 and ERG240) significantly reduced inflammatory gene expression and vascular leakage in diabetic retinas in vivo.</p><p><strong>Conclusions: </strong>Bcat1 activation mediates BCAA metabolism remodeling in Müller cells and epigenetically induces retinal inflammation, which offers a potential therapeutic target for diabetic retinopathy. Diabetes and diabetic retinopathy are potentially driven not only by hyperglycemia but also by dysregulated amino acid metabolism.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"59"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325721","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":"Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes.","authors":"Abraham Hang, Andy Shao, Michael Shea, Michel J Roux, Denise M Imai-Leonard, David J Adams, Takanori Amano, Oana V Amarie, Zorana Berberovic, Raphaël Bour, Lynette Bower, Brian C Leonard, Steve D Brown, Soo Young Cho, Sharon Clementson-Mobbs, Abigail J D'Souza, Mary Dickinson, Mohammad Eskandarian, Ann M Flenniken, Helmut Fuchs, Valerie Gailus-Durner, Jason Heaney, Yann Hérault, Martin Hrabe de Angelis, Chih-Wei Hsu, Shundan Jin, Russell Joynson, Yeon Kyung Kang, Haerim Kim, Hiroshi Masuya, Ki-Hoan Nam, Hyuna Noh, Lauryl M J Nutter, Marcela Palkova, Jan Prochazka, Miles Joseph Raishbrook, Fabrice Riet, Jason Salazar, John Richard Seavitt, Radislav Sedlacek, Mohammed Selloum, Kyoung Yul Seo, Je Kyung Seong, Hae-Sol Shin, Toshihiko Shiroishi, Tania Sorg, Michelle Stewart, Masaru Tamura, Heather Tolentino, Uchechukwu Udensi, Sara Wells, Wolfgang Wurst, Atsushi Yoshiki, Hamid Meziane, Glenn C Yiu, Paul A Sieving, Louise Lanoue, K C Kent Lloyd, Colin McKerlie, Ala Moshiri","doi":"10.1167/iovs.66.6.64","DOIUrl":"10.1167/iovs.66.6.64","url":null,"abstract":"<p><strong>Purpose: </strong>Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.</p><p><strong>Methods: </strong>The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes (KEGG).</p><p><strong>Results: </strong>Screening of 587 late-adult mouse genes yielded 12 with abnormal retinal phenotypes, which corresponded to 20 human orthologs. Three of the 12 mouse genes and two of the 20 human orthologs were previously implicated in retinal pathology or physiology in a literature review. Although all of the genes demonstrated retinal pathology when deleted from the mouse genome, most do not have established roles in human retinal disease. Furthermore, human protein-protein analysis and biological pathway analysis yielded only a few relationships between the candidate gene list and that of known IRD and AMD genes, suggesting they may represent novel retinal functions.</p><p><strong>Conclusions: </strong>We identified 12 mouse genes with significant late-adult abnormal retinal pathology, eight of which have not been previously implicated in either mouse or human retinal physiology or pathology. These serve as novel retinal disease gene candidates for late-onset retinal disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"64"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475180","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":"Small-Molecule Inhibition of the Hippo Pathway Induces Regeneration of Retinal Pigment Epithelium.","authors":"Erik A Souverein, Sanyukta Oak, Zachary Fouladian, Mark W Reid, G Esteban Fernandez, Andrew Salas, Jennifer G Aparicio, Aaron Nagiel, Ksenia Gnedeva","doi":"10.1167/iovs.66.6.69","DOIUrl":"10.1167/iovs.66.6.69","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether Hippo pathway inhibition via a novel Lats kinase inhibitor (LKI) induces regeneration of retinal pigment epithelium (RPE).</p><p><strong>Methods: </strong>An in vitro scratch \"injury\" on confluent RPE monolayers was produced using the Woundmaker Tool. A 6×6 grid of laser spots was delivered to the central retinae of Dutch Belted rabbits via indirect laser. Following laser injury, eyes received 50 µL intravitreal LKI or vehicle. Fundus photography and optical coherence tomography (OCT) were performed prior to sacrifice for immunohistological analyses.</p><p><strong>Results: </strong>In vitro RPE demonstrated accelerated wound healing 24 to 96 hours after injury with LKI versus control treatment (P < 0.0001). In the in vivo rabbit model of retinal degeneration, laser spots in LKI-injected eyes demonstrated hyperpigmentation and RPE layer thickening with shadowing on OCT beginning at 1 week after treatment. There was a marked increase in RPE cross-sectional area (P < 0.0001) and percentage of Ki67+ RPE and Müller glia (P < 0.001), specifically at the laser spots. At 4 weeks, the increase in RPE cross-sectional area persisted (P < 0.001), but Ki67+ cells were no longer observed within the RPE (P = 0.36) or Müller glia (P = 0.48). The response was limited to the damaged regions, and there was no proliferation seen in the intact retina in either control or LKI-treated eyes.</p><p><strong>Conclusions: </strong>Hippo pathway inhibition via a novel LKI promotes wound healing and RPE proliferation in RPE monolayers in vitro. In a rabbit model of geographic atrophy, LKI treatment facilitated robust RPE regeneration and Müller glia proliferation specifically at the sites of injury.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"69"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475182","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":"Serum gp100 as an Independent Prognostic Biomarker in Early-Stage Uveal Melanoma.","authors":"Manuel F Bande, Carmen Piñeiro, Nerea Lago-Baameiro, Paula Silva-Rodríguez, María Pardo, María José Blanco-Teijeiro","doi":"10.1167/iovs.66.6.80","DOIUrl":"10.1167/iovs.66.6.80","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the prognostic significance of serum gp100 levels in patients with uveal melanoma (UM) without detectable metastases at diagnosis.</p><p><strong>Methods: </strong>This prospective study included 37 patients with UM and no clinical evidence of metastasis at baseline. Serum gp100 concentration was quantified using a commercial ELISA kit. Tumors were molecularly profiled and categorized into high- or low-risk classes. Patients were stratified based on the median gp100 concentration (1.23 ng/mL). Survival analysis was performed using Kaplan-Meier estimates, and multivariate logistic regression was used to identify independent predictors of metastasis.</p><p><strong>Results: </strong>During a mean follow-up of 24.6 months, 14 patients (37.8%) developed metastases. Patients with baseline gp100 >1.23 ng/mL had significantly shorter metastasis-free survival (P < 0.001). Receiver operating characteristic (ROC) analysis yielded an area under the curve of 0.89, with a cutoff of 1.387 ng/mL, achieving 85.7% sensitivity and 82.6% specificity. In multivariate analysis, serum gp100 remained an independent predictor of metastasis (odds ratio = 3849.9; 95% confidence interval, 9.66-1,534,206; P = 0.007), regardless of molecular classification. No significant correlations were found between gp100 and clinical or genetic parameters.</p><p><strong>Conclusions: </strong>Elevated serum gp100 is an independent biomarker of early metastatic risk in UM, even in the absence of clinical or genetic high-risk features. ELISA-based measurement of gp100 may support noninvasive stratification and personalized surveillance strategies in clinical practice.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"80"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496679","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 and Patient-Centered, Health-Related, and Economic Impact of Under-Corrected Refractive Error in Community-Based Older Singaporean Adults: A Population-Based Study.","authors":"Preeti Gupta, Ryan E K Man, Chiew Meng Johnny Wong, Sahil Thakur, Eva K Fenwick, Tai Anh Vu, Amudha Aravindhan, Alex A Black, Joanne M Wood, Ecosse L Lamoureux","doi":"10.1167/iovs.66.6.3","DOIUrl":"10.1167/iovs.66.6.3","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the prevalence of under-corrected refractive error (UCRE) and its associated risk factors and patient-reported, health-related, and economic impact in a multiethnic cohort of older adults.</p><p><strong>Methods: </strong>This study included 2592 older participants from a population-based cohort study. UCRE was defined as an improvement of at least 0.2 logMAR in best-corrected distance visual acuity from presenting distance visual acuity (PDVA) in the better-eye with PDVA worse than 20/40 (>0.3 logMAR). Patient-reported and economic outcomes, including visual functioning and healthcare expenditures, were assessed using validated questionnaires. Prevalence was weighted according to Singapore's 2020 population census, and multivariable regression models were used to analyze the risk factors of UCRE and its association with patient-reported and economic outcomes.</p><p><strong>Results: </strong>The weighted prevalence of UCRE was 8%. Lower socioeconomic status (odds ratio [OR] = 2.98; P < 0.001) and greater spherical equivalent (per 0.50-D increase, OR = 1.07; P = 0.018) were associated with increased odds of UCRE, contributing 39.2% and 23.2%, respectively, of the total variance. UCRE was significantly associated with lower visual functioning scores (-5.7%; β = -0.22; P = 0.046), higher likelihood of loneliness (OR = 2.96; P = 0.015), slower gait speed (OR = 2.03; P = 0.02), and presence of sarcopenia (OR = 2.41; P < 0.001). Individuals with UCRE incurred 2.33-times higher healthcare costs (P = 0.05) compared to those without.</p><p><strong>Conclusions: </strong>One in 12 older Singaporeans had UCRE. Given the substantial adverse patient-centered and health-related impact and economic burden associated with UCRE, targeted vision screening, treatment for visual impairment, and public health education on the importance of regular eye examinations and wearing appropriate glasses are recommended to mitigate these challenges and reduce associated costs.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"3"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199152","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":"Systemic Hypoxia Increases Retinal Blood Flow but Reduces the Oxygen Saturation Less in Peripheral Than in Macular Vessels in Normal Persons.","authors":"Jacob Drachmann, Line Petersen, Signe Krejberg Jeppesen, Toke Bek","doi":"10.1167/iovs.66.6.43","DOIUrl":"10.1167/iovs.66.6.43","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal vascular diseases are characterized by regional differences in the distribution of morphological lesions that may be related to regional differences in the autoregulation of retinal blood flow. The purpose of the present study was to investigate how systemic hypoxia affects blood flow and oxygen saturation in different vascular areas in normal persons.</p><p><strong>Methods: </strong>In 28 normal persons, oxygen saturation and vessel diameters were measured by dual wavelength retinal oximetry, and blood flow velocity by Doppler OCT in the peripapillary arterioles supplying and venules draining the four retinal quadrants, and in an arteriolar and a venular branch from the upper temporal arcade towards respectively the retinal periphery and the macular area. The measurements were performed during normoxia and during breathing of a gas mixture containing 12.5% oxygen.</p><p><strong>Results: </strong>Systemic hypoxia reduced the oxygen saturation in peripapillary arterioles by approximately 11% (P < 0.001) and increased the peripapillary blood flow by approximately 40% (P < 0.001). Systemic hypoxia also reduced the oxygen saturation in the macular arterioles and venules and in the peripheral arterioles (P < 0.003), but not in the peripheral venules (P = 95). The blood flow increased significantly in both macular and peripheral arterioles and venules (P < 0.04).</p><p><strong>Conclusions: </strong>Systemic hypoxia can affect the venous oxygen saturation in vessels draining the retinal periphery and the macular area differently. The findings may help to understand the regionally varying manifestations of retinal vascular disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"43"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284394","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 Sensory Denervation Causes Epithelial Ferroptosis and Delayed Healing in Mice.","authors":"Ning Wang, Yizhou Li, Xiaolei Wang, Lingling Yang, Jing Zhang, Jun Cheng, Xiaoyue Jiang, Xia Qi, Chao Wei, Qingjun Zhou, Ya Li, Suxia Li","doi":"10.1167/iovs.66.6.28","DOIUrl":"10.1167/iovs.66.6.28","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate the role and mechanism of corneal nerves in regulating epithelial cell response against ferroptosis.</p><p><strong>Methods: </strong>Denervated mouse models were established via surgical axotomy and capsaicin treatment. Monochlorobimane staining was employed to detect cellular glutathione (GSH) levels in the corneal epithelium, and real-time quantitative PCR and immunofluorescence staining were used to evaluate GSH-related gene expression in denervated models and corneas of patients with neurotrophic keratitis. Scanning electron microscopy was utilized to observe mitochondrial morphology in corneal epithelial cells. Ferroptosis inhibitor ferrostatin-1 was administered post-corneal scrape in capsaicin-treated mice, followed by transcriptomic sequencing. The p53 agonist Kevetrin activated p53 in scraped corneas and cultured corneal epithelial cells. Furthermore, capsaicin was topically applied to Trp53+/- mice, followed by corneal epithelial scraping.</p><p><strong>Results: </strong>In denervated models, the expression of GSH-related genes was downregulated, and mitochondrial morphology exhibited characteristics of ferroptosis in corneal epithelial cells. The delay in corneal wound healing induced by TRPV1+ sensory denervation was ameliorated by ferrostatin-1 treatment. RNA sequencing and immunofluorescence staining demonstrated upregulated p53 in TRPV1-denervated mice, which was subsequently downregulated following ferrostatin-1 treatment. Kevetrin exacerbated wound healing delays, whereas Trp53+/- mice exhibited accelerated healing post-capsaicin denervation compared to wild-type controls.</p><p><strong>Conclusions: </strong>TRPV1+ sensory nerves play a regulatory role in preventing ferroptosis of corneal epithelial cells through the p53/AKT/mTOR signaling pathway. Targeting this pathway may offer therapeutic potential for neurotrophic keratopathy and related disorders.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247914","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}