Investigative ophthalmology & visual science最新文献

{"title":"Development of Crowding Distance in Children Is Faster and Later Than Visual Acuity and Better Predicts Reading Performance.","authors":"Sarah J Waugh, Monika A Formankiewicz, Leticia Álvaro, Denis G Pelli","doi":"10.1167/iovs.67.5.8","DOIUrl":"https://doi.org/10.1167/iovs.67.5.8","url":null,"abstract":"<p><strong>Purpose: </strong>Visual crowding is a failure of object recognition due to nearby clutter. Crowding distance (CD) is the threshold spacing for identification of a target among flankers. Visual acuity (VA) is the smallest recognizable letter size. In normal adult vision, CD worsens more than VA with increasing eccentricity and is worse than VA in central vision of strabismic amblyopia. CD is not measurable in mature central vision with standard optotypes but is with tall, skinny optotypes. We reveal developments of CD and VA in children and consider their impacts on teacher-assessed reading performance.</p><p><strong>Methods: </strong>VA (isolated Sloan letter size threshold) and CD (Pelli optotype spacing threshold) were measured in 227 normal, healthy children aged three to 11 years and 40 adults. CD was measured for trigram and repeated arrangements. Teacher-assessed reading indicators for 200 of these children were converted to a study reading indicator (SRI).</p><p><strong>Results: </strong>From age three years, VA improves 1.4×, reaching near-adult levels at six years (P > 0.05). CD reduces 4.8×, reaching near-adult levels at eight years (P > 0.05). Correlations between vision measures and SRI were higher for CD than VA (CD-trigram: r = -0.68; CD-repeated: r = -0.67; VA: r = -0.37; all P < 0.0001). Removing age shows CD, but not VA, matters for reading (CD-trigram: r = -0.24, P = 0.00065; CD-repeated r = -0.25, P = 0.00049; VA: r = -0.13, P = 0.075).</p><p><strong>Conclusions: </strong>Crowding develops more quickly and matures later than acuity and is significantly linked to children's reading performance, unlike acuity. Crowding distance measures may be more sensitive diagnostically than acuity for detecting exaggerated crowding found in strabismic amblyopia and may help identify children who struggle to read.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"8"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837974","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":"Oxidative Stress in Keratoconus Is Evident in Tear Fluid and Stromal Cells and Alleviated in Cell Culture by Sulforaphane.","authors":"Madhuri A Koduri, Mackenzie Charter, Rohini Sonar, Rashmi Deshmukh, Christina R Prescott, Rose Mandel, Laurence Sperber, Ting-Fang Lee, Elias H Kahan, Ilyse D Haberman, Vivek Singh, Andrea L Blitzer, George Maiti, Shukti Chakravarti","doi":"10.1167/iovs.67.5.1","DOIUrl":"https://doi.org/10.1167/iovs.67.5.1","url":null,"abstract":"<p><strong>Purpose: </strong>Keratoconus (KC) is a common eye disease characterized by progressive corneal thinning and steepening. Despite multiple treatment options, there is no definitive cure for KC. Previously we identified loss and dysregulation of nuclear factor erythroid 2-related factor 2 (NRF2) mediated antioxidant functions in stromal cells and extracellular matrix (ECM) in KC. Here we used tear fluid samples and cell culture models to investigate oxidative stress in KC.</p><p><strong>Methods: </strong>Primary human KC and donor (DN) stromal fibroblasts were exposed to hydrogen peroxide (H2O2) to induce oxidative stress and treated with sulforaphane (SFN) for antioxidant rescue. The fibroblasts were then assessed for NRF2 activation and apoptosis by measuring TXNRD1, HMOX1, NRF2, and GPX3 expression and caspase-3/7 activity. ML385 was used to inhibit NRF2 functions in DN fibroblast cultures followed by measurements of cell death (Caspase 3/7), proliferation (BrdU and Ki-67 labeling) and ECM deposition by immunohistology. Oxidative stress was directly assessed in KC and non-KC subjects by measuring malondialdehyde (MDA) and glutathione peroxidase 3 (GPX3) levels in the tear fluid.</p><p><strong>Results: </strong>H2O2-stressed KC fibroblasts displayed increased apoptosis and suboptimal NRF2 activation, which could be rescued with SFN. Conversely, DN fibroblasts treated with ML385 elicited KC-like cellular phenotypes, including decreased antioxidant response, reduced cell growth, myofibroblastic changes and poor ECM deposition. Compared to unaffected controls, KC patient tear fluid exhibited elevated levels of GPX3 and MDA, a byproduct of lipid peroxidation.</p><p><strong>Conclusions: </strong>NRF2-mediated anti-oxidative functions are dysregulated in KC. In the future SFN antioxidant treatments may be therapeutic in KC, while MDA and GPX3 may lead to promising biomarkers for diagnosis and severity predictions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"1"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815276","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":"PEDF Prevents Corneal Endothelial Dysfunction of Fuchs Endothelial Corneal Dystrophy.","authors":"Shuangqing Yao, Yujie Qiao, Yujing Lin, Xin Sui, Qingjun Zhou, Ting Wang, Qun Wang, Can Zhao","doi":"10.1167/iovs.67.5.2","DOIUrl":"https://doi.org/10.1167/iovs.67.5.2","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to explore the protection of pigment epithelium-derived factor (PEDF) on the corneal endothelium in Fuchs endothelial corneal dystrophy (FECD).</p><p><strong>Methods: </strong>PEDF levels in aqueous humor of FECD patients were quantified by enzyme-linked immunosorbent assay. PEDF receptor expression of corneal endothelium was validated by immunofluorescence staining and single-cell RNA sequencing datasets. In vitro cultured human corneal endothelial cells (HCECs) were treated with menadione (MN) alone or in combination with PEDF. Cellular viability, oxidative stress, mitochondrial membrane potential, adenosine triphosphate (ATP) production, mitochondrial DNA copy number, and mitochondrial bioenergetics were evaluated. The ultraviolet A (UVA)-induced FECD mouse model was employed to assess the protective effects of PEDF on corneal thickness and endothelial cell density, morphology, and functions. In addition, RNA sequencing, quantitative PCR, immunofluorescence staining, and automated simple western assay were performed to analyze the downstream signaling pathways of PEDF-treated HCECs.</p><p><strong>Results: </strong>Human and mouse corneal endothelial cells express PEDF receptor, but PEDF levels were significantly reduced in the aqueous humor of FECD patients. In cultured human corneal endothelial cells exposed to MN, PEDF effectively enhanced cellular viability, attenuated oxidative stress, and improved mitochondria-related functions. In the UVA-induced FECD mouse model, PEDF pretreatment prevented the decline of corneal endothelial cells and promoted the recovery of endothelial cell density, morphology, and functions. Mechanistically, the protective effects of PEDF were associated with the suppression of p53, TGF-β, and Hippo signaling pathways elevated in FECD.</p><p><strong>Conclusions: </strong>PEDF effectively prevents corneal endothelial dysfunction in FECD mouse and cellular models, highlighting its preclinical promise as a protective and therapeutic approach.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"2"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815279","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":"Longitudinal Changes in Nystagmus Following Late Treatment for Congenital Blindness.","authors":"Chetan Ralekar, Marin Vogelsang, Lukas Vogelsang, Abhishek Kumar, Naviya Lall, Priti Gupta, Sidney Diamond, Suma Ganesh, Pawan Sinha","doi":"10.1167/iovs.67.5.5","DOIUrl":"https://doi.org/10.1167/iovs.67.5.5","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to quantify longitudinal changes in nystagmus following sight surgery for congenital blindness using a low-cost smartphone-based technique, in order to gain insight into the plasticity of oculomotor control late in childhood.</p><p><strong>Methods: </strong>Thirteen children aged 6 to 16 years (mean = 9.5 years, 9 girls) were surgically treated for bilateral congenital cataracts as part of Project Prakash in India. They were examined at 5 longitudinal time points: presurgery and 1 week, 1 month, 6 months, and 1 year postsurgery. Eye movements were recorded with a smartphone camera and macro lens. Pupil trajectories were extracted using computer vision techniques, analyzed in the frequency domain, and a nystagmus magnitude metric was defined as the mean magnitude of horizontal (0-5 hertz [Hz]) movements. This metric was examined longitudinally, and additional comparisons were made with 14 separate patients examined 4 years after surgery.</p><p><strong>Results: </strong>Nystagmus magnitude in the longitudinal group decreased significantly (1.7-fold, P = 0.006) during the first postsurgical year. Cross-sectional comparisons indicate stabilization by approximately 1 year postoperatively. Variability across individuals was not explained by visual acuity, age at surgery, or eye axial length. Binocular recordings revealed strong interocular coordination despite persistent nystagmus.</p><p><strong>Conclusions: </strong>Sight restoration after prolonged congenital blindness yields significant but incomplete reductions in nystagmus, indicating notable but circumscribed neural plasticity in the oculomotor system beyond infancy. In addition to demonstrating the feasibility of smartphone-based quantification of nystagmus in resource-limited settings, these results reinforce the importance of early visual input for calibrating eye movements and highlight important paths for rehabilitation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"5"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815301","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":"A Common Prescription Lens Correction Causes Motion Illusions in the Presbyopic and General Populations.","authors":"Victor Rodriguez-Lopez, Callista M Dyer, Johannes Burge","doi":"10.1167/iovs.67.5.6","DOIUrl":"https://doi.org/10.1167/iovs.67.5.6","url":null,"abstract":"<p><strong>Purpose: </strong>Monovision is a common correction for presbyopia that focuses one eye at far distances and the other at near distances, resulting in a difference in blur between the eyes. Because blur increases the speed of visual processing by a few milliseconds, these optical conditions can induce dramatic misperceptions of the distances and three-dimensional directions of moving objects. To date, the illusion has been demonstrated only in individuals without presbyopia.</p><p><strong>Methods: </strong>We analyze both the induced processing speed differences and the visibility of the resulting illusions in presbyopic (n = 17, 22.2 ± 5.0 years) and non-presbyopic (n = 36, 54.4 ± 5.9 years) populations, with proportions approximately matching those in the general population. Participants viewed two horizontally moving strips of bars on an autostereoscopic display with interocular blur and light-level differences, and reported which strip appeared closer in depth. Interocular delay and an illusion visibility index-the ratio of interocular delay and the detection threshold-were computed for each participant in each condition.</p><p><strong>Results: </strong>Delays were highly consistent in both the presbyopic and general populations. Interocular differences in optical blur and light-level caused highly consistent interocular differences in processing speed in all participants, although they created visible (suprathreshold) illusions in only a subset of participants. This subset, however, included individuals with processing delays that were many times larger than the detection threshold. Such individuals are likely to be afflicted by large, highly visible illusions in real-world conditions.</p><p><strong>Conclusions: </strong>Methods for identifying high-risk individuals and for reducing or eliminating the illusions are discussed.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"6"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815312","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":"High-Dose Sucralose Is Associated With Lacrimal Circadian Remodeling, Reduced Immunometabolic Signatures, and Reduced Tear Secretion.","authors":"Di Qi, Tingting Yang, Xiaoting Pei, Dingli Lu, Shenzhen Huang, Liu Yang, Jingwen Yang, Shuting Xuan, Mengru Ba, Wenxiao Zhang, Xiaohui Liu, Shufan Yu, Zhijie Li","doi":"10.1167/iovs.67.5.11","DOIUrl":"https://doi.org/10.1167/iovs.67.5.11","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether high-dose sucralose (SUC) exposure alters circadian organization of the mouse extraorbital lacrimal gland, immunometabolic pathways, and tear film function using multi-omics and functional assays.</p><p><strong>Methods: </strong>Male C57BL/6J mice received SUC (0.72 mg/mL in drinking water) or water under a 12:12 hour light-dark cycle for 30 days. Extraorbital lacrimal glands were collected every 3 hours across 24 hours (n = 3/time point/group) for RNA sequencing and 4D-data-independent acquisition proteomics. Rhythms were identified with JTK_CYCLE, differential expression with DESeq2/MSstats followed by Kyoto Encyclopedia of Genes and Genomes pathway analysis. Oil Red O and CD4/CD8 immunohistochemistry assessed lipid and immune signatures. Tear secretion, tear film breakup time, and corneal fluorescein staining were measured at ZT0, ZT6, ZT12, and ZT18.</p><p><strong>Results: </strong>SUC increased rhythmic transcripts (3074 to 4600) and proteins (378 to 984), redistributing acrophases (transcript peaks shifted toward ZT3-ZT6; protein peaks toward ZT21-ZT24), indicating clock phase remodeling. Both omics layers converged at the pathway level, showing downshifts in metabolic and immune programs, including complement- and T-cell-related signatures. SUC elevated water intake and body weight without altering glucose tolerance. Functionally, SUC-treated mice showed reduced stimulated tear secretion, whereas tear film breakup time and corneal fluorescein staining did not differ significantly.</p><p><strong>Conclusions: </strong>Under this high-exposure paradigm, SUC was associated with lacrimal circadian remodeling, reduced metabolic and immune pathway signatures, and lower stimulated tear secretion, identifying candidate pathways for mechanistic testing without establishing direct causality.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"11"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838021","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":"The Transcription Factor 12 of Basic Helix-Loop-Helix Plays an Essential Role in Retinal Health.","authors":"Tian Yu, Gizem Ulker-Yilmazer, Dogan Can Kirman, Emily R Turpin, Seher Yuksel, Yu-Guang He, Sara Ludwig, Ashwani Kumar, Chao Xing, Bret Evers, Eva Marie Y Moresco, Bruce A Beutler, Bogale Aredo, Rafael L Ufret-Vincenty","doi":"10.1167/iovs.67.5.13","DOIUrl":"https://doi.org/10.1167/iovs.67.5.13","url":null,"abstract":"<p><strong>Purpose: </strong>To study a non-redundant role of Tcf12 in retinal health.</p><p><strong>Methods: </strong>A loss-of-function mutation in Tcf12 was identified by applying optical coherence tomography (OCT) to a forward genetic pipeline. CRISPR/Cas9-generated Tcf12ra/ra mice, expressing a replacement allele (\"ra\") were used to validate the findings from the mutagenesis screen. Retinal morphology was assessed using OCT, fundus photography, histology, and immunohistochemistry. Retinal function was evaluated by electroretinography (ERG). Bulk RNA sequencing and proteomic analyses were performed, with select targets validated by RT-qPCR and immunoblotting.</p><p><strong>Results: </strong>Tcf12ra/ra mice exhibited outer nuclear layer thinning on OCT, which was confirmed by histology. Fundus imaging revealed age-dependent accumulation of retinal fundus spots. Subretinal accumulation of Iba1⁺/Tmem119⁺ cells was observed, many of which stained positively for Gal3, suggestive of activated resident microglia. ERG deficits were noticed at 12 to 15 months of age in Tcf12ra/ra mice. Transcriptomic and proteomic profiling using two independent pathway analyses identified dysregulated pathways related to protein and RNA metabolism, mitochondrial and energy metabolism, cell cycle, signal transduction, cellular response to stimuli, and inflammation. RT-qPCR results showed upregulation of Tmem233 and downregulation of Doc2b, Alpk2, Agr2, and Apobec2 in Tcf12ra/ra retinas. Western blot analysis demonstrated upregulation of Selenbp1 and downregulation of Neurod1 and Faah in Tcf12ra/ra retinas.</p><p><strong>Conclusions: </strong>Deficiency in Tcf12 induces early-onset retinal structural alterations, and late-onset subretinal microglial activation and functional decline. Widespread dysregulation in metabolic and signaling pathways was documented in transcriptomic and proteomic analyses. These findings establish Tcf12 as a key contributor to retinal development and homeostasis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"13"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838033","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":"Neural Innervation of Cyclovertical Extraocular Muscles During Asymmetric Vertical Vergence.","authors":"Samuel Adade, Vallabh E Das","doi":"10.1167/iovs.67.4.17","DOIUrl":"10.1167/iovs.67.4.17","url":null,"abstract":"<p><strong>Purpose: </strong>Vertical vergence is a critical involuntary eye movement used to make relatively small and slow adjustments of the vertical position of each eye to achieve and maintain binocular fusion for daily activity. Little is known about the mechanisms driving vertical vergence, beginning with the contribution of specific extraocular muscle (EOM) groups and extending to its neural control. Here, we describe activity of cyclovertical extraocular motoneurons during vertical vergence in non-human primates to determine their role in generating this movement.</p><p><strong>Methods: </strong>In two non-human primates, we recorded and analyzed single-unit activity of motoneurons (n = 149) that innervate the four cyclovertical EOMs during conjugate vertical smooth pursuit and an asymmetrical vertical vergence task in which one eye is stationary and the other eye moves vertically.</p><p><strong>Results: </strong>Firing activity of all neurons within the four cyclovertical motoneuron subgroups (inferior rectus, superior rectus, inferior oblique, and superior oblique) correlated with vertical position of the innervated eye during the vertical vergence task. Analysis of position sensitivities suggested that cyclovertical motoneurons contribute differently during vertical vergence compared to vertical smooth pursuit. During asymmetric vertical vergence, 67 of the 149 cyclovertical motoneurons supplying the stationary eye modulated their activity.</p><p><strong>Conclusions: </strong>Neural innervation patterns suggest that contraction and relaxation of all cyclovertical EOMs result in vertical vergence. The differences in activity between vertical vergence and conjugate pursuit and the presence of matched and unmatched neurons are parallel to observations of motoneuron activity during horizontal asymmetric vergence and add to the literature showing the complex relationship between EOM innervation and oculomotor plant behavior.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 4","pages":"17"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638867","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":"Hypoxia-Induced Ferroptosis Resistance Drives Orbital Fibrosis in Thyroid Eye Disease.","authors":"Chengzhen Gong, Shu Liu, Jing Zhao, Jingya Zhu, Chenqi Xing, Kelin Li, Chifeng Xie, Naijia Wu, Rongxin Chen","doi":"10.1167/iovs.67.4.15","DOIUrl":"10.1167/iovs.67.4.15","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether hypoxia promotes a ferroptosis-resistant phenotype in patient-derived thyroid eye disease (TED) orbital fibroblasts (OFs), and whether hypoxia-associated metabolic changes (lactate) relate to profibrotic activation readouts, as well as to test whether modulating ferroptosis alters these readouts.</p><p><strong>Methods: </strong>Primary OFs from TED patients and controls were exposed to graded hypoxia (21% to 1% O₂). Ferroptosis sensitivity was assessed by reactive oxygen species, mitochondrial membrane potential, viability, and SLC7A11/GPX4/ACSL4. The profibrotic phenotype was assessed by COL1A1/α-SMA/fibronectin, immunofluorescence, and scratch assays. We perturbed metabolism with exogenous lactate and 2-deoxy-D-glucose, induced ferroptosis with RSL3, and inhibited ferroptosis with liproxstatin-1.</p><p><strong>Results: </strong>TED fibroblasts exhibited baseline ferroptosis resistance, marked by higher GPX4 and SLC7A11 and lower ACSL4 than controls, which intensified under hypoxia. Hypoxia alone was sufficient to increase fibrotic marker expression and further augmented TGF-β-evoked fibrotic responses. Under hypoxia, RSL3 at 50 to 100 nM reduced profibrotic marker expression in TED OFs, an effect lost at 150 nM where viability declined; liproxstatin-1 attenuated the RSL3-associated changes. Hypoxia increased intracellular lactate; lactate alone upregulated GPX4 and promoted fibrotic activation, whereas 2-deoxy-D-glucose decreased lactate, restored RSL3 sensitivity, and diminished fibrotic readouts.</p><p><strong>Conclusions: </strong>Our data suggest that hypoxia-associated lactate accumulation contributes to GPX4-linked ferroptosis resistance and amplifies profibrotic activation in TED OFs. Mechanism-guided intervention combining metabolic inhibition with calibrated ferroptosis induction warrants further investigation as a rational strategy to restrain fibrotic remodeling.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 4","pages":"15"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633245","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":"Cytomegalovirus-Specific T Cell Immunity and Clinical Associations in Patients With CMV Anterior Uveitis.","authors":"Yung-Ray Hsu, Chia-Mao Gao, Wei-Yao Chin, Shi-Chuen Miaw, I-Jong Wang, Chien-Chia Su","doi":"10.1167/iovs.67.4.5","DOIUrl":"10.1167/iovs.67.4.5","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate T cell immunity in patients with cytomegalovirus anterior uveitis (CMV AU) and examine their correlation with clinical manifestations.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells were isolated from 31 patients with CMV AU and 32 CMV-seropositive healthy controls. Cells were stimulated in vitro with CMV antigens IE1 and PP65. Flow cytometry was performed to evaluate the expression of cytokines IFN-γ, TNF-α, granzyme B, and PD-1 in CD4 and CD8 T cells. Clinical parameters, including disease duration, the mean deviation (MD) from 24-2 visual field (VF) and corneal endothelial cell density, were collected and analyzed for correlations with immunological findings.</p><p><strong>Results: </strong>Patients with CMV AU had a median disease duration of 4 years (interquartile range [IQR] = 2-7 years), moderate VF loss (MD = -8.27 decibels [dB], SD = 8.04), and a median corneal endothelial cell density of 2076 cells/mm² (IQR = 1078-2378). Patients with CMV AU exhibited baseline cytokine levels comparable to seropositive controls but showed increased IFN-γ production in CD4 T cells and heightened IFN-γ and TNF-α responses in CD8 T cells following CMV antigen stimulation. In patients with CMV AU, greater CMV-specific IFN-γ and TNF-α responses but not granzyme B or PD-1 expression were linked to longer disease duration after adjusting for age. Greater CMV-specific IFN-γ activity was associated with higher corneal endothelial cell density but more severe glaucomatous VF loss, after adjustment for age and disease duration.</p><p><strong>Conclusions: </strong>Our study highlights that immune sensitization and CMV-specific IFN-γ T-cell responses may shape the clinical presentation of CMV AU.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 4","pages":"5"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592212","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}