Investigative ophthalmology & visual science最新文献

{"title":"USP10 Silencing Prevents Scarring and Inflammation in a Modified Rabbit Model of Glaucoma Filtration Surgery.","authors":"Christine Tilstra-Smith, Nileyma Castro, Mohammad Anjum Shaik, Arpan Banerjee, Andrew T Phillips, Adrian G Temnycky, Arunkumar Venkatesan, Jelissa Reynoso-Garcia, Michael Zuber, Preethi S Ganapathy, Audrey M Bernstein","doi":"10.1167/iovs.67.12.38","DOIUrl":"10.1167/iovs.67.12.38","url":null,"abstract":"<p><strong>Purpose: </strong>Trabeculectomy remains the gold standard for lowering intraocular pressure (IOP) in glaucoma, but postoperative scarring and inflammation can cause bleb failure. Because USP10 knockdown is anti-inflammatory and anti-fibrotic in the cornea, we tested whether USP10 silencing reduces bleb scarring and inflammation in a rabbit glaucoma filtration surgery model.</p><p><strong>Methods: </strong>Primary rabbit Tenon's fibroblasts (RTFs) were transfected with fully modified in vivo self-delivering siRNA targeting USP10 (sdRNA, US09) or non-targeting control sdRNA (NTC) to assess myofibroblast conversion and fibronectin expression. Female New Zealand White rabbits underwent modified glaucoma filtering surgery with tube insertion and subconjunctival US09, NTC, or mitomycin C (MMC). Bleb health and vascularity were scored using a modified Moorfields system, IOP was measured with TonoVet Plus, and excised blebs were analyzed for tissue width, apoptosis (TUNEL), α-SMA, and CD45+ cell infiltration. Inflammatory cytokines were profiled from aqueous humor by ELISA.</p><p><strong>Results: </strong>US09 transfection in RTFs reduced USP10 expression and suppressed myofibroblast activation, lowering α-SMA and fibronectin expression and disrupting fibrillar organization. In vivo, a single US09 dose reduced postoperative apoptosis versus NTC and MMC. Although both US09 and MMC inhibited myofibroblast differentiation and early immune infiltration, only US09 preserved bleb architecture, sustained immune suppression, and avoided MMC-associated ischemic vascularity. US09 treatment was also associated with lower mean levels of several aqueous humor cytokines.</p><p><strong>Conclusions: </strong>Perioperative USP10-targeting sdRNA reduced myofibroblast development and sustained an anti-inflammatory, tissue-preserving phenotype after rabbit glaucoma filtration surgery, with advantages over MMC in tissue-preservation and inflammatory endpoints. USP10 silencing may represent a promising anti-scarring strategy to improve long-term trabeculectomy outcomes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"38"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238334","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 First 40 Years of Molecular Ophthalmology Part One: Inherited Retinal Disease: The 2026 Friedenwald Lecture.","authors":"Edwin M Stone","doi":"10.1167/iovs.67.12.43","DOIUrl":"10.1167/iovs.67.12.43","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"43"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238414","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":"Alpha-Asarone Ameliorates Dry Age-Related Macular Degeneration by Modulating the P2X7/NLRP3 Inflammasome Axis.","authors":"Xin Wang, Yuxiu Bi, Yuxiang Liu, Yao Nie, Junzhou Ding, Lei Yu, Shengjun Mao","doi":"10.1167/iovs.67.12.30","DOIUrl":"10.1167/iovs.67.12.30","url":null,"abstract":"<p><strong>Purpose: </strong>To examine whether α-asarone (ASA) protects dry age-related macular degeneration (dAMD) from sodium iodate (SI) injury by modulating the P2X7-mediated NLRP3 inflammasome axis.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were treated with SI to establish a dAMD model. Retinal structure and function were evaluated using electroretinography (ERG), optical coherence tomography (OCT), and hematoxylin-eosin staining, whereas the expression of functional and inflammatory proteins was analyzed via immunofluorescence and Western blotting. Molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assays (CETSA) were performed to explore the potential interaction between ASA and P2X7. In vitro, SI-stimulated ARPE-19 cells were used to evaluate the protective effects of ASA and the involvement of P2X7 through Cell Counting Kit-8 assays, Annexin V-FITC/PI staining, Fluo-4 staining, YO-PRO-1 uptake detection, ELISA, and Western blotting.</p><p><strong>Results: </strong>ASA preserved retinal structure and function, maintained the expression of key functional proteins, suppressed microglial activation, and attenuated inflammatory responses. Computational modeling suggested a stable potential interaction between ASA and P2X7, and CETSA further supported ASA-induced modulation of P2X7 thermal stability in cells. In vitro, ASA enhanced cell viability, reduced apoptosis, attenuated Ca²⁺ influx and P2X7 macropore formation, decreased the release of inflammatory cytokines, and downregulated P2X7/NLRP3 pathway, all of which were effectively abolished by activating P2X7.</p><p><strong>Conclusions: </strong>The findings demonstrate that ASA mitigates SI-induced dAMD injury by suppressing the P2X7/NLRP3 inflammatory pathway. This study identifies a promising new therapeutic strategy for dAMD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"30"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193859","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":"Regeneration and Cancer-The Two Sides of a \"Stem Cell\" Coin: The 2025 Mildred Weisenfeld Award Lecture.","authors":"Geeta K Vemuganti","doi":"10.1167/iovs.67.12.11","DOIUrl":"10.1167/iovs.67.12.11","url":null,"abstract":"<p><p>Stem cells endowed with properties of self-renewal and differentiation have opened new avenues for restoration and regeneration of damaged tissues. The same adult stem cells, when they undergo irreversible mutations, transform into cancer cells and generate a tumor. In this lecture, I present our work on these two aspects of stem cells: one focuses on regeneration of the ocular surface, whereas the other targets cancer stem cells (CSCs) in retinoblastoma (Rb). In regeneration, I present our experience of transplantation of the cultured limbal epithelial cells to restore the ocular surface in severe limbal stem cell deficiency, with 60% to 70% success. The technique proved that transplanted cells survive, network, integrate, contribute to function, and cause no harm to the patient. We also developed a technique wherein both limbal and conjunctival cells could be cultured on a single membrane utilized ring barrier. This approach was effective in reconstructing the conjunctiva and fornices in patients with severe ocular disease. Furthermore, our work led identification of a subpopulation of limbal-derived stromal cells with features of mesenchymal stem cells. We also saw success with culturing human lacrimal gland tissues marked by the presence of epithelial stem cells and mesenchymal stem cells with secretory potential. These cultures we believe could pave the way of lacrimal gland regeneration through cell therapy. We then flip to the \"dark side\" of stem cells: the isolation and characterization of CSCs in Rb. We worked on both primary tumors as well as Rb y79 cell lines, with a special focus on reversing their chemoresistant properties. Our work demonstrated the possible role of small extracellular vesicles in Rb as a diagnostic and prognostic marker. The reduction of chemoresistance using nano-formulated drugs and targeted delivery of drug-loaded small extracellular vesicles derived from the tumor cells shows promise.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"11"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109686","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":"Multimodal Retinal Structural and Functional Tests Identify Local and Layer-Related Alterations in Early Type 2 Diabetes.","authors":"Bismark Owusu-Afriyie, Christopher S Wu, Rachana Kafle, Liam Burhans, Barsha Lal, Julia S Benoit, Daniel R Coates, Wendy W Harrison","doi":"10.1167/iovs.67.12.3","DOIUrl":"10.1167/iovs.67.12.3","url":null,"abstract":"<p><strong>Purpose: </strong>To use a multimodal approach to provide deeper insights into subclinical, layer-related, and localized retinal structural and functional deficits associated with prediabetes (PreDM) and early type 2 diabetes (T2DM).</p><p><strong>Methods: </strong>Twenty controls, 13 PreDM, and 15 T2DM age-matched (45.58 ± 9.40 years) groups participated. Color perimetry was performed at four locations 3° from fixation, using 0.5° circular red, green, blue, and yellow stimuli. Multifocal electroretinograms (mfERGs) were recorded (103 hexagons), and implicit times (ITs) and amplitudes were averaged and analyzed in ring 2, approximately corresponding to the perimetric testing. Then, 20° optical coherence tomography (OCT) and 10° OCT angiography (OCTA) images were acquired. Perfusion density (PD; all plexuses), retinal layers, and choroidal thicknesses were analyzed (central 2 mm).</p><p><strong>Results: </strong>mfERG P1 ITs were delayed in T2DM (P = 0.03 vs. controls). Thresholds obtained for red increased with delayed P1 ITs (P = 0.02) and with increasing thickness of the inner nuclear layer (P = 0.03). Choroidal thickness showed a negative relationship with blue and yellow thresholds (P < 0.05). Thresholds obtained for red and yellow were higher in the T2DM (all P < 0.05 vs. controls) but green and blue were not (P > 0.05). PD of the intermediate capillary plexus was lower in the T2DM group (P = 0.001 vs. all groups) and was associated with HbA1c (P = 0.02).</p><p><strong>Conclusions: </strong>This combination of tests showed alterations in middle retinal health, which could occur in retinal bipolar cells early in T2DM. A longitudinal investigation would clarify the temporal onset of these neural and vascular changes in the disease process.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"3"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109688","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":"From Exosomal Cargo to In Vivo Causality: Interpreting the miR-146a-5p/SMAD4 Axis After Glaucoma Filtration Surgery.","authors":"Peiwen Chen","doi":"10.1167/iovs.67.12.48","DOIUrl":"10.1167/iovs.67.12.48","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"48"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244663","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":"Introducing Geeta K. Vemuganti: The 2025 Recipient of the Weisenfeld Award.","authors":"Martine J Jager, Sarah E Coupland, Hans E Grossniklaus","doi":"10.1167/iovs.67.12.12","DOIUrl":"https://doi.org/10.1167/iovs.67.12.12","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"12"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109664","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":"Seeing the Bias: Hemifield‑Dependent Remapping of Sensory, Sighting, and Acuity Eye Dominance.","authors":"Lujia Jian, Dorita H F Chang","doi":"10.1167/iovs.67.12.66","DOIUrl":"https://doi.org/10.1167/iovs.67.12.66","url":null,"abstract":"<p><strong>Purpose: </strong>Eye dominance may refer to sensory, sighting, and acuity dominance, yet their correspondence across the visual field is unclear. Here, we indexed these three dominance metrics across 17 visual field locations: the fovea and 16 locations at 3° and 6° eccentricities along eight polar angles.</p><p><strong>Methods: </strong>Forty-three visually normal adults were tested. Sensory dominance was indexed with a dichoptic signal-in-noise motion coherence threshold task, sighting dominance with a Porta-derived pointing alignment task, and acuity dominance with a grating acuity task. Peripheral stimuli across all tasks were size scaled according to the cortical magnification function.</p><p><strong>Results: </strong>Along the horizontal and oblique meridians, both sensory and sighting dominance shifted from foveal dominance toward the left eye in the left hemifield and toward the right eye in the right hemifield. There were no shifts in sensory or sighting dominance along the vertical meridian. Sensory and sighting dominance were thus spatially well matched. Within subjects, sensory dominance significantly predicted sighting dominance across the visual field, and this correspondence was selective to the meridians exhibiting hemifield asymmetries. In contrast, acuity dominance was weak in magnitude and spatially invariant, with weak, nonsignificant correlations with the other two metrics.</p><p><strong>Conclusions: </strong>Sensory and sighting eye dominance are not uniform across the visual field. We speculate that both tap into binocular combination processes at the primary visual cortex (V1), where the contralateral eye is weighted more strongly due to structural asymmetries across the visual pathway. In contrast, acuity dominance likely reflects monocular optical and retinal factors independent of binocular interactions, explaining its spatial invariance and weak correlations with other dominance metrics. Our results suggest that the clinical convention of relying on a single foveal test (e.g., hole-in-the-card or Porta) cannot capture an individual's dominant eye across the visual field or across sensory, sighting, and acuity dimensions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"66"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267572","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":"Age-Related Lens Membrane Composition and N101D Deamidation Modulate αA-Crystallin Membrane Interactions Relevant to Cataract.","authors":"Preston Hazen, Jordyn Anderson, Navdeep Kalkat, Binod Aryal, Nawal K Khadka, Laxman Mainali","doi":"10.1167/iovs.67.12.18","DOIUrl":"10.1167/iovs.67.12.18","url":null,"abstract":"<p><strong>Purpose: </strong>αA-crystallin (αAc), the predominant subunit comprising α-crystallin (αABc), becomes increasingly deamidated and membrane bound with cataract formation. Furthermore, the lens lipids and cholesterol (Chol) composition significantly change with age and cataract formation. Despite this, the relationship between αAc deamidation and lens membrane composition in cataractogenesis remains unclear. To address this, we analyzed the role of N101 deamidation and membrane composition in the membrane interactions of αAc.</p><p><strong>Methods: </strong>Experimentation involved using electron paramagnetic resonance (EPR) to analyze wild-type (WT) and N101D-αAc membrane binding and its physical effects on the membrane properties of 60-year-old (yo) and 20-yo model human lens lipid (MHLL) membranes containing 2 mol% cholestane spin label and increasing Chol concentrations.</p><p><strong>Results: </strong>Without Chol, WT-αAc and N101D-αAc do not significantly differ in their 60-yo MHLL membrane binding, but N101D deamidation significantly diminishes αAc binding in 20-yo MHLL membranes. With Chol, the binding of WT-αAc and N101D-αAc to 60-yo and 20-yo MHLL membranes is significantly reduced. However, N101D-αAc consistently binds less and with a lower affinity than WT-αAc to both membranes at all Chol contents. Additionally, both WT-αAc and N101D-αAc membrane binding decreases 60-yo and 20-yo MHLL membrane mobility while increasing hydrophobicity and order near the headgroup region.</p><p><strong>Conclusions: </strong>These data indicate that lens membrane composition significantly modulates the membrane association of WT-αAc and N101D-αAc while N101D deamidation generally diminishes αAc membrane binding regardless of membrane composition. Consequently, it appears that N101D deamidation may synchronously function with the membrane composition alterations to diminish αAc membrane binding throughout life and prevent cataract formation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"18"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136503","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":"Spontaneous Achromatopsia-Like Phenotype in Albino Swiss CD-1 Mice: Retinocortical Dysfunction, Neurovascular Remodeling, and Glial Activation.","authors":"José A Matamoros, Santiago Milla-Navarro, Elena Salobrar-García, José A Fernández-Albarral, Víctor Paleo-García, Marta Cantero, Inés López-Cuenca, Lorena Elvira-Hurtado, Francisco J Germain, Lluis Montoliu, Rosa de Hoz, Juan José Salazar, Pedro de la Villa, Ana I Ramírez","doi":"10.1167/iovs.67.12.20","DOIUrl":"10.1167/iovs.67.12.20","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize the functional, structural, vascular, genetic, and histologic correlates of spontaneous retinal electrophysiological phenotypes in male CD-1 mice to ensure accurate phenotyping in vision research.</p><p><strong>Methods: </strong>Baseline full-field flash ERG (ffERG) was recorded in 205 male CD-1 mice. Subsets were evaluated using visual evoked potentials (VEP; n = 12), optical coherence tomography/optical coherence tomography angiography (OCT/OCTA) (n = 17), Gnat2 genotyping (n = 8), and quantitative immunohistochemistry (n = 5-6/phenotype) for cone arrestin, rhodopsin, PKCα (bipolar cells), Brn3a (ganglion cells), Iba1 (microglia), and GFAP (macroglia).</p><p><strong>Results: </strong>FfERG identified three phenotypes: normal (n = 74), cone dysfunction (n = 126), and severe retinal dysfunction (n = 5). FfERG and VEP showed absent cone responses in cone dysfunction mice and complete response abolition in the severe group. OCT/OCTA revealed outer retinal thinning and deep capillary plexus remodeling in severe dysfunction, whereas the cone dysfunction mice retained overall structure. Genotyping confirmed Gnat2 mutations in affected groups. Histology confirmed isolated cone loss in cone dysfunction and combined rod-cone loss in severe dysfunction, both with increased glial activation. Brn3a+ ganglion cells were significantly reduced in both affected groups compared to in normal mice.</p><p><strong>Conclusions: </strong>Spontaneous Gnat2-associated retinal dysfunction is common in CD-1 mice, causing photoreceptor loss, neuroinflammation, and ganglion cell reduction. Baseline electrophysiological screening is crucial when using this strain for vision research.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"20"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136512","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}