Investigative ophthalmology & visual science最新文献

{"title":"Nicotinamide Riboside Mitigates Retinal Degeneration by Suppressing Damaged DNA-Stimulated Microglial Activation and STING-Mediated Pyroptosis.","authors":"Shanshan Zhu, Lusi Zhang, Ping Tong, Jiawei Chen, Cong Wang, Zewei Wang, Jingyuan Liu, Peiyun Duan, Qian Jiang, Yubing Zhou, Guangshuang Tan, Xian Zhang, Bing Jiang","doi":"10.1167/iovs.66.4.14","DOIUrl":"10.1167/iovs.66.4.14","url":null,"abstract":"<p><strong>Purpose: </strong>Microglial activation plays a pivotal role in the pathogenesis of retinal degeneration, contributing to neuroinflammation within the retina. Previous studies identified that nicotinamide riboside (NR) mitigated light-induced retinal degeneration (LIRD) and inhibited microglial activation. The cGAS-STING signaling pathway has been recognized as a key mediator of inflammation in response to cellular stress and tissue damage. This study further explores the regulatory impact of NR on microglial activation and STING-mediated pyroptosis in retinal degeneration.</p><p><strong>Methods: </strong>Balb/c mice were subjected to bright light exposure to induce retinal degeneration. Bioinformatics analysis was used to identify the upregulated key genes and signaling pathways involved in the progression of retinal degeneration, based on mouse transcriptomes from the LIRD model. Molecular biology techniques and immunofluorescence staining were used to assess cGAS-STING activation and expression of pyroptosis-associated molecules. Retinal function, photoreceptor apoptosis and inflammatory response were evaluated in the presence and absence of NR supplementation.</p><p><strong>Results: </strong>Exposure to bright light resulted in mitochondrial dysfunction and the release of dsDNA, significantly triggering the activation of cGAS-STING pathway and microglial pyroptosis. In contrast, NR treatment preserved mitochondrial biosynthesis, inhibited STING expression in reactive microglia, and dampened the pro-inflammatory response. Additionally, intraperitoneal administration of the STING inhibitor H151 reduced light-induced microglial activation and pyroptosis, while improving retinal function and promoting photoreceptor survival.</p><p><strong>Conclusions: </strong>These findings suggest that NR confers neuroprotection by attenuating damaged DNA-triggered STING-mediated microglial activation and pyroptosis. Targeting the cGAS-STING pathway presents a promising therapeutic avenue for retinal degeneration.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795506","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":"Evaluating the Volume of Eyes With Pathologic Myopia Using 3D MRI.","authors":"Tomonari Takahashi, Tae Yokoi-Igarashi, Hiroyuki Takahashi, Noriko Nakao, Kengo Uramoto, Takeshi Yoshida, Muka Moriyama, Koju Kamoi, Koichiro Kimura, Ukihide Tateishi, Kyoko Ohno-Matsui","doi":"10.1167/iovs.66.4.13","DOIUrl":"10.1167/iovs.66.4.13","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the volume of eyes and its relationship to the shape and the presence of posterior staphylomas in patients with high myopia (HM).</p><p><strong>Methods: </strong>We studied 370 eyes of 199 patients with HM (refractive error >8.00 diopters [D] or an axial length ≥26.5 mm) and 44 eyes of 35 control patients without HM (refractive error from -7.50 to +2.50 D). Magnetic resonance imaging (MRI) of the ocular orbit was used to measure the volume of the eye using three-dimensional (3D) MRI. Reconstructed 3D images of eye were classified according to symmetry and steepness of the posterior curvature.</p><p><strong>Results: </strong>The mean volume was 12.42 ± 2.40 mL of the 370 HM eyes and 9.67 ± 1.41 mL of the 44 non-HM eyes. Thus, the volume of the HM eyes was 1.3 times larger than the mean volume of the non-HM eyes. The mean volume of the eye was significantly smaller in the cylindrically shaped and larger in barrel-shaped eyes than the eyes with other shapes. The mean eye volume in the HM eyes with a posterior staphyloma was not significantly different from that of HM eyes without a posterior staphyloma.</p><p><strong>Conclusions: </strong>The volume of HM eyes is larger than non-HM eyes and is associated with steepness of posterior curvature but not with the presence of a posterior staphyloma, suggesting that local outward protrusion of the posterior eye wall is not directly caused by global expansion of eyes and should be monitored specifically in HM eyes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"13"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795597","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":"Deep Corneal Nerve Plexus Selective Damage in Persistent Neurotrophic Corneal Epithelial Defects Detected by In Vivo Multiphoton Confocal Microscopy.","authors":"Seitaro Komai, Manuel E Quiroga-Garza, Raul E Ruiz-Lozano, Nadim S Azar, Hazem M Mousa, Sofia Murillo, Symon Ma, Ali Khodor, Sejiro Littleton, Daniel R Saban, Alain Chédotal, Victor L Perez","doi":"10.1167/iovs.66.4.1","DOIUrl":"10.1167/iovs.66.4.1","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the corneal nerve damage in neurotrophic corneal persistent epithelial defects by an in vivo imaging system using in vivo multiphoton confocal microscopy (MCM) and calcitonin gene-related peptide (CGRP):GFP Tg mice.</p><p><strong>Methods: </strong>Corneal epithelium was scraped, followed by administering a single dose of benzalkonium chloride (BAK) to develop a neurotrophic persistent epithelial defect. The defect was imaged with fluorescein staining for up to 24 hours, and wound closure percentage (%, WCP) was calculated. CGRP:GFP Tg mice were used in combination with in vivo MCM to acquire in vivo images of corneal nerve before and 24 hours after the creation of a corneal epithelial defect. GFP signals from CGRP-positive nerves were reconstructed into three-dimensional (3D) images, and nerve volume was analyzed. Additionally, corneal mechanosensation was evaluated using Cochet-Bonnet esthesiometry.</p><p><strong>Results: </strong>BAK-treated eyes showed a significant delay in WCP at 24 hours. In CGRP:GFP Tg mice, CGRP-positive nerves were successfully captured by in vivo MCM and reconstructed into 3D images. BAK-treated eyes showed a significant decrease in both stromal nerve volume and corneal mechanosensation compared to no BAK eyes at 24 hours after corneal scraping, suggesting that BAK impaired the stromal nerves in both structural and functional asides.</p><p><strong>Conclusions: </strong>Our in vivo corneal nerve imaging system using the combination of in vivo MCM and CGRP:GFP Tg mice demonstrated a longitudinal observation of murine corneal nerves. This system revealed that corneal stromal nerves were selectively damaged in persistent neurotrophic corneal epithelial defects and offered outstanding potential for various applications.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763953","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":"Enlarged Blind Spot Linked to Gamma Zone and Peripapillary Hyperreflective Ovoid Mass-Like Structures in Non-Pathological Highly Myopic Eyes.","authors":"Qiuyan Wu, Ruihan Hu, Qihong Liu, Fang Li, Yuanyuan Wang, Zuohuizi Yi, Jiajia Yuan, Yilei Shao, Meixiao Shen, Hongmei Zheng, Changzheng Chen","doi":"10.1167/iovs.66.4.5","DOIUrl":"10.1167/iovs.66.4.5","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the prevalence and risk factors of enlarged blind spots in non-pathological highly myopic eyes.</p><p><strong>Methods: </strong>Visual field conditions of 313 eyes in 172 individuals with high myopia were evaluated. Clinical characteristics of 116 eyes with enlarged blind spots and 116 eyes with normal visual fields were compared. Generalized-estimating equation (GEE) regression model were used to assess the factors associated with enlarged blind spots.</p><p><strong>Results: </strong>The frequency of enlarged blind spots in non-pathological highly myopic eyes was 37.06% in this sample. Eyes with enlarged blind spots had larger gamma zone (P = 0.038), larger PHOMS area (P < 0.001), increased peripapillary retinal nerve fiber layer thickness (P = 0.006), and decreased macular ganglion cell-inner plexiform layer thickness (P = 0.016) compared with eyes with normal visual fields. In multivariate regression analysis, an expanded gamma zone (OR = 2.004; P = 0.022) and a larger PHOMS area (OR = 4.414; P = 0.009) were associated with an enlarged blind spot.</p><p><strong>Conclusions: </strong>An expanded gamma zone and a larger PHOMS area are associated with an enlarged blind spot, indicating that these two parameters may suggest a possibility of functional damage in early nonpathological, highly myopic eyes. This pattern of impairment might provide clues for the differential diagnosis between high myopia and glaucoma.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763090","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":"Phenotypic and Genotypic Characterization of RP1L1-Associated Retinopathy.","authors":"Alessio Antropoli, Lorenzo Bianco, Xavier Zanlonghi, Amine Benadji, Christel Condroyer, Aline Antonio, Julien Navarro, Claire-Marie Dhaenens, José-Alain Sahel, Christina Zeitz, Isabelle Audo","doi":"10.1167/iovs.66.4.7","DOIUrl":"10.1167/iovs.66.4.7","url":null,"abstract":"<p><strong>Purpose: </strong>Pathogenic variants in RP1L1 are associated with autosomal dominant occult macular dystrophy (OMD) and autosomal recessive retinitis pigmentosa (RP). In this study, we investigated the phenotypic and genotypic landscape of RP1L1-associated retinopathy in an ethnically heterogeneous cohort.</p><p><strong>Methods: </strong>This multicenter cohort study retrospectively collected the following data: best-corrected visual acuity (BCVA), color fundus photograph (CFP), optical coherence tomography (OCT), short-wavelength fundus autofluorescence (SW-AF), and full-field electroretinography (ffERG). Patients were classified based on their clinical phenotype in OMD or RP. Atypical cases were analyzed separately and reappraised according to their clinical and genetic findings.</p><p><strong>Results: </strong>This study included 20 patients (40 eyes) from 19 families: 12 (60%) with OMD, 4 (20%) with RP, and 4 (20%) atypical cases (3 \"non-occult\" macular dystrophy, 1 rod-cone dystrophy with vitelliform maculopathy). Autosomal dominant OMD was the most common phenotype, with one autosomal recessive OMD case identified. Autosomal recessive RP had the latest onset, best visual acuity, and highest refractive error. OMD BCVA declined by ∼0.5 lines/year over a median follow-up of 3.2 years.</p><p><strong>Conclusions: </strong>Mutations in RP1L1 cause a spectrum of diseases, including autosomal dominant OMD, autosomal recessive OMD, and autosomal recessive rod-cone dystrophies, occasionally presenting with pseudovitelliform maculopathy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763445","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":"Histopathological Evaluation of Corneal Tissues in Microsporidia Stromal Keratitis.","authors":"Sohini Mandal, Soumya Sucharita, Vishwajeet Deshmukh, Smruti Rekha Priyadarshini, Srikant Kumar Sahu, Sujata Das","doi":"10.1167/iovs.66.4.9","DOIUrl":"10.1167/iovs.66.4.9","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the histopathological factors in non-resolving cases of microsporidia stromal keratitis (MSK) through the study of corneal buttons obtained during therapeutic penetrating keratoplasty (TPK).</p><p><strong>Methods: </strong>This was a retrospective noncomparative consecutive case series. This case series included 22 corneal buttons (22 patients) of histologically diagnosed MSK between June 2015 and April 2023. Records of preoperative clinical and microbiological data, and postoperative microbiological and histopathologic data of the corneal buttons were evaluated.</p><p><strong>Results: </strong>Histologic evaluation was conducted of the buttons for morphologic changes, degree and distribution of inflammatory cells, presence of microsporidial spores, and their degree and distribution within the corneal buttons. This study evaluated 22 patients with MSK, highlighting clinical, microbiological, treatment, and histopathological findings. The mean patient age was 57.1 ± 13.4 years (range = 22-83 years). The median interval from symptom onset to presentation was 4 months, and the mean time from presentation to keratoplasty was 1 month. Microsporidia spores were detected in 59% of cases through smears, with 41% of cases showing no organisms on microbiological tests. Targeted therapy using polyhexamethylene biguanide (PHMB) 0.02% was given in 13 cases, whereas 9 cases were treated empirically. Histopathology showed no significant correlation between the distribution of inflammatory cells and that of microsporidia. Moderate microsporidia severity correlated with longer symptom duration (10.0 ± 6.36 months). These findings underscore the complexity of MSK management and the variable outcomes.</p><p><strong>Conclusions: </strong>The progression of MSK in advanced stages appears to be influenced by a combination of pathogen-related factors, such as high microsporidial load with deep stromal penetration, and host-related factors, including a pronounced inflammatory response. Additionally, the limited effectiveness of topical PHMB may contribute to disease progression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"9"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772105","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":"Iron-Sulfur Clusters and Iron Responsive Element Binding Proteins Mediate Iron Accumulation in Corneal Endothelial Cells in Fuchs Dystrophy.","authors":"Emma M Hartness, Hanna Shevalye, Jessica M Skeie, Timothy Eggleston, Matthew G Field, Gregory A Schmidt, Pornpoj Phruttiwanichakun, Aliasger K Salem, Mark A Greiner","doi":"10.1167/iovs.66.4.23","DOIUrl":"10.1167/iovs.66.4.23","url":null,"abstract":"<p><strong>Purpose: </strong>Evidence suggests that corneal endothelial cell (CEC) death in Fuchs endothelial corneal dystrophy (FECD) is due to ferroptosis, an iron-mediated cell death. Iron-sulfur cluster (ISC)-containing aconitases and the iron responsive element binding proteins IREBP1 and IREBP2 are known mediators of iron homeostasis. This study investigates mechanisms underlying iron dysregulation in CECs and proposes a role for ISCs and IREBPs in the context of FECD pathogenesis.</p><p><strong>Methods: </strong>We studied gene expression of proteins responsible for ISC synthesis and iron homeostasis in human and mouse CECs and analyzed published RNA sequencing datasets. We validated a subset of transcriptional changes between FECD and control tissues using microfluidic Western blotting with human CEC tissues. Finally, we silenced proteins involved in ISC synthesis or iron homeostasis in cell cultures and assessed ferroptosis susceptibility.</p><p><strong>Results: </strong>RNA-seq and qPCR data demonstrated significantly decreased transcription of genes required for ISC synthesis in FECD tissues (P < 0.05). Protein quantification revealed a significant decrease in mitochondrial aconitase (P < 0.05), ferredoxin 1 (P < 0.001), and mitofusin (P < 0.05), and a significant increase in cysteine desulfurase (P < 0.05), cytosolic aconitase/IREBP1, and IREBP2 (P < 0.05) in FECD tissues. Silencing studies revealed increased susceptibility to ferroptosis upon siRNA knockdown of ferredoxin 1 (P < 0.05).</p><p><strong>Conclusions: </strong>We identified differential gene expression of proteins responsible for ISC synthesis, ISC-containing proteins, IREBPs that mediate cellular iron homeostasis, and mitofusin, which promotes mitochondrial fusion in FECD. We also identified increased susceptibility to ferroptosis after ferredoxin 1 knockdown in CECs. These results advance an ISC- and IREBP-mediated mechanism of iron accumulation in FECD CECs.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"23"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Pigment Epithelium Specific Metabolic Phenotypes Are Regulated by High-Mobility Group Protein N1.","authors":"Toshiaki Abe, Reiko Daigaku, Xie Yuting, Yasukazu Daigaku, Nobuhiro Nagai, Hirokazu Kaji, Aya Katsuyama, Yuki Katsukura, Yasuko Izumida, Atsuko Suzuki, Shinji Yamada, Yao-Wen Chang, Keiko Terada, Sei-Ichi Ishiguro, Noriko Osumi, Hiroshi Kunikata, Toru Nakazawa","doi":"10.1167/iovs.66.4.70","DOIUrl":"https://doi.org/10.1167/iovs.66.4.70","url":null,"abstract":"<p><strong>Purpose: </strong>The retinal pigment epithelium (RPE) performs life-long phagocytosis of lipid-rich photoreceptor outer segments and exchanges energy metabolites with photoreceptors to support retinal function. The metabolites of glucose and lipid metabolism are interconnected, but it is unclear how the specialized lipid metabolism of RPE and glucose metabolism are regulated. We have investigated this unique mechanism.</p><p><strong>Methods: </strong>To identify factors involved in regulation of metabolism in RPE we compared and screened the human retinal pigment epithelial cell line, ARPE-19 under different conditions. Using the results of these experiments we selected the high-mobility group nucleosome-associated protein 1 (HMGN1) as a candidate and analyzed HMGN1 deleted ARPE-19 (HGMN1-/--ARPE-19) and Hmgn1 knock-out mice (Hmgn1-/- mice).</p><p><strong>Results: </strong>HMGN1 was identified as being involved in energy metabolism via altered expression. HMGN1-/--ARPE-19 cells prefer fatty acid oxidation over glucose metabolism as an energy source. Hmgn1-/- mice had a lower lipid weight of epididymal fat mass and serum lipids than those of control on a standard diet and showed impaired glucose tolerance. The mice also showed retinal dysfunction, similar to that observed in aged control retina as measured by electroretinogram. However, a palmitate-rich diet, as well as RPE-specific HMGN1 re-expression mitigated retinal dysfunction. HMGN1 is specifically downregulated in the RPE/choroid with aging, which is reminiscent of age-related metabolic changes in RPE/choroid.</p><p><strong>Conclusions: </strong>HMGN1 is involved in energy metabolism and its altered expression modulates RPE-specific metabolic phenotypes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"70"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025014","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":"Prox1 Protein in Corneal Limbal Lymphatic Vessels Maintains Limbal Stem Cell Stemness and Regulates Corneal Injury Repair.","authors":"An Wang, Zongyuan Li, Yilin Jiang, Mingxiong Chen, Hanrui Yu, Zhao Li, Shengshu Sun, Ge Bai, Qun Wang, Yifei Huang, Liqiang Wang","doi":"10.1167/iovs.66.4.81","DOIUrl":"https://doi.org/10.1167/iovs.66.4.81","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to elucidate the role of the corneal lymphatic Prox1 gene in modulating limbal stem cell stemness and facilitating corneal injury repair.</p><p><strong>Methods: </strong>The limbal Prox1 gene was knocked down by adeno-associated virus (AAV). The alkali burn model was induced in the naive group, the AAV-sham group, and the AAV-shProx1 group. Anterior segment photography, fluorescein sodium staining, and hematoxylin and eosin (H&E) staining were conducted immediately on days 1, 3, 7, 14, and 21 post-injury. Immunofluorescent (IF) staining was used to assess Ki67, ΔNp63, and K14. Additionally, seq-mRNA technology facilitated a comparative transcriptomic analysis between the AAV-sham and the AAV-shProx1 groups 7 days post-injury. Key regulated genes were verified by protein level. Furthermore, a co-culture model of lymphatic endothelial cells (LECs) and limbal stem cells (LSCs) was used to investigate the proliferation capacity and stemness expression of LSCs.</p><p><strong>Results: </strong>Fluorescein sodium staining revealed that the epithelial defect area was significantly larger in the AAV-shProx1 group than in the AAV-sham group on days 1 and 3 post-injury (P < 0.05). Ki67, ΔNp63, and K14 expressions were consistently lower in the AAV-shProx1 group than in the AAV-sham group at distinct time points. Additionally, seq-mRNA results demonstrated that genes (Prox1 and Lyve1) were downregulated while inflammatory factors (Ccl2, Ccl7, IL16, IL1R, and TNFsf11) were upregulated in the AAV-shProx1 group compared with the AAV-sham group. When Prox1 was silenced in LECs, the proliferation and stemness of LSCs were markedly downregulated.</p><p><strong>Conclusions: </strong>The Prox1 and Lyve1 proteins in lymphatic vessels served as pivotal regulated proteins in corneal injury repair. The draining role of lymphatic vessels during corneal injury was indispensable.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"81"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depth-Related Visuomotor Performance in Keratoconus and Its Relationship to Stereopsis.","authors":"Preetirupa Devi, Christa M Bhengra, Deepak Kumar, Rashmi Deshmukh, Pravin K Vaddavalli, Joshua A Solomon, Christopher W Tyler, Shrikant R Bharadwaj","doi":"10.1167/iovs.66.4.31","DOIUrl":"https://doi.org/10.1167/iovs.66.4.31","url":null,"abstract":"<p><strong>Purpose: </strong>The purposes of this study were to quantify the impact of degraded binocularity in keratoconus and its improvement with rigid contact lenses on a depth-related visuomotor task that emulates complex activities in daily living; and to determine whether visuomotor performance may be predicted from psychophysical estimates of stereo threshold.</p><p><strong>Methods: </strong>Participants were instructed to pass a metal loop around a wire convoluted in depth. Error rate and speed were measured in 26 controls, 30 cases with keratoconus with best-corrected spectacles, a subset of 17 cases with rigid contact lenses, and 10 uncorrected myopes with acuity and stereo thresholds comparable to the keratoconic cohort. Stereo thresholds were determined using random-dot stimuli.</p><p><strong>Results: </strong>Binocular error rates were lower than monocular error rates for controls, uncorrected myopes, and the better-performing half of cases (p < 0.001, for each), but not for the worst-performing half (p = 0.07). Error rates in cases improved with contact lenses (p < 0.001). Within each cohort, the error rate was poorly correlated with the stereo threshold (r2 < 0.12, for each). Monocular speeds were significantly lower than binocular speeds for controls than for cases (p = 0.003) and for uncorrected myopes than cases (p = 0.001).</p><p><strong>Conclusions: </strong>Degraded binocularity in keratoconus may limit the ability to perform depth-related visuomotor tasks. A portion of this loss may be overcome by using rigid contact lenses. The attributes of visuomotor task performance are, however, not predictable from the psychophysical estimates of stereo thresholds.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"31"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012598","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}