Investigative ophthalmology & visual science最新文献

{"title":"Progressive Optic Neuropathy in Hydrocephalic Ccdc13 Mutant Mice Caused by Impaired Axoplasmic Transport at the Optic Nerve Head.","authors":"Mingjuan Wu, Xinyi Zhao, Shanzhen Peng, Xiaoyu Zhang, Jiali Ru, Lijing Xie, Tao Wen, Yingchun Su, Shujuan Xu, Dianlei Guo, Jianmin Hu, Haotian Lin, Tiansen Li, Chunqiao Liu","doi":"10.1167/iovs.65.13.5","DOIUrl":"10.1167/iovs.65.13.5","url":null,"abstract":"<p><strong>Purpose: </strong>Optic nerve head (ONH) atrophy is frequently associated with hydrocephalic conditions. Cerebrospinal fluid (CSF)-containing meninges form a subarachnoid space that terminates at the ONH, which physically impacts it. This study aims to characterize optic neuropathy in congenital hydrocephalic mice with genetic disruption of the Ccdc13 gene.</p><p><strong>Methods: </strong>The ccdc13 germline knockout mice were generated. The hydrocephalus phenotype and subarachnoid space surrounding the optic nerve were evaluated using routine histology and Evans blue stain. Optic neuropathy was examined with immunohistochemistry and transmission electron microscopy (TEM). Axon transport was indicated by cholera toxin subunit B (CTB) fluorescence conjugate. Retinal function was evaluated by electroretinography (ERG), and Ccdc13 expression was revealed by a knock-in Gfp reporter.</p><p><strong>Results: </strong>Ccdc13 mutant mice manifested hydrocephalus at birth. ONH displacement, or negative cupping, and enlarged subarachnoid space at the optic terminus occurred as early as 1 month after birth. Intraocular pressure (IOP) was normal. Optic neuropathy was first observed at the ONH, followed by a distal-to-proximal progression of optic nerve pathology indicated by alteration of axonal ultrastructure and deposition of unphosphorylated neurofilament heavy chain. Anterograde axonal transport was also hampered. Retinal ganglion cell (RGC) function was compromised as early as postnatal day 21 (P21), along with reduced neurofilament heavy chain expression. Optic neuropathy caused by disruption of Ccd13 was non-cell autonomous, stemming from hydrocephalus with presumed high intracranial pressure (ICP), which physically impacts the ONH by increasing the translaminar pressure gradient.</p><p><strong>Conclusions: </strong>We provided knowledge of optic neuropathy from a congenital mouse model for hydrocephalus. The hydrocephalus in mice could damage the ONH by increasing the translaminar pressure gradient and negative cupping, leading to impairment in axoplasmic transport and RGC pathology. Our findings highlight the importance of the interplay between IOP and ICP in the development of glaucoma.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583017","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":"Interpericyte Tunneling Nanotubes Are Nonuniformly Distributed in the Human Macula.","authors":"Martin Hein, Hassanain Qambari, Paula Yu, Dao-Yi Yu, Chandrakumar Balaratnasingam","doi":"10.1167/iovs.65.13.28","DOIUrl":"10.1167/iovs.65.13.28","url":null,"abstract":"<p><strong>Purpose: </strong>Pericyte-to-pericyte communication via interpericyte tunneling nanotubes (IP-TNTs) is an important mechanism by which spatial and temporal precision in neurovascular coupling is achieved. This study quantifies the distribution and morphologic characteristics of IP-TNTs in the normal human macula.</p><p><strong>Methods: </strong>Ultra high-resolution, three-dimensional microscopic imaging of 11 perfusion-labeled normal human donor eyes was performed. Immunofluorescent markers for collagen IV, glial fibrillary acidic protein, nuclei, α-smooth muscle actin and phalloidin were used to distinguish IP-TNTs from perfused/nonperfused capillaries and glia processes. IP-TNT length, diameter and density in each capillary plexus was quantified and compared.</p><p><strong>Results: </strong>IP-TNTs were present in all capillary plexuses. IP-TNTs bridged capillary segments within and between capillary plexuses but did not connect capillaries to arterioles or venules. Mean length of IP-TNTs was 72.6 ± 39.5µm (range 14.0 to 202 µm) and mean diameter was 1.0 ± 0.42µm. IP-TNT length was non-normally distributed with a right-skewed distribution and 43% were 'short' (<55µm). Diameters were greater in the \"long\" (1.13 ± 0.44 µm) than \"short\" (0.82 ± 0.33 µm; P < 0.001) IP-TNTs. Density of IP-TNTs was greater in the superficial vascular plexus (3.80 ± 0.69 per 500 µm2) compared to the intermediate (1.85 ± 0.80 per 500 µm2; P < 0. 0001) and deep capillary plexus (1.58 ± 0.84 per 500 µm2; P < 0.0001). No significant difference in IP-TNT density was found between the four macula quadrants (P = 0.98).</p><p><strong>Conclusions: </strong>The distribution of IP-TNTs in the human macula is non-uniform and is associated with the compartmentalized nature of retinal energy consumption and microvascular perfusion. The nonuniform properties of IP-TNTs may predispose distinct vascular beds to injury in conditions such as diabetes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620770","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":"Midperipheral Microvascular Defects and Their Associations With Vitreoretinal Abnormalities in Early-Stage Familial Exudative Vitreoretinopathy.","authors":"Juan Zhang, Lu Ruan, Chen Jiang, Qian Yang, Qing Chang, Xin Huang","doi":"10.1167/iovs.65.13.4","DOIUrl":"10.1167/iovs.65.13.4","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate microvascular growth defects in the temporal midperipheral retina and their correlations with vitreoretinal microstructural abnormalities (VRMAs) in early-stage familial exudative vitreoretinopathy (FEVR).</p><p><strong>Methods: </strong>We enrolled 127 patients (127 eyes) with early-stage FEVR and 31 healthy subjects (31 eyes). Widefield optical coherence tomography angiography was conducted for all enrolled eyes. Vessel density (VD), vessel diameter index (VDI), and vessel index (VI; VD/VDI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in temporal midperiphery were further evaluated. The distance from the vessel sprouting point of the optic disc to the avascular area margin (Optic-AVA) was measured to assess retinal vascular dysplasia.</p><p><strong>Results: </strong>In early-stage FEVR, 61.42% of eyes showed retinal microvascular abnormalities (MVAs) in the temporal midperiphery, all combined with VRMAs. Common MVAs presented disordered vascular anastomoses in the SCP and capillary loss in the DCP, corresponding to deficient neuroretina. The preretinal vasculature (PRV) was detected in 36 eyes. VD and VI were lower in FEVR eyes compared to controls, whereas the VDI in the SCP was larger (all P < 0.001). Optic-AVA was positively correlated with VD and VI in both plexuses and negatively correlated with the VDI in the SCP. PRV existence was independently correlated with decreased VI in the DCP (odds ratio [OR] = 0.322; P < 0.001), and VRMA existence was independently correlated with decreased VI in SCP and DCP (SCP OR = 0.282, P = 0.010; DCP OR = 0.562, P = 0.002).</p><p><strong>Conclusions: </strong>MVAs in the temporal midperipheral retina were revealed. Microvascular loss may be correlated with Optic-AVA reduction, PRV, and the presence of VRMAs.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568576","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":"Age-Associated Alterations in the Metabolome of Human Vitreous in Bacterial Endophthalmitis.","authors":"Sreyasi Maiti, Lakshminarayanan Gowtham, Dhanwini Rudraprasad, Vivek P Dave, Joveeta Joseph","doi":"10.1167/iovs.65.13.6","DOIUrl":"10.1167/iovs.65.13.6","url":null,"abstract":"<p><strong>Purpose: </strong>Endophthalmitis is a severe inflammatory condition due to intraocular infections that often leads to irreversible blindness. This study aimed to understand the age-dependent metabolic alterations in the vitreous of patients with bacterial endophthalmitis.</p><p><strong>Methods: </strong>The study included the vitreous metabolome of patients with bacterial endophthalmitis (group 1, n = 15) and uninfected controls (group 2, n = 14), which were further stratified into three groups according to their age: young (0-30 years), middle (31-60 years), and elderly (>60 years). Vitreous samples were subjected to untargeted metabolomic analysis using high-resolution mass spectrometry (HRMS)m and acquired mass spectrometry data were analyzed using MetaboAnalyst 6.0. The altered metabolites with log2FC of ≥2/≤2, P < 0.05, and variable importance in projection > 1 were considered significant.</p><p><strong>Results: </strong>In a total of 109 endogenous metabolites identified, young and elderly patients with endophthalmitis showed 52 (elevated, 25; reduced, 27; P < 0.05) and 27 (elevated, 19; reduced, 8; P < 0.05) significantly altered metabolites, respectively, compared to their age-matched controls. Additionally, 27 metabolites were differentially expressed in young patients with endophthalmitis compared to the older group. The crucial metabolic pathways dysregulated in the older infected population were de novo purine synthesis and salvage, carnitine, polyamine (spermidine), lipids (prostaglandins), and amino acid (taurine, methionine, histidine) which could possibly be attributed to the increased disease severity and inflammation observed in a clinical setting.</p><p><strong>Conclusions: </strong>Despite the erratic metabolic changes observed in the younger group infected with endophthalmitis when compared to age-matched controls, dysregulation in the specific pathways such as purine, carnitine, arachidonic acid, and polyamine metabolism could possibly alter the immunological exacerbation observed in the older group.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582896","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":"Distortion-Corrected Posterior Ocular Shape in Myopic Eyes Assessed by Ultrawide OCT Detects Deformations Associated With Vision-Threatening Changes.","authors":"Bingyao Tan, Janika N Shah, Ryan P McNabb, Swathi Jayaraman, Damon Wong, Jacqueline Chua, Marcus Ang, Seang Mei Saw, Jost B Jonas, Anthony N Kuo, Quan V Hoang, Leopold Schmetterer","doi":"10.1167/iovs.65.13.22","DOIUrl":"10.1167/iovs.65.13.22","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a quantitative tool for assessing the posterior ocular shape using widefield, volumetric optical coherence tomography (OCT) in eyes with myopia.</p><p><strong>Methods: </strong>This observational, cross-sectional study included 178 eyes from 113 participants. Participants underwent a standardized eye examination, including ocular biometry and a custom ultrawide OCT. True ocular shape was reconstructed by tracing the beam propagation from the system to the posterior eye. Gaussian curvature quantified the localized ocular shape, which was further categorized into five distinct categories. An ocular shape irregularity (OSI) was calculated using principal component analysis. Linear regression with breakpoints analyzed the relationship between ocular shape parameters and axial length (AL).</p><p><strong>Results: </strong>Increased curvature mean and variance were associated with more severe myopia (P < 0.001). Curvature categories (convex, normal, concave, and highly concave) differed significantly between the groups (all P < 0.001). Their correlations with AL revealed significant breakpoints between 27.1 and 27.2 mm. OSI, as a single metric for quantifying ocular shape distortion, was associated with more severe myopia (P < 0.001), and its correlation with AL revealed a breakpoint at 27.2 mm with a fourfold increase in slope steepness beyond this pivot. Determination of OSI was highly reproducible and could also be obtained with fewer scans.</p><p><strong>Conclusions: </strong>Eyes exceeding 27.2 mm in length exhibit pronounced shape changes. Our framework can be seamlessly integrated into commercial OCTs for ocular shape deformation detection, which could aid in identifying eyes with pathologic myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"22"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620758","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 Impact of Retinal Vessel Segmentation Metrics on Retest Reliability in a Clinical Setting: A Comparative Analysis Using AutoMorph.","authors":"Samuel D Giesser, Ferhat Turgut, Amr Saad, Jay R Zoellin, Chiara Sommer, Yukun Zhou, Siegfried K Wagner, Pearse A Keane, Matthias Becker, Delia Cabrera DeBuc, Gábor Márk Somfai","doi":"10.1167/iovs.65.13.24","DOIUrl":"10.1167/iovs.65.13.24","url":null,"abstract":"<p><strong>Purpose: </strong>Current research on artificial intelligence-based fundus photography biomarkers has demonstrated inconsistent results. Consequently, we aimed to evaluate and predict the test-retest reliability of retinal parameters extracted from fundus photography.</p><p><strong>Methods: </strong>Two groups of patients were recruited for the study: an intervisit group (n = 28) to assess retest reliability over a period of 1 to 14 days and an intravisit group (n = 44) to evaluate retest reliability within a single session. Using AutoMorph, we generated test and retest vessel segmentation maps; measured segmentation map agreement via accuracy, sensitivity, F1 score and Jaccard index; and calculated 76 metrics from each fundus image. The retest reliability of each metric was analyzed in terms of the Spearman correlation coefficient, intraclass correlation coefficient (ICC), and relative percentage change. A linear model with the input variables contrast-to-noise-ratio and fractal dimension, chosen by a P-value-based backward selection process, was developed to predict the median percentage difference on retest per image based on image-quality metrics. This model was trained on the intravisit dataset and validated using the intervisit dataset.</p><p><strong>Results: </strong>In the intervisit group, retest reliability varied between Spearman correlation coefficients of 0.34 and 0.99, ICC values of 0.31 to 0.99, and mean absolute percentage differences of 0.96% to 223.67%. Similarly, in the intravisit group, the retest reliability ranged from Spearman correlation coefficients of 0.55 and 0.96, ICC values of 0.40 to 0.97, and mean percentage differences of 0.49% to 371.23%. Segmentation map accuracy between test and retest never dropped below 97%; the mean F1 scores were 0.85 for the intravisit dataset and 0.82 for the intervisit dataset. The best retest was achieved with disc-width regarding the Spearman correlation coefficient in both datasets. In terms of the Spearman correlation coefficient, the worst retests of the intervisit and intravisit groups were tortuosity density and artery tortuosity density, respectively. The intravisit group exhibited better retest reliability than the intervisit group (P < 0.001). Our linear model, with the two independent variables contrast-to-noise ratio and fractal dimension predicted the median retest reliability per image on its validation dataset, the intervisit group, with an R2 of 0.53 (P < 0.001).</p><p><strong>Conclusions: </strong>Our findings highlight a considerable volatility in the reliability of some retinal biomarkers. Improving retest could allow disease progression modeling in smaller datasets or an individualized treatment approach. Image quality is moderately predictive of retest reliability, and further work is warranted to understand the reasons behind our observations better and thus ensure consistent retest results.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"24"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620763","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":"Overcoming Low mRNA Expression in White Matter: A Protocol for RNA Extraction From the Optic Nerve in Large Animals for Transcriptomic Analysis.","authors":"Zhonghao Yu, Yue Guan, Tian Xia, Xuanwen Li, Mingyue Liu, Yujia Huo, Zhuowei Wang, Zhirong Liu, Yuting Luo, Wentao Yan, Lanfang Sun, Wencan Wu, Baoguo Shen, Yikui Zhang","doi":"10.1167/iovs.65.13.25","DOIUrl":"10.1167/iovs.65.13.25","url":null,"abstract":"<p><strong>Purpose: </strong>White matter (WM) abnormalities are associated with various central nervous system (CNS) disorders, and the optic nerve provides a unique opportunity to study WM pathology. Large animal models offer a more suitable platform for preclinical testing of novel therapeutic strategies for optic neuropathy due to their similarities to humans in size and relevant anatomy. Transcriptomic analyses of optic nerve tissue are essential for understanding the underlying pathological mechanisms. However, extracting high-quality RNA from the optic nerve in large animals remains challenging.</p><p><strong>Methods: </strong>We utilized in situ hybridization and single-nucleus RNA sequencing (snRNA-seq) to examine mRNA expression in WM cells and gray matter (GM) cells.</p><p><strong>Results: </strong>We discovered that mRNA expression levels in WM cells were only 15% to 66% of those in GM neurons. To overcome the low mRNA yield, we developed a specialized RNA extraction protocol for the intra-canalicular optic nerve in large animal models, achieving an RNA integrity number (RIN) of 6.8 ± 0.06. For single-cell transcriptomics (scRNA-seq), we obtained a cell density of 1.0 × 105 cells/µL, cell viability of 93% ± 1.84%, and an agglomeration rate of 5.37% ± 0.75%. This approach is also applicable for postmortem human optic nerve with a RIN of 8.3 ± 0.3 using snRNA-seq.</p><p><strong>Conclusions: </strong>We first discovered that the mRNA expression in the WM was significantly lower than that in the GM. Our RNA extraction protocol from large animal models enhances transparency and reproducibility in transcriptomic studies of optic nerve and other WM tissues.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"25"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620777","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":"Oxidative Stress and Inflammation-Related mRNAs Are Elevated in Serum of a Finnish Wet AMD Cohort.","authors":"Mikko Liukkonen, Hanna Heloterä, Leea Siintamo, Bishwa Ghimire, Pirkko Mattila, Niko Kivinen, Joanna Kostanek, Cezary Watala, Maria Hytti, Juha Hyttinen, Ali Koskela, Janusz Blasiak, Kai Kaarniranta","doi":"10.1167/iovs.65.13.30","DOIUrl":"10.1167/iovs.65.13.30","url":null,"abstract":"<p><strong>Purpose: </strong>Localized diseases can be affected by and affect the systemic environment via blood circulation. In this study, we explored the differences in circulating serum mRNAs between patients with wet AMD (wAMD) and controls.</p><p><strong>Methods: </strong>Blood samples were obtained from 60 Finnish patients with wAMD and 64 controls. After serum preparation and RNA sequencing, the count data was examined for differentially expressed genes (DEGs) and further checked for enriched molecular pathways and ontology terms as well as links to clinical data.</p><p><strong>Results: </strong>We found many DEGs and some enriched pathways, including the inflammation and cell survival-associated pathway tumour necrosis factor alpha (TNF-α) signaling via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The related DEGs were oxidized low-density lipoprotein receptor 1 (OLR1), salt inducible kinase 1 (SIK1), and coagulation factor III (F3). DEGs from degradative macular and retinal processes were also examined, many of which were also related to cardiovascular disease and maintenance. Additionally, DEG counts were inspected in relation to clinical and anti-VEGF treatment parameters, and glutamine amidotransferase-like class 1 domain-containing 3A (GATD3A) levels were found to be significantly lower in patients with wAMD treated with anti-VEGF.</p><p><strong>Conclusions: </strong>Differentially expressed systemic mRNAs that are linked to mitochondrial function, oxidative stress, and inflammation may have a role in the pathology of wAMD. Our observations provide new data for the understanding of the progression of wAMD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"30"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638878","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":"Diabetes Renders Photoreceptors Susceptible to Retinal Ischemia-Reperfusion Injury.","authors":"David A Antonetti, Cheng-Mao Lin, Sumathi Shanmugam, Heather Hager, Manjing Cao, Xuwen Liu, Alyssa Dreffs, Adam Habash, Steven F Abcouwer","doi":"10.1167/iovs.65.13.46","DOIUrl":"10.1167/iovs.65.13.46","url":null,"abstract":"<p><strong>Purpose: </strong>Studies have suggested that photoreceptors (PR) are altered by diabetes, contributing to diabetic retinopathy (DR) pathology. Here, we explored the effect of diabetes on retinal ischemic injury.</p><p><strong>Methods: </strong>Retinal ischemia-reperfusion (IR) injury was caused by elevation of intraocular pressure in 10-week-old BKS db/db type 2 diabetes mellitus (T2DM) mice or C57BL/6J mice at 4 or 12 weeks after streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM), and respective nondiabetic controls. Retinal neurodegeneration was evaluated by retinal layer thinning, TUNEL staining, and neuron loss. Vascular permeability was evaluated as retinal accumulation of circulating fluorescent albumin. The effects of pretreatment with a sodium-glucose co-transporter (SGLT1/2) inhibitor, phlorizin, were examined.</p><p><strong>Results: </strong>Nondiabetic control mice exhibited no significant outer retinal layer thinning or PR loss after IR injury. In contrast, db/db mice exhibited significant outer retina thinning (49%, P < 0.0001), loss of PR nuclei (45%, P < 0.05) and inner segment (IS) length decline (45%, P < 0.0001). STZ-induced diabetic mice at 4 weeks showed progressive thinning of the outer retina (55%, by 14 days, P < 0.0001) and 4.3-fold greater number of TUNEL+ cells in the outer nuclear layer (ONL) than injured retinas of control mice (P < 0.0001). After 12 weeks of diabetes, the retinas exhibited similar outer layer thinning and PR loss after IR. Diabetes also delayed restoration of the blood-retinal barrier after IR injury. Phlorizin reduced outer retinal layer thinning from 49% to 3% (P < 0.0001).</p><p><strong>Conclusions: </strong>Diabetes caused PR to become highly susceptible to IR injury. The ability of phlorizin pretreatment to block outer retinal thinning after IR suggests that the effects of diabetes on PR are readily reversible.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"46"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681928","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 Impact of HLA-A29 Homozygosity and of the Second HLA-A Allele on Susceptibility and Severity of Birdshot Chorioretinitis.","authors":"Jordan Loeliger, Romain Lhotte, Sahar Gelfman, Eli A Stahl, Dominique Monnet, Valentin Clichet, Linda Imikirene, Souhila Kecili, Jean-Luc Taupin, Thierry Tabary, Jacques H M Cohen, Antoine P Brézin","doi":"10.1167/iovs.65.13.47","DOIUrl":"10.1167/iovs.65.13.47","url":null,"abstract":"<p><strong>Purpose: </strong>HLA-A29 is the main susceptibility factor for birdshot chorioretinitis (BSCR). Our study assessed the impact of the second HLA-A allele alongside HLA-A29 on BSCR severity and susceptibility, focusing on HLA-A29 homozygous patients and those with alleles from the HLA-Aw19 group.</p><p><strong>Methods: </strong>We included 120 additional cases to our previous analysis of 286 patients with BSCR, all HLA-A29 positive. Patients were categorized based on the second allele being also HLA-A29 (A29/nonA29 vs. A29/A29) or belonging to the HLA-Aw19 family, including A29, A30, A31, and A33 (A29/nonAw19 vs. A29/Aw19). HLA-A32 was analyzed separately (A29/nonA32 vs. A29/A32). The prevalence of these groups among patients with BSCR was compared with their frequencies in a sample of 151,997 French subjects. Disease severity was approximated by assessing disease onset and visual function at the last visit and was compared between patient groups.</p><p><strong>Results: </strong>When comparing the HLA-A29-positive patients with BSCR to HLA-A29-positive French subjects, we found an overrepresentation of HLA-A29 for the second HLA-A allele (χ² = 4.34; P = 0.037; odds ratio, 1.57; confidence interval, 1.01-2.44). Within the HLA-Aw19 broad antigen family, HLA-A32 was found to be under-represented (χ² = 6.15; P = 0.013; odds ratio, 0.40; confidence interval, 0.19-0.85). The nature of the second HLA-A allele did not impact disease severity.</p><p><strong>Conclusions: </strong>Homozygosity for HLA-A29 increased the risk of developing BSCR without affecting disease severity. The under-representation of HLA-A32 in patients with BSCR suggests a potential protective role.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"47"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681965","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}