Experimental eye research最新文献

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Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration 血液整合素和产生细胞因子的 T 细胞与老年性黄斑变性的分期和遗传风险评分有关。
IF 3 2区 医学
Experimental eye research Pub Date : 2024-11-14 DOI: 10.1016/j.exer.2024.110154
Rianne Rijken , Els M. Pameijer , Bram Gerritsen , Sanne Hiddingh , Marilette Stehouwer , Joke H. de Boer , Saskia M. Imhof , Redmer van Leeuwen , Jonas JW. Kuiper
{"title":"Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration","authors":"Rianne Rijken ,&nbsp;Els M. Pameijer ,&nbsp;Bram Gerritsen ,&nbsp;Sanne Hiddingh ,&nbsp;Marilette Stehouwer ,&nbsp;Joke H. de Boer ,&nbsp;Saskia M. Imhof ,&nbsp;Redmer van Leeuwen ,&nbsp;Jonas JW. Kuiper","doi":"10.1016/j.exer.2024.110154","DOIUrl":"10.1016/j.exer.2024.110154","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of AMD patients. A standardized 31-parameter flow cytometry analysis was conducted on peripheral blood mononuclear cells from 59 patients with early and advanced AMD and 39 controls without AMD, all older than 65 years. Fundus photography and optical coherence tomography were used to classify disease stages and a custom genotype array was used to compute an AMD genetic risk score based on 52 AMD disease risk variants (GRS-52). A generalized linear regression model corrected for age, sex, and smoking status revealed that AMD patients showed decreased frequencies of CD4<sup>+</sup> T helper cell population expressing Integrin Alpha E (CD103) (<em>Padj = 0.019</em>). We further noted that early AMD was characterized by increased interleukin-4 (IL-4)-producing CD4<sup>+</sup> T helper cells (<em>Padj = 0.013; &lt;0.001</em>), as well as IL-4-producing cytotoxic CD8<sup>+</sup> T cells (<em>Padj = 0.016; &lt;0.001</em>). Reclassification of samples based on the GRS-52 revealed that IL-17-producing T cells decreased incrementally across GRS-52 categories. In AMD, alterations in peripheral blood leukocyte populations are associated with genetic risk score and disease stage and include specifically IL-4 and IL-17A cytokine-producing and CD103 integrin-expressing T cell populations.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110154"},"PeriodicalIF":3.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638279","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}
引用次数: 0
Association of a COL1A1 gene haplotype with pathologic myopia in a Northern Chinese Han population 中国北方汉族人群中 COL1A1 基因单倍型与病理性近视的关系
IF 3 2区 医学
Experimental eye research Pub Date : 2024-11-13 DOI: 10.1016/j.exer.2024.110151
Guangqi An , Min Zhang , Wenna Gao , Fan Yang , Lin Li , Youmei Xu , Xuemin Jin , Liping Du
{"title":"Association of a COL1A1 gene haplotype with pathologic myopia in a Northern Chinese Han population","authors":"Guangqi An ,&nbsp;Min Zhang ,&nbsp;Wenna Gao ,&nbsp;Fan Yang ,&nbsp;Lin Li ,&nbsp;Youmei Xu ,&nbsp;Xuemin Jin ,&nbsp;Liping Du","doi":"10.1016/j.exer.2024.110151","DOIUrl":"10.1016/j.exer.2024.110151","url":null,"abstract":"<div><div>To investigate the relationship between <em>COL1A1</em> variations and the susceptibility to pathologic myopia (PM) among the general population in Northern China, we included 525 PM patients and 1105 non-myopic controls. All PM patients underwent comprehensive ophthalmologic examinations. DNA was extracted from peripheral venous blood samples and genotyped using the MassArray System. Statistical analyses, including Hardy-Weinberg equilibrium, χ<sup>2</sup> test, and linkage disequilibrium analysis, were conducted to compare the genotypic and allelic distributions of SNPs between PM patients and controls. The results showed no significant differences in the genotypic and allelic distributions of rs2075555, rs2269336, and rs1107946 between the PM and control groups. However, haplotype analysis revealed that the G-G-C and T-C-A haplotypes are risk factors for PM (G-G-C: OR = 1.399, 95% CI = 1.206–1.623, <em>P</em> &lt; 0.001, <em>Pc</em> &lt; 0.001; T-C-A: OR = 1.248, 95% CI = 1.064–1.456, <em>P</em> = 0.007, <em>Pc</em> = 0.021). Although individual SNPs in COL1A1 were not significantly associated with PM, specific haplotypes (G-G-C and T-C-A) were identified as risk factors. This suggests a potential role of <em>COL1A1</em> in the development of PM.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110151"},"PeriodicalIF":3.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617747","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}
引用次数: 0
Comparative study of physicochemical properties on corneal stromal lenticules following four decellularization methods 四种脱细胞方法角膜基质皮孔理化性质的比较研究
IF 3 2区 医学
Experimental eye research Pub Date : 2024-11-12 DOI: 10.1016/j.exer.2024.110148
Bingqing Sun , Zhe Zhang , Yanze Yu , Fei Xia , Yong Ma , Xuan Ding , Xiaosong Han , Ti Wang , Xingtao Zhou , Jing Zhao
{"title":"Comparative study of physicochemical properties on corneal stromal lenticules following four decellularization methods","authors":"Bingqing Sun ,&nbsp;Zhe Zhang ,&nbsp;Yanze Yu ,&nbsp;Fei Xia ,&nbsp;Yong Ma ,&nbsp;Xuan Ding ,&nbsp;Xiaosong Han ,&nbsp;Ti Wang ,&nbsp;Xingtao Zhou ,&nbsp;Jing Zhao","doi":"10.1016/j.exer.2024.110148","DOIUrl":"10.1016/j.exer.2024.110148","url":null,"abstract":"<div><div>This study compares the physicochemical properties of corneal stromal lenticules following decellularization via four methods. Human corneal stromal lenticules, derived from small incision lenticule extraction surgery, underwent decellularization with sodium dodecyl sulfate (SDS), Triton X-100 (Tx) combined with SDS, trypsin-ethylenediaminetetraacetic acid (TE), or NaCl combined with deoxyribonuclease (DNase), respectively. Lenticule DNA and glycosaminoglycan (GAG) content, immunofluorescence staining of cell nuclei and collagen, transparency, biomechanics, histological structure, and immunogenicity were examined in each group and compared with fresh lenticules. All decellularized groups exhibited effective cell removal, with no significant decrease in GAG content (all P &gt; 0.05). DNA content decreased in all decellularization groups (all P &lt; 0.01), most notably in the SDS and Tx + SDS groups. Additionally, collagen I and IV fluorescence intensity was reduced in the TE group only (P &lt; 0.0001). Histological staining revealed close similarity in collagen arrangement between the Tx + SDS group and fresh lenticules. Collagen fiber density increased while spacing and diameter decreased in all decellularized groups (all P &lt; 0.05), with partial collagen degradation detected in the TE group. Light transmittance remained above 60% in the visible light spectrum in all groups. The Young's modulus or elastic modulus did not decrease significantly among decellularized lenticules (all P &gt; 0.05). Human leukocyte antigen (HLA)-DR, HLA-ABC, and CD45 expression decreased in the Tx + SDS and NaCl + DNase groups (all P &lt; 0.001). Although all four decellularization methods showed varying decellularization efficacy, Tx + SDS effectively removed cells without damaging corneal morphology, extracellular matrix, or biomechanics, indicating its potential for lenticule storage, transplantation, and bio-scaffold fabrication.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110148"},"PeriodicalIF":3.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617748","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}
引用次数: 0
Endomucin regulates the endothelial cytoskeleton independently of VEGF. 内黏蛋白调节内皮细胞骨架与血管内皮生长因子无关。
IF 3 2区 医学
Experimental eye research Pub Date : 2024-11-12 DOI: 10.1016/j.exer.2024.110150
Jean Moon, Suman Chaudhary, Lorena Rodriguez-Martinez, Zhengping Hu, Patricia A D'Amore
{"title":"Endomucin regulates the endothelial cytoskeleton independently of VEGF.","authors":"Jean Moon, Suman Chaudhary, Lorena Rodriguez-Martinez, Zhengping Hu, Patricia A D'Amore","doi":"10.1016/j.exer.2024.110150","DOIUrl":"10.1016/j.exer.2024.110150","url":null,"abstract":"<p><p>The endothelial glycocalyx, lining the apical surface of the endothelium, is involved in a host of vascular processes. The glycocalyx is comprised of a network of membrane-bound proteoglycans and glycoproteins along with associated plasma proteins. One such glycoprotein is endomucin (EMCN), which our lab has revealed is a modulator of VEGFR2 function. Intravitreal injection of siEMCN into the eyes of P5 mice impairs vascular development. In vitro silencing of EMCN suppresses VEGF-induced proliferation and migration. Signaling pathways that drive cell migration converge on cytoskeletal remodeling. By coupling co-immunoprecipitation with liquid chromatography/mass spectrometry, we identified interactions between EMCN and proteins associated with actin cytoskeleton organization. The aim of the study was to investigate the influence of EMCN on cytoskeleton dynamics in angiogenesis. EMCN depletion resulted in reduction of F-actin levels, whereas overexpression of EMCN induced increased membrane protrusions in cells that were rich in stress fibers. The reorganization of the actin filaments did not depend on VEGFR2 signaling, suggesting that EMCN connects the cytoskeleton and the glycocalyx.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110150"},"PeriodicalIF":3.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617749","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}
引用次数: 0
Pigment epithelium-derived factor exerts neuroprotection in oxygen-induced retinopathy by targeting endoplasmic reticulum stress and oxidative stress 色素上皮源性因子通过靶向内质网应激和氧化应激,在氧气诱导的视网膜病变中发挥神经保护作用。
IF 3 2区 医学
Experimental eye research Pub Date : 2024-11-05 DOI: 10.1016/j.exer.2024.110147
Ya'nuo Wang , Sha Gao , Shuang Gao , Na Li , Hanwen Huang , Xiaohong Liu , Huiping Yao , Xi Shen
{"title":"Pigment epithelium-derived factor exerts neuroprotection in oxygen-induced retinopathy by targeting endoplasmic reticulum stress and oxidative stress","authors":"Ya'nuo Wang ,&nbsp;Sha Gao ,&nbsp;Shuang Gao ,&nbsp;Na Li ,&nbsp;Hanwen Huang ,&nbsp;Xiaohong Liu ,&nbsp;Huiping Yao ,&nbsp;Xi Shen","doi":"10.1016/j.exer.2024.110147","DOIUrl":"10.1016/j.exer.2024.110147","url":null,"abstract":"<div><div>Endoplasmic reticulum (ER) stress and oxidative stress have been involved in the occurrence of neuronal apoptosis in ischemic retinopathy. Pigment epitheliu-derived factor (PEDF) is well known for its multifunctional properties, including neuroprotection, anti-inflammation and antioxidant. However, the association between PEDF and ER stress or oxidative stress in ischemic retinopathy remain incompletely understood. In this study, the concentration of the key factor of ER stress C/EBP homologous protein (CHOP) in aqueous humor (AqH) and vitreous samples of proliferative diabetic retinopathy (PDR) patients were measured by ELISA assays. Oxygen-induced retinopathy (OIR) mice model was established and PEDF intravitreal injections were conducted. Primary bone marrow derived macrophages (BMDMs) were isolated and cultured under hypoxic conditions in vitro. Western blotting, real-time RT-PCR, immunofluorescence, transmission electron microscopy (TEM), TUNEL assays were performed to explore roles of PEDF on ER stress and oxidative stress, as well as subsequently neuronal apoptosis under hypoxic conditions in vivo and in vitro. The results revealed that ER stress and oxidative stress were notably activated under hypoxic conditions. We also observed that hypoxia evoked ultrastructural damage of ER and mitochondrion in the retina. However, PEDF significantly prevented ER stress and oxidative stress, as well as the damage of ultrastructure, resulting in diminution of photoreceptor apoptosis in OIR retinas. These results indicate that PEDF may play its neuroprotection role through inhibiting ER stress and oxidative stress in ischemic retinopathy, which is a novel molecular mechanism of PEDF protecting photoreceptors from ischemic damage, thereby suggesting that PEDF is an effective therapeutic agent for the treatment of neuron damage in ischemic retinal diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110147"},"PeriodicalIF":3.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602826","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}
引用次数: 0
Role of angiopoietin-like 4 in neovascularization associated with retinopathy of prematurity 血管生成素样 4 在与早产儿视网膜病变相关的新生血管中的作用。
IF 3 2区 医学
Experimental eye research Pub Date : 2024-11-02 DOI: 10.1016/j.exer.2024.110145
Xiaofeng Lu , Zixin Fan , Shuo Yang, Lei Zheng, Zhen Yu, Yuhang Yang, Mianying Zheng, Jian Zeng, Guoming Zhang
{"title":"Role of angiopoietin-like 4 in neovascularization associated with retinopathy of prematurity","authors":"Xiaofeng Lu ,&nbsp;Zixin Fan ,&nbsp;Shuo Yang,&nbsp;Lei Zheng,&nbsp;Zhen Yu,&nbsp;Yuhang Yang,&nbsp;Mianying Zheng,&nbsp;Jian Zeng,&nbsp;Guoming Zhang","doi":"10.1016/j.exer.2024.110145","DOIUrl":"10.1016/j.exer.2024.110145","url":null,"abstract":"<div><div>To elucidate the mechanisms of angiopoietin-like 4 (ANGTPL4) in neovascularization (NV) in retinopathy of prematurity (ROP). We compared ANGPTL4 expression levels of aqueous humour and vitreous fluid samples in infants with acute-phase ROP and control group. ANGPTL4<sup>−/−</sup> mice and WT mice were used to constructed oxygen-induced retinopathy (OIR) mouse models, with retinal tissues collected on postnatal days 12 (P12), 15 (P15) and 17 (P17). Analysis of retinal vessels and transcriptomics were performed to explore the role of ANGTPL4 in NV. The results showed ANGPTL4 level was significantly higher in the aqueous humour and vitreous fluid of children with ROP than that of control group. At P15 and P17, the vascular indices in the ANGPTL4<sup>−/−</sup>-CON group were lower than those in the WT-CON group. The central non-perfused area of the retina and number of neovascular nuclei were also smaller in the ANGPTL4<sup>−/−</sup>-OIR group than in the WT-OIR group. Immunofluorescence results showed the overexpression of ANGPTL4 protein in the WT-OIR group than in the WT-CON group, especially at P17. Furthermore, extracellular matrix (ECM) organisation was one of the key involved pathways based on gene ontology (GO) enrichment analyses. ANGPTL4 was one of the core genes involved in ECM organization, and neuralized E3 ubiquitin protein ligase 1B (NEURL1B), cd36 Molecule (CD36), matrix metallopeptidase 3 (MMP3) and collagen type III alpha 1 chain (COL3A1) were the first nodes interacting with ANGPTL4.In conclusion, ANGPTL4 is involved in the pathological NV by regulating NEURL1B, CD36, MMP3, and COL3A1. Thus, ANGPTL4 is a potential therapeutic target for ROP.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110145"},"PeriodicalIF":3.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568271","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}
引用次数: 0
Optical and retinal changes influenced by different lighting conditions 受不同照明条件影响的光学和视网膜变化。
IF 3 2区 医学
Experimental eye research Pub Date : 2024-11-02 DOI: 10.1016/j.exer.2024.110146
Elvira Orduna-Hospital , Juan J. Sanchez-Bautista , Guisela Fernández-Espinosa , María Arcas-Carbonell , Ana Sanchez-Cano
{"title":"Optical and retinal changes influenced by different lighting conditions","authors":"Elvira Orduna-Hospital ,&nbsp;Juan J. Sanchez-Bautista ,&nbsp;Guisela Fernández-Espinosa ,&nbsp;María Arcas-Carbonell ,&nbsp;Ana Sanchez-Cano","doi":"10.1016/j.exer.2024.110146","DOIUrl":"10.1016/j.exer.2024.110146","url":null,"abstract":"<div><div>Retinal morphology, specifically in its curvature, and ocular aberrations change when the eye adapts to different lighting conditions, including photopic, scotopic, mesopic, blue light, and red light. Sixty healthy young subjects with refractive error less than ±4.00 D of sphere and 3.00 D of cylinder, not suffering from accommodative problems, ocular or systemic pathology, and not having used electronic devices half an hour before or having taken substances that alter the retina during the 2 h prior to the study were included. The subjects adapted to five lighting conditions, each for 5 min, in a controlled environment. Ocular aberrometry and Optical Coherence Tomography (OCT) were taken to capture images of the central and peripheral retina before (baseline measurements) and after adaptation to each lighting condition. The OCT images were exported and processed to analyze retinal curvature, obtaining parameters such as eccentricity, asphericity and shape factor. The results showed that the shape of the retina was hyperbolic prolate, becoming flatter in scotopic and blue light conditions, and more curved in mesopic conditions. Retinal curvature was closest to baseline under red light and photopic conditions. Aberrometric differences, particularly in the C(2,0) polynomial for defocus, showed higher values in mesopic, baseline, and scotopic conditions, and lower values in photopic, blue light, and red light. Significant differences were also observed in spherical aberrations C(4,0) and C(6,0), vertical coma C(3,-1), and trefoil C(3,-3). The spherical equivalent indicated more myopic values in mesopic, baseline, and scotopic conditions, and more hyperopic values in blue, photopic, and red light, suggesting a link between myopia and lower luminosity. This study concludes that illumination affects retinal curvature and ocular refraction, influencing myopia.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110146"},"PeriodicalIF":3.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568269","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}
引用次数: 0
The aryl hydrocarbon receptor: A crucial mediator in ocular disease pathogenesis and therapeutic target 芳基烃受体:眼部疾病发病机制和靶向治疗的关键介质。
IF 3 2区 医学
Experimental eye research Pub Date : 2024-10-31 DOI: 10.1016/j.exer.2024.110144
Juanjuan Ji , Chanyu Xiong , Huining Yang , Zhilin Jiang , Yun Zhang , Xiao Wang , Tianshu Yu , Qiong Li , Shikai Zhu , Yu Zhou
{"title":"The aryl hydrocarbon receptor: A crucial mediator in ocular disease pathogenesis and therapeutic target","authors":"Juanjuan Ji ,&nbsp;Chanyu Xiong ,&nbsp;Huining Yang ,&nbsp;Zhilin Jiang ,&nbsp;Yun Zhang ,&nbsp;Xiao Wang ,&nbsp;Tianshu Yu ,&nbsp;Qiong Li ,&nbsp;Shikai Zhu ,&nbsp;Yu Zhou","doi":"10.1016/j.exer.2024.110144","DOIUrl":"10.1016/j.exer.2024.110144","url":null,"abstract":"<div><div>The aryl hydrocarbon receptor (AHR) is a pivotal nuclear receptor involved in mediating cellular responses to a wide range of environmental pollutants and endogenous ligands. AHR plays a central role in regulating essential physiological processes, including xenobiotic metabolism, immune response modulation, cell cycle control, tumorigenesis, and developmental events. Recent studies have identified AHR as a critical mediator and a potential therapeutic target in the pathogenesis of ocular diseases. This review provides a thorough analysis of the various functions of AHR signalling in the ocular environment, with a specific emphasis on its effects on the retina, retinal pigment epithelium (RPE), choroid, and cornea. We provide a detailed discussion on the molecular mechanisms through which AHR integrates environmental and endogenous signals, influencing the development and progression of age-related macular degeneration (AMD), retinitis pigmentosa, uveitis, and other major ocular disorders. Furthermore, we evaluate the therapeutic potential of modulating AHR activity through novel ligands and agonists as a strategy for treating eye diseases. Understanding the molecular mechanisms of AHR in ocular tissues may facilitate the development of AHR-targeted therapies, which is crucial for addressing the pressing clinical demand for novel treatment strategies in ocular diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110144"},"PeriodicalIF":3.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564230","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}
引用次数: 0
Neuroprotective effect of Sigma-2 modulator CT2074 in a mouse model of ocular hypertension Sigma-2调节剂CT2074在眼压过高小鼠模型中的神经保护作用
IF 3 2区 医学
Experimental eye research Pub Date : 2024-10-29 DOI: 10.1016/j.exer.2024.110143
Nina Donkor , Charles C. Kiehlbauch , Nathaniel Pappenhagen , Gary C. Look , Autumn B. Morgan , Rick Shin , Mary E. Hamby , Denise M. Inman
{"title":"Neuroprotective effect of Sigma-2 modulator CT2074 in a mouse model of ocular hypertension","authors":"Nina Donkor ,&nbsp;Charles C. Kiehlbauch ,&nbsp;Nathaniel Pappenhagen ,&nbsp;Gary C. Look ,&nbsp;Autumn B. Morgan ,&nbsp;Rick Shin ,&nbsp;Mary E. Hamby ,&nbsp;Denise M. Inman","doi":"10.1016/j.exer.2024.110143","DOIUrl":"10.1016/j.exer.2024.110143","url":null,"abstract":"<div><div>Ocular neurodegenerative diseases, particularly glaucoma, represent a significant global cause of blindness, with current therapies inadequately addressing the degeneration of the retina and optic nerve. Recent research has identified the sigma-2 receptors as a potential druggable target to offer neuroprotection in managing ocular neurodegenerative disorders. This study investigates the neuroprotective potential of CT2074, a sigma-2 receptor modulator, in a mouse model of primary open-angle glaucoma.</div><div>Male mice were subjected to unilateral magnetic bead-induced elevation of intraocular pressure (IOP) and received daily oral administration of CT2074, commencing three days prior to ocular hypertension (OHT) induction, and continuing for three weeks. Mice received bilateral intraocular injections of cholera toxin B-488 (CTB) to assess retinal ganglion cell (RGC) anterograde transport. Retina, optic nerve, and brain tissues were collected three weeks post OHT induction for quantification of RGC and axon number, with contralateral retinas and cerebelli preserved for assessment of drug exposure.</div><div>CT2074 was observed in the retina at levels exceeding the 95% receptor occupancy concentration. RGC quantification showed a significant reduction in the Vehicle group compared to Naïve and CT2074 groups. Notably, the CT2074 treatment group exhibited significantly higher RGC density than the Vehicle (p &lt; 0.0001) and was no different than Naïve. Analysis of RGC axons in optic nerve cross-sections revealed significant axonal loss in both the Vehicle and CT2074 groups compared to Naïve, though the CT2074-treated group had significantly higher axon number compared to the Vehicle. Anterograde transport in the Vehicle and CT2074 groups did not differ.</div><div>This study underscores the potential of CT2074 administered orally to protect RGCs exposed to elevated IOP, as evidenced by substantial preservation of RGCs and their axons compared to Vehicle-treated mice. These findings signify a promising avenue for the development of sigma-2 receptor-targeted therapeutics in glaucoma and related neurodegenerative diseases, addressing a critical unmet need in the field of ocular neuroprotection.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110143"},"PeriodicalIF":3.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557488","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}
引用次数: 0
A comprehensive review of experimental models for investigating blue light-induced ocular damage: Insights into parameters, limitations, and new opportunities 全面回顾研究蓝光诱发眼损伤的实验模型:洞察参数、局限性和新机遇。
IF 3 2区 医学
Experimental eye research Pub Date : 2024-10-28 DOI: 10.1016/j.exer.2024.110142
Wan-Ju Yeh , Pin-Ting Chien , Yao-Tseng Wen , Chi-Hao Wu
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