Experimental eye research最新文献_第9页

Monochromatic light effects on refractive error, cone cell density and retinoic acid signaling in dorsal and ventral retina in guinea pigs 单色光对豚鼠背侧和腹侧视网膜屈光不正、视锥细胞密度和视黄酸信号的影响

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-14 DOI: 10.1016/j.exer.2024.110155

Leilei Zou , Cheng Fang , Hong Liu , Rui Liu , Jinhui Dai

Cone cells have been found to influence refractive states. This study investigated whether cone cells and retinal acid (RA) plays a role in refractive states under monochromatic lights. Guinea pigs were exposed to blue (BL), green (GL), or white light (WL), respectively, for 8 weeks. Refractive error (RE), cone cell density, RA, retinoic acid receptor-β (RAR-β), collagen-I expression, and scleral thickness in dorsal and ventral eyes were assessed. Eyes exposed to BL showed a slower shift from hyperopia to emmetropia, particularly in the ventral retina, where higher S-cone density was linked to greater remaining hyperopia. In contrast, GL exposure led to myopic shifts, notably in the dorsal retina, where increased M-cone density was associated with greater reductions in refractive error. BL exposure resulted in similar decreases in RA and retinoic acid receptor-β (RAR-β) expression in both dorsal and ventral regions, along with elevated scleral collagen-I and thicker sclera. In contrast, GL exposure increased RA and RAR-β levels, while reducing scleral collagen-I and thickness. GL-associated changes in RAR-β expression and scleral thinning were more pronounced in the dorsal retina compared to the ventral retina, despite similar RA levels in both regions. These findings suggested that RA may not contribute to the hyperopic shifts with increased S-cone cell density in BL. However, increased RA and RAR-β may be correlated with ocular growth in guinea pigs exposed to GL, it may underlie myopic shifts with increased M-cone cell density.

研究发现视锥细胞会影响屈光状态。本研究调查了锥状细胞和视网膜酸（RA）是否在单色光下屈光状态中发挥作用。将豚鼠分别暴露在蓝光（BL）、绿光（GL）或白光（WL）下 8 周。对屈光不正（RE）、视锥细胞密度、RA、视黄酸受体-β（RAR-β）、胶原蛋白-I表达以及背侧和腹侧眼睛的巩膜厚度进行了评估。暴露于BL的眼睛从远视向屈光转变的速度较慢，尤其是在视网膜腹侧，较高的S锥密度与较大的剩余远视有关。与此相反，暴露于 GL 会导致近视度数的改变，尤其是在背侧视网膜，M 锥体密度的增加与屈光不正的进一步减少有关。BL暴露导致背侧和腹侧区域的RA和视黄酸受体-β（RAR-β）表达类似减少，同时巩膜胶原蛋白-I升高，巩膜变厚。相反，暴露于 GL 会增加 RA 和 RAR-β 的水平，同时降低巩膜胶原蛋白-I 和厚度。与腹侧视网膜相比，背侧视网膜的 RAR-β 表达和巩膜变薄与 GL 相关的变化更为明显，尽管这两个区域的 RA 水平相似。这些发现表明，RA可能不会导致BL中S锥细胞密度增加的远视偏移。然而，RA和RAR-β的增加可能与暴露于GL的豚鼠的眼球生长有关，它可能是M锥细胞密度增加的近视转变的原因。

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引用次数: 0

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 Q1 OPHTHALMOLOGY

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

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⁺ T helper cell population expressing Integrin Alpha E (CD103) (Padj = 0.019). We further noted that early AMD was characterized by increased interleukin-4 (IL-4)-producing CD4⁺ T helper cells (Padj = 0.013; <0.001), as well as IL-4-producing cytotoxic CD8⁺ T cells (Padj = 0.016; <0.001). 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.

老年性黄斑变性（AMD）仍然是老年人视力丧失的主要原因。外周血白细胞组成存在与年龄相关的变化，但其对老年性黄斑变性的意义尚不清楚。我们旨在确定 AMD 患者血液中免疫细胞群的变化。我们对 59 名早期和晚期 AMD 患者的外周血单核细胞以及 39 名 65 岁以上无 AMD 的对照者的外周血单核细胞进行了标准化的 31 参数流式细胞术分析。眼底摄影和光学相干断层扫描用于疾病分期，定制基因型阵列用于计算基于 52 个 AMD 疾病风险变异的 AMD 遗传风险评分 (GRS-52)。一个校正了年龄、性别和吸烟状况的广义线性回归模型显示，AMD 患者的 CD4 阳性 T 辅助细胞群表达 Integrin Alpha E (CD103) 的频率降低（Padj = 0.019）。我们还注意到，早期 AMD 的特征是产生白细胞介素-4（IL-4）的 CD4+ T 辅助细胞增多（Padj = 0.013；

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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 Q1 OPHTHALMOLOGY

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

To investigate the relationship between COL1A1 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, χ² 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, P < 0.001, Pc < 0.001; T-C-A: OR = 1.248, 95% CI = 1.064–1.456, P = 0.007, Pc = 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 COL1A1 in the development of PM.

为了研究COL1A1变异与中国北方普通人群病理性近视（PM）易感性之间的关系，我们纳入了525名PM患者和1105名非近视对照者。所有近视患者均接受了全面的眼科检查。从外周静脉血样本中提取 DNA，并使用 MassArray 系统进行基因分型。通过哈代-温伯格平衡、χ2检验和连锁不平衡分析等统计分析，比较了原发性近视患者和对照组之间SNPs的基因型和等位基因分布。结果显示，在 PM 组和对照组之间，rs2075555、rs2269336 和 rs1107946 的基因型和等位基因分布无明显差异。然而，单倍型分析表明，G-G-C 和 T-C-A 单倍型是 PM 的风险因素（G-G-C：OR=1.399，95% CI=1.206-1.623，P<0.001，Pc<0.001；T-C-A：OR=1.248，95% CI=1.064-1.456，P=0.007，Pc=0.021）。虽然COL1A1中的单个SNP与PM无明显相关性，但特定的单倍型（G-G-C和T-C-A）被确定为风险因素。这表明 COL1A1 在 PM 的发病过程中起着潜在的作用。

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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 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-13 DOI: 10.1016/j.exer.2024.110150

Jean Moon , Suman Chaudhary , Lorena Rodriguez-Martinez , Zhengping Hu , Patricia A. D'Amore

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.

内皮糖萼衬于内皮顶端表面，参与了一系列血管过程。糖萼由与膜结合的蛋白多糖和糖蛋白网络以及相关的血浆蛋白组成。内黏蛋白（EMCN）就是这样一种糖蛋白，我们的实验室发现它是 VEGFR2 功能的调节剂。将 siEMCN 注入 P5 小鼠眼内会损害血管发育。体外沉默 EMCN 可抑制血管内皮生长因子诱导的增殖和迁移。驱动细胞迁移的信号通路汇聚于细胞骨架重塑。通过共免疫沉淀与液相色谱/质谱联用，我们确定了 EMCN 与肌动蛋白细胞骨架组织相关蛋白之间的相互作用。该研究旨在探讨 EMCN 对血管生成过程中细胞骨架动力学的影响。消耗 EMCN 会导致 F-肌动蛋白水平下降，而过表达 EMCN 则会诱导富含应力纤维的细胞膜突起增加。肌动蛋白丝的重组并不依赖于 VEGFR2 信号，这表明 EMCN 连接了细胞骨架和糖萼。

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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 Q1 OPHTHALMOLOGY

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

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 > 0.05). DNA content decreased in all decellularization groups (all P < 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 < 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 < 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 > 0.05). Human leukocyte antigen (HLA)-DR, HLA-ABC, and CD45 expression decreased in the Tx + SDS and NaCl + DNase groups (all P < 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.

本研究比较了角膜基质透镜通过四种方法脱细胞后的理化性质。人类角膜基质皮孔来自小切口皮孔提取手术，分别用十二烷基硫酸钠（SDS）、结合 SDS 的 Triton X-100 (Tx)、胰蛋白酶-乙二胺四乙酸（TE）或含脱氧核糖核酸酶（DNase）的氯化钠进行脱细胞处理。对各组皮孔的 DNA 和糖胺聚糖（GAG）含量、细胞核和胶原的免疫荧光染色强度、透明度、生物力学、组织学结构和免疫原性进行了检测，并与新鲜皮孔进行了比较。所有脱细胞组都能有效去除细胞，且 GAG 含量无明显下降（均 P > 0.05）。所有脱细胞组的 DNA 含量均有下降（均 P < 0.01），其中以 SDS 组和 Tx+SDS 组最为明显。此外，只有 TE 组的胶原 I 和 IV 荧光强度降低（P < 0.0001）。组织学染色显示，Tx+SDS 组与新鲜皮孔的胶原排列非常相似。所有脱细胞组的胶原纤维密度都有所增加，而间距和直径都有所减少（P < 0.05），TE 组出现部分胶原降解。在可见光光谱下，所有组的透光率都保持在 60% 以上。脱细胞皮孔的杨氏模量或弹性模量没有明显降低（均为 P > 0.05）。人类白细胞抗原 (HLA)-DR、HLA-ABC 和 CD45 的表达在 Tx+SDS 组和 NaCl+DNase 组均有所下降（均 P <0.001）。虽然四种脱细胞方法的脱细胞效果各不相同，但 Tx+SDS 能有效去除细胞，且不会破坏角膜形态、细胞外基质或生物力学，这表明它具有用于角膜透镜储存、移植和生物杖制造的潜力。

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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 Q1 OPHTHALMOLOGY

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

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.

内质网（ER）应激和氧化应激与缺血性视网膜病变中神经元凋亡的发生有关。众所周知，色素上皮衍生因子（PEDF）具有多功能特性，包括神经保护、抗炎和抗氧化。然而，PEDF与缺血性视网膜病变中的ER应激或氧化应激之间的关系仍不完全清楚。本研究采用酶联免疫吸附法测定了增殖性糖尿病视网膜病变（PDR）患者房水（AqH）和玻璃体样本中ER应激的关键因子C/EBP同源蛋白（CHOP）的浓度。建立了氧诱导视网膜病变（OIR）小鼠模型，并进行了 PEDF 玻璃体内注射。分离并在体外缺氧条件下培养原代骨髓巨噬细胞（BMDMs）。通过Western印迹、实时RT-PCR、免疫荧光、透射电子显微镜（TEM）和TUNEL检测，探讨PEDF对体内和体外缺氧条件下ER应激和氧化应激以及神经元凋亡的作用。结果表明，缺氧条件下ER应激和氧化应激被显著激活。我们还观察到，缺氧诱发了视网膜中ER和线粒体的超微结构损伤。然而，PEDF能明显阻止ER应激和氧化应激以及超微结构的损伤，从而减少OIR视网膜中感光细胞的凋亡。这些结果表明，PEDF可能通过抑制缺血性视网膜病变中的ER应激和氧化应激发挥其神经保护作用，这是PEDF保护光感受器免受缺血性损伤的一种新的分子机制，从而提示PEDF是治疗缺血性视网膜疾病中神经元损伤的一种有效的治疗药物。

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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 Q1 OPHTHALMOLOGY

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

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^−/− 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^−/−-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^−/−-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.

为了阐明血管生成素样 4（ANGTPL4）在早产儿视网膜病变（ROP）新生血管（NV）中的作用机制。我们比较了急性期 ROP 患儿和对照组患儿房水和玻璃体液样本中 ANGPTL4 的表达水平。我们用ANGPTL4-/-小鼠和WT小鼠构建了氧诱导视网膜病变（OIR）小鼠模型，并在出生后第12天（P12）、第15天（P15）和第17天（P17）采集了视网膜组织。研究人员对视网膜血管和转录组学进行了分析，以探讨ANGTPL4在NV中的作用。结果显示，ROP患儿水样液和玻璃体液中的ANGPTL4水平明显高于对照组。P15和P17时，ANGPTL4-/-CON组的血管指数低于WT-CON组。ANGPTL4-/-OIR组视网膜中央无灌注区和新生血管核的数量也小于WT-OIR组。免疫荧光结果显示，WT-OIR组的ANGPTL4蛋白表达高于WT-CON组，尤其是在P17时。此外，根据基因本体（GO）富集分析，细胞外基质（ECM）组织是关键的参与通路之一。ANGPTL4是参与ECM组织的核心基因之一，而神经化E3泛素蛋白连接酶1B（NEURL1B）、CD36分子（CD36）、基质金属肽酶3（MMP3）和胶原Ⅲ型α1链（COL3A1）是与ANGPTL4相互作用的第一个节点。因此，ANGPTL4 是治疗 ROP 的潜在靶点。

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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 Q1 OPHTHALMOLOGY

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

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.

当眼睛适应不同的光照条件时，视网膜形态（特别是曲率）和眼像差都会发生变化，这些条件包括光照、散光、中光、蓝光和红光。研究对象包括 60 名健康的年轻受试者，他们的球面屈光不正小于 ±4.00D ，柱面屈光不正小于 3.00D，没有适应性问题、眼部或全身性疾病，在研究前半小时内没有使用过电子设备，也没有服用过改变视网膜的药物。受试者在受控环境中适应五种照明条件，每种条件持续 5 分钟。在适应每种照明条件之前（基线测量）和之后，受试者通过眼球像差仪和光学相干断层扫描（OCT）捕捉视网膜中央和周边的图像。输出并处理 OCT 图像以分析视网膜曲率，从而获得偏心率、非球面度和形状因子等参数。结果表明，视网膜的形状呈双曲线状，在散光和蓝光条件下变得扁平，而在中近视条件下则更加弯曲。在红光和光照条件下，视网膜曲率最接近基线。视差差异，尤其是散焦的 C(2,0) 多项式，在中视、基线和散光条件下显示较高值，而在光视、蓝光和红光条件下显示较低值。球面像差 C(4,0) 和 C(6,0)、垂直彗差 C(3,-1) 和三叶形像差 C(3,-3) 也有显著差异。球面等效度在中视、基线和散光条件下显示出更多的近视值，而在蓝光、光照和红光条件下显示出更多的远视值，这表明近视与低照度之间存在联系。研究得出结论，光照会影响视网膜曲率和眼屈光度，从而影响近视。

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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 Q1 OPHTHALMOLOGY

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

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.

芳基烃受体（AHR）是一种关键的核受体，参与介导细胞对多种环境污染物和内源性配体的反应。AHR 在调节基本生理过程中发挥着核心作用，包括异生物代谢、免疫反应调节、细胞周期控制、肿瘤发生和发育事件。最近的研究发现，AHR 是眼部疾病发病机制中的关键介质和潜在治疗靶点。本综述深入分析了 AHR 信号在眼部环境中的各种功能，特别强调了它对视网膜、视网膜色素上皮（RPE）、脉络膜和角膜的影响。我们详细讨论了 AHR 整合环境和内源性信号，影响老年性黄斑变性（AMD）、视网膜色素变性、葡萄膜炎和其他主要眼部疾病的发生和发展的分子机制。此外，我们还评估了通过新型配体和激动剂调节 AHR 活性作为眼科疾病治疗策略的治疗潜力。了解 AHR 在眼部组织中的分子机制有助于开发 AHR 靶向疗法，这对于满足临床对眼部疾病新型治疗策略的迫切需求至关重要。

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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 Q1 OPHTHALMOLOGY

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

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.

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.

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 < 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.

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.

眼部神经退行性疾病，尤其是青光眼，是全球失明的重要原因之一，目前的疗法不足以解决视网膜和视神经的退化问题。最近的研究发现，sigma-2 受体是一种潜在的药物靶点，可为治疗眼部神经退行性疾病提供神经保护。本研究在原发性开角型青光眼小鼠模型中研究了σ-2受体调节剂CT2074的神经保护潜力。雄性小鼠在单侧磁珠诱导下眼压升高，每天口服 CT2074，从诱导眼压升高前三天开始，持续三周。小鼠双侧眼内注射霍乱毒素 B-488（CTB），以评估视网膜神经节细胞（RGC）的逆行运输。在诱导OHT三周后收集视网膜、视神经和脑组织，以量化RGC和轴突数量，并保留对侧视网膜和脑组织以评估药物暴露情况。在视网膜中观察到的 CT2074 水平超过了 95% 的受体占用浓度。与正常组和 CT2074 组相比，车辆组的 RGC 数量明显减少。值得注意的是，CT2074 治疗组的 RGC 密度明显高于车辆组（p

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引用次数: 0