Experimental eye research最新文献_第10页

SREBF1 facilitates pathological retinal neovascularization by reprogramming the fatty acid metabolism of endothelial cells SREBF1通过重新编程内皮细胞的脂肪酸代谢来促进病理性视网膜新生血管。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-01-10 DOI: 10.1016/j.exer.2025.110239

Hangjia Zuo , Xianyang Liu , Yakun Wang , Huannan Ding , Wenjuan Wan , Shijie Zheng , Shengping Hou , Ke Hu

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disorder that critically affects the visual development of premature infants, potentially leading to irreversible vision loss or even blindness. Despite its significance, the underlying mechanisms of this disease remain insufficiently understood. In this study, we utilized the oxygen-induced retinopathy (OIR) mouse model and conducted endothelial functional assays to explore the role of Sterol Regulatory Element-Binding Protein 1 (SREBF1) in ROP pathogenesis. SREBF1 expression levels, along with its downstream targets, were investigated through Western blotting, RT-qPCR, and immunofluorescence staining techniques. Furthermore, Co-Immunoprecipitation (Co-IP) was employed to examine the molecular mechanisms involved. Our results demonstrated a significant increase in SREBF1 expression in both the OIR mouse model and hypoxic primary human retinal microvascular endothelial cells (HRMECs). Interventions conducted both in vivo and in vitro showed notable efficacy in reducing pathological neovascularization. Importantly, we discovered that SREBF1 plays a key role in modulating lipid metabolism in HRMECs by regulating the expression of ACC1 and FASN, leading to cellular reprogramming. This reprogramming influences HRMEC proliferation, migration, and tube formation through the HIF-1α/TGF-β signaling pathway, ultimately contributing to pathological retinal neovascularization. These findings provide new insights into the role of SREBF1 in angiogenesis within the context of ROP, offering potential therapeutic targets for the management and treatment of this disease.

早产儿视网膜病变（Retinopathy of prematurity， ROP）是一种严重影响早产儿视力发育的增殖性视网膜血管疾病，可能导致不可逆的视力丧失甚至失明。尽管其意义重大，但该病的潜在机制仍未得到充分了解。在本研究中，我们利用氧诱导视网膜病变（OIR）小鼠模型，并进行内皮功能测定，探讨甾醇调节元件结合蛋白1 （SREBF1）在ROP发病机制中的作用。通过Western blotting、RT-qPCR和免疫荧光染色技术研究SREBF1及其下游靶点的表达水平。此外，采用共免疫沉淀（Co-Immunoprecipitation, Co-IP）技术研究了相关的分子机制。我们的研究结果表明，在OIR小鼠模型和缺氧原代人视网膜微血管内皮细胞（HRMECs）中，SREBF1的表达均显著增加。在体内和体外进行的干预都显示出显著的减少病理性新生血管的功效。重要的是，我们发现SREBF1通过调节ACC1和FASN的表达，导致细胞重编程，在调节hrmes的脂质代谢中起关键作用。这种重编程通过HIF-1α/TGF-β信号通路影响HRMEC的增殖、迁移和管形成，最终导致病理性视网膜新生血管形成。这些发现为SREBF1在ROP背景下血管生成中的作用提供了新的见解，为该疾病的管理和治疗提供了潜在的治疗靶点。

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引用次数: 0

Corrigendum to “Anti-inflammatory and neuroprotective properties of the corticosteroid fludrocortisone in retinal degeneration” [Exp. Eye Res. 212 (2021) 108765] 对 "皮质类固醇氟氢可的松在视网膜变性中的抗炎和神经保护特性 "的更正 [Exp. Eye Res. 212 (2021) 108765]。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-12-01 DOI: 10.1016/j.exer.2024.110092

Tanja Racic , Andrew Chang , Nilisha Fernando , Alice Brandli , Riccardo Natoli , Philip Penfold , Jan M. Provis , Matt Rutar

引用次数: 0

Comparison of rose bengal-green light scleral crosslinking in rabbit eyes using different infiltration protocols - An Ex Vivo study 不同浸润方案下兔眼玫瑰红-绿光巩膜交联的体外研究。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-26 DOI: 10.1016/j.exer.2024.110183

Rongrong Gao , Yuyan Huang , Aodong Chen , Qingqing Jiang , Shengnan Ding , Keith M. Meek , Qinmei Wang , A-Yong Yu , Jinhai Huang

Different concentrations and infiltration times of rose bengal (Rb) were assessed for their impact on penetration depth and crosslinking efficacy in rabbit sclera. Fresh rabbit eyes were used. Rb solution with concentrations of 0.1%–0.9% were applied for 5–30 min to infiltrate the sclera. The penetration depth of Rb was observed with confocal microscopy. After infiltration, the sclera was irradiated by green light for crosslinking. The sclera's biomechanical stiffness and the resistance to enzyme digestion post-treatment were evaluated. Histopathological analysis and transmission electron microscopy were performed to observe the morphology. As the infiltration time increased, the penetration depth and the fluorescence intensity of the Rb in sclera increased. After 32 h, 48.6% of the scleral tissue was undissolved in the 0.5% Rb-10min group, followed by the 0.1% Rb-20min group (13.8%) and 0.05% Rb-30min group (7.7%). At 8% strain, the Young's modulus of the 0.05%Rb-30min, the 0.1% Rb-20min and the 0.5% Rb-10min group were respectively 1.77, 2.45 and 3.19 times greater than that of the untreated group. There were no morphological differences between the experimental group and the untreated group. RG-SXL significantly increased the diameter of large collagen fibers in the middle and inner layers of the sclera. Ultimately, 0.5% Rb infiltration for 10 min achieves an appropriate infiltration depth and crosslinking effect, and may thus be a feasible schedule for scleral crosslinking.

研究了不同浓度和浸渍时间对红曲（Rb）在家兔巩膜中的渗透深度和交联效果的影响。使用新鲜的兔眼。应用浓度为0.1% ~ 0.9%的Rb溶液浸润巩膜5 ~ 30min。用共聚焦显微镜观察Rb的穿透深度。浸润后，用绿光照射巩膜进行交联。观察术后巩膜的生物力学刚度和酶消化阻力。采用组织病理学和透射电镜观察组织学形态。随着浸润时间的增加，Rb在巩膜内的穿透深度和荧光强度增加。32 h后，0.5% Rb-10min组巩膜组织未溶解率为48.6%，其次是0.1%Rb-20min组（13.8%）和0.05%Rb-30min组（7.7%）。在8%应变下，0.05%Rb-30min、0.1%Rb-20min和0.5%Rb-10min组的杨氏模量分别是未处理组的1.77、2.45和3.19倍。实验组与未治疗组之间无形态学差异。RG-SXL显著增加了巩膜中层和内层大胶原纤维的直径。最终，0.5% Rb浸润10min可获得合适的浸润深度和交联效果，可能是可行的巩膜交联时间。

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引用次数: 0

MiR-23a-3p targets PTEN as a novel anti-ferroptosis regulator in Fuchs endothelial corneal dystrophy MiR-23a-3p 靶向 PTEN，成为福氏内皮角膜营养不良症中一种新型的抗软化调节因子。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-22 DOI: 10.1016/j.exer.2024.110180

Miaomiao Chi , Yaning Zhao , Bowei Yuan , Zifeng Qiu , Rongmei Peng , Jing Hong

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of keratoplasty without drug treatment. Research indicated that oxidative stress and lipid peroxidation play significant roles in FECD. However, the underlying pathogenesis and potential treatment remain poorly understood. We analyzed the mRNA expression of FECD using the GEO database (GSE171830). Utilizing the STRING database and Cytoscape's MCODE plugin, we identified hub genes that intersect with ferroptosis-related genes listed in FerrDb. FECD cell and animal models were developed, induced by Ultraviolet A exposure. We assessed ferroptosis by measuring GPX4 expression and ROS fluorescence intensity. MiR-23a-3p was compared between FECD model and normal control, and the target gene PTEN was confirmed through Western blot and dual-luciferase reporter assays. Treatment with PTEN, PI3K, Akt, and mTOR inhibitors provided insights into the role of the PTEN/PI3K/Akt/mTOR pathway in FECD model. Corneal endothelium and cellular structure were evaluated before and after delivery of miR-23a-3p. Bioinformatics analysis of the GSE171830 revealed the top five hub genes: TP53, PTEN, EGFR, EPAS1, and IL-1β. Ferroptosis is the predominant mechanism in FECD pathogenesis, distinct from apoptosis and necrosis. We uncovered a protective role for miR-23a-3p in corneal endothelial cells (CEnCs), mitigating ferroptosis by downregulating PTEN. Corroborating this, bpV (a PTEN inhibitor) was found to attenuate ferroptosis in CEnCs. Mechanistically, PTEN inhibition coupled with sustained PI3K/Akt/mTOR pathway activation emerged as a protective strategy against ferroptosis in CEnCs. Ferroptosis contributes to FECD pathogenesis, and targeted delivery of miR-23a-3p as a ferroptosis inhibitor may offer therapeutic potential by regulating PTEN/PI3K/Akt/mTOR signaling.

福氏内皮性角膜营养不良症（FECD）是导致不经药物治疗而进行角膜移植的主要原因。研究表明，氧化应激和脂质过氧化在 FECD 中起着重要作用。然而，人们对其潜在的发病机制和治疗方法仍然知之甚少。我们利用 GEO 数据库（GSE171830）分析了 FECD 的 mRNA 表达。利用 STRING 数据库和 Cytoscape 的 MCODE 插件，我们确定了与 FerrDb 中列出的铁突变相关基因交叉的枢纽基因。我们建立了由紫外线 A 暴露诱导的 FECD 细胞和动物模型。我们通过测量 GPX4 的表达和 ROS 荧光强度来评估铁变态反应。MiR-23a-3p 在 FECD 模型和正常对照组之间进行了比较，靶基因 PTEN 通过 Western 印迹和双荧光素酶报告实验得到了确认。使用PTEN、PI3K、Akt和mTOR抑制剂治疗可深入了解PTEN/PI3K/Akt/mTOR通路在FECD模型中的作用。在施用 miR-23a-3p 之前和之后，对角膜内皮和细胞结构进行了评估。对 GSE171830 的生物信息学分析显示了前五大枢纽基因：TP53、PTEN、表皮生长因子受体、EPAS1 和 IL-1β。铁凋亡是 FECD 发病的主要机制，有别于细胞凋亡和坏死。我们发现了 miR-23a-3p 在角膜内皮细胞（CEnCs）中的保护作用，它通过下调 PTEN 来减轻铁突变。与此相印证的是，bpV（一种 PTEN 抑制剂）可减轻 CEnCs 中的铁突变。从机理上讲，PTEN抑制与PI3K/Akt/mTOR通路的持续激活相结合，成为了防止CEnCs铁突变的一种保护性策略。铁蜕变是 FECD 的发病机制之一，而作为铁蜕变抑制剂的 miR-23a-3p 靶向递送可通过调节 PTEN/PI3K/Akt/mTOR 信号传导提供治疗潜力。

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引用次数: 0

Role of vitamin A on the ocular surface 维生素 A 在眼表的作用

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-22 DOI: 10.1016/j.exer.2024.110179

Huanhuan Ge , Guohu Di , Peirong Song , Wenshuo Han , Peng Chen , Ye Wang

Vitamin A is an essential fat-soluble vitamin that cannot be endogenously synthesized by the human body. Retinoic acid (RA) is the biologically active form of vitamin A. Utilizing both nuclear and non-nuclear receptor-mediated pathways, RA plays a crucial role in regulating various biological processes, including apoptosis, differentiation, and anti-inflammatory properties within the cornea and conjunctiva. In addition, RA has been demonstrated to exert a significant influence on anti-tumor mechanisms. Disruption of RA signaling can result in corneal defects, anophthalmia, and microphthalmia. However, the beneficial effects of RA are only observed when it is administered at appropriate dosages, and higher doses have an adverse impact. Ocular abnormalities are often early indicators of a vitamin A deficiency. The lacrimal gland secretes vitamin A onto the ocular surface, where it is metabolized into RA via two sequential steps. This article provides a comprehensive overview of how vitamin A is transformed and transported from the intestine to the ocular surface, ultimately contributing to the maintenance of the normal physiological function of the ocular surface.

维生素 A 是一种必需的脂溶性维生素，人体无法从内源性合成。视黄酸（RA）是维生素 A 的生物活性形式。通过核受体和非核受体介导的途径，视黄酸在调节各种生物过程中发挥着至关重要的作用，包括角膜和结膜的凋亡、分化和抗炎特性。此外，RA 还被证明对抗肿瘤机制有重大影响。RA 信号的中断会导致角膜缺损、无眼症和小眼球症。然而，只有在适当剂量的情况下才能观察到 RA 的有益作用，剂量过大则会产生不利影响。眼部异常通常是维生素 A 缺乏症的早期征兆。泪腺将维生素 A 分泌到眼球表面，然后通过两个连续步骤代谢成 RA。本文全面概述了维生素 A 如何从肠道转化和运输到眼表，最终帮助维持眼表的正常生理功能。

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引用次数: 0

Electroacupuncture improves V1 cortex synaptic plasticity via the CREB/BDNF/TrkB pathway in juvenile rats with monocular deprivation 电针通过CREB/BDNF/TrkB途径改善单眼剥夺幼鼠V1皮层突触可塑性

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-21 DOI: 10.1016/j.exer.2024.110169

Lin Wang , Yangbin Ji , Haibo Mei , Xin Gong , Huachun Miao , Zaiman Zhu , Jian Ding

The present study aims to investigate the impact of the CREB/BDNF/TrkB signaling pathway on synaptic plasticity in the visual cortex of juvenile amblyopic rats that have undergone monocular deprivation (MD). This study involved sixty 2-week-old Sprague-Dawley (SD) juvenile rats, which were not specified by gender. In the first part of the study, 24 rats were randomized into control and MD groups; In the second part, 36 rats were randomized into MD, electroacupuncture (EA) and EA + CREB antagonist (666–15) groups. The MD model was established using the monocular suture method. 14 d after monocular suture, EA treatment was started for 30 min daily, at a frequency of 2–10 Hz and an intensity of 1 mA, for 2 weeks. According to the results from part 1, the P100 wave latency in the MD group was prolonged, and its amplitude was lower compared to the control group. Additionally, the neuron number in the V1 cortex of the MD group decreased, along with reduced expression levels of CREB, BDNF, p-TrkB, and the key plasticity proteins PSD95 and SYN. In part 2, EA treatment significantly increased the electrophysiological activity of neurons in V1 cortex, shortened the latency of P100 peaks to varying degrees, increased the amplitude significantly, and restored the morphology and structure of neurons to normal levels; The expression of synaptic proteins PSD95 and SYN, as well as the expression of signaling molecules CREB, BDNF, and p-TrkB proteins were increased. However, the effects of EA were reversed when the specific CREB inhibitor 666–16 was administered. These data indicate that EA enhances the expression of V1 cortical synaptic plasticity-related proteins by regulating the expression of CREB/BDNF/TrkB signaling pathway, thereby enhancing V1 neural synaptic plasticity and reversing the effects of MD on visual acuity.

本研究旨在探讨CREB/BDNF/TrkB信号通路对接受单眼剥夺（MD）的幼年弱视大鼠视皮层突触可塑性的影响。本研究涉及60只2周大的Sprague-Dawley（SD）幼年大鼠，这些大鼠没有性别区分。在第一部分研究中，24只大鼠被随机分为对照组和MD组；在第二部分研究中，36只大鼠被随机分为MD组、电针（EA）组和EA+CREB拮抗剂（666-15）组。MD 模型采用单眼缝合法。单眼缝合 14 天后开始电针治疗，每天 30 分钟，频率为 2-10 Hz，强度为 1 mA，持续 2 周。根据第一部分的结果，与对照组相比，MD 组的 P100 波潜伏期延长，波幅降低。此外，MD组V1皮层的神经元数量减少，CREB、BDNF、p-TrkB、关键可塑性蛋白PSD95和SYN的表达水平降低。在第二部分中，EA治疗明显提高了V1皮层神经元的电生理活性，不同程度地缩短了P100峰的潜伏期，振幅明显增大，神经元的形态和结构恢复到正常水平；突触蛋白PSD95和SYN的表达以及信号分子CREB、BDNF和p-TrkB蛋白的表达均有所增加。然而，在使用特异性 CREB 抑制剂 666-16 后，EA 的作用被逆转。这些数据表明，EA通过调节CREB/BDNF/TrkB信号通路的表达，增强了V1皮层突触可塑性相关蛋白的表达，从而增强了V1神经突触可塑性，逆转了MD对视敏度的影响。

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引用次数: 0

A novel three-dimensional method for detailed analysis of RGC central projections under acute ocular hypertension 详细分析急性眼压过高症下 RGC 中央投影的新型三维方法

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-20 DOI: 10.1016/j.exer.2024.110157

Wenhan Lu , Yu Wang , Wei Hu , Xinyi Lin , Xiaoyu Tong , Yi Tian , Yuning Chen , Yicong Wang , Yan Xiao , Hongfang Yang , Yi Feng , Xinghuai Sun

Normal perception of visual information relies not only on the quantity and quality of retinal ganglion cells (RGCs), but also on the integrity of the visual pathway, within which RGC central projection predominates. However, the exact changes of RGC central projection under particular pathological conditions remain to be elucidated. Here, we report a whole-brain clearing method modified from iDISCO for 3D visualization of RGC central projection. The CTB-labeled RGC central projection was visualized three-dimensionally with minimized both fluorescence quenching and the time taken. For observation of RGC axonal degeneration pattern under pathological conditions, we took acute ocular hypertension (AOH) as an example. Mice were intracamerally irrigated, and fluorescent signal in brain subregions where RGC axons projected to were quantified. The novel methodology is well-applied for rapid clearing and observation of RGC central projection in C57BL/6J, showing damaged RGC central projection on the AOH side and the most statistically significant degeneration in the superior colliculi (SC). Detailed analysis also revealed a distinct injury pattern among lateral geniculate nuclei (LGN) subregions, with the parvocellular part of the pregeniculate nuclei (PrGPC) being more vulnerable compared with the magnocellular part (PrGMC). The intracranial retrograde labeling of RGC subgroups based on brain damage variation showed PrGPC-projecting RGCs (Plgn RGC) being smaller than PrGMC-projecting RGCs (Mlgn RGC) in size and less in number, yet more vulnerable in terms of degeneration under AOH. Our data revealed the methodology for visualizing selective neuronal vulnerability under AOH, and in the meantime provided novel approach for future mechanisms exploration regarding RGC degeneration.

正常的视觉信息感知不仅依赖于视网膜神经节细胞（RGC）的数量和质量，还依赖于视觉通路的完整性，而在视觉通路中，RGC的中心投射占主导地位。然而，RGC中心投射在特定病理条件下的确切变化仍有待阐明。在此，我们报告了一种改良自 iDISCO 的全脑清除方法，用于 RGC 中央投射的三维可视化。在三维观察CTB标记的RGC中心投影时，荧光淬灭和所需时间都降到了最低。为了观察病理条件下RGC轴突变性的模式，我们以急性眼压升高（AOH）为例。对小鼠进行组内灌洗，并对RGC轴突投射到的脑亚区域的荧光信号进行量化。这种新方法适用于快速清除和观察C57BL/6J的RGC中心投射，结果显示AOH一侧的RGC中心投射受损，而上丘脑（SC）的退化在统计学上最为显著。详细分析还显示，外侧膝状核（LGN）亚区域之间存在不同的损伤模式，与大细胞部分（PrGMC）相比，前膝状核的旁细胞部分（PrGPC）更容易受到损伤。根据脑损伤变化对RGC亚群进行的颅内逆行标记显示，PrGPC投射的RGC（Plgn RGC）比PrGMC投射的RGC（Mlgn RGC）体积更小，数量更少，但在AOH作用下更容易发生变性。我们的数据揭示了AOH条件下神经元选择性脆弱性的可视化方法，同时也为未来探索RGC变性的机制提供了新方法。

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引用次数: 0

TGF-β1-induced apoptosis in retinal endothelial cells is implicated in retinal vein occlusion TGF-β1诱导的视网膜内皮细胞凋亡与视网膜静脉闭塞有关。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-20 DOI: 10.1016/j.exer.2024.110168

Fengyu Chen , Qi Wang , Yujin Li , Fen Li , Lin Zhang , Xuezhong Gu

Retinal vein occlusion (RVO) is a serious vascular condition that impairs vision due to retinal endothelial cell injury and apoptosis. This study aimed to identify key molecular pathways and therapeutic targets involved in RVO pathogenesis. Transcriptomic analysis of the retinal tissues from a mouse RVO model was performed to identify differentially expressed genes and co-expression modules associated with RVO. Protein-protein interaction network analysis pinpointed putative hub genes. In vitro experiments using human retinal microvascular endothelial cells (HRMECs) validated the involvement of identified genes/pathways in apoptosis induced by oxygen-glucose deprivation/reperfusion (OGD/R) and UV exposure. Gene expression was assessed by RT-qPCR, while protein levels and phosphorylation were measured by ELISA and Western blotting. Apoptosis was evaluated using flow cytometry, and reactive oxygen species (ROS) were quantified using a fluorescence-based assay. A total of 392 genes were identified as putatively involved in RVO-associated apoptosis, enriched in MAPK, TGF-β and other signaling pathways. Among top hub genes, TGF-β1 emerged as a central regulator whose expression and signaling (pSmad2/3) increased after OGD/R induction or UV exposure in HRMECs. TGF-β1-induced HRMEC apoptosis was mediated by p38/JNK activation. Similar effects were observed for OGD/R and UV triggering TGF-β1-dependent p38/JNK signaling and apoptosis. Pharmacological inhibition of TGF-β signaling attenuated the apoptotic and oxidative stress responses induced by OGD/R and UV exposure. This study elucidates TGF-β1 as a crucial mediator of retinal endothelial injury through p38/JNK-induced apoptosis, suggesting TGF-β1 pathway inhibition as a potential therapeutic strategy for RVO.

视网膜静脉闭塞（RVO）是一种严重的血管疾病，由于视网膜内皮细胞损伤和凋亡而损害视力。本研究旨在确定参与 RVO 发病机制的关键分子通路和治疗靶点。研究人员对小鼠 RVO 模型的视网膜组织进行了转录组分析，以确定与 RVO 相关的差异表达基因和共表达模块。蛋白质-蛋白质相互作用网络分析确定了潜在的枢纽基因。使用人视网膜微血管内皮细胞（HRMECs）进行的体外实验验证了已确定的基因/通路参与氧-葡萄糖剥夺/再灌注（OGD/R）和紫外线照射诱导的细胞凋亡。基因表达通过 RT-qPCR 进行评估，蛋白质水平和磷酸化则通过 ELISA 和 Western 印迹进行测量。采用流式细胞术评估细胞凋亡，并采用荧光检测法量化活性氧（ROS）。共鉴定出392个基因可能参与了RVO相关的细胞凋亡，这些基因富集在MAPK、TGF-β和其他信号通路中。在最重要的枢纽基因中，TGF-β1是一个中心调控因子，其表达和信号转导（pSmad2/3）在OGD/R诱导或紫外线暴露后在HRMECs中增加。TGF-β1 诱导的 HRMEC 细胞凋亡是由 p38/JNK 激活介导的。OGD/R 和紫外线触发 TGF-β1 依赖性 p38/JNK 信号转导和细胞凋亡也有类似的效果。药物抑制 TGF-β 信号传导可减轻 OGD/R 和紫外线照射诱导的细胞凋亡和氧化应激反应。这项研究阐明了TGF-β1是通过p38/JNK诱导细胞凋亡导致视网膜内皮损伤的关键介质，建议将TGF-β1通路抑制作为RVO的一种潜在治疗策略。

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引用次数: 0

Tracking astrocyte polarization in the retina in retinopathy of prematurity 跟踪早产儿视网膜病变中视网膜星形胶质细胞的极化。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-20 DOI: 10.1016/j.exer.2024.110170

Xiaoxiao Feng, Liwei Zhang, Kangwei Jiao, Yunqing Li, Min Wu, Yu Xie, Libo Xiao

Astrocyte patterns affect the normal development of the retinal vascular network in retinopathy of prematurity (ROP), which is associated with VEGF secretion. However, the role of the astrocyte polarization in this process remains unknown. Therefore, this study aimed to track the status of A1/A2 reactive astrocytes in the retinas of the oxygen-induced retinopathy (OIR) model and their association with VEGF expression. The C57BL/6 mouse OIR model was constructed to characterize the pathological changes in ROP. Immunofluorescence of iB4 and GFAP staining was performed to observe changes in the vascular network and astrocyte pattern at different time points (P0, P7, P12, P17, and P21). C3-labeled A1 reactive and S100A10-labeled A2 reactive astrocytes and VEGF were also observed. The pattern of GFAP-labeled astrocyte was altered concurrently with the iB4-positive vascular network during OIR. Astrocyte activity was significantly weakened at P12 and significantly enhanced at P17. Notably, the number of C3-labeled A1 reactive astrocytes was significantly increased at P12, decreased at P17, and normalized at P21 in OIR models. S100A10-labeled A2 reactive astrocytes were significantly increased at P17 but did not change significantly at P12 or P17. VEGF levels were decreased at P7-P12 and increased at P12-P17. The expression pattern of VEGF was opposite to that of C3-labeled A1 reactive astrocytes and identical to that of S100A10-labeled A2 reactive astrocytes. In conclusion, the astrocyte pattern and vascular network exhibited similar changes during the OIR process, and the periods of vaso-obliteration and neo-vascularization display an abnormal activation in A1-and A2-reactive astrocytes.

星形胶质细胞模式会影响早产儿视网膜病变（ROP）视网膜血管网络的正常发育，这与血管内皮生长因子的分泌有关。然而，星形胶质细胞极化在这一过程中的作用仍然未知。因此，本研究旨在追踪氧诱导视网膜病变（OIR）模型视网膜中 A1/A2 反应性星形胶质细胞的状态及其与血管内皮生长因子表达的关系。构建了 C57BL/6 小鼠 OIR 模型来描述 ROP 的病理变化。对 iB4 和 GFAP 进行免疫荧光染色，以观察不同时间点（P0、P7、P12、P17 和 P21）血管网络和星形胶质细胞模式的变化。此外，还观察了 C3 标记的 A1 反应性星形胶质细胞和 S100A10 标记的 A2 反应性星形胶质细胞以及血管内皮生长因子。在 OIR 期间，GFAP 标记的星形胶质细胞模式与 iB4 阳性的血管网络同时发生了改变。星形胶质细胞的活性在 P12 时明显减弱，在 P17 时明显增强。值得注意的是，在 OIR 模型中，C3 标记的 A1 反应性星形胶质细胞的数量在 P12 时明显增加，在 P17 时减少，在 P21 时恢复正常。S100A10标记的A2反应性星形胶质细胞在P17时明显增加，但在P12或P17时没有明显变化。VEGF 水平在 P7-P12 期下降，在 P12-P17 期升高。VEGF 的表达模式与 C3 标记的 A1 反应性星形胶质细胞相反，而与 S100A10 标记的 A2 反应性星形胶质细胞相同。总之，在 OIR 过程中，星形胶质细胞模式和血管网络表现出相似的变化，血管闭塞期和血管新生期显示了 A1 和 A2 反应性星形胶质细胞的异常激活。

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引用次数: 0

Choroidal macrophages in homeostasis, aging and age-related macular degeneration 脉络膜巨噬细胞在平衡、衰老和老年性黄斑变性中的作用。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2024-11-20 DOI: 10.1016/j.exer.2024.110159

Adnan H. Khan , Kelly Mulfaul

With increasing age, the optimal functioning of the choroid is essential for efficient removal of waste products formed from photoreceptor renewal. A decline in regulatory elements of the immune system, termed immunosenescence, and the failure of para-inflammation to restore tissue homeostasis can result in the progression of healthy aging to sight-threatening inflammation of the choroid. Macrophages are uniquely situated between the innate and adaptive immune systems, with a high capacity for phagocytosis, recognition of complement components, as well as antigen presentation. In this review, we provide an overview of macrophages and their properties in the healthy choroid and cover the impact of aging, immunosenescence and inflammaging on the function of choroidal macrophages. We will discuss the impact of age on macrophage phenotype and behaviour in the pathophysiology of age-related macular degeneration.

随着年龄的增长，脉络膜的最佳功能对于有效清除感光细胞更新所产生的废物至关重要。免疫系统调节元素的衰退（称为免疫衰老）以及副炎症无法恢复组织平衡，会导致脉络膜从健康衰老发展为危及视力的炎症。巨噬细胞位于先天性免疫系统和适应性免疫系统之间，具有很强的吞噬、识别补体成分和抗原呈递能力。在这篇综述中，我们将概述巨噬细胞及其在健康脉络膜中的特性，并介绍衰老、免疫衰老和炎症对脉络膜巨噬细胞功能的影响。我们将讨论年龄对巨噬细胞表型和行为在老年性黄斑变性病理生理学中的影响。

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