年龄相关性黄斑变性（age-related macular degeneration, AMD）是一种与氧化应激及多基因调控异常密切相关的视网膜黄斑区域进行性退化性疾病。由于黄斑区缺乏血管，因此对氧气的高度依赖使其特别容易受到氧化应激的影响。氧化应激反应影响视网膜色素上皮细胞（retinal pigment epithelium, RPE）功能，导致RPE细胞代谢异常、RPE细胞凋亡与损伤；影响脉络膜血管功能，表现为新生血管异常和血管内皮细胞功能障碍；过度激活补体系统，使炎症细胞浸润与炎症因子释放引发炎症；这三者构成了AMD的发病机制之一。文章列举了抗氧化酶基因家族（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶）、炎症相关基因（补体系统相关基因和细胞因子相关基因）和其他相关基因（血管内皮生长因子、血红素加氧酶-1、载脂蛋白E、铁死亡相关基因、年龄相关性黄斑病变易感因子2基因）的异常表达与AMD产生的关联性，并阐述了基因编辑技术纠正氧化应激相关基因缺陷和基于氧化应激基因靶点的药物治疗手段，以期为AMD的防治提供思路。

Age-related macular degeneration (AMD) is a retinal degenerative disease closely associated with oxidative stress and dysregulation of polygenic mechanisms. Due to the absence of blood vessels in the macular region, its high dependence on oxygen renders it particularly susceptible to oxidative stress. Oxidative stress impairs the function of retinal pigment epithelium (RPE) cells, leading to metabolic dysregulation, apoptosis, and cellular damage. It also disrupts choroidal vascular function, characterized by abnormal neovascularization and endothelial dysfunction. Moreover, excessive activation of the complement system promotes inflammatory cell infiltration and the release of pro-inflammatory cytokines. Collectively, these processes constitute one of the key pathogenic mechanisms underlying AMD. This paper highlights the pathogenic associations between AMD progression and dysregulated expression in antioxidant enzyme genes (e.g., superoxide dismutase, catalase, glutathione peroxidase), inflammation-related genes (e.g., complement and cytokine-related genes), and other relevant genes (e.g., vascular endothelial growth factor, heme oxygenase-1, apolipoprotein E, ferroptosis-related genes, age-related maculopathy susceptibility 2 gene). Potential therapeutic strategies, including gene editing to correct oxidative stress-related genetic defects and pharmacological interventions targeting oxidative stress-associated genes, are also elaborated, aiming to provide new insights into AMD prevention and treatment.

目的：通过在人小梁网细胞(human trabecular meshwork cell，HTMC)中过表达沉默信息调节因子2相关酶1(silent information regulator 1，SIRT1)，探讨SIRT1对氧化应激下HTMC功能的影响。方法：将SIRT1过表达慢病毒和GFP阴性对照慢病毒按照最佳(multiplicity of infection，MOI)分别转染入HTMC，并用实时定量PCR法对SIRT1是否在细胞中过表达进行验证。实验分为以下4组：正常组、H₂O₂组、H₂O₂+Lv-SIRT1-OE(过表达)组、H₂O₂+Lv-GFP组，分别采用Transwell法和CCK8法检测氧化应激下HTMC的迁移能力和活性。两组间比较采用独立样本t检验。结果：在正常组、H₂O₂组、H₂O₂+Lv-SIRT1-OE组、H₂O₂+Lv-GFP组这4组中，Transwel l实验结果分别为436±73、254±25、510±51、327±46，H₂O₂+Lv-SIRT1-OE组分别与H₂O₂组和H₂O₂+Lv-GFP组差异均有统计学意义(P<0.01)。CCK8法结果显示，H₂O₂+Lv-SIRT1-OE组分别与H₂O₂组和H₂O₂+Lv-GFP组相比差异均有统计学意义(P<0.01)。H₂O₂+Lv-SIRT1-OE组分别与H₂O₂组和阴性对照组(H₂O₂+Lv-GFP)相比，Bax表达水平明显下降，Bcl-2表达水平明显提高，差异均有统计学意义(P<0.01)。ROS活性氧测定显示H₂O₂+Lv-SIRT1-OE组比H₂O₂组的细胞活性氧水平显著降低(P<0.05)。结论：在HTMC中过表达SIRT1能有效降低氧化应激对HTMC迁移能力和活性的影响，从而对HTMC起到一定的保护作用，为后续研究SIRT1保护氧化应激下HTMC的调控机制打下基础。

Objective: To explore the effect of Silent Information Regulator 1 (SIRT1) on cell function of human trabecular meshwork cell (HTMC) under oxidative stress by overexpressing SIRT1 in HTMC. Methods: This is an experiment research. HTMCs were transfected with SIRT1-ovexpressed lentivirus and GFP-negative control lentivirus (Lv-GFP) at the optimal multiplicity of infection (MOI). Real-time quantitative PCR was used to verify whether SIRT1 was overexpressed in HTMC. The following experiments were divided into four groups: normal control group, H₂O₂ group,H₂O₂+Lv-SIRT1-OE group, H₂O₂+Lv-GFP group. Cell migration was detected by transwell assay. Cell viability was detected by CCK8 assay. Student’s t-test was used for two groups. P<0.05 was set as statistical signifificance. Results: The number of migration per well of normal control group, H₂O₂ group, H₂O₂+Lv-SIRT1-OE group, H₂O₂+Lv-GFP group were 436±73,254±25, 510±51, 327±46, respectively. Compared with H₂O₂ group and H₂O₂+Lv-GFP group, transwell assay demonstrated that the number of migrations per well of H₂O₂+Lv-SIRT1-OE group significantly increased (P<0.01). Likewise, CCK8 assay indicated that cell viability of H₂O₂+Lv-SIRT1-OE group was higher than both of H₂O₂ group and H₂O₂+Lv-GFP group (P<0.01). Compared with H₂O₂+Lv-SIRT1-OE group and negative control group (H2O2+Lv-GFP), the expression level of Bax decreased significantly,and the expression level of Bcl-2 increased significantly (P<0.01). ROS assay showed that the ROS level in H₂O₂+Lv-SIRT1-OE group was significantly lower than that in H2O2 group (P<0.05). Conclusion:SIRT1 overexpressed in HTMC can effectively reduce the effect of oxidative stress on migration ability and proliferation activity of HTMC, which lays a foundation for further study on the regulatory mechanism of SIRT1 protecting HTMC under oxidative stress.