Mitochondria are central to retinal cell function and survival. There is increasing evidence to support an association between mitochondrial dysfunction and a number of retinal pathologies including age-related macular degeneration (AMD), diabetic retinopathy and glaucoma. The past decade has highlighted mitochondrial genomic instability as an important factor in mitochondrial impairment culminating in age-related changes and age-related pathology. This represents a combination of the susceptibility of mitochondrial DNA (mtDNA) to oxidative damage and a limited base excision repair pathway. This random cumulative mtDNA damage leads to cellular heteroplasmy and, if the damage affects a sufficient proportion of mitochondria within a given cell, results in loss of cell function and greater susceptibility to stress. mtDNA damage is increased in the neural retina and RPE with ageing and appears to be greatest in AMD. It thus appears that the mitochondrial genome is a weak link in the antioxidant defenses of retinal cells and that deficits in mitochondrial DNA (mtDNA) repair pathways are important contributors to the pathogenesis of retinal degeneration. Specifically targeting mitochondria with pharmacological agents able to protect against oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of retinal degenerations such as AMD.

中文翻译：

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线粒体DNA损伤及其在视网膜变性中的潜在作用。

线粒体是视网膜细胞功能和存活的中心。越来越多的证据支持线粒体功能障碍与许多视网膜病变之间的关联，包括年龄相关性黄斑变性（AMD），糖尿病性视网膜病变和青光眼。在过去的十年中，线粒体基因组不稳定是线粒体损伤的重要因素，最终导致年龄相关的变化和年龄相关的病理。这代表了线粒体DNA（mtDNA）对氧化损伤的敏感性和有限的碱基切除修复途径的结合。这种随机累积的mtDNA损伤会导致细胞异质性，如果损伤影响给定细胞内足够比例的线粒体，则会导致细胞功能丧失和对压力的敏感性更高。随着年龄的增长，mtDNA损伤在神经视网膜和RPE中增加，在AMD中似乎最大。因此，似乎线粒体基因组是视网膜细胞抗氧化剂防御中的薄弱环节，线粒体DNA（mtDNA）修复途径的缺陷是视网膜变性发病机理的重要原因。用能够防止氧化应激或促进mtDNA损伤修复的药理剂特异性靶向线粒体可能为视网膜变性（例如AMD）的治疗提供潜在的替代方法。因此，似乎线粒体基因组是视网膜细胞抗氧化剂防御中的薄弱环节，线粒体DNA（mtDNA）修复途径的缺陷是视网膜变性发病机理的重要原因。用能够防止氧化应激或促进mtDNA损伤修复的药理剂特异性靶向线粒体可能为视网膜变性（例如AMD）的治疗提供潜在的替代方法。因此，似乎线粒体基因组是视网膜细胞抗氧化剂防御中的薄弱环节，线粒体DNA（mtDNA）修复途径的缺陷是视网膜变性发病机理的重要原因。用能够防止氧化应激或促进mtDNA损伤修复的药理剂特异性靶向线粒体可能为视网膜变性（例如AMD）的治疗提供潜在的替代方法。