THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET.
THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET.
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DOI：
10.1097/iae.0000000000001392
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Brittain C
中科院分区：
文献类型：
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作者：
Boyer DS;Schmidt-Erfurth U;van Lookeren Campagne M;Henry EC;Brittain C
地理萎缩是年龄相关性黄斑变性的一种晚期形式，可显着影响视觉功能，但尚无批准的治疗方法。本综述重点关注地理萎缩的病理生理学，特别是补体级联失调的作用和针对补体级联的新兴疗法。地理萎缩 (GA) 是一种严重的、威胁视力的年龄相关性黄斑变性 (AMD)，影响全球约 500 万人。迄今为止，尚无批准的 GA 治疗方法；然而，有一些正在进行临床试验。本综述重点关注 GA 的病理生理学，特别是补体级联失调的作用以及针对补体级联的新兴疗法。在 PubMed 上检索 GA、补体级联在年龄相关性黄斑变性中的主要文献。 ClinicalTrials.gov 搜索了 GA 的自然史研究以及针对 GA 补体级联的药物的临床试验。衰老、环境压力和其他因素对视网膜的累积损伤会通过多种途径引发炎症，包括补体级联反应。当这些途径中的调节成分受到损害时，就像补体级联中的几个与 GA 相关的遗传危险因素一样，慢性炎症最终会导致 GA 的视网膜细胞死亡特征。补体抑制已被确定为治疗干预的关键候选药物，针对补体途径的药物目前正在进行临床试验。补体级联是 GA 治疗的战略目标。进一步的研究，包括自然史和遗传学方面的研究，对于扩大对 GA 病理生理学的理解和确定有效的治疗靶点至关重要。
Geographic atrophy is an advanced form of age-related macular degeneration that can significantly impact visual function, but has no approved treatment. This review focuses on the pathophysiology of geographic atrophy, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade. Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade. Primary literature search on PubMed for GA, complement cascade in age-related macular degeneration. ClinicalTrials.gov was searched for natural history studies in GA and clinical trials of drugs targeting the complement cascade for GA. Cumulative damage to the retina by aging, environmental stress, and other factors triggers inflammation via multiple pathways, including the complement cascade. When regulatory components in these pathways are compromised, as with several GA-linked genetic risk factors in the complement cascade, chronic inflammation can ultimately lead to the retinal cell death characteristic of GA. Complement inhibition has been identified as a key candidate for therapeutic intervention, and drugs targeting the complement pathway are currently in clinical trials. The complement cascade is a strategic target for GA therapy. Further research, including on natural history and genetics, is crucial to expand the understanding of GA pathophysiology and identify effective therapeutic targets.