Institut de Chimie de Nice UMR 7272, Université Côte d'Azur, CNRS, 06108 Nice, France.
CiTCoM, UMR 8038 CNRS, Faculté de Pharmacie, Université de Paris Cité, 4, Avenue de l'Observatoire, 75006 Paris, France.
Molecules. 2022 Aug 10;27(16):5089. doi: 10.3390/molecules27165089.
Age-related macular degeneration (AMD) was described for the first time in the 1840s and is currently the leading cause of blindness for patients over 65 years in Western Countries. This disease impacts the eye's posterior segment and damages the macula, a retina section with high levels of photoreceptor cells and responsible for the central vision. Advanced AMD stages are divided into the atrophic (dry) form and the exudative (wet) form. Atrophic AMD consists in the progressive atrophy of the retinal pigment epithelium (RPE) and the outer retinal layers, while the exudative form results in the anarchic invasion by choroidal neo-vessels of RPE and the retina. This invasion is responsible for fluid accumulation in the intra/sub-retinal spaces and for a progressive dysfunction of the photoreceptor cells. To date, the few existing anti-AMD therapies may only delay or suspend its progression, without providing cure to patients. However, in the last decade, an outstanding number of research programs targeting its different aspects have been initiated by academics and industrials. This review aims to bring together the most recent advances and insights into the mechanisms underlying AMD pathogenicity and disease evolution, and to highlight the current hypotheses towards the development of new treatments, i.e., symptomatic vs. curative. The therapeutic options and drugs proposed to tackle these mechanisms are analyzed and critically compared. A particular emphasis has been given to the therapeutic agents currently tested in clinical trials, whose results have been carefully collected and discussed whenever possible.
年龄相关性黄斑变性(AMD)于 19 世纪 40 年代首次被描述,目前是西方国家 65 岁以上患者失明的主要原因。这种疾病影响眼睛的后段,损害黄斑,黄斑是视网膜中具有高浓度光感受器细胞的部分,负责中央视力。晚期 AMD 分为萎缩性(干性)和渗出性(湿性)两种形式。萎缩性 AMD 表现为视网膜色素上皮(RPE)和外视网膜层的进行性萎缩,而渗出性形式则导致脉络膜新生血管对 RPE 和视网膜的无序侵袭。这种侵袭导致视网膜内/下空间的液体积累,并使光感受器细胞逐渐功能失调。迄今为止,为数不多的现有的 AMD 治疗方法可能只能延缓或阻止其进展,而不能为患者提供治愈方法。然而,在过去十年中,学术界和工业界已经启动了许多针对 AMD 不同方面的研究计划。本综述旨在汇集关于 AMD 发病机制和疾病演变的最新进展和见解,并强调目前针对新治疗方法的假说,即对症治疗与根治治疗。对用于解决这些机制的治疗选择和药物进行了分析和批判性比较。特别强调了目前正在临床试验中测试的治疗剂,只要有可能,就仔细收集和讨论了这些治疗剂的结果。