Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy.
Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy.
Int J Mol Sci. 2022 Oct 31;23(21):13280. doi: 10.3390/ijms232113280.
Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.
年龄相关性黄斑变性（AMD）是一种复杂的多因素疾病，由环境和遗传因素的相互作用引起。遗传多态性与 AMD 之间不断发现的关联，使得遗传因素在其发病机制中起着关键作用。有鉴于此，已经开发出基因检测和多基因评分来预测发病风险和对治疗的反应。然而，这些方法尚未得到验证。此外，临床试验没有证据表明确定个体的遗传结构可以改善治疗效果。在这篇全面的综述中，我们总结了与 AMD 发展相关的主要发病途径的多态性，以确定其中哪些构成了潜在的治疗靶点。由于补体过度激活起着重要作用，靶向补体蛋白的调节似乎是一种很有前途的治疗方法。本文总结了目前正在进行临床试验的补体调节分子，重点介绍了处于试验后期的分子。基因治疗是一种有潜力的一次性创新治疗方法，在视网膜疾病领域的相关性正在迅速发展。我们描述了目前正在进行临床试验的补体抑制剂和抗 VEGF 基因治疗的最新进展。
