Fursova A Zh, Derbeneva A S, Vasilyeva M S, Niculich I F, Tarasov M S, Gamza Yu A, Chubar N V, Gusarevich O G, Dmitrieva E I, Kozhevnikova O S, Kolosova N G, Elizarova A A
Novosibirsk State Medical University, Novosibirsk, Russia.
Novosibirsk State Regional Clinical Hospital, Novosibirsk, Russia.
Vestn Oftalmol. 2022;138(2):120-130. doi: 10.17116/oftalma2022138021120.
Age-related macular degeneration (AMD) is a complex multifactorial disease that occurs due to disfunction and degeneration of retinal pigment epithelium (RPE) and choriocapillaris, as well as death of photoreceptors. The exact pathogenetic mechanism remains uncertain. The aging process is the main and the clearest risk factor of AMD. In the development of this condition, a special role belongs to the secretory phenotype of aging spreading from one cell to another and mediated by the secretion and release of growth factors, cytokines, chemokines, proteases, and other molecules. Another major contributor is oxidative stress caused by violations in the recirculation of vitamin A in the vision cycle and accompanied by accumulation of lipofuscin, which mediates the formation of iron-based oxidants that are toxic for mitochondria. Furthermore, prolonged oxidative stress and constant light exposure induce the development of inflammation in the retina. Accumulation of metabolic products and cellular defects with age can induce an inflammatory reaction that amplifies the damage. The inflammatory processes including innate immune response, activation of microglia and parainflammation that occur locally in the vascular membrane, pigment epithelium and neuroretina are very significant contributors to the age-related changes, their progression, and the development of advanced stages of AMD. Various growth factors play a special role in the development of choroidal neovascularization (CNV). Vascular endothelial growth factor A (VEGF-A) has traditionally been considered the main factor of neoangiogenesis and, consequently, the main therapeutic target, but in recent years various studies have determined the role of other factors - VEGF-B, C, D, PGF, Gal-1, angiopoietins. This article describes the main underlying mechanisms in the development of choroidal neovascularization including retinal aging, impaired metabolic activity, mitochondrial dysfunction, inflammatory reactions and genetic variations, as well as the role of various growth factors.
年龄相关性黄斑变性（AMD）是一种复杂的多因素疾病，其发生是由于视网膜色素上皮（RPE）和脉络膜毛细血管功能障碍与变性，以及光感受器死亡。确切的发病机制仍不确定。衰老过程是AMD的主要且最明显的危险因素。在这种疾病的发展过程中，衰老的分泌表型从一个细胞扩散到另一个细胞，并由生长因子、细胞因子、趋化因子、蛋白酶和其他分子的分泌与释放介导，发挥着特殊作用。另一个主要因素是视觉循环中维生素A再循环紊乱引起的氧化应激，并伴有脂褐素积累，脂褐素介导对线粒体有毒的铁基氧化剂的形成。此外，长期的氧化应激和持续的光照会诱发视网膜炎症。随着年龄增长，代谢产物的积累和细胞缺陷会引发炎症反应，加剧损伤。包括先天免疫反应、小胶质细胞激活和副炎症在内的炎症过程在血管膜、色素上皮和神经视网膜局部发生，是与年龄相关变化、其进展以及AMD晚期发展的非常重要的因素。各种生长因子在脉络膜新生血管（CNV）的发展中发挥特殊作用。血管内皮生长因子A（VEGF - A）传统上被认为是新生血管形成的主要因素，因此也是主要治疗靶点，但近年来各种研究确定了其他因子——VEGF - B、C、D、PGF、Gal - 1、血管生成素的作用。本文描述了脉络膜新生血管形成发展中的主要潜在机制，包括视网膜衰老、代谢活性受损、线粒体功能障碍、炎症反应和基因变异，以及各种生长因子的作用。
