New findings on pathogenetic mechanisms in the development of age-related macular degeneration

• Published in: Vestnik oftal'mologii Vol. 138; no. 2; p. 120
• Main Authors: 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
• Format: Journal Article
• Language: English; Russian
• Published: Russia (Federation) 2022
• Subjects: Choroid - pathology; Choroidal Neovascularization - metabolism; Humans; Inflammation; Macular Degeneration - etiology; Macular Degeneration - metabolism; Retinal Pigment Epithelium - pathology; Vascular Endothelial Growth Factor A - metabolism; retinal pigment epithelium; secretory phenotype of aging; age-related macular degeneration; vascular endothelial growth factor
• ISSN: 0042-465X
• 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.