Age-related macular degeneration (AMD) involves progressive degeneration of the central retina, termed the macula, which provides high-acuity vision needed to recognize faces, drive, etc. AMD is the leading cause of blindness in the aging population. A plethora of paradigm-shifting perspectives regarding AMD’s multifaceted pathophysiology is emerging. This review will endeavor to gather novel insights and attempts to identify translational implications and new areas of research. The concept of aberrant inflammation being at the center of age-related diseases, particularly AMD, is being received with increasing credence. Retinal angiogenesis, at the forefront of the neovascular complications of AMD (nAMD), is now being understood as an imbalance between trophic factors released by retinal cells secretome. Additionally, mechanisms involving oxidative stress and inflammatory complement pathways have also been identified, along with genetic and other risk factors that play a key role in AMD’s onset and progression. Associations have been drawn with AMD and other degenerative deposit diseases such as Alzheimer’s disease, atherosclerosis, and glomerulonephritis, which are providing further insight into this maculopathy.
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