Recent research has shed light on the genetic and omics-based factors that may significantly impact the retinal pigment epithelium and the mechanisms underlying age-related macular degeneration.

“Aging is recognized as the highest risk factor for age-related macular degeneration (AMD), the leading cause of adult visual impairment and blindness in the Northern Hemisphere, which is directly linked to specific pathological changes of the retinal pigmented epithelium (RPE) located in the macula,” a recent editorial in Aging described. Among the effects on central vision caused by AMD are impacts on every day functional activities, from reading and driving to “discerning details of pictures, faces, shapes and colors.”

The RPE is a highly specialized and metabolically active cellular layer that supports retinal health but lacks regenerative capacity. With age, it undergoes notable morphological and physiological alterations that exacerbate its susceptibility to damage. Specifically, aging reduces RPE cell density, especially in the macula, with significant declines noted from 56 to 81 years. The aging process also leads to a downregulation of extracellular matrix and endocytosis-related genes. Moreover, the central RPE shows higher rates of somatic mutations due to metabolic stress, increasing the risk of AMD.

Recent molecular omics profiling has highlighted similarities between age-related changes and those induced by AMD-associated gene variants. These processes include increased transcription of visual cycle genes in the RPE that are associated with the buildup of lipofuscin, a marker of aging and AMD, as well as macular cells that show higher expression of genes that protect against oxidative stress, and peripheral cells that are more involved in light perception and lipid metabolism.

Additional research into these genes and processes is needed to “shed light on the key mechanisms by … which these disruptions occur,” according to the editorial authors.