Research progress in 7-ketocholesterol and age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in older adults, with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and choroidal neovascularization in advanced stages. The dysregulation of ocular lipid metabolism, oxidative stress, and inflammation are critical risk factors for AMD pathogenesis. 7-ketocholesterol (7-KC), a hallmark of ocular lipid metabolism disorders, is a significant component of subretinal lipid deposits in AMD patients, exhibiting toxicity to retinal cells and exacerbating lipotoxic aging. This review elaborates on the biosynthesis and metabolism of 7-KC in the retina, investigates its detoxification mechanisms by examining its binding proteins, and summarizes recent progress on kinase signaling pathways induced by 7-KC through inflammatory cytokines and intracellular effectors. The aim is to pinpoint potential pharmacological targets, nutritional compounds, and synthetic molecules to explore the potential of targeting 7-KC for AMD treatment.