RPE necroptosis in response to oxidative stress and in AMD.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. The underlying mechanism of non-neovascular AMD (dry AMD), also named geographic atrophy (GA) remains unclear and the mechanism of retinal pigment epithelial (RPE) cell death in AMD is controversial. We review the history and recent progress in understanding the mechanism of RPE cell death induced by oxidative stress, in AMD mouse models, and in AMD patients. Due to the limitation of toolsets to distinguish between apoptosis and necroptosis (or necrosis), most previous research concludes that apoptosis is a major mechanism for RPE cell death in response to oxidative stress and in AMD. Recent studies suggest necroptosis as a major mechanism of RPE cell death in response to oxidative stress. Moreover, ultrastructural and histopathological studies support necrosis as major mechanism of RPE cells death in AMD. In this review, we discuss the mechanism of RPE cell death in response to oxidative stress, in AMD mouse models, and in human AMD patients. Based on the literature, we hypothesize that necroptosis is a major mechanism for RPE cell death in response to oxidative stress and in AMD.