Kevin R Zhang, Connor S R Jankowski, Rayna Marshall, Rohini Nair, Néstor Más Gómez, Ahab Alnemri, Yingrui Liu, Elizabeth Erler, Julia Ferrante, Ying Song, Brent A Bell, Bailey H Baumann, Jacob Sterling, Brandon Anderson, Sierra Foshe, Jennifer Roof, Hossein Fazelinia, Lynn A Spruce, Jen-Zen Chuang, Ching-Hwa Sung, Anuradha Dhingra, Kathleen Boesze-Battaglia, Venkata R M Chavali, Joshua D Rabinowitz, Claire H Mitchell, Joshua L Dunaief
Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly, with retinal pigment epithelial (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured iPS-RPE cells increased lysosomal abundance, impaired proteolysis, and reduced the activity of a subset of lysosomal enzymes, including lysosomal acid lipase and acid sphingomyelinase...
July 4, 2023: Disease Models & Mechanisms