Fig 8. Schematic depicting proposed mechanism of AMD pathogenesis and the role cysteamine and fisetin play in augmenting proteostasis and autophagy mechanisms in CS exposed ARPE-19 cells.

CS induces ROS formation in ARPE-19 cells, resulting in protein misfolding and peri-nuclear aggregation of these proteins in aggresome bodies. Moreover, these proteins cannot be appropriately degraded that eventually leads to chronic inflammatory-oxidative stress and AMD pathogenesis. Through our experiments, we have shown that cysteamine can significantly reduce ARPE-19 apoptosis while cysteamine or fisetin both can relieve ARPE-19 cells of CS induced proteostasis/autophagy-impairment.