Figure 2.

Schematic representation of the ER stress induced by tunicamycin leading to apoptosis in RPE and the protective effect of exogenous Humanin on RPE apoptosis.

TM induced ER stress activates procaspase 4 to active caspase 4 which leads to increased apoptosis via activation of caspase 3. TM treatment caused increased ROS and decreased GSH in mitochondria. HN enters mitochondria in RPE co-treated with TM and HN and an inhibition of the formation of active caspase 4 and caspase 3 is found which blocks apoptosis. Attenuation of ROS generation and an increase in mitochondrial GSH occur with TM and HN co-treatment. The zones of close contact between ER and mitochondria called MAM is also shown. EM: Endoplasmic reticulum; HN: humanin; GSH: glutathione; MAM: mitochondria associated membranes; TM: tunicamycin; ROS: reactive oxygen species; RPE: retinal pigment epithelium.