Endoplasmic reticulum, mitochondria, and their crosstalk in retinal ganglion cell degeneration.

Retinal ganglion cells (RGCs) serve as the terminal output neurons in the retina and are responsible for transmitting visual information from photoreceptors to higher-level centers in the brain. Because of their highly polarized structure, substantial energy demands, and complex protein synthesis activities, the function of RGCs is critically dependent on the homeostasis of intracellular organelles, particularly the endoplasmic reticulum (ER) and mitochondria. Recent studies have shown that these two organelles engage in close physical and functional crosstalk through specific microdomains known as "mitochondria-associated ER membranes" (MAMs), which are crucial for the survival and function of RGCs. This review delves into the critical roles of the ER and mitochondria in the mechanisms of RGC degeneration. Furthermore, the mechanisms by which mitochondrial-ER contact site (MERC)-mediated interorganelle communication exacerbates RGC degeneration by disrupting Ca2 + homeostasis and inducing ER stress and oxidative stress are elucidated. Drugs targeting mitochondria, ER, and MERCs to prevent and treat RGC degeneration are summarized to provide new perspectives and references for studying the pathological mechanisms of RGC degeneration and developing targeted therapeutic strategies.