Autophagy in retina and axonal degeneration

Abstract

AbstractAutophagy is a catabolic pathway that degrades and recycles intracellular components inside lysosomes to maintain cell homeostasis. This pathway is essential to keep postmitic cells such are neurons free of garbaje and damaged cell components. There are several types of autophagy. During macroautophagy, simply called autophagy, parts of the cytosol and even entire organelles are engulfed in an autophagosome that will finally fuse with a lysosome where degradation will take place. In chaperone mediated autophagy (CMA) proteins harbouring a specific aminoacid sequence will be recognized by a chaperone Hsc70 and delivered inside lysosomes thanks to the lysosomal receptor LAMP‐2A. The role of autophagy in the physiology and pathology of the retina is just starting to be investigated. We have demonstrated the cytoprotective role of autophagy in a model of optic nerve axotomy in mice. We show that autophagy‐deficient animals have reduced number of surviving RGCs after ONT and that pharmacological induction of autophagy delays neuronal cell death. We have also observed a reduction in the levels of autophagy during retinal aging and Atg5 deficient animals in the retina show increased photoreceptor death and reduced scotopic vision. Unexpectedly CMA seems to increase in these conditions and we postulate that this is a compensatory response to sustain cell survival. Thus balance in autophagic pathways plays important roles to maintain retinal homestasis.