Autophagy and retinal ganglion cell death in glaucoma: Friend or foe?

Abstract

AbstractGlaucoma, a leading cause of irreversible blindness worldwide, is an age‐related neurodegenerative disease characterized by progressive alterations of the optic nerve head and degeneration of retinal ganglion cells (RGCs). Although elevated intraocular pressure (IOP) has been identified as the main and the only modifiable risk factor, the pathogenesis of the disease is still unclear. Indeed, lowering IOP is often insufficient to prevent the damage progression leaving unmet the therapeutic need of IOP‐independent pharmacological targets.Autophagy, and the more selective mitophagy, are responsible for breaking down cellular components, preserving cellular homeostasis and preventing the accumulation of altered and aggregated proteins and damaged organelles.Several evidence have shown that modulation of autophagy is a recurrent and functional response of RGCs to IOP‐dependent or independent glaucoma‐related insults. However, in RGCs, autophagy has been found to take part to either neuroprotection as well as neuronal death, depending on the experimental setting (i.e. animal model, timing of the experiments, drugs/doses used to modulate the pathway).Here we describe the dynamic changes of autophagy flux and the modulation of mitophagy related proteins in a model of acute glaucoma induced in C57BL/6J mice by transient elevation of intraocular pressure (IOP). We also report and discuss experimental evidence supporting the pro‐survival role of autophagy and mitophagy induction in mice subjected to ocular hypertension suggesting the possibility to targeting autophagy to achieve retinal neuroprotection in glaucoma.