Retinal ganglion cell autophagy: a housekeeper essential for neuronal homeostasis and survival.

Abstract

Retinal ganglion cells (RGCs) are the sole projection neurons of the retina and the only direct link between retinal circuitry and the brain. Maintaining this lifelong connection requires constitutive autophagy to preserve organelle quality control and neuronal homeostasis. Although autophagy has been widely studied following ocular hypertension and optic nerve injury, its physiological role in healthy RGCs has remained unclear. We have recently revealed that basal autophagy is highly active in RGCs and that conditional deletion of Atg5 or Atg7 is sufficient to induce progressive RGC dysfunction, optic nerve degeneration, and neurodegeneration. Autophagy deficiency caused the accumulation of swollen mitochondria, distended endoplasmic reticulum, fragmented Golgi, synaptic vesicles, and incomplete autophagosomes accompanied by increased p62 and LC3B levels. These findings establish basal autophagy as an essential housekeeping mechanism that preserves organelle quality control and long-term RGC integrity.