Autophagy Impairment in Retinal Ganglion Cells Following Hypoglycemia in Mice.

(1)

Background

Diabetic retinopathy (DR), caused by hypo- and hyperglycaemia, is the leading cause of blindness. Hypoglycemia induces endoplasmic reticulum stress and retinal cell death in mice, and low-glucose conditions induce macroautophagy/autophagy defects in 661W photoreceptor cells and retinal explants. Very few studies have analyzed the effect of hypoglycemia on retinal autophagy, so we decided to fill this gap. (2)

Methods

We use C57BL/6 and GFP-LC3 mice and isolated retinal ganglion cells (RGCs) from both mouse models to study the autophagy process. (3)

Results

Intraocular injection of rapamycin and 5 h hypoglycemia showed an increase in autophagosomes formation, specifically in the RGCs. Isolated GFP-LC3 RGCs showed an increase in autophagosome formation under low-glucose conditions. In contrast, infection of isolated C57BL/6 RGCs with the RFP-GFP-LC3 lentivirus revealed a defect in autophagosome/lysosome fusion under these conditions. (4)

Conclusions

This study showed that 5 h hypoglycemia induces autophagosomes formation in mouse RGCs; however, a defect in the fusion process inhibits the protective effect of autophagy. Therefore, modulating both autophagic and apoptotic pathways might be important to avoid complications associated with DR.