Protective effects of liraglutide on the injury of retinal ganglion cells induced by hyperglycemia

Objective To investigate the effects of liraglutide on high glucose induced retinal ganglion cells injury and explore potential mechanisms. Methods RGC-5 cells were cultured in vitro and divided into the following groups: control group, high glucose group, liraglutide group, high glucose+liraglutide group, high glucose+liraglutide+rapamycin group, high glucose+rapamycin group, high glucose+normal control small interfering RNA (NC siRNA) group, high glucose+optineurin (OPTN) siRNA group. Cell viability was detected with the CCK-8 kit. LC3A/B, Beclin-1, p62 and OPTN were examined via western blotting analysis. Autophagy was also evaluated using the transmission electron microscopy (TEM). The expression of OPTN and LC3A/B was detected by western blotting after transfection with OPTN siRNA. Data were expressed by ±s, data among multiple groups were compared by using one-way ANOVA. Results Our results showed that treatment with 65 mmol/L glucose for 24 h decreased cell viability of RGC-5 cells (0.74±0.06 vs 1.26±0.29, F=16.75, P<0.05). High glucose induced increased cell viability, expression of LC3A/B Ⅱ/Ⅰ, Beclin-1 and OPTN, along with p62 degradation and liraglutide suppressed the changes (0.55±0.04 vs 0.40±0.02, 1.08±0.05 vs 1.40±0.14, 0.55±0.06 vs 0.89±0.11, 0.44±0.06 vs 0.71±0.09, 0.82±0.15 vs 0.49±0.05, F=3.53, 10.79, 7.80, 7.52, 11.70, all P<0.05). TEM revealed that high glucose induced mitochondrial morphological changes and autophagosome formation which could be reversed by liraglutide. However, rapamycin induced autophagy and blocked the protective process (0.95±0.19 vs 1.52±0.29, F=13.87, P<0.05). Knockdown of OPTN by transfection with OPTN siRNA significantly down-regulated the expression of LC3A/B Ⅱ/Ⅰ (0.84±0.08 vs 1.61±0.26, F=15.88, P<0.01). Conclusion Liraglutide attenuates high glucose induced RGC-5 cell injury by inhibiting autophagy through regulating OPTN.