Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension

Abstract

Autophagy is an essential cellular process for the degradation and recycling of cellular components, and its dysregulation has been linked to neuronal cell death and neurodegeneration. In glaucoma, the role of autophagy in retinal ganglion cell (RGC) survival remains contradictory. Moreover, the effects of autophagy modulation at different time-points on RGC survival in a glaucoma model have not been investigated. In this study, we assessed the time-dependent role of autophagy in RGC survival in a circumlimbal suture-induced ocular hypertensive (OHT) rat model. Intraocular pressure (IOP) elevation led to a gradual autophagy induction, which reached a maximum between 1 and 4 weeks after OHT induction. On the other hand, early autophagy was impaired between 1 and 3 days after circumlimbal suturing, indicated by increased p62 levels due to reduced autophagosomal turnover. The intravitreal administration of rapamycin at different time-points after the application of the circumlimbal suture indicated that autophagy induction early during OHT development had potent survival-promoting effects in RGCs. In conclusion, our findings suggest that the role of autophagy in RGCs during OHT development might differ in a time-dependent manner. Modulating autophagy at the appropriate time might serve as a potential therapeutic approach to enhance RGC survival in OHT.