Abstract
Purpose :
To assess the role of the UV-sensitive photoreceptor protein OPN5 in inducing retinal ganglion cells autophagy under violet light exposure and the underlying mechanisms.
Methods :
The retinal ganglion cell line 5 (RGC-5) was cultured under violet light. The functional role of Opn5 in Egr-1 expression, viability, apoptosis as well as LC3II/LC3I, P62 and Beclin-1 expression in RGCs were detected by CCK-8, flow cytometry, western blot, quantitative real-time PCR and immunofluorescence staining. The effects of Egr-1 on autophagy activity were determined by CO-IP, nucleocytoplasmic separation, CHIP-seq and bioinformatics.
Results :
First, violet light irradiation resulted in increased Opn5 expression in RGC-5 cells, accompanied by increased Egr-1 expression and attenuated autophagy. Moreover, Opn5 knockdown decreased Egr-1 expression, enhanced autophagy in response to violet light in RGC-5. Autophagy of RGC-5 cells, which was inhibited by violet light, was mediated via Opn5 inducing the nuclear translocation of Egr-1 to regulate LC3, P62 and Beclin-1 expression. Then, Egr-1 knockdown reversed autophagy in RGC-5 cells treated with violet light. Inhibition of Egr-1 protected RGC-5 cells against damage, cell death, and inflammation in the presence of violet light. Finally, we detected that Egr-1 binds to LC3 promoter.
Conclusions :
The Opn5/Egr-1/LC3 pathway mediates the response to the violet light environment in RGC-5 cells by negatively regulating autophagy. Activating Opn5 expression can induce the nuclear translocation of Egr-1 to alleviate autophagy damage under violet light irradiation in RGC-5 cells and may provide experimental evidence for treating myopia.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.