AUF1 mitigates retinal ganglion cell apoptosis in glaucoma by regulating the Nrf2/HO-1 pathway.

Objective: This study investigates the protective effects of AU-rich element RNA-binding protein 1 (AUF1) on retinal ganglion cells (RGCs) in a model of retinal injury, focusing on its interaction with the nuclear factor erythroid 2-related factor 2 / heme oxygenase-1 (Nrf2/HO-1) signalling pathway.

Methods: Using a combination of histological, molecular, and flow cytometry analyses, we evaluated retinal thickness, apoptosis, and gene/protein expression in four experimental groups: one control, one model, and 2 intervention groups-AUF1 and AUF1+Nrf2/HO-1 inhibitor.

Results: The results revealed that compared to the control group, the model group and the AUF1+Nrf2/HO-1 inhibitor group exhibited significant retinal damage, characterized by reduced retinal thickness and increased RGC apoptosis. Notably, the AUF1 intervention group showed a marked increase in retinal thickness and a significant reduction in RGC apoptosis, indicating that AUF1 overexpression protects RGCs from ischemic injury. Further analysis through Western blotting and quantitative real-time reverse transcription polymerase chain reaction demonstrated that AUF1 overexpression led to increased expression of Nrf2 and HO-1 proteins and mRNA, while inhibition of the Nrf2/HO-1 pathway reversed these effects.

Conclusion: These findings suggest that AUF1 mediates its protective effects through activation of the Nrf2/HO-1 pathway, offering a potential therapeutic target for retinal diseases involving RGC apoptosis. This study provides novel insights into the molecular mechanisms by which AUF1 regulates retinal cell survival and highlights the importance of the Nrf2/HO-1 signalling axis in retinal protection.