MiR-30b-5p ameliorates experimental autoimmune uveitis by inhibiting the Atg5/Atg12/Becn1 Axis

Context: Uveitis is a severe autoimmune eye disease that poses a significant threat to visual health. Autophagy is essential for maintaining cellular homeostasis and becomes dysregulated in autoimmune conditions like uveitis. MicroRNAs (miRNAs) can influence autophagy and apoptosis by targeting autophagy-related genes (Atg). Objective: This study aimed to investigate the role of miR-30b-5p in regulating autophagy-related genes and to explore its therapeutic potential in experimental autoimmune uveitis (EAU). Materials and methods: EAU was induced and RT(Vega-Tapia et al., 2021 [2]) Profiler PCR Arrays were used to identify significant interactions among Atg genes and their role in uveitic pathogenesis. Both in vitro and in vivo experiments were used to assess the expression of Atg-related genes. Additionally, miR-30b-5p-carrying lentivirus injections were administered, and the levels of Atg5, Atg12, and Becn1 were measured, along with autophagosome formation through electron microscopy. Meanwhile, we also assessed inflammatory markers (i.e., IL- 10, IL-17), the Th17/Treg ratio, and apoptosis. Results: In vitro experiments demonstrated that miR-30b-5p led to decreased expression of Atg5, Atg12, and Becn1, which resulted in a lower number of autophagosomes. In vivo validation confirmed these outcomes, showing reduced mRNA and protein levels of Atg-related molecules and diminished autophagosome formation after the injection of miR-30b-5p. Furthermore, miR-30b-5p exhibited anti-inflammatory effects by increasing IL- 10 levels and decreasing IL-17, thereby improving the balance of the Th17/Treg ratio. Conclusion: This study highlights the importance of autophagy in the pathogenesis of uveitis and identifies miR30b-5p as a regulator of autophagy and inflammation. Targeting miR-30b-5p presents a promising therapeutic approach for treating uveitis.