Melatonin ameliorates diabetic retinopathy by inhibiting PANoptosis via the LncSNHG5/miR-26a-5p/Hippo signaling axis.

Background

High glucose-induced injury to human retinal endothelial cells (HRCCs) is closely associated with retinal disorders, and melatonin has potential protective effects. However, its underlying mechanism remains unclear.

Methods

human retinal endothelial cells (HRCCs) were exposed to high glucose and treated with melatonin. Cell viability, apoptosis, and intracellular reactive oxygen species (ROS) levels were assessed using CCK-8, TUNEL staining, and DCFH-DA probe assays, respectively. The expression of PANoptosis-related proteins and components of the Hippo pathway were analyzed by Western blot. LncSNHG5 and miR-26a-5p expression were detected via RT-PCR. Luciferase reporter and RNA-pulldown assays, along with FISH, were employed to confirm direct interactions. Overexpression of LncSNHG5 and co-transfection with miR-26a-5p mimic were utilized to elucidate their roles.

Results

Melatonin dose-dependently improved HRCC viability, inhibited apoptosis, ROS accumulation and PANoptosis-related proteins (N-GSDMD, p-MLKL, p-RIP3) expression induced by high glucose. High glucose upregulated LncSNHG5, which was dose-dependently downregulated by melatonin. LncSNHG5 directly interacted with miR-26a-5p, and melatonin regulated the Hippo pathway (LATS1/YAP phosphorylation) and PANoptosis via the LncSNHG5/miR-26a-5p axis. Overexpression of LncSNHG5 reversed melatonin's protective effects, which was attenuated by miR-26a-5p mimic.

Conclusion

Melatonin alleviates high glucose-induced HRCC injury by regulating PANoptosis, ROS accumulation and Hippo pathway via the LncSNHG5/miR-26a-5p axis.