Curcumol ameliorates diabetic retinopathy via modulating fat mass and obesity-associated protein-demethylated MAF transcription factor G antisense RNA 1.

BACKGROUND: Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus, leading to significant visual impairment and blindness among adults. Current treatment options are limited, making it essential to explore novel therapeutic strategies. Curcumol, a sesquiterpenoid derived from traditional Chinese medicine, has shown anti-inflammatory and anti-cancer properties, but its potential role in DR remains unclear. AIM: To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms, particularly its impact on the fat mass and obesity-associated (FTO) protein and the long non-coding RNA (lncRNA) MAF transcription factor G antisense RNA 1 (MAFG-AS1). METHODS: A streptozotocin-induced mouse model of DR was established, followed by treatment with curcumol. Retinal damage and inflammation were evaluated through histological analysis and molecular assays. Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro. Cell proliferation, migration, and inflammation markers were assessed in curcumol-treated cells. LncRNA microarray analysis identified key molecules regulated by curcumol, and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR. RESULTS: Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocin-induced DR mouse models. In high-glucose-treated human retinal vascular endothelial cells, curcumol inhibited cell proliferation, migration, and inflammatory responses. LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment. Mechanistically, FTO demethylated MAFG-AS1, stabilizing its expression. Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway. CONCLUSION: Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis, providing a novel therapeutic pathway for the treatment of DR. These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.