Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.97201
Revised: October 28, 2024
Accepted: January 6, 2025
Published online: April 15, 2025
Processing time: 278 Days and 21.7 Hours
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.
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).
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.
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.
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.
Core Tip: This groundbreaking discovery led to the identification of a previously unknown signaling pathway involving curcumol, fat mass and obesity-associated protein, and MAF transcription factor G antisense RNA 1 in diabetic retinopathy. The elucidation of this molecular cascade enhanced our understanding of the therapeutic mechanisms of curcumol, revealing potential molecular targets for developing more targeted interventions to treat or prevent retinal complications associated with diabetes.