Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2025; 16(4): 97201
Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.97201
Curcumol ameliorates diabetic retinopathy via modulating fat mass and obesity-associated protein-demethylated MAF transcription factor G antisense RNA 1
Han Rong, Yu Hu, Wei Wei
Han Rong, Wei Wei, Department of Ophthalmology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Han Rong, Department of Ophthalmology, Huai’an Maternal and Child Health Care Hospital Affiliated to Yangzhou University, Huai’an 223002, Jiangsu Province, China
Yu Hu, Department of Nephrology, The Affiliated Huai’an Hospital of Xuzhou Medical University, The Second People’s Hospital of Huai’an, Huai’an 223002, Jiangsu Province, China
Yu Hu, Wei Wei, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
Co-first authors: Han Rong and Yu Hu.
Author contributions: Han R and Yu H performed the major experiments and wrote this manuscript; they contributed equally as co-first authors. Wei W designed the research and edited the manuscript; Yu H and Wei W edited and revised the manuscript.
Institutional animal care and use committee statement: The study adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and was approved by the Animal Ethics Board of the Affiliated Hospital of Yangzhou University, Huai’an Maternal and Child Health Care Center (ethics approval No. 202402884).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author Professor Wei at <weiwei1111ww@163.com>.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei Wei, MD, Department of Ophthalmology, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, China. weiwei1111ww@163.com
Received: May 25, 2024
Revised: October 28, 2024
Accepted: January 6, 2025
Published online: April 15, 2025
Processing time: 278 Days and 21.7 Hours
Abstract
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.

Keywords: Diabetic retinopathy; Curcumol; MAF transcription factor G antisense RNA 1; Fat mass and obesity-associated protein; Diabetes mellitus

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.