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Research Paper|Volume 14, Issue 15|pp 6255—6268

Targeting circRNA-MAP4K2 for the treatment of diabetes-induced retinal vascular dysfunction

Cong Ma1,2, Ze-Hui Shi3, Xiao-Yan Han3, Chang Liu3, Biao Yan3, Jian-Ling Du1
  • 1Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
  • 2Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
  • 3Eye Institute, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Received: February 18, 2022Accepted: July 27, 2022Published: August 11, 2022
https://doi.org/10.18632/aging.204215

Copyright: © 2022 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Diabetic retinopathy (DR) is an important ocular vascular disease in working-age adults. However, the molecular mechanism underlying retinal vascular dysfunction is still not fully understood in DR. Circular RNAs have been recognized as the crucial regulators in many biological processes and human diseases. Herein, we determined the role of circular RNA-MAP4K2 (cMAP4K2) in diabetes-induced retinal vascular dysfunction. The results showed that high glucose treatment led to increased levels of cMAP4K2 expression in vitro and in vivo. Silencing of cMAP4K2 could reduce endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviate retinal vascular dysfunction in vivo as shown by decreased vascular leakage and inflammation. By contrast, cMAP4K2 overexpression had an opposite effect on retinal vascular dysfunction. Mechanistically, cMAP4K2 acted as miR-377 sponge to affect the biological activity of miR-377, which led to increased expression of vascular endothelial growth factor A (VEGFA). Clinically, cMAP4K2 expression was significantly up-regulated in the clinical sample of DR patients. Collectively, cMAP4K2 is shown as a potential target for the diagnosis and treatment of diabetic retinopathy.