Long Noncoding RNA PPT2-EGFL8 Regulates Pathological Retinal Neovascularization in PDR by Functioning as a Competing Endogenous RNA

• DOI: 10.2337/db22-0342
• Publication Date: 2023-04-21T16:27:30Z
• Authors: Zifan Xu; Jiahui Yang; Haohan Zheng; Tianhua Xie; Qian Yang; Jiping Cai; Chao Sun; Yujuan Cao; Meili Wu; Yanqiu Liu; Yuqing Cui; Yong Yao; Xiaolu Wang
• Keywords: Angiopoietin; ANGPTL4

Diabetic retinopathy (DR) is a common complication in patients with diabetes, and proliferative DR (PDR) has become an important cause of blindness; however, the mechanisms involved have not been fully elucidated. miRNAs long noncoding RNAs can play role DR, they accurately regulate expression target genes through new regulatory model: competing endogenous RNAs. We isolated total RNA extracellular vesicles (EVs) serum healthy individuals diabetes without non-PDR, or PDR, performed deep sequencing. found aberrantly low PPT2-EGFL8 significantly increased level miR-423-5p. adsorbs miR-423-5p as molecular sponge inhibits hypoxia-induced human retinal microvascular endothelial cells proliferation. In oxygen-induced (OIR) model streptozotocin-induced model, Egfl8-overexpression treatment reduces diabetes-related reactive gliosis, inflammation, acellular capillaries attenuates development pathological neovascularization. addition, targeting plays peroxisome proliferator-activated receptor-β/δ (PPARD)/angiopoietin-like 4 (ANGPTL4) signaling activation, especially C-terminal ANGPTL4 fragment. Finally, induces vessel breakage inner limiting membrane facilitates sprouting into vitreous OIR mice. Thus, either biomarkers therapeutic targets may be identified translation these findings.