Research Paper Volume 13, Issue 7 pp 10584—10602
Suppression of choroidal neovascularization by silencing of long non-coding RNA IPW
- 1 The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China
- 2 The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China
- 3 Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- 4 NHC Key Laboratory of Myopia Fudan University, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
- 5 Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China
Received: January 23, 2021 Accepted: February 18, 2021 Published: April 4, 2021
https://doi.org/10.18632/aging.202822How to Cite
Copyright: © 2021 Yang 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
Long noncoding RNAs (lncRNAs) have emerged as the key regulators in the pathogenesis of human disorders. This study aimed to investigate the role of lncRNA-IPW in the progression of choroidal neovascularization (CNV) and the underlying molecular mechanism. IPW was significantly up-regulated in the choroidal tissues of laser-induced CNV mice and in the endothelial cells in response to hypoxic stress. IPW silencing led to reduced formation of CNV in laser-induced CNV model and ex vivo choroidal sprouting model, which could achieve similar therapeutic effects of anti-VEGF on CNV formation. Silencing or transgenic overexpression of IPW could alter endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, IPW silencing led to increased expression of miR-370. Increased miR-370 could mimic the effects of IPW silencing on CNV formation and endothelial angiogenic phenotypes in vivo and in vitro. This study suggests that IPW silencing is a promising strategy for the treatment of neovascular ocular diseases.
Abbreviations
LncRNAs: long noncoding RNAs; CNV: choroidal neovascularization; AMD: age-related macular degeneration; VEGF: vascular endothelial growth factor; PWS: Prader-Willi syndrome; MEGs: maternally expressed genes; RF/6A: chorioretinal endothelial cells; AAV: adeno-associated viral vector; PFA: paraformaldehyde; IB4: Isolectin-B4; FAA: formaldehyde-acetic acid-ethanol fixative solution; FBS: fetal bovine serum; DMEM: Dulbecco’s Modified Eagle Medium; EdU: 5-Ethynyl-2'-deoxyuridine; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide; PI: propidium iodide; Calcein-AM: Calcein-acetoxymethyl.