Chan, EC and van Wijngaarden, P and Liu, GS and Jiang, F and Peshavariya, H and Dusting, GJ, Involvement of Nox2 NADPH oxidase in retinal neovascularization, Investigative Ophthalmology and Visual Science, 54, (10) pp. 7061-7067. ISSN 0146-0404 (2013) [Refereed Article]
Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc.
Methods: Neonatal C57BL/6 mice aged 7 days (P7) were placed in a hyperoxic chamber (75% O2) for 5 days, followed by 5 days of exposure to room air. Eyes were harvested on P8 and P17 for the quantification of retinal vaso-obliteration and neovascularization, respectively. The retinal expression of Nox2 and VEGF-A were measured by RT-PCR, while superoxide generation was detected by in situ dihydroethidium (DHE) staining of fresh frozen sections.
Results: In wild type (WT) mice, OIR was characterized by central retinal vaso-obliteration at P8 and neovascularization at P17, which was associated with increases in Nox2 and VEGF-A gene expression, superoxide generation, and accumulation of Iba-1 positive cells in the inner retina. In contrast, Nox2 knockout mice exhibited markedly less retinal neovascularization and VEGF-A mRNA expression at P17, despite showing comparable vaso-obliteration at P8. These changes were accompanied by reductions in DHE fluorescence and Iba-1-positive cell accumulation in the hypoxic retina.
Conclusions: The Nox2-generated reactive oxygen species (ROS) facilitate the retinal expression of VEGF-A and neovascularization in this mouse model of OIR. Therapies targeting Nox2 could be of value to reduce aberrant retinal neovascularization in retinopathy of prematurity, diabetes, and other disease processes driven by VEGF.
|Item Type:||Refereed Article|
|Keywords:||NADPH oxidase, mouse OIR, retinal neovascularization|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Medical biotechnology|
|Research Field:||Gene and molecular therapy|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Liu, GS (Associate Professor Guei-Sheung Liu)|
|Web of Science® Times Cited:||38|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||112 View Download Statistics|
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