Regulation of Vascular Endothelial Growth Factor by Oxygen in a Model of Retinopathy of Prematurity
- 1 October 1996
- journal article
- research article
- Published by American Medical Association (AMA) in American Journal of Ophthalmology
- Vol. 114 (10), 1219-1228
- https://doi.org/10.1001/archopht.1996.01100140419009
Abstract
Objectives: To investigate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of the first phase of retinopathy of prematurity (ROP) and to examine the mechanism by which supplemental oxygen therapy might inhibit neovascularization in the second phase of ROP. Methods: A novel combination of fluorescein-dextran perfusion and colorimetric whole-retina in situ hybridization was used to evaluate the expression of VEGF messenger RNA in relationship to the location of blood vessels in retinas from neonatal mice that were exposed to hyperoxia. Northern blot and immunoblot analyses were used to quantify the changes in VEGF messenger RNA and protein expression caused by hyperoxia. The ability of VEGF to prevent hyperoxia-induced vasoobliteration was evaluated by injecting exogenous VEGF into the vitreous cavity prior to oxygen exposure. Results: Vascular endothelial growth factor messenger RNA was produced in a reticular pattern just anterior to the developing blood vessels in normal retina on postnatal day 7. The expression of VEGF in the peripheral retina was down-regulated by hyperoxia in conjunction with the arrest of growth and the loss of some of the developing vasculature. Total VEGF messenger RNA and protein levels in retinas from animals on postnatal day 7 were decreased 55% and 85%, respectively, after 6 hours in 75% oxygen. Vaso-obliteration was inhibited 57% by pretreatment of animals with exogenous VEGF. In animals with retinal ischemia secondary to loss of vasculature, treatment with supplemental oxygen therapy decreased stimulated retinal VEGF levels by approximately 70%. Conclusions: Down-regulation of VEGF expression by hyperoxia may be partly responsible for the vasoobliteration and cessation of normal retinal blood vessel growth observed in premature infants in whom ROP develops. Hyperoxia also has the potential to be used therapeutically to down-regulate VEGF expression in hypoxic retina in the hope of limiting the neovascular complications of ROP. Based on these findings about the regulation of VEGF expression in the retina, an explanation of the pathogenesis of ROP is proposed.This publication has 16 references indexed in Scilit:
- Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Controversies in the Management of Retinopathy of PrematurityInternational Ophthalmology Clinics, 1994
- Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.Molecular Biology of the Cell, 1992
- Retinopathy of Prematurity: Pathogenesis, Diagnosis, and TreatmentInternational Ophthalmology Clinics, 1992
- Vascular Endothelial Growth Factor Is a Secreted Angiogenic MitogenScience, 1989
- Retinopathy of prematurity: clinical implications of retinal development.Archives of Disease in Childhood, 1988
- Reduced Severity of Oxygen-Induced Retinopathy in Kittens Recovered in 28% OxygenPediatric Research, 1988
- Oxygen and the Growth and Development of Retinal VesselsAmerican Journal of Ophthalmology, 1966
- Effect of Oxygen Weaning in Retrolental FibroplasiaAmerican Journal of Ophthalmology, 1955
- Effect of Oxygen on Developing Retinal Vessels with Particular Reference to the Problem of Retrolental FibroplasiaBritish Journal of Ophthalmology, 1954