Systemic hyperoxia decreases vascular endothelial growth factor gene expression in ischemic primate retina
C. J. Pournaras, J. W. Miller, E. S. Gragoudas, D. Husain, J. L. Munoz, M. J. Tolentino, M. Kuroki and A. P. Adamis
Department of Clinical Neurosciences, University Hospital Eye Department, Geneva, Switzerland.
OBJECTIVES: To determine whether systemic hyperoxia can reverse retinal
hypoxia and decrease vascular endothelial growth factor (VEGF) gene
expression in ischemic nonhuman primate retina. METHODS: Six eyes of 3
cynomolgus monkeys were studied. Retinal ischemia was induced via laser
vein occlusion and confirmed with fluorescein angiography. Animals were
randomly assigned to treatment with either 21% or 100% inhaled oxygen.
Arterial PO2 was monitored while systemic acid-base status was maintained.
An oxygen microelectrode on a micromanipulator was used to measure
preretinal oxygen concentrations in ischemic and nonischemic retina in
situ. RNA was isolated from fresh whole retinas, and VEGF messenger RNA
levels were quantified with Northern blotting. RESULTS: The preretinal PO2
in ischemic retina was less than the PO2 in nonischemic retina in animals
breathing 21% oxygen (intervascular zone PO2, 14.3+/-0.53 vs 21.8+/-0.55 mm
Hg; P=.002). After 8 hours of systemic hyperoxia (arterial PO2, 512+/-18 mm
Hg), the preretinal PO2 in ischemic retina increased to 166.2+/-15.6 mm Hg
(21.8% oxygen) and retinal VEGF messenger RNA levels were reduced by an
average of 55%. CONCLUSIONS: These data demonstrate that systemic hyperoxia
can lower retinal VEGF gene expression and reoxygenate ischemic adult
primate retina.
