Systemic hyperoxia decreases vascular endothelial growth factor gene expression in ischemic primate retina.
OBJECTIVE
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.
Pournaras
C J
CJ
Department of Clinical Neurosciences, University Hospital Eye Department, Geneva, Switzerland.
Miller
J W
JW
Gragoudas
E S
ES
Husain
D
D
Munoz
J L
JL
Tolentino
M J
MJ
Kuroki
M
M
Adamis
A P
AP
D000818:Animals; D015152:Blotting, Northern; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D015870:Gene Expression; D018496:Hyperoxia / Q000378:metabolism* / Q000503:physiopathology; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008252:Macaca fascicularis; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology; D012169:Retinal Vein / Q000378:metabolism* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012313:RNA; D010100:Oxygen