Role of arteries in oxygen induced vaso-obliteration.
In mice the retinal vasculature develops in the first postnatal week by spreading from the optic nerve head towards the retinal periphery. During this growth period, exposure to hyperoxia causes vaso-obliteration of capillaries in the retinal center but not in peripheral regions. High oxygen levels lead to downregulation of vascular endothelial growth factor (VEGF), an important survival factor for vascular endothelial cells, which could explain the vaso-obliteration caused by hyperoxia. However, it is not clear why only capillaries in the center of the retina are affected. We therefore investigated how capillary obliteration correlates with VEGF mRNA distribution by in situ hybridization in retinal whole mount preparations. In mouse pups reared under normoxic conditions VEGF mRNA was detectable across the entire vascular network but was virtually absent in the immediate vicinity of arteries. This was true along developing retinal arteries but also around the optic nerve head through which the entire arterial blood supply for the retinal and hyaloid vasculature passes. In these areas capillaries were absent, resulting in so-called capillary free zones. Exposure to hyperoxia caused an expansion of areas with low VEGF mRNA which correlated with capillary obliteration in these regions. Combined capillary obliteration around the optic nerve head and along retinal arteries lead to a large capillary free zone in the center of the retina. Thus, our observations suggest that hyperoxia affects the retinal vasculature by reducing VEGF mRNA levels near arteries and causing a widening of capillary free zones.
Claxton
Suzanne
S
Wolfson Institute for Biomedical Research, University College London, Gower Street, WC1E 6AU, London, UK.
Fruttiger
Marcus
M
D000818:Animals; D001158:Arteries / Q000502:physiology; D001253:Astrocytes / Q000502:physiology; D002196:Capillaries / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000032:analysis; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D051379:Mice; D009900:Optic Nerve; D010100:Oxygen / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012171:Retinal Vessels / Q000503:physiopathology*; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010100:Oxygen