Aquaporin-1 independent microvessel proliferation in a neonatal mouse model of oxygen-induced retinopathy.
OBJECTIVE
Aquaporin-1 (AQP1) water channels are expressed widely in organ and tumor microvascular endothelia. Rapid microvessel proliferation occurs in growing tumors, diabetic and other retinopathies, and prenatal development. The purpose of this study was to investigate the role of AQP1 in retinal vessel proliferation.


METHODS
Comparative studies were performed on wild-type compared with AQP1 null mice using an established mouse model of oxygen-induced retinopathy. Neonatal mice were maintained in a 75% oxygen atmosphere for 5 days to suppress angiogenesis and then were returned to room air to induce vessel proliferation. AQP1 expression was also studied in extraocular microvessels and in primary endothelial cell cultures from pig retina.


RESULTS
Surprisingly, AQP1 immunoreactivity was detected in only a small percentage of newly formed retinal microvessels, whereas AQP1 was strongly expressed in all choroidal and hyaloid vessels and in various extraocular microvessels in neonatal and prenatal mice. Oxygen-induced retinal microvessel proliferation was not significantly impaired in neonatal mice lacking AQP1, as quantified in flat-mounted retinas and thin sections. However, AQP1 was expressed in endothelial cells cultured from retinal microvessels.


CONCLUSIONS
Microvessel proliferation in oxygen-induced retinopathy is AQP1-independent. Retinal endothelia have the capacity to express AQP1, though intact retinal vessels chronically suppress AQP1 expression.
Ruiz-Ederra
Javier
J
Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Verkman
A S
AS
D000818:Animals; D000831:Animals, Newborn; D051398:Aquaporin 1 / Q000502:physiology*; D002196:Capillaries; D018929:Cell Culture Techniques; D002829:Choroid / Q000098:blood supply; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D020868:Gene Silencing; D006801:Humans; D015151:Immunoblotting; D007231:Infant, Newborn; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010100:Oxygen / Q000633:toxicity; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
C496021:Aqp1 protein, mouse; D051398:Aquaporin 1; D010100:Oxygen