title: Exposure to high-concentration oxygen in the neonatal period induces abnormal retinal vascular patterning in mice.
abstract: The interruption of vascular development could cause structural and functional abnormalities in tissues. We have previously reported that short-term treatment of newborn mice with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors induces abnormal retinal vascular growth and patterns. An exposure of neonatal mice to high-concentration oxygen disturbs normal retinal vascular development. The present study aimed to determine (1) whether vascular abnormalities are observed in the retina of newborn mice exposed to high concentrations of oxygen, and (2) how astrocyte network formation is affected following the exposure to hyperoxia. Newborn (postnatal day 0) mice were exposed to 75% oxygen for 48 or 96 hr. During hyperoxia exposure, VEGF expression decreased, and the onset of retinal vascularization was completely suppressed. After completion of the hyperoxic period, retinal vascularization occurred, but it was delayed in a hyperoxic exposure duration-dependent manner. In retinas of hyperoxia-exposed mice, dense capillary plexuses were found, and the number of arteries and veins decreased. The astrocyte network formation was slightly delayed under hyperoxic conditions, and the network became denser in retinas of mice with an episode of hyperoxia. Expression of VEGF levels in the avascular retina of mice that were exposed to hyperoxia was higher than that of control mice. These results suggest that short-term interruption of the onset of vascular development resulting from the reduction in VEGF signals induces abnormal vascular patterns in the mouse retina. The abnormalities in retinal astrocyte behavior might contribute to the formation of an abnormal retinal vascular growth.
authors: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo, Japan.
authors: Akane
authors: A
authors: Morita
authors: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo, Japan.
authors: Hiroko
authors: H
authors: Ushikubo
authors: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo, Japan.
authors: Asami
authors: A
authors: Mori
authors: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo, Japan.
authors: Kenji
authors: K
authors: Sakamoto
authors: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo, Japan.
authors: Tsutomu
authors: T
authors: Nakahara
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018496:Hyperoxia / Q000150:complications / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010100:Oxygen / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina; D015861:Retinal Neovascularization / Q000139:chemically induced* / Q000175:diagnosis; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen
keywords: hyperoxia; retina; vascular development; vascular endothelial growth factor; vascular patterning