title: AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen-induced retinopathy.
abstract: We investigated the effect of receptor blockade induced by an angiotensin II type-1 receptor antagonist (AT(1)-RB) on glial and vascular changes in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity (ROP). OIR was induced in Sprague-Dawley rats by exposure to 80% oxygen from postnatal (P) days 0-11, followed by 7 days in room air. Control animals were in room air for the entire duration. One cohort of OIR and control pups received the AT(1)-RB valsartan (40 mg/kg/day intraperitoneal) from P11 to P18. The vascular response was examined immunocytochemically using retinal wholemounts and vertical sections labeled with endothelial (Isolectin-B4) and pericyte (NG2, desmin) markers. Glial cell changes were assessed by measuring cell numbers and immunoreactivity (S100beta, connexin-26, and glial fibrillary acidic protein). OIR resulted in extensive intravitreal neovascularization and under-development of the outer vascular plexus. Pericyte numbers were not significantly affected in OIR, although pericyte-endothelial (desmin-IB4) interactions were impaired. Peripheral astrocyte degeneration occurred between P11 and P13 with prominent Müller cell reactivity at P18. Valsartan imparted a protective effect on glia and blood vessels in OIR. At P18, valsartan-treated OIR retinae showed significantly greater astrocyte survival, improved revascularization of the retina, and reduced preretinal neovascularization and Müller cell reactivity. This study identifies a glio-vascular protective effect with AT(1)-RB in OIR.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Downie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pianta
authors.forename: Algis J
authors.initials: AJ
authors.lastname: Vingrys
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wilkinson-Berka
authors.forename: Erica L
authors.initials: EL
authors.lastname: Fletcher
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism* / Q000502:physiology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects / Q000254:growth & development*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D010100:Oxygen