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AT 1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen‐induced retinopathy
Author(s) -
Downie Laura E.,
Pianta Michael J.,
Vingrys Algis J.,
WilkinsonBerka Jennifer L.,
Fletcher Erica L.
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20680
Subject(s) - astrocyte , retina , glial fibrillary acidic protein , retinopathy of prematurity , pericyte , biology , retinal , retinopathy , neovascularization , endocrinology , pathology , medicine , angiogenesis , endothelial stem cell , immunology , central nervous system , cancer research , neuroscience , immunohistochemistry , pregnancy , biochemistry , genetics , gestational age , in vitro , diabetes mellitus
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 (S100β, 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. © 2008 Wiley‐Liss, Inc.