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Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy.
Wilkinson-Berka, Jennifer L; Babic, Sanja; De Gooyer, Tanyth; Stitt, Alan W; Jaworski, Kassie; Ong, Leslie G T; Kelly, Darren J; Gilbert, Richard E.
Afiliação
  • Wilkinson-Berka JL; Department of Physiology, University of Melbourne, Parkville, Victoria, Australia. jlaberka@unimelb.edu.au
Am J Pathol ; 164(4): 1263-73, 2004 Apr.
Article em En | MEDLINE | ID: mdl-15039215
We investigated whether inhibition of platelet-derived growth factor (PDGF) receptor tyrosine kinase activity would affect pericyte viability, vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) expression and angiogenesis in a model of retinopathy of prematurity (ROP). ROP was induced in Sprague Dawley rats by exposure to 80% oxygen from postnatal (P) days 0 to 11 (with 3 hours/day in room air), and then room air from P12-18 (angiogenesis period). Shams were neonatal rats in room air from P0-18. STI571, a potent inhibitor of PDGF receptor tyrosine kinase, was administered from P12-18 at 50 or 100 mg/kg/day intraperitoneal (i.p.). Electron microscopy revealed that pericytes in the inner retina of both sham and ROP rats appeared normal; however STI571 induced a selective pericyte and vascular smooth muscle degeneration. Immunolabeling for caspase-3 and alpha-smooth muscle cell actin in consecutive paraffin sections of retinas confirmed that these degenerating cells were apoptotic pericytes. In all groups, VEGF and VEGFR-2 gene expression was located in ganglion cells, the inner nuclear layer, and retinal pigment epithelium. ROP was associated with an increase in both VEGF and VEGFR-2 gene expression and blood vessel profiles in the inner retina compared to sham rats. STI571 at both doses increased VEGF and VEGFR-2 mRNA and exacerbated angiogenesis in ROP rats, and in sham rats at 100 mg/kg/day. In conclusion, PDGF is required for pericyte viability and the subsequent prevention of VEGF/VEGFR-2 overexpression and angiogenesis in ROP.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retinopatia da Prematuridade / Fator de Crescimento Derivado de Plaquetas / Pericitos / Inibidores Enzimáticos / Neovascularização Patológica Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Newborn Idioma: En Revista: Am J Pathol Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Austrália País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retinopatia da Prematuridade / Fator de Crescimento Derivado de Plaquetas / Pericitos / Inibidores Enzimáticos / Neovascularização Patológica Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Newborn Idioma: En Revista: Am J Pathol Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Austrália País de publicação: Estados Unidos