Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy
| Autor: | Tanyth E. de Gooyer, Jennifer L. Wilkinson-Berka, Leslie G.T. Ong, Darren J. Kelly, Kassie Ann Jaworski, Alan W. Stitt, Sanja Babic, Richard E. Gilbert |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Platelet-derived growth factor Angiogenesis Apoptosis Biology Muscle Smooth Vascular Retina Pathology and Forensic Medicine Neovascularization Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Humans Retinopathy of Prematurity Enzyme Inhibitors In Situ Hybridization Platelet-Derived Growth Factor Neovascularization Pathologic Infant Newborn Receptor Protein-Tyrosine Kinases Retinal Vessels Kinase insert domain receptor Immunohistochemistry Vascular Endothelial Growth Factor Receptor-2 Rats Vascular endothelial growth factor Vascular endothelial growth factor A Disease Models Animal Microscopy Electron Endocrinology medicine.anatomical_structure chemistry Animals Newborn Gene Expression Regulation Immunology biology.protein Pericyte sense organs medicine.symptom Pericytes Platelet-derived growth factor receptor Regular Articles |
| Zdroj: | The American journal of pathology. 164(4) |
| ISSN: | 0002-9440 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|