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L.G. Ong, R.E. Gilbert, J.L. Wilkinson–Berka; Platelet Derived Growth Factor Is Required For Pericyte And Endothelial Cell Patency In Diabetic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1740.
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Pericytes can regulate vascular tone and permeability, and endothelial cell growth and differentiation. Pericyte death in the retinal vasculature is the earliest feature of diabetic retinopathy, resulting in a weakened vessel wall and compromised endothelial cell viability. Platelet derived growth factor (PDGF) and its receptor tyrosine kinase (RTK) are implicated in this process.
We investigated whether inhibition of PDGF–RTK would lead to vascular and glial abnormalities in early diabetic retinopathy.
Diabetes was induced in 8–week old transgenic Ren–2 rats with streptozotocin (50mg/kg), while non–diabetic rats received vehicle (0.1M citrate buffer). Rats were administered STI571, a potent inhibitor of PDGF–RTK, by oral gavage (60mg/kg/day) for 4 weeks. Immunohistochemistry was used to evaluate pericyte apoptosis (alpha–smooth muscle cell actin and caspase–3), HIF–1alpha and glial fibrillary acidic protein (GFAP) on 3 micron paraffin sections of retina and quantified using image analysis software. Trypsin digested retinae were quantified for acellular capillaries, and the Evans Blue method was used to estimate vascular leakage.
Only in diabetic Ren–2 rats treated with STI571 was pericyte apoptosis, vascular leakage and GFAP immunohistochemistry increased by approximately 2 fold. Acellular capillaries in the mid, central and peripheral retina were also increased by 2 fold in diabetic Ren–2 rats treated with STI571. HIF–1alpha localised to the ganglion cell layer in all rats, and was only increased in diabetic+STI571.
Inhibition of PDGF–RTK has deleterious effects on pericyte and endothelial cell viability in the retina of diabetic transgenic Ren–2 rats, and promotes vascular and glial abnomalities. Hence, PDGF is important in maintaining the patency of the vascular wall early in diabetic retinopathy.
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