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X. Zhang, B. Bao, D. Lai, R. Rapkins, M. Gillies; Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier Through Differential Regulation of VEGF-A and Its Receptors in Early Diabetic Retinas. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3480. doi: https://doi.org/.
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To elucidate the mechanism of the unique beneficial effect of intravitreal steroid therapy on diabetic macular edema, we investigated the effect of locally administered triamcinolone acetonide (TA) on the expression of vascular endothelial growth factor(VEGF-A)and its receptors in streptozotocin (STZ) - induced diabetic rat retinas. We then correlated the expression of these proteins with breakdown of the blood-retinal barrier (BRB).
32 eyes of 16 diabetic and non-diabetic rats were divided into four groups. TA was injected into the vitreous of the right eye and saline was injected into the left eye (control) 3.5 weeks after induction of diabetes. Retinas were harvested 48h following treatment. mRNA and protein expression of VEGF-A, VEGF-A receptor 1 (FLT-1)andVEGF-A receptor 2 (FLK-1) were determined by real time RT-PCR and immunohistochemistry. BRB permeability was quantitated by measuring extravasated endogenous albumin and retinal thickness.
Diabetes induced retinal thickness and albumin extravasation were significantly reduced in TA-treated diabetic retinas to a level that was similar to sham-treated non-diabetic eyes. A close correlation between albumin leakage and increased expression of both Vegf-a and Flk-1 was noted in the diabetic retinas. TA down-regulated the expression of Vegf-a and Flk-1, but up-regulated the expression of Flt-1. TA did not alter the expression of these genes in non-diabetic retinas.
Intravitreal injection of TA stabilizes the BRB in association with regulation of Vegf-a, Flk-1 and Flt-1 expression in early diabetic rat retinas.
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