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Diabetes Publish Ahead of Print published online ahead of print January 3, 2008
DOI: 10.2337/db07-0982

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Original Research

Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier through Differential Regulation of VEGF-A and its Receptors in Early Diabetic Rat Retinas

Xinyuan Zhang, MD1,2, Shisan Bao, MD, PhD3, Donna Lai, PhD4, Robert W Rapkins1, and Mark C Gillies, MD, PhD1

1Retinal Therapeutic Research Group, Save Sight Institute, Department of Clinical Ophthalmology, University of Sydney, Level 2, South Block, Sydney Eye Hospital, Macquarie St, Sydney NSW 2000, Australia
2Beijing Institute of Ophthalmology, Ophthalmic Center, Tongren Hospital, Beijing University of Medical Science, 100730, PR China
3Department of Pathology, D06, University of Sydney, 2006
4Molecular Biology Facility, Bosch Institute, F13, University of Sydney,2006

Objective: 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).

Research Design and Methods: 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) and VEGF-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.

Results: 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.

Conclusions: 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.


Correspondence: xzhang{at}eye.usyd.edu.au

Key Words: VEGF-A/VEGF-A Receptors • Triamcinolone Acetonide • Diabetic Retinopathy • Blood-Retinal Barrier


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