Increased Transcription of Connective Tissue Growth Factor in Daibetic Rat Retina: Attenuation With Aminoguanidine

Abstract

Abstract: : The thickening of the basement membrane of the retinal vasculature is a hallmark of early pre–clinical diabetic retinopathy (DR). Connective tissue growth factor (CTGF) is a known inducer of extracellular matrix molecules including components of the vascular basement membrane. Purpose: In this study we used real–time quantitative PCR to evaluate the gene expression of CTGF in the retinas of diabetic rats with and without aminoguanidine treatment. Methods: Gene expression levels of CTGF were measured using real–time qPCR at 6 and 12 weeks post induction of diabetes in three groups of rats; non–diabetic controls, diabetic and diabetic with aminoguanidine treatment. Results: Retinal gene expression of CTGF in 12 week diabetic rats increased 1.74–fold ( P = 0.01 ) as compared to control rats. Treatment with the anti–advanced glycation endproduct (AGE) agent aminoguanidine significantly reduced this increase returning CTGF levels to those of the controls. Conclusions: In this study we demonstrate for the first time the inhibitory effect of aminoguanidine on CTGF expression in the diabetic retina. Previous studies have shown that aminoguanidine treatment protected against diabetic induced thickening of the retinal vascular basement membrane. We propose that diabetic vascular basement membrane thickening is caused, in part, by AGE induced increases in retinal CTGF expression. Furthermore, the protective effects of aminoguanidine (and possibly other AGE inhibitors as well) on retinal pathology may partly be mediated via effects on retinal CTGF expression.

Keywords: diabetic retinopathy • growth factors/growth factor receptors