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Connective Tissue Growth Factor Is Up-Regulated in the Diabetic Retina: Amelioration by Angiotensin-Converting Enzyme Inhibition

Department of Medicine, University of Melbourne, Austin and Repatriation Medical Center (C.T., M.E.C., W.C.B., M.T.), Heidelberg West 3081, Australia; Baker Medical Research Institute (C.T., M.E.C., W.C.B.), St. Kilda Central, Melbourne 8008, Australia; and Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital (S.M.T.), St. Leonards 2065, Australia

Address all correspondence and requests for reprints to: Dr. Chris Tikellis, Baker Medical Research Institute, P.O. Box 6492, St. Kilda Central, Melbourne 8008, Australia. E-mail: chris.tikellis{at}baker.edu.au.

Connective tissue growth factor (CTGF) has been postulated to have prosclerotic and angiogenic properties. The aim of this present study was to characterize retinal CTGF expression in the absence and presence of diabetes and in the context of treatment with the angiotensin-converting enzyme (ACE) inhibitor, perindopril. Retinas were obtained from control, diabetic, and diabetic plus perindopril-treated (3 mg/d) rats. CTGF gene expression was quantitated by RT-PCR and localized by in situ hybridization. CTGF protein expression was analyzed by Western blotting and localized by immunohistochemistry. Diabetes was associated with a greater than 2-fold increase in CTGF mRNA levels, which was attenuated by perindopril treatment. CTGF immunoreactivity was increased almost 2-fold in diabetes and was ameliorated by the ACE inhibitor perindopril. By in situ hybridization and immunohistochemistry, the major site of CTGF gene expression in the retina of diabetic rats was the ganglion cell layer. Based on the known in vivo effects of CTGF, it is postulated that this growth factor plays a pivotal role in mediating diabetes-associated retinal pathology. Furthermore, the protective effects of ACE inhibitors on retinal pathology may partly be mediated via effects on retinal CTGF expression.

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