Connective Tissue Growth Factor Is Necessary for Retinal Capillary Basal Lamina Thickening in Diabetic Mice

Abstract

Purpose: : Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes due to diabetes. Connective tissue growth factor (CTGF) is upregulated early in diabetes in the human retina and is a potent inducer of expression of BL components such as fibronectin and collagen type IV. We hypothesize that CTGF is causally involved in diabetes-induced BL thickening of retinal capillaries.

Methods: : To test this hypothesis, we compared the effects of streptozotocin (STZ)-induced diabetes on retinal capillary BL thickness between wild type mice (CTGF^+/+) and mice lacking one functional CTGF allele (CTGF^+/-). Differences in BL thickness were calculated by quantitative analysis of electron microscopical images of transversal sectioned capillaries in and around the inner nuclear layer of the retina.

Results: : It is shown that BL thickening was significant in diabetic CTGF^+/+ mice compared to control CTGF^+/+ mice, whereas diabetes did not significantly induce BL thickening in CTGF^+/- mice.

Conclusions: : CTGF expression is necessary for diabetes-induced BL thickening and suggests that reduction of CTGF levels may be protective against the development of diabetic retinopathy.

Keywords: diabetic retinopathy • growth factors/growth factor receptors • extracellular matrix