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

Esther J. Kuiper, Rogier van Zijderveld, Peggy Roestenberg, Karen M. Lyons, Roel Goldschmeding, Ingeborg Klaassen, Cornelis J.F. Van Noorden and Reinier O. Schlingemann

Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (EJK,RVZ,IK,CJFVN,ROS); Department of Pathology, Academic Medical Center of Utrecht, Utrecht, The Netherlands (PR,RG); and Department of Orthopedic Surgery, University of California, Los Angeles, California (KML)

Correspondence to: C.J.F. Van Noorden, Department of Cell Biology and Histology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail: c.j.vannoorden{at}amc.uva.nl

Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes caused by 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. We hypothesize that CTGF is causally involved in diabetes-induced BL thickening of retinal capillaries. 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 microscopic images of transversally sectioned capillaries in and around the inner nuclear layer of the retina. We show that BL thickening was significant in diabetic CTGF^+/+ mice compared with control CTGF^+/+ mice, whereas diabetes did not significantly induce BL thickening in CTGF^+/– mice. We conclude that CTGF expression is necessary for diabetes-induced BL thickening and suggest that reduction of CTGF levels may be protective against the development of diabetic retinopathy. (J Histochem Cytochem 56:785–792, 2008)

Key Words: connective tissue growth factor • diabetes • diabetic retinopathy • basal lamina • basement membrane • retina • capillary • transgenic

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