Differential expression of connective tissue growth factor in microglia and pericytes in the human diabetic retina

Differential TGF-β Signaling in Retinal Vascular Cells: A Role in Diabetic Retinopathy?

“…This is in line with our previous work where we have shown that profibrotic factors involved in BL thickening of retinal capillaries in diabetes are mainly expressed in pericytes. 6,19,36,[43][44][45] In eyes of STZ-induced diabetic rats and in rats injected intraocularly with VEGF, gene expression of CTGF, FN, collagen, and TIMP1 was increased, but we found that in vitro, FN and collagen were only induced by VEGF in BRPCs and not in BRECs. Furthermore, we have previously reported that CTGF is not only involved in the angiofibrotic switch in proliferative DR, 43,44 but is also necessary for diabetic retinal BL thickening in PCDR, since CTGF ϩ/Ϫ mice failed to develop this response.…”

“…Our results suggest that pericytes could play a major role in the process of BL thickening which occurs early in the pathogenesis of diabetic retinopathy (DR) by upregulation of profibrotic genes. 36 Recent evidence shows that TGF-␤ is also necessary for normal retinal vascular barrier function. 37 In the retina, the pericyte-to-endothelial ratio is relatively high (1:1) compared with other microvascular beds (1:10), 38 suggesting that pericytes largely contribute to effects of TGF-␤ on the retinal microvasculature.…”

Bone Morphogenetic Protein-7 and Connective Tissue Growth Factor: Novel Targets for Treatment of Renal Fibrosis?

“…Furthermore, severity of diabetic nephropathy was aggravated in transgenic mice with specific overexpression of CTGF in podocytes (127). Upregulation of CTGF was also confirmed in the diabetic myocardium, liver, retina, and aorta (126,(128)(129)(130). The potential use of CTGF as a biomarker for renal damage in diabetes was assessed in several clinical studies, in which soluble levels of CTGF were increased in plasma and urine of patients with diabetic nephropathy, and correlated with clinical markers of renal disease (131)(132)(133)(134).…”

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

“…CTGF expression in the retina was found to be upregulated in rats treated with vascu-lar endothelial growth factor (Kuiper et al 2007a), after STZ-induced diabetes (Tikellis et al 2004;Hughes et al 2007), as well as in mice repeatedly infused with advanced glycation end products (AGEs) (Hughes et al 2007). CTGF is expressed in vascular cells in the retina of diabetic humans with early diabetic microangiopathy (Kuiper et al 2004) and is associated with fibrosis in the human diabetic eye (Kuiper et al 2006).…”