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M.S. Razzaque, T. Khan, E.A. Khan, B. Ahmed, C.S. Foster, A.R. Ahmed; Connective Tissue Growth Factor in Ocular Cicatricial Pemphigoid: Possible Role in Conjunctival Scarring . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3771.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Conjunctival fibrosis due to excessive accumulation of matrix proteins is an important histological feature in ocular cicatricial pemphigoid (OCP). The fibrogenic role of transforming growth factor-ß1 (TGF-ß1) in conjunctival scarring in patients with OCP has been documented. Connective tissue growth factor (CTGF) is an important downstream mediator of TGF-ß1-induced matrix protein synthesis, and plays important role in fibrogenesis in various organs. We studied the role of CTGF in conjunctival scarring in patients with OCP. Methods: Biopsy specimens from conjunctiva of 10 patients with OCP, and 5 normal subjects, were studied for the expression of CTGF and interstitial type I collagen, by immunohistochemistry and real time PCR. Using conjunctival fibroblast cell culture system, we also determined the effects of TGF-ß1 on the induction of CTGF and type I collagen. Results: An increased stromal accumulation of interstitial type I collagen with an increased expression of CTGF was observed in biopsy sections of patients with OCP, compared to control. By quantitative real-time PCR, a 3.2 fold increase in the expression of CTGF was detected in conjunctival tissues obtained from OCP patients, compared to control conjunctiva. Similarly, fibroblasts isolated from conjunctiva of OCP patients showed increased expression CTGF, both at the mRNA and protein level, compared to control conjunctival fibroblasts. Furthermore, when conjunctival fibroblasts were treated with TGF-ß1, about 9 fold increase in the expression of CTGF, and about 3 fold increase in the expression of type I collagen were detected, compared to unstimulated fibroblasts, by real-time PCR; suppressing the bioactivities of TGF-ß1 by adding neutralizing antibody to its type II receptor resulted in reduced expression of type I collagen and CTGF. Conclusions: We have demonstrated an increased expression of CTGF in conjunctiva of OCP patients, and that TGF-ß1 is able to induce CTGF by conjunctival fibroblasts. Hence CTGF may play a fibrogenic role in the pathogenesis of conjunctival scarring in patients with OCP.
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