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O. Yamanaka, K. Ikeda, S. Saika, A. Ooshima, Y. Ohnishi; Suppression of Conjunctival Scarring by Adenoviral Gene Transfer of BMP7 cDNA in Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):55.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine the suppressing effect of ectopic expression of bone morphogenic protein–7 (BMP7) on post–traumatic conjunctival scaring in mice. BMP7 has antagonistic effects on TGF–ß that is involved in the response to tissue fibrosis. Methods: Adult C57BL/6 mice were generally anesthetized (n=48). A circumferential incision was made in conjunctiva in the equator by using scissors in the right eye. BMP7cDNA was transferred by topical aplication of adenoviruses of Cre/LoxP system, which uses CAG promoter (therapy group). Eyes received CAG/Cre virus alone reserved as control. At 5, 7 days (each, n=24) the eyes were processed for histological or immunohistochemical examination after being sacrificed. In addition, the effect of BMP7 cDNA gene transfer on m–RNA expressions of type I collagen α1 chain (1A1) and connective tissue growth factor (CTGF) were examined in the cultured human subconjunctival fibroblasts. Results: Exoegnous BMP7 was expressed in conjunctiva epithelium and fibroblasts in the therapy group in vivo. In the control group endogenous BMP7 was hardly detected. Immunohistochemistry showed reduction of phosphorylation of Smad2 with up–regulation of phospho–Smad1/5/8 in regenerated conjuncitva in the therapy group, whereas it was readily observed in epithelial nuclei in the control group. Smooth muscle alpha–actin expression by fibroblasts and invasion of F4/80–labeled macrophages were both less in the treated group as compared with those in the control group. Expressions of 1A1 mRNA and CTGF were reduced by BMP7cDNA introduction in cultured fibroblasts. Conclusions: BMP7 gene transfer suppresses scarring in injured, healing, conjunctiva in mice, suggesting it can be a strategy to prevent excess scarring following glaucoma filtration surgery.
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