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Effect of Smad7 Gene Overexpression on Transforming Growth Factor β–Induced Retinal Pigment Fibrosis in a Proliferative Vitreoretinopathy Mouse Model
Shizuya Saika, MD, PhD;
Osamu Yamanaka, MD, PhD;
Iku Nishikawa-Ishida, MD, PhD;
Ai Kitano, MD;
Kathleen C. Flanders, MD, PhD;
Yuka Okada, MD, PhD;
Yoshitaka Ohnishi, MD, PhD;
Yuji Nakajima, MD, PhD;
Kazuo Ikeda, MD, PhD
Arch Ophthalmol. 2007;125(5):647-654.
Objective To determine the effects of Smad7 gene transfer in the prevention of fibrogenic responses by the retinal pigment epithelium, a major cause of proliferative vitreoretinopathy after retinal detachment, in mice.
Methods Retinal detachment–induced proliferative vitreoretinopathy in a mouse model. Forty-eight eyes received either an adenoviral gene transfer of Smad7 or Cre recombinase gene only. The eyes were histologically analyzed. A retinal pigment epithelial cell line, ARPE-19, was used to determine whether Smad7 gene transfection suppresses the fibrogenic response to transforming growth factor (TGF) β2 exposure.
Results The Smad7 gene transfer inhibited TGF-β2/Smad signaling in ARPE-19 cells and expression of collagen type I and TGF-β1 but had no effect on their basal levels. In vivo Smad7 overexpression resulted in suppression of Smad2/3 signals and of the fibrogenic response to epithelial-mesenchymal transition by the retinal pigment epithelium.
Conclusion Smad7 gene transfer suppresses fibrogenic responses to TGF-β2 by retinal pigment epithelial cells in vitro and in vivo.
Clinical Relevance Smad7 gene transfer might be a new strategy to prevent and treat proliferative vitreoretinopathy.
Author Affiliations: Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan (Drs Saika, Yamanaka, Nishikawa-Ishida, Kitano, Okada, and Ohnishi); Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Md (Dr Flanders); and Department of Anatomy, Graduate School of Medicine, Osaka City University, Osaka, Japan (Drs Nakajima and Ikeda).
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