Effect of Smad7 gene overexpression on transforming growth factor beta-induced retinal pigment fibrosis in a proliferative vitreoretinopathy mouse model.
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) beta2 exposure.


RESULTS
The Smad7 gene transfer inhibited TGF-beta2/Smad signaling in ARPE-19 cells and expression of collagen type I and TGF-beta1 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.


CONCLUSIONS
Smad7 gene transfer suppresses fibrogenic responses to TGF-beta2 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.
Saika
Shizuya
S
Department of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. shizuya@wakayama-med.ac.jp
Yamanaka
Osamu
O
Nishikawa-Ishida
Iku
I
Kitano
Ai
A
Flanders
Kathleen C
KC
Okada
Yuka
Y
Ohnishi
Yoshitaka
Y
Nakajima
Yuji
Y
Ikeda
Kazuo
K
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000502:physiology*; D005822:Genetic Vectors; D051379:Mice; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D024042:Collagen Type I; D005353:Fibronectins; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1