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.
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.
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.
Smad7 gene transfer suppresses fibrogenic responses to TGF-β2 by retinal pigment epithelial cells in vitro and in vivo.
Smad7 gene transfer might be a new strategy to prevent and treat proliferative vitreoretinopathy.