siRNA Targeting Mammalian Target of Rapamycin (mTOR) Attenuates Experimental Proliferative Vitreoretinopathy

Abstract

Purpose: To investigate the effect of mammalian target of rapamycin (mTOR) specific siRNA on proliferative vitreoretinopathy (PVR). Methods: Cultured human retinal pigment epithelial (hRPE) cell line D407 was treated with three mTOR specific small interfering RNAs. Cell proliferation, attachment, spreading, and migration were performed. The impact of the mTOR specific siRNA on PVR was tested using a rabbit model in which PVR was induced by the injection of hRPE cells. Results: Decreasing mTOR expression by about 82% using small interfering RNA resulted in a significant decrease in cell spreading and migration. Whereas retinal detachment occurred in 100% of the control group animals, co-injection of the mTOR specific siRNA substantially reduced the severity and incidence (50%) of retinal detachments. Conclusions: Gene therapy with mTOR specific siRNA attenuates PVR in a rabbit model of the disease. This may be a new approach to preventing PVR in humans.

KEYWORDS:

• human retinal pigment epithelial cell
• mammalian target of rapamycin
• migration
• proliferative vitreoretinopathy
• small interfering RNA