siRNA targeting mammalian target of rapamycin (mTOR) attenuates experimental proliferative vitreoretinopathy.
OBJECTIVE
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.
Zhou
Peng
P
Department of Ophthalmology, Peking University People's Hospital, Beijing, China.
Zhao
Ming-Wei
MW
Li
Xiao-Xin
XX
Yu
Wen-Zhen
WZ
Bian
Zong-Mei
ZM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011494:Protein Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D011817:Rabbits; D012163:Retinal Detachment / Q000209:etiology / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases; D014162:Transfection; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology / Q000517:prevention & control*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases