title: Resveratrol inhibits epithelial-mesenchymal transition of retinal pigment epithelium and development of proliferative vitreoretinopathy.
abstract: Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and ocular trauma, and its recurrence may lead to irreversible vision loss. Epithelial to mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a critical step in the pathogenesis of PVR, which is characterized by fibrotic membrane formation and traction retinal detachment. In this study, we investigated the potential impact of resveratrol (RESV) on EMT and the fibrotic process in cultured RPE cells and further examined the preventive effect of RESV on PVR development using a rabbit model of PVR. We found that RESV induces mesenchymal to epithelial transition (MET) and inhibits transforming growth factor-β2(TGF-β2)-induced EMT of RPE cells by deacetylating SMAD4. The effect of RESV on MET was dependent on sirtuin1 activation. RESV suppressed proliferation, migration and fibronectin synthesis induced by platelet-derived growth factor-BB or TGF-β2. In vivo, RESV inhibited the progression of experimental PVR in rabbit eyes. Histological findings showed that RESV reduced fibrotic membrane formation and decreased α-SMA expression in the epiretinal membranes. These results suggest the potential use of RESV as a therapeutic agent to prevent the development of PVR by targeting EMT of RPE.
authors.affiliation: Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, USA.|Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.|Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Shikun
authors.initials: S
authors.lastname: He
authors.affiliation: Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, USA.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Terasaki
authors.affiliation: Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nazari
authors.affiliation: Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Huiming
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Spee
authors.affiliation: Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Kannan
authors.affiliation: Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.|Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
mesh_terms: D000107:Acetylation; D000818:Animals; D015415:Biomarkers; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000096:biosynthesis; D011817:Rabbits; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D056564:Sirtuin 1 / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D005353:Fibronectins; D051901:Smad4 Protein; D013267:Stilbenes; D053781:Transforming Growth Factor beta2; D056564:Sirtuin 1; D000077185:Resveratrol