title: TGF-β2 secretion from RPE decreases with polarization and becomes apically oriented.
abstract: Retinal pigmented epithelium (RPE) secretes transforming growth factor beta 1 and 2 (TGF-β1 and -β2) cytokines involved in fibrosis, immune privilege, and proliferative vitreoretinopathy (PVR). Since RPE cell polarity may be altered in various disease conditions including PVR and age-related macular degeneration, we determined levels of TGF-β from polarized human RPE (hRPE) and human stem cell derived RPE (hESC-RPE) as compared to nonpolarized cells. TGF-β2 was the predominant isoform in all cell culture conditions. Nonpolarized cells secreted significantly more TGF-β2 supporting the contention that loss of polarity of RPE in PVR leads to rise of intravitreal TGF-β2. Active TGF-β2, secreted mainly from apical side of polarized RPE, represented 6-10% of total TGF-β2. In conclusion, polarity is an important determinant of TGF-β2 secretion in RPE. Low levels of apically secreted active TGF-β2 may play a role in the normal physiology of the subretinal space. Comparable secretion of TGF-β from polarized hESC-RPE and hRPE supports the potential for hESC-RPE in RPE replacement therapies.
authors.affiliation: Department of Ophthalmology, Keck School of Medicine of the University of Southern California, United States.
authors.forename: Louis
authors.initials: L
authors.lastname: Hirsch
authors.affiliation: Department of Ophthalmology, Keck School of Medicine of the University of Southern California, United States.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nazari
authors.affiliation: Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, United States.
authors.forename: Parameswaran G
authors.initials: PG
authors.lastname: Sreekumar
authors.affiliation: Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, United States.
authors.forename: Ram
authors.initials: R
authors.lastname: Kannan
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, United States.
authors.forename: Laurie
authors.initials: L
authors.lastname: Dustin
authors.affiliation: Department of Ophthalmology, Keck School of Medicine of the University of Southern California, United States; Department of Pathology, Keck School of Medicine of the University of Southern California, United States.
authors.forename: Danhong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, United States.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Barron
authors.affiliation: Department of Ophthalmology, Keck School of Medicine of the University of Southern California, United States; Department of Pathology, Keck School of Medicine of the University of Southern California, United States. Electronic address: dhinton@usc.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
mesh_terms: D017690:Cell Transplantation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000276:immunology; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*; D018630:Vitreoretinopathy, Proliferative / Q000473:pathology
chemical_list: D020033:Protein Isoforms; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2
keywords: Embryonic stem cell; Polarity; Proliferative vitreoretinopathy; Retinal pigment epithelium; TGF-β