title: A TGF-β receptor 1 inhibitor for prevention of proliferative vitreoretinopathy.
abstract: This study evaluates the use of the TGF-β receptor 1 inhibitor LY-364947 (LY) to prevent proliferative vitreoretinopathy (PVR). For the in vitro experiments Human Tenon's Fibroblasts (HTFs) and retinal pigment epithelial (RPE) cells were treated with different concentrations of LY to determine HTF proliferation and RPE transdifferentiation. For in vivo testing 30 rabbits underwent a PVR trauma model. The animals received different concentrations of intravitreally injected LY, with or without vitrectomy. LY treatment reduced HTF proliferation and RPE transdifferentiation in vitro. In vivo intravitreal injection of LY prevented PVR development significantly. This positive effect was also present when LY injection was combined with vitrectomy. Intravitreal injection of LY prevented tractional retinal detachment in 14 out of 15 animals. In conclusion, treatment with the TGF-β receptor 1 inhibitor LY reduces HTF proliferation and RPE transdifferentiation in vitro and prevents proliferative vitreoretinopathy and subsequent tractional retinal detachment in vivo.
authors.affiliation: University of Luebeck, Department of Ophthalmology, Ratzeburger Allee 160, D-23538 Luebeck, Germany; Fayoum University, Department of Ophthalmology, 63514 Fayoum, Egypt. Electronic address: khaledmohnassar@yahoo.com.
authors.forename: Khaled
authors.initials: K
authors.lastname: Nassar
authors.affiliation: University of Luebeck, Department of Ophthalmology, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
authors.forename: Swaantje
authors.initials: S
authors.lastname: Grisanti
authors.affiliation: University of Luebeck, Department of Ophthalmology, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Tura
authors.affiliation: University of Luebeck, Department of Ophthalmology, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Lüke
authors.affiliation: University of Luebeck, Department of Ophthalmology, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lüke
authors.affiliation: Cairo University, Department of Ophthalmology, 11956 Cairo, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
authors.affiliation: University of Luebeck, Department of Ophthalmology, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D058449:Intravitreal Injections; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D055213:Retinal Pigment Epithelium / Q000166:cytology; D058475:Tenon Capsule / Q000166:cytology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011804:Quinolines
chemical_list: D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D011758:Pyrroles; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D013778:Tetrazolium Salts; D013844:Thiazoles; C506615:HTS 466284; D011804:Quinolines; C022616:thiazolyl blue
keywords: LY-364947; TGF-β receptor 1; penetrating eye injury; proliferative vitreoretinopathy; vitrectomy