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: Khaled Nassar, Swaantje Grisanti, Aysegul Tura, Julia Lüke, Matthias Lüke, Mahmoud Soliman, Salvatore Grisanti
• Journal: Experimental eye research (Exp Eye Res) Vol. 123 Pg. 72-86 (Jun 2014) ISSN: 1096-0007 [Electronic] England
• PMID: 24742493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• HTS 466284
• Pyrazoles
• Pyrroles
• Receptors, Transforming Growth Factor beta
• Tetrazolium Salts
• Thiazoles
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type I
• thiazolyl blue

Topics

• Animals
• Cell Proliferation (drug effects)
• Cell Transdifferentiation (drug effects)
• Disease Models, Animal
• Fibroblasts (drug effects)
• Humans
• Intravitreal Injections
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Pyrazoles (pharmacology)
• Pyrroles (pharmacology)
• Rabbits
• Receptor, Transforming Growth Factor-beta Type I
• Receptors, Transforming Growth Factor beta (antagonists & inhibitors)
• Retinal Pigment Epithelium (cytology)
• Tenon Capsule (cytology)
• Tetrazolium Salts (metabolism)
• Thiazoles (metabolism)
• Vitreoretinopathy, Proliferative (metabolism, pathology, prevention & control)