A TGF-β receptor 1 inhibitor for prevention of proliferative vitreoretinopathy

- Proliferative vitreoretinopathy (PVR) limits the success of vitreoretinal surgery.
- LY-364947 (LY) is a selective pyrazole-based inhibitor of the TGFBR1.
- In vitro, LY inhibits cell proliferation and RPE transdifferentiation.
- Intravitreal injection of LY prevents PVR in a rabbit model of traumatic PVR.
- Vitrectomy plus intravitreal LY completely prevents tractional retinal detachment.

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.

179