SU9518 inhibits proliferative vitreoretinopathy in fibroblast and genetically modified Muller cell-induced rabbit models
Department of Opthomology; Gene Therapy Center; Department of Microbiology and Physiological Systems
Animals; Cell Division; Cells, Cultured; Disease Models, Animal; Fibroblasts; Humans; Indoles; Rabbits; Receptors, Platelet-Derived Growth Factor; Retinal Pigment Epithelium; Vitreoretinopathy, Proliferative; Vitreous Body
Eye Diseases | Genetics and Genomics | Ophthalmology
PURPOSE: Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment that can lead to surgical failure and vision loss. Previous studies suggest that a variety of retinal cells, including RPE and Muller glia, may be responsible. Platelet-derived growth factor receptor alpha (PDGFRalpha) has been strongly implicated in the pathogenesis, and found to be intrinsic to the development of PVR in rabbit models. We examine whether SU9518, a tyrosine kinase inhibitor with PDGFRalpha specificity, can inhibit the development of PVR in fibroblast and Muller cell rabbit models of PVR.
METHODS: SU9518 was injected in rabbit eyes along with fibroblasts, Muller cells (MIO-M1), or Muller cells transfected to increase their expression of PDGFRalpha (MIO-M1alpha). Indirect ophthalmoscopy and histopathology were used to assess efficacy and toxicity.
RESULTS: SU9518 was an effective inhibitor of PVR in both fibroblast and Muller cell models of PVR. No toxic effects were identified by indirect ophthalmoscopy or histopathology.
CONCLUSIONS: SU9518 is an effective and safe inhibitor of PVR in rabbit models, and could potentially be used in humans for the treatment of this and other proliferative diseases of the retina involving fibrosis and gliosis. Further animal studies need to be performed to examine retinal toxicity and sustained delivery mechanisms.
DOI of Published Version
Invest Ophthalmol Vis Sci. 2013 Feb 19;54(2):1392-7. doi: 10.1167/iovs.12-10320. Link to article on publisher's site
Investigative ophthalmology and visual science
Velez, Gisela; Weingarden, Alexa R.; Lei, Hetian; Kazlauskas, Andrius; and Gao, Guangping, "SU9518 inhibits proliferative vitreoretinopathy in fibroblast and genetically modified Muller cell-induced rabbit models" (2013). University of Massachusetts Medical School Faculty Publications. 181.