SU9518 inhibits proliferative vitreoretinopathy in fibroblast and genetically modified Müller cell-induced rabbit models.

Abstract

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 Müller glia, may be responsible. Platelet-derived growth factor receptor alpha (PDGFRα) 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 PDGFRα specificity, can inhibit the development of PVR in fibroblast and Müller cell rabbit models of PVR.

METHODS:

SU9518 was injected in rabbit eyes along with fibroblasts, Müller cells (MIO-M1), or Müller cells transfected to increase their expression of PDGFRα (MIO-M1α). Indirect ophthalmoscopy and histopathology were used to assess efficacy and toxicity.

RESULTS:

SU9518 was an effective inhibitor of PVR in both fibroblast and Müller 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.

• Authors: Gisela Velez, Alexa R Weingarden, Hetian Lei, Andrius Kazlauskas, Guangping Gao
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 54 Issue 2 Pg. 1392-7 (Feb 19 2013) ISSN: 1552-5783 [Electronic] United States
• PMID: 23341018 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Indoles
• SU9518
• Receptors, Platelet-Derived Growth Factor

Topics

• Animals
• Cell Division
• Cells, Cultured
• Disease Models, Animal
• Fibroblasts (drug effects, pathology)
• Humans
• Indoles (pharmacology)
• Rabbits
• Receptors, Platelet-Derived Growth Factor (antagonists & inhibitors, metabolism)
• Retinal Pigment Epithelium (drug effects, pathology)
• Vitreoretinopathy, Proliferative (drug therapy, metabolism, pathology)
• Vitreous Body (drug effects, metabolism, pathology)