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Shawn A. Morales, David G. Telander, Alfred K. Yu, Krisztina I. Forward, Jonathan Braun, Lynn K. Gordon; Dasatinib inhibits experimental PVR progression. Invest. Ophthalmol. Vis. Sci. 2012;53(14):899.
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The retinal pigment epithelium (RPE) plays an important role in proliferative vitreoretinopathy (PVR), an aberrant wound-healing process caused in part by RPE cell migration, membrane formation, and contractile cellular forces leading to tractional retinal detachment. Using an in vitro model of PVR, collagen gel contraction, we have previously shown that EMP2 regulates collagen gel contraction through FAK recruitment and activation in ARPE-19 cells. The purpose of this study is to design a preclinical efficacy study targeting the FAK/Src pathway with the Src kinase inhibitor Dasatinib.
ARPE-19 cells were used in a rabbit model of PVR. The cells were pretreated with various concentrations of Dasatinib or vehicle control. The capacity of the cells to generated PVR was assessed by weekly examinations in a masked fashion by indirect ophthalmoscopy. A gross exam was performed at week 6 and PVR was scored by the Fastenberg method.
Collagen gel contraction is significantly reduced in Dasatinib treated ARPE-19 cells. Dasatinib did not show any toxicity in the ARPE-19 cells. Dose escalation of Dasatinib demonstrated a dose response with ARPE-19 cells in reducing PVR progression in the rabbit model.
Pharmacologic inhibition of the FAK/Src pathway significantly reduced the PRV potential of RPE cells. Dasatinib has been approved for use in patients with certain forms of cancer. Dasatinib may prove to be a novel and effective therapeutic against PVR associated vision loss.
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