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Rintaro Tsukahara, Kazuhiko Umazume, Kevin McDonald, Hiroshi Goto, Henry J Kaplan, Shigeo Tamiya; Dasatinib inhibits contraction of Müller and RPE cells on type I collagen gel assay. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1081.
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Proliferative vitreoretinopahty (PVR) is the major complication of retinal detachment surgery and traumatic ocular injury. We have recently demonstrated that Dasatinib, a FDA approved cancer medication, can prevent the complications of PVR in our swine model induced by RPE cells. In this study, we examined the effect of Dasatinib on Müller glial cells, another cell type implicated in PVR development.
Müller cells and RPE cells were isolated from porcine eyes using a papain/DNase kit and dispase, respectively. Primary cultures were maintained in FBS-supplemented DMEM, and used between passages 3-6 for contraction assays. Müller or RPE cells were cultured on type I collagen matrices for 3 days in DMEM, supplemented with 25% vitreous fluid or 5%FBS, in the presence or absence of Dasatinib. Collagen matrices released from the adhering culture plates were photographed 4 hours later and the change in size measured to determine the degree of contraction.
As previously reported, contraction of RPE cells on collagen matrices was significantly inhibited by dasatinib. We now observed that matrix contraction of Müller cells was also inhibited by dasatinib, in a dose dependent manner. Dasatinib concentrations of 0.1 μM or higher significantly reduced collagen matrix contraction by Müller cells stimulated with either 25% vitreous or 5%FBS.
Contraction by cells involved in the development of PVR leads to retinal folds and traction retinal detachment, the debilitating complications of PVR. The FDA approved cancer medication Dasatinib significantly inhibits contraction of the matrix in a collagen I gel assay caused by both RPE and Müller cells, the two major cellular phenotypes implicated in PVR. Therefore, dasatinib may be clinically useful for the prevention of the complications of PVR.
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