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Kazuhiko Umazume, Ryousuke Matsushima, Rintaro Tsukahara, Naoyuki Yamakawa, Shigeo Tamiya, Hiroshi Goto; The effect of Dasatinib in PVR model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5975.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of Dasatinib, a tyrosine kinase inhibitor currently used in the treatment of chronic myeloid leukemia, on experimental in vitro proliferative vitreoretinopathy (PVR) models.
Freshly isolated porcine retinal pigment epithelium (RPE) sheets were cultured in 25% vitreous supplemented DMEM in the presence or absence of Dasatinib. Dasatinib was used at concentrations of 0.1, 0.3 and 1.0 μM. RPE sheet enlargement was measured, and immunohistochemical staining of epithelial mesenchymal transition (EMT) marker S100A4 was performed. Cultured RPE cells were seeded on collagen gels to evaluate proliferative membrane contractions by measuring the shrinkage of peeled gel after 6 days in culture (collagen gel contraction assay). Dasatinib at varying concentration was either added on days 0, 3 and 5, designated groups 1, 2, and 3, respectively.
Dasatinib significantly prevented the enlargement of RPE sheet in a concentration dependent manner. Reduced expression of S100A4 by immunohistochemical staining on cultured RPE sheets confirmed suppression of EMT by Dasatinib. Proliferative membrane in group 3 and in the absence of Dasatinib strongly expressed α-SMA compared to groups 1 and 2 at day 6. Dasatinib inhibited collagen gel contraction in groups 1 and 2(p<0.05). On the other hand, shrinkage of collagen gel was not suppressed in group 3 that had dense fibrotic membranes, despite the addition of Dasatinib.
Dasatinib significantly inhibited PVR associated cellular changes of RPE cells at early stages. However, relatively short exposure (24hrs) of dasatinib failed to prevent contraction of well-established fibrotic membranes.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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