June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The effect of Dasatinib in PVR model
Author Affiliations & Notes
  • Kazuhiko Umazume
    Ophthalmology & Visual Sciences, Tokyo Medical University, Tokyo, Japan
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky, United States
  • Ryousuke Matsushima
    Ophthalmology & Visual Sciences, Tokyo Medical University, Tokyo, Japan
  • Rintaro Tsukahara
    Ophthalmology & Visual Sciences, Tokyo Medical University, Tokyo, Japan
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky, United States
  • Naoyuki Yamakawa
    Ophthalmology & Visual Sciences, Tokyo Medical University, Tokyo, Japan
  • Shigeo Tamiya
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky, United States
  • Hiroshi Goto
    Ophthalmology & Visual Sciences, Tokyo Medical University, Tokyo, Japan
  • Footnotes
    Commercial Relationships   Kazuhiko Umazume, None; Ryousuke Matsushima, None; Rintaro Tsukahara, None; Naoyuki Yamakawa, None; Shigeo Tamiya, None; Hiroshi Goto, None
  • Footnotes
    Support  JSPS KAKENHI Grant Number 16K20335 (K Umazume)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5975. doi:
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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