March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
A Novel Function of p53: A Gatekeeper of Retinal Detachment
Author Affiliations & Notes
  • Hetian Lei
    Ophthalmology of Harvard Medical School, Schepens Eye Research Institute/Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Marc-Andr Rheaume
    Ophthalmology of Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Jing Z. Cui
    Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Shizuo Mukai
    Ophthalmology of Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • David Maberley
    Ophthalmology & Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada
  • Arif Samad
    Ophthalmology & Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada
  • Joanne A. Matsubara
    Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Andrius Kazlauskas
    Ophthalmology of Harvard Medical School, Schepens Eye Research Institute/Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Hetian Lei, None; Marc-Andr Rheaume, None; Jing Z. Cui, None; Shizuo Mukai, None; David Maberley, None; Arif Samad, None; Joanne A. Matsubara, None; Andrius Kazlauskas, None
  • Footnotes
    Support  NIH grant EY012509 to AK.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 894. doi:
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      Hetian Lei, Marc-Andr Rheaume, Jing Z. Cui, Shizuo Mukai, David Maberley, Arif Samad, Joanne A. Matsubara, Andrius Kazlauskas; A Novel Function of p53: A Gatekeeper of Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2012;53(14):894.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The goals of this study were to 1) test if the previously noted correlation between the platelet-derived growth factor receptor α (PDGFRα)-mediated decline in the level of p53 and development of proliferative vitreoretinopathy (PVR) was causally related, and 2) test if Nutlin-3-mediated stabilization of p53 is effective in inhibiting PVR progression to retinal detachment (RD).

Methods: : The effect of altering p53 expression on cell contraction was assessed with an in vitro collagen gel contraction assay, whereas its impact on RD was monitored in a model of PVR that involves injecting fibroblasts in the vitreous of rabbits. Expression of p53 was manipulated by either short-hairpin (sh) RNA or with Nutlin-3, a pharmacological inhibitor of p53 degradation. The efficacy of these approaches was assessed by Western blotting using antibodies specific for p53.

Results: : Suppression of p53 expression was required for PDGFRα-mediated contraction of cells in a collagen gel, and for RD in the rabbit model of PVR. Furthermore, maintenance of p53 expression with Nutlin-3 protected rabbits from RD. In addition, Nutlin-3 prevented human PVR vitreous-induced contraction of cells isolated from a patient PVR membrane.

Conclusions: : p53 appears to be a gatekeeper of RD in PVR. Nutlin-3, which enforces p53 expression, may be effective in suppressing RD in patients afflicted by PVR.

Keywords: retinal detachment • proliferative vitreoretinopathy • signal transduction 
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