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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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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).
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.
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.
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.
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