p53 的新功能：视网膜脱离的守门员。
A novel function of p53: a gatekeeper of retinal detachment.
机构信息
The Schepens Eye Research Institute, Boston, Massachusetts, USA.
出版信息
Am J Pathol. 2012 Sep;181(3):866-74. doi: 10.1016/j.ajpath.2012.05.036.
Abstract
Proliferative vitreoretinopathy (PVR) is a blinding disease associated with rhegmatogenous retinal detachment, for which there is no satisfactory treatment. Surgery helps in many cases, but, to our knowledge, there are no pharmacological approaches to reduce PVR risk. We report that suppressing expression of p53 was a required event in two assays of PVR (namely, platelet-derived growth factor receptor α-mediated contraction of cells in a collagen gel and retinal detachment in an animal model of PVR). Furthermore, preventing the decline in the level of p53 with agents such as Nutlin-3 protected from retinal detachment, which is the most vision-compromising component of PVR. Finally, Nutlin-3 may be effective in the clinical setting because it prevented human PVR vitreous-induced contraction of cells isolated from a patient PVR membrane. These studies identify Nutlin-3 as a potential PVR prophylaxis.
摘要
增生性玻璃体视网膜病变（PVR）是一种与孔源性视网膜脱离相关的致盲性疾病，目前尚无满意的治疗方法。手术在许多情况下都有帮助，但据我们所知，目前还没有药物方法来降低 PVR 风险。我们报告称，抑制 p53 的表达是两种 PVR 检测方法中的必需事件（即血小板衍生生长因子受体α介导的细胞在胶原凝胶中的收缩和 PVR 动物模型中的视网膜脱离）。此外，用 Nutlin-3 等药物防止 p53 水平下降可预防视网膜脱离，这是 PVR 中最损害视力的部分。最后，Nutlin-3 在临床环境中可能是有效的，因为它阻止了来自患者 PVR 膜的细胞的人 PVR 玻璃体诱导的收缩。这些研究将 Nutlin-3 确定为一种潜在的 PVR 预防药物。
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