Marti A, Hafezi F, Lansel N, Hegi M E, Wenzel A, Grimm C, Niemeyer G, Remé C E
Department of Ophthalmology, University Hospital, Zurich, Switzerland.
Invest Ophthalmol Vis Sci. 1998 Apr;39(5):846-9.
Cell death by apoptosis is essential for normal development and tissue homeostasis, and it is involved also in a variety of pathologic processes. Apoptosis is the final common pathway of photoreceptor cell death in retinal dystrophies and degeneration. So far, little is known about genes regulating apoptosis in the retina. The tumor-suppressor gene product p53 is a potent regulator of apoptosis in numerous systems. However, p53-independent apoptotic pathways also have been described. In this study the authors investigated the role of p53 in the light-induced apoptosis of retinal photoreceptors using mice lacking p53.
Free-moving p53-/- and p53+/+ mice were dark adapted and were exposed to 8,500 or 15,000 lux of diffuse, cool, white fluorescent light for 2 hours. Animals were killed before and immediately after light exposure or at 12 hours in darkness after light exposure. Eyes were enucleated and processed for light and electron microscopy and histochemistry (TdT-dUTP terminal nick-end labeling method). Isolated retinas were subjected to the extraction of total retinal DNA. Electroretinogram (ERG) recordings were performed at all time points.
Morphologic, biochemical, histochemical, and ERG analysis showed that the retinas of untreated p53-/- mice and wild-type control mice were structurally and functionally indistinguishable. After exposure to diffuse white fluorescent light, light-induced photoreceptor cell death was analyzed and was found to be the same in both groups of mice.
These data suggest that light-induced apoptosis of photoreceptors is independent of functional p53.
细胞凋亡对于正常发育和组织稳态至关重要，并且还参与多种病理过程。凋亡是视网膜营养不良和变性中光感受器细胞死亡的最终共同途径。到目前为止，关于调节视网膜细胞凋亡的基因知之甚少。肿瘤抑制基因产物p53是众多系统中细胞凋亡的有效调节因子。然而，也有p53非依赖的凋亡途径的报道。在本研究中，作者利用缺乏p53的小鼠研究了p53在光诱导的视网膜光感受器细胞凋亡中的作用。
自由活动的p53基因敲除小鼠和野生型小鼠暗适应后，暴露于8500或15000勒克斯的漫射、冷白色荧光下2小时。在光照前、光照后即刻或光照后黑暗环境中12小时处死动物。摘除眼球，进行光镜、电镜和组织化学（TdT-dUTP末端脱氧核苷酸转移酶介导的缺口末端标记法）处理。分离视网膜提取总视网膜DNA。在所有时间点进行视网膜电图（ERG）记录。
形态学、生化、组织化学和ERG分析表明，未经处理的p53基因敲除小鼠和野生型对照小鼠的视网膜在结构和功能上无明显差异。暴露于漫射白色荧光下后，分析光诱导的光感受器细胞死亡情况，发现两组小鼠相同。
这些数据表明，光诱导的光感受器细胞凋亡与功能性p53无关。
