Effect of p75NTR on the regulation of photoreceptor apoptosis in the rd mouse.
Effect of p75NTR on the regulation of photoreceptor apoptosis in the rd mouse.
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DOI：
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发表时间：
2005-12
期刊：
影响因子：
2.2
通讯作者：
Kazuaki Nakamura;C. Harada;A. Okumura;K. Namekata;Y. Mitamura;Kazuhiko Yoshida;S. Ohno;H. Yoshida;T. Harada
中科院分区：
文献类型：
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作者：
Kazuaki Nakamura;C. Harada;A. Okumura;K. Namekata;Y. Mitamura;Kazuhiko Yoshida;S. Ohno;H. Yoshida;T. Harada
目的细胞凋亡是几种类型的视网膜色素变性中感光细胞的最终共同途径。最近的研究表明，持续光照可上调低亲和力神经营养素受体p75(P75NTR)，而p75NTR参与了光诱导的大鼠视网膜光感受器的凋亡。然而，p75NTR在遗传性感光细胞变性中的作用尚未被研究。本研究旨在阐明p75NTR在视网膜色素变性动物模型中的作用。方法用双突变(RD/RD，p75NTR-/-)小鼠与RD/RD和p75NTR-/-小鼠杂交。从出生后第9天至第20天，对对照组(+/+，p75NTR+/+；RD/RD，p75NTR+/+；RD/RD，p75NTR+/-)和双突变(RD/RD，p75NTR-/-)小鼠的视网膜进行了光镜观察和TdT介导的dUTP缺口末端标记(TUNEL)。用实时荧光定量聚合酶链式反应检测p75NTR基因在+/+、p75NTR+/+和RD/RD、p75NTR+/+小鼠中的表达。免疫组织化学方法检测p75NTR蛋白在+/+、p75NTR+/+、RD/RD、p75NTR+/+、RD/RD、p75NTR-/-小鼠中的表达。结果与+/+，p75NTR+/+小鼠相比，RD/RD，p75NTR+/+小鼠在P13和P20时p75NTR基因表达显著上调。P75NTR蛋白主要在Müler胶质细胞中表达，光感受器变性过程中p75NTR蛋白在外核层表达上调。然而，组织化学分析显示，RD/RD，p75NTR-/-双突变小鼠的视网膜变性的时间进程和光感受器凋亡的程度与携带功能性p75NTR(RD/RD，p75NTR+/+和RD/RD，p75NTR+/-)的RD小鼠没有区别。结论与p75NTR在光诱导的光感受器变性中的作用不同，p75NTR对RD小鼠的细胞凋亡不是必需的。
PURPOSE Apoptosis is the final common pathway for photoreceptors in several forms of retinitis pigmentosa. Recent study has shown that continuous light exposure upregulates low-affinity neurotrophin receptor p75 (p75NTR), which is involved in light-induced photoreceptor apoptosis in rat retina. However, the function of p75NTR in inherited forms of photoreceptor degeneration has not yet been examined. This study was conducted to elucidate the potential role of p75NTR in the rd mouse, one of the best characterized animal models of retinitis pigmentosa. METHODS Double-mutant (rd/rd, p75NTR-/-) mice were crossbred from rd/rd and p75NTR-/- mice. Retinas from control (+/+, p75NTR+/+; rd/rd, p75NTR+/+; rd/rd, p75NTR+/-), and double-mutant (rd/rd, p75NTR-/-) mice were examined by light microscopy and TdT-mediated dUTP nick end labeling (TUNEL) from postnatal day (P)9 through P20. p75NTR mRNA expression in +/+, p75NTR+/+, and rd/rd, p75NTR+/+ mice were examined by real-time PCR analysis. p75NTR protein expression in +/+, p75NTR+/+; rd/rd, p75NTR+/+; and rd/rd, p75NTR-/- mice were examined by immunohistochemistry. RESULTS p75NTR mRNA expression in rd/rd, p75NTR+/+ mice was significantly upregulated compared with +/+, p75NTR+/+ mice at P13 and P20. p75NTR protein expression was observed mainly in Müller glial cells, and its expression was upregulated in the outer nuclear layer during photoreceptor degeneration. However, histochemical analyses showed that the time course of retinal degeneration and the extent of photoreceptor apoptosis in rd/rd, p75NTR-/- double-mutant mice was indistinguishable from that in rd mice carrying functional p75NTR (rd/rd, p75NTR+/+, and rd/rd, p75NTR+/-). CONCLUSIONS These results suggest that in contrast to its role in light-induced photoreceptor degeneration, p75NTR is not essential for apoptosis in the rd mouse.