Hsu Cheng-Da, Whaley Michelle A, Frazer Kristin, Miller Douglas A, Mitchell Kathleen A, Adams Sheila M, O'Tousa Joseph E
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556-0369, USA.
J Neurosci. 2004 Jan 14;24(2):500-7. doi: 10.1523/JNEUROSCI.3328-02.2004.
We examined the role of programmed cell death (PCD) pathways in retinal degeneration caused by a mutation in the norpA gene. norpA degeneration shows morphological hallmarks of programmed cell death, specifically cytoplasmic condensation and engulfment of the dying photoreceptor cells by neighboring retinal pigment cells. However, genetic mosaic analysis of adult photoreceptors lacking rpr, hid, and grim show that these PCD inducers are not required for norpA degeneration. We showed previously that ectopic expression of either rpr or hid triggers rapid PCD in adult photoreceptors, and this is completely suppressed by the coexpression of the baculoviral P35 caspase inhibitor. In contrast, expression of P35 does not suppress norpA retinal degeneration, although a small delay in the rate of degeneration is observed in low light-low temperature conditions. P35 does not alter the morphological characteristics of norpA cell death. Overexpression of the Drosophila inhibitor of apoptosis Diap1 or a dominant-negative form of the Dronc caspase, even when coexpressed with P35, does not dramatically alter the time course of norpA degeneration. These results establish that the pathways responsible for PCD in development do not play a major role in adult retinal degeneration caused by norpA.
我们研究了程序性细胞死亡（PCD）通路在由norpA基因突变引起的视网膜变性中的作用。norpA变性表现出程序性细胞死亡的形态学特征，特别是细胞质浓缩以及临近的视网膜色素细胞对濒死光感受器细胞的吞噬。然而，对缺乏rpr、hid和grim的成年光感受器进行的遗传镶嵌分析表明，norpA变性并不需要这些PCD诱导因子。我们之前表明，rpr或hid的异位表达会在成年光感受器中触发快速的PCD，而杆状病毒P35半胱天冬酶抑制剂的共表达可完全抑制这一过程。相比之下，尽管在低光照-低温条件下观察到变性速率有小幅度延迟，但P35的表达并不能抑制norpA视网膜变性。P35不会改变norpA细胞死亡的形态学特征。果蝇凋亡抑制剂Diap1或Dronc半胱天冬酶的显性负性形式的过表达，即使与P35共表达，也不会显著改变norpA变性的时间进程。这些结果表明，发育过程中负责PCD的通路在由norpA引起的成年视网膜变性中并不起主要作用。
