Role of BCL-XL in Photoreceptor Survival
Photoreceptors are post-mitotic neurons and understanding their survival mechanisms holds a key to the treatment of retinal degeneration. Many studies have demonstrated that phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol-3,4,5-trisphosphate (PIP3) are involved in the survival of neurons through growth factor receptor-mediated activation of the serine-threonine kinase, AKT (Barber et al., 2000; D’Mello et al., 1997; Yao and Cooper, 1995). Activation of AKT further activates a number of down-stream targets, including the anti-apoptotic protein BCL-XL, which can serve as a survival factor in a number of alternative pathways(Bui et al., 2001; Kim et al., 2005; Zha et al., 1996). For the past few years, we have investigated the roles of PI3K, insulin receptor, AKT, and BCL-XL in photoreceptor survival.
KeywordsRetinal Degeneration Outer Nuclear Layer Cone Photoreceptor Light Damage Photoreceptor Survival
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- Hao, W., Wenzel, A., Obin, M. S., Chen, C. K., Brill, E., Krasnoperova, N. V., Eversole-Cire, P., Kleyner, Y., Taylor, A., Simon, M. I., Grimm, C., Reme, C. E., and Lem, J. (2002). Evidence for two apoptotic pathways in light-induced retinal degeneration. Nat Genet 32, 254–60.PubMedCrossRefGoogle Scholar
- He, L., Perkins, G. A., Poblenz, A. T., Harris, J. B., Hung, M., Ellisman, M. H., and Fox, D. A. (2003). Bcl-xL overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice. Proc Natl Acad Sci USA 100, 1022–27.PubMedCrossRefGoogle Scholar
- Le, Y., Zheng, L., Zheng, W., Agbaga, M., Zhu, M., Ash, J. D., and Anderson, R. E. (2006a). Mouse opsin promoter controlled expression of Cre recombinase in transgenic mice. Mol Vis 12, 389–98.Google Scholar
- Le, Y. Z., Ash, J. D., Al-Ubaidi, M. R., Chen, Y., Ma, J. X., and Anderson, R. E. (2006b). Conditional gene knockout system in cone photoreceptors. Adv Exp Med Biol 572, 173–78.Google Scholar