Role of BCL-XL in Photoreceptor Survival

摘要

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. BCL-Xl was postulated as a survival factor in photoreceptors, as it was up-regulated in the bright light-stressed retina (Zheng et al., 2006). To determine the significance of BCL-XLup-regulation in the bright light damage model, the Bcl-x gene was disrupted specifically in murine rod or cone photoreceptors using the Cre//ax-based conditional gene knockout strategy (Le and Sauer, 2000). Effects of Bcl-x disruption on photoreceptor function and morphology were characterized. This report reviews the results from rod-specific Bcl-x knockout mice and summarizes new information on cone-specific Bcl-x knockout mice