bax-induced apoptosis in lebers congenital amaurosis a dual role in rod and cone degenerationbax-induced细胞凋亡在雷伯氏先天性黑内障视杆细胞和视锥变性的双重角色.pdfVIP

Bax-Induced Apoptosis in Leber’s Congenital Amaurosis: A Dual Role in Rod and Cone Degeneration ´ 1,3 1,2,3 1,2 Severine Hamann , Daniel F. Schorderet , Sandra Cottet * 1 IRO, Institute for Research in Ophthalmology, Sion, Switzerland, 2 Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland, 3 School of Life Sciences, Federal Institute of Technology (EPFL), Lausanne, Switzerland Abstract Pathogenesis in the Rpe652/ 2 mouse model of Leber’s congenital amaurosis (LCA) is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe652/ 2 mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65), was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe652/ 2 mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors. Quanti- tative PCR analysis showed that increased expression of pro-apoptotic Bax and decreased level of anti-apoptotic Bcl-2 were restored in Rpe6