Characterization of cell death pathways in murine retinal neurodegeneration implicates cytochrome c release, caspase activation, and bid cleavage

Apoptosis is considered to be the final common pathway of photoreceptor cel l death in different inherited retinal diseases. However, apoptosis encompa sses diverse pathways of molecular interactions culminating in cellular dem ise. To begin dissecting these interactions, we have investigated key parti cipants in the rd (retinal degeneration) model of retinal neurodegeneration . By Western blot analysis and immunocytochemistry, we found that cytochrom e c release occurs in rd retinas concurrently with the activation of the pr oapoptotic protein Bid. Active forms of caspase-8 and the mitogen-activated protein kinase p38, both of which are capable of cleaving Bid, were detect ed in rd retinas at the peak time of photoreceptor death. In addition, the activated form of the cell death effector caspase-3 was detectable particul arly at the photoreceptors in parallel with this peak degenerative phase. T hese data suggest that activation of both major apoptotic pathways occurs d uring photoreceptor degeneration in the rd mouse model of inherited blindne ss.