Author:

Abstract:

Since the adult mammalian central nervous system (CNS) lacks the capacity to replace lost nerve cells or to regenerate injured axons, neurodegenerative disorders seriously affect life quality and human wellbeing. Understanding the pathophysiological mechanisms underlying neurodegeneration is essential to support and develop novel therapeutic strategies to promote neural repair. Rho kinases (ROCK) regulate pleiotropic cellular functions, but importantly, the selective inhibition of ROCK was shown to be a very efficient strategy to achieve neuroprotection and axonal regeneration in animals CNS models. The overal aim of this project is to elucidate the cellular and molecular mechanisms by which ROCK modulates neuronal apoptosis, axonal de/regeneration and glial reactivity. In this project, a detailed study on the spatiotemporal expression of ROCKI/II in the healthy and pathological retina after optic nerve crush will be characterized first. Subsequently, in vitro retinal cell cultures, isolated from adolescent porcine eyes, will be optimized to unravel the cellular interactions by which ROCK influence RGC survival/axonal outgrowth. Finally, downstream targets in the ROCK mediated pathways during RGC apoptosis and axonal degeneration will be identified by proteomics and subsequently validated.