The role of mTOR signalling in RGC axon regeneration

[摘要] Axons from the central nervous system (CNS) do not regenerate, causing a major problem for recovery after CNS injury. One possible reason why axon growth is inhibited is intracellular suppression of growth signals. In this work, we examined the role of RTP801 during axon regeneration in vitro and in vivo. RTP801 is an upstream inhibitor of mTOR signalling, which is central to cell growth. We report here that retinal ganglion cells (RGC) in vitro and in vivo responded to siRNA designed against RTP801 (siRTP801). Due to a limited amount of time not all experiments could be repeated in triplicate however a trend shows that siRTP801 treatment does not enhance RGC survival or neurite outgrowth in vitro but increases neurite length. Treatment with siRTP801 in combination with ciliary neurotrophic factor (CNTF) and an anti-apoptotic caspase-2 inhibitor seems to be most effective in promoting long RGC neurites. The in vitro results support the data from the in vivo work where an increase of long distant axons has been documented. However, the generated data is not conclusive and more experiments need to be carried out. Nevertheless, these findings demonstrate a potential for siRTP801 as a novel strategy to enhance axon regeneration in RGC.

[发布机构] University:University of Birmingham;Department:School of Clinical and Experimental Medicine

[关键词] R Medicine;RC Internal medicine