Adult mouse retina explants: an ex vivo window to explore central nervous system diseases

Abstract

ABSTRACTWhen the developing central nervous system (CNS) becomes mature, it loses its ability to regenerate. Therefore, any insult to adult CNS leads to a permanent and irreversible loss of motor and cognitive functions. For a long time, much effort has been deployed to uncover mechanisms of axon regeneration in the CNS. It is now well understood that neurons themselves lose axon regeneration capabilities during development, and also after a lesion or in pathological conditions. Since then, many molecular pathways such as mTOR and JAK/STAT have been associated with axon regeneration. However, no functional recovery has been achieved yet. Today, there is a need not only to identify new molecules implicated in adult CNS axon regeneration, but also to decipher the fine molecular mechanisms associated with regeneration failure. This is critical to make progress in our understanding of neuroprotection and neuroregeneration and for the development of new therapeutic strategies. In this context, it remains particularly challenging to address molecular mechanisms in in vivo models of CNS regeneration. The extensive use of embryonic neurons as in vitro model is a source of bias, as they have the intrinsic competence to grow their axon upon injury, unlike mature neurons. In addition, this type of dissociated neuronal cultures lack a tissue environment to recapitulate properly molecular and cellular events in vitro. Here, we propose to use cultures of adult retina explants to fill this gap. The visual system - which includes the retina and optic nerve - is a gold-standard model to study axon regeneration and degeneration in the mature CNS. Cultures of adult retina explants combine two advantages: they have the simplicity of embryonic neurons cultures and they recapitulate all the aspects of in vivo features in the tissue. Importantly, it is the most appropriate tool to date to isolate molecular and cellular events of axon regeneration and degeneration of the adult CNS in a dish. This ex vivo system allows to set up a large range of experiments to decipher the fine molecular and cellular regulations underlying mature CNS axon growth.