NCAM influences RGC numbers: mechanisms and implications for vision

Our laboratory has been interested in exploring mechanisms that are relevant to the survival of central nervous system (CNS) neurons. Our recent studies, made possible by NSERC funding, have demonstrated that the neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) play roles in survival of young adult CNS neurons in the retina. NCAM is a cell surface protein and PSA is a carbohydrate localized almost exclusively on NCAM; both have been implicated in various functions of cellular development and regeneration. There is increasing evidence suggesting that NCAM plays an essential role in the adult nervous system; however, its influence on neuron survival and function in aging has not yet been described. The rodent visual system provides a versatile model for studying the survival of retinal ganglion cells (RGCs), which are CNS neurons within the retina, as well as for evaluating the effectiveness of pharmacotherapies and other potential treatments. We now have preliminary data indicating that NCAM plays an important role in influencing CNS neuron survival as the animal ages: RGC densities are significantly higher in young adult and older NCAM -/- mice. Despite having higher numbers of RGCs, we have preliminary data concerning visual abilities in these animals indicating that neuronal function may not be normal. These findings constitute the foundational work upon which we plan to more completely define the role as well as investigate molecular mechanisms of NCAM/PSA-NCAM in neuron survival in adult and aging animals. The overall aim of this project is to evaluate the role of NCAM and PSA-NCAM in mediating the survival of RGCs in the aging CNS. Specifically, we are asking the following questions: (1) is the survival of CNS neurons in the retina altered during aging by the presence or absence of NCAM and PSA-NCAM; (2) does the absence of NCAM and PSA-NCAM have functional consequences for the visual system; and (3) what are the mechanisms by which NCAM and PSA-NCAM mediate RGC survival? Research designed to answer these questions is important as it is relevant to fundamentally understanding why neurons die as they age.