Neurotrophic factors and the regeneration of adult retinal ganglion cell axons.

The adult central nervous system (CNS) has only a limited capacity to regenerate axons after injury. This is due to a number of factors including the presence of extrinsic inhibitory factors that limit plasticity, lack of effective trophic support, and intrinsic changes in neuronal responsiveness. In this review, we describe the expression and role of neurotrophins in retinal ganglion cells (RGCs) during development and adulthood, and the receptors and miscellaneous signaling systems that influence axonal regeneration after injury. The impact of exogenous neurotrophic factors on adult RGCs injured at different sites in the visual pathway is described for several modes of delivery, including recombinant factors, viral vectors, cell transplantation, as well as combinatorial treatments involving other pharmacotherapeutic agents. Indirect, off-target effects of neurotrophic factors on RGC axonal regeneration are also considered. There remain unresolved issues relating to optimal delivery of neurotrophic factors, and we emphasize the need to develop safe, reliable methods for the regulation of exogenous supply of these factors to the injured CNS.