Glia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration

Abstract

Glia, the support cells of the central nervous system, have recently attracted considerable attention both as mediators of neural cell survival and as sources of neural regeneration. To further elucidate the role of glial and neural cells in neurodegeneration, we generated TrkBGFAP and TrkBc-kit knockout mice in which TrkB, a receptor for brain-derived neurotrophic factor (BDNF), is deleted in retinal glia or inner retinal neurons, respectively. Here, we show that the extent of glutamate-induced retinal degeneration was similar in these two mutant mice. Furthermore in TrkBGFAP knockout mice, BDNF did not prevent photoreceptor degeneration and failed to stimulate Müller glial cell proliferation and expression of neural markers in the degenerating retina. These results demonstrate that BDNF signalling in glia has important roles in neural protection and regeneration, particularly in conversion of Müller glia to photoreceptors. In addition, our genetic models provide a system in which glia- and neuron-specific gene functions can be tested in central nervous system tissues in vivo. The central nervous system contains glial cells, which have been shown to have an important role in neuronal survival. Haradaet al. use transgenic mouse models to show that TrkB, a receptor for the growth factor brain-derived neurotrophic factor, is required for retinal Müller glial cells to provide neuroprotection and regeneration.