| dc.description | The loss of neurons in the central nervous system (CNS) is accompanied by a range of pathophenotypes, ranging from mild to profound functional deficits. The discovery of cells within the CNS that are capable of producing new neurons, however, has spawned a litany of interest in "adult neural precursor" science. It is clear that adult neural precursors respond to CNS pathology, and increase their production of neurons when treated with selected factors and genes that are amenable to neurogenesis. In the adult mammalian retina, bonafide retinal stem/progenitor cells reside in a quiescent state. Furthermore, the mammalian eye provides a convenient and well studied model to investigate CNS injury and cell replacement treatments. In this thesis, I investigated the effects of selective neuronal injury, as well as the exogenous application of mitogenic growth factors, on the activation of cells in the eye that bear functional and phenotypic resemblance to retinal progenitor cells (RPCs). Induction of retinal ganglion cell (RGC) death resulted in a proliferative response, the up-regulation of transcriptional and cytoskeletal phenotypes akin to those seen in RPCs, and the emergence of a population of cells in the ciliary body (CB) resembling retinal neurons (Chapter 2). When exposed to intravitreally administered epidermal growth factor (EGF) and/or erythropoietin (EPO), Muller glia, the principal glial cell of the retina and neural precursor in lower-vertebrate animals, display RPC-like behaviors ranging from proliferation to expression of transcriptional machinery involved in progenitor function (Chapter 3). Finally, the isolation of Muller glia and maintenance in culture in the absence of retinal neurons permits these cells to exhibit hallmark features of neural precursors, including the formation of sphere-like aggregates, the up-regulation of pro-neural phenotypes, and production of cells that express neuronal phenotypes when exposed to growth factors (Chapter 4). Collectively, these data indicate that the adult mammalian eye contains neural precursors, including those derived from mature Muller glia, that respond to injury and exogenous growth factor treatment, and retain functional and phenotypic characteristics of RPCs. | en_US |
