A hallmark of the adult human nervous system is that damage is permanent. Neurons that die as a result of trauma or disease are never naturally replaced. In marked contrast, an injury to the retina of an adult teleost fish stimulates neuronal regeneration and recovery of function. An improved understanding of the cellular and molecular events that underlie the ability of this animal to functionally repair this part of its central nervous system may yield new strategies or applications for repairing the nervous system in man. The long-term objectives of this research project are to identify the molecules and cells that are critical for neuronal regeneration and fully reconstruct the cellular and molecular cascade of events that are initiated when the teleost retina is injured. The investigators propose to undertake four specific aims that will: (1) test the general hypothesis that in teleosts, retinal regeneration recapitulates retinal ontogeny; (2) identify the cellular patterns of expression of the insulin receptor and the insulin-like growth factor system (IGF-I; IGF-IR and IGFBP-2); (3) test the hypothesis that the IGF-I system is involved in the signaling pathways that initiate regeneration; and (4) characterize the population of slowly-dividing neuronal progenitors that were recently discovered to be present in the differentiated retina, and test whether or not these cells participate in the regenerative response. Both normal and injured/regenerating retinas will be studied utilizing a variety of cellular and molecular techniques. If the hypotheses are correct, then the investigators expect to identify important molecular mechanisms that regulate both neuronal development and regeneration in a vertebrate retina.
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