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K. T. Tchedre, C. Antolik, K.-S. Cho, Y. Fang, D. Chen; Differential Effects of Insulin-Like Growth Factor-1 on Retinal Ganglion Cell Survival and Axon Regeneration in Neonates and Adult Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):144.
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© ARVO (1962-2015); The Authors (2016-present)
A primary obstacle for functional recovery after neural damage or neurodegenerative diseases in adult mammals is the failure of self-repair or regeneration by damaged nerve pathways in the central nervous system (CNS), including the optic nerve. The previous research from my lab as well as those of others has suggested a role for insulin-like growth factor-1 (IGF-1) in the regulation of CNS axon regeneration. In the present research project, we tempt to further elucidate the function of IGF-1 in retinal ganglion (RGCs) cell axon growth and regeneration in mice.
The expression profile of IGF-1 in the retinas of embryonic days 14, 16, 18, and adult mice were examined using immunocytochemistry and western blot. The effects of IGF-1 on RGC survival and axonal outgrowth were assessed quantitatively in purified RGC cultures. Small molecule inhibitors and neutralizing antibodies that target IGF-1 and its receptors were used to define the intracellular signaling pathways that mediate the effects of IGF-1 on RGC survival and axonal outgrowth. Moreover, the survival and regenerative effects of IGF-1 were further examined in vivo in IGF-1 transgenic mice using an optic nerve crush injury model. Retinal and optic nerve sections were collected at 14 days post crush and were analyzed and quantified for nerve regeneration and neuronal survival.
Application of IGF-1 promotes both the survival and axonal outgrowth of RGCs isolated from neonatal mice; however, in the adult, IGF-1 supports only the survival, but not axon regeneration, of RGCs.
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