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I Soto, C del Cueto, RE Blanco; FGF-2 Enhances Adult Retinal Ganglion Cell Regeneration After Axotomy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):755.
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Purpose: Fibroblast growth factor (FGF-2) has been implicated as a trophic factor that promotes survival and neurite outgrowth of neurons. Previously, we found that application of FGF-2 to the proximal stump of the injured optic nerve increases retinal ganglion cells (RGCs) survival. The purpose of this investigation was to study the effect of FGF-2 on the regeneration and reconnection to the target of the optic nerve axons after axotomy. Methods: Optic nerves of Rana pipiens were cut between eyeball and chiasm and treated immediately with FGF-2. The expression of GAP-43, a protein correlated with axonal growth, was analyzed by quantifying immunopositive RGCs and by using RT-PCR to measure GAP-43 mRNA. GAP-43 expression was also analyzed in the optic tectum during the course of regeneration. Ultrastructural analysis of the optic nerves was also performed at different times after axotomy with and without treatment. Results: In control retinas GAP-43 immunoreactivity was found only in the optic nerve fiber layer and in the optic nerve; the mRNA levels were very low. After axotomy a subpopulation of RGCs was labeled with the GAP-43 antibody and mRNA levels of GAP-43 increased significantly. In retinas treated with FGF-2 there was an additional increase in the mRNA levels at 2 weeks after treatment, and we observed an increase in the numbers of GAP-43-labeled regenerating retinal axons in the optic nerve and tectum. Conclusion: FGF-2 contributes to the survival of injured RGCs, and upregulates the expression of GAP-43. FGF-2 also stimulates the regeneration of injured RGC axons, which reconnect with the tectum at earlier times.
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