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Basic fibroblast growth factor (bFGF or FGF-2) has been implicated as a trophic factor that promotes survival and neurite outgrowth of neurons. The authors previously found that the application of FGF-2 to the proximal stump of the injured axon increased retinal ganglion cell (RGC) survival. They determine here the effect of FGF-2 on expression of the axonal growth-associated phosphoprotein (GAP)-43 in retinal ganglion cells and tectum of Rana pipiens during regeneration of the optic nerve. In control retinas, GAP-43 protein was found in the optic fiber layer and in optic nerve; mRNA levels were low. After axotomy, mRNA levels increased seven-fold and GAP-43 protein was significantly increased. GAP-43 was localized in retinal axons and in a subset of RGC cell bodies and dendrites. This upregulation of GAP-43 was sustained through the period in which retinal axons reconnect with their target in the tectum. FGF-2 application to the injured nerve, but not to the eyeball, increased GAP-43 mRNA in the retina but decreased GAP-43 protein levels and decreased the number of immunopositive cell bodies. In the tectum, no treatment affected GAP-43 mRNA but FGF-2 application to the axotomized optic nerve increased GAP-43 protein in regenerating retinal projections. It is concluded that FGF-2 upregulates the synthesis and alters the distribution of the axonal growth-promoting protein GAP-43, suggesting that it may enhance axonal regrowth.
Dr. R.E. Blanco, Institute of Neurobiology, University of Puerto Rico Medical Science Campus, 201 Boulevard del Valle, San Juan 00901, Puerto Rico
5 Experimental glaucoma; animal models
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)