FGF-2 modulates expression and distribution of GAP-43 in frog retinal ganglion cells after optic nerve injury.
Basic fibroblast growth factor (bFGF or FGF-2) has been implicated as a trophic factor that promotes survival and neurite outgrowth of neurons. We found previously that application of FGF-2 to the proximal stump of the injured axon increases retinal ganglion cell (RGC) survival. We 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 sevenfold 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. We conclude 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.
Soto
Ileana
I
Department of Anatomy, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
Marie
Bruno
B
Baro
Deborah J
DJ
Blanco
Rosa E
RE
D000818:Animals; D019771:Axotomy / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011894:Rana pipiens; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013477:Superior Colliculi / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D019922:GAP-43 Protein; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2