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D Hicks, N Kinkl, E Vecino, JA Sahel; Fibroblast Growth Factor Signaling Stimulates Retinal Ganglion Cell Survival in Adult Porcine Retinal Cultures . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2193.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine the distribution of fibroblast growth factor (FGF) receptors (FGFR) within, and the effects of their activation upon, retinal ganglion cell (RGC) survival. Methods: Specific antibodies for FGFR-1, -2, -3 and –4 were used to immunolabel adult mammalian (rat, pig and human) retina in vivo and in vitro. Recombinant FGF1, FGF2, FGF4 and FGF9, as well as other candidate neurotrophic factors [brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF)] were added to primary cell cultures prepared from adult pig retinas, and the dose- and time-dependent effects on RGC neurite outgrowth and survival were quantified through immunochemistry. Results: Each of the four FGFR exhibited a distinct pattern of immunolabeling of in vivo retina: FGFR-1 and -4 were strongly present in photoreceptors as well as inner retina, while FGFR-2 and FGFR-3 were more prevalent over inner nuclear and ganglion cell layers. All four FGFR were also abundantly expressed in the retinal pigment epithelium. FGFR-3 was especially concentrated over RGC cell bodies and dendrites. Similar observations were made in adult retinal cultures. Addition of different FGF family members did not influence neurite outgrowth of identified RGC in vitro, but FGF9 showed a dose-dependent stimulation of RGC survival. This effect was blocked by co-addition of FGF9 neutralising antibody, but not with non-immune IgG. On the other hand, selected neurotrophins (BDNF and CNTF) demonstrated strong synergistic effects on neurite outgrowth without influencing detectably RGC survival. Conclusion: FGFs and FGFR are expressed in RGC, and the distinct presence of FGFR-3 implies involvement of particular FGF ligands, especially FGF9, in regulating RGC survival and/or neuritogenesis. Cocktails of survival-promoting and neuritogenic growth factors may prove of therapeutic interest in RGC pathologies.
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