FGF19 exhibits neuroprotective effects on adult mammalian photoreceptors in vitro.
OBJECTIVE
Several fibroblast growth factors (FGFs) exhibit neuroprotective influences against retinal photoreceptor degeneration. The expression of FGF receptor (FGFR) 4 on photoreceptors suggests a specific ligand, FGF-19, might also be beneficial. The authors hence examined the potential role of FGF-19 in this regard.


METHODS
Adult human retinal sections were processed for anti-FGFR-4 immunohistochemistry. Total RNA and proteins were extracted from parallel cultures of human Y79 retinoblastoma and primary adult pig photoreceptors; RNA samples were used for RT-PCR analysis of FGF-19, and proteins were subjected to immunoprecipitation for FGFR-1 and FGFR-4 or to Western blotting of FGF-19. Cultures were incubated with increasing concentrations of FGF-19 before extraction and Western blotting for phosphotyrosine. Photoreceptor cultures were screened for cell survival and processed for immunocytochemistry using anti-neural retina leucine zipper (Nrl) antibody.


RESULTS
FGF-19 mRNA was detected in adult pig retinal pigment epithelial cells, and FGF-19 protein was found in cell extracts and conditioned medium prepared from retinal pigment epithelium. The addition of FGF-19 to Y79 retinoblastoma or primary adult pig photoreceptor cultures led to time- and dose-dependent changes in proliferation (for Y79) or survival (for primary photoreceptors). FGF-19 induced the phosphorylation of an FGFR-4-immunoreactive band of approximately 80 kDa and led to the heterodimerization of FGFR-1 and FGFR-4. Y79 and primary photoreceptor cells maintained in serum-supplemented media exhibited Nrl immunoreactivity by Western blotting, which decreased after serum deprivation. The addition of FGF-19 led to the reexpression of Nrl immunoreactivity in both culture models.


CONCLUSIONS
These data indicate a physiological role for FGF-19 in adult photoreceptor phenotypic maintenance and survival and argue in favor of its use as a neuroprotectant.
Siffroi-Fernandez
Sandrine
S
Laboratoire de Neurobiologie des Rythmes, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
Felder-Schmittbuhl
Marie-Paule
MP
Khanna
Hemant
H
Swaroop
Anand
A
Hicks
David
D
D000328:Adult; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology; D013552:Swine; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
C117476:FGF19 protein, human; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4