FGFR1, signaling, and AP-1 expression after retinal detachment: reactive Müller and RPE cells.
OBJECTIVE
To identify changes in cellular signaling pathways and AP-1 expression in retina and retinal pigmented epithelium (RPE) after experimental retinal detachment (RD).


METHODS
Cat and rabbit neural retinas were separated from the RPE in vivo for 5 minutes to 28 days. Tissues were removed and processed for Western blotting, immunohistochemistry, in situ hybridization, and immunoprecipitation experiments.


RESULTS
An ordered sequence of events occurs after RD: (1) fibroblast growth factor (FGF) receptor 1 (FGFR1, flg) is phosphorylated in the retina within 15 minutes and dephosphorylated 2 hours after RD; (2) The extracellular signal-regulated kinase (ERK) is phosphorylated in both Müller and RPE cells within 15 minutes and remains so for several days; (3) De novo expression of c-fos mRNA coincides with increased c-Fos and c-Jun immunoreactivity in both Müller and RPE cells; (4) CREB is phosphorylated in a subpopulation of photoreceptors; and (5) STAT3 and NF-kappaB are activated in inner nuclear layer cells by 1 day of RD.


CONCLUSIONS
These data suggest that nonneuronal cells (RPE and Müller cells) respond to RD very rapidly by stimulating ERK signaling and AP-1 transcription factor expression. Furthermore, these data suggest that basic fibroblast growth factor (FGF-2, bFGF) is involved in initiating the retina's earliest responses to RD. The events described here precede changes in gene expression and morphology that can have serious effects on visual outcome in humans treated for retinal detachment or other retinal injuries.
Geller
S F
SF
Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
Lewis
G P
GP
Fisher
S K
SK
D000818:Animals; D015153:Blotting, Western; D002415:Cats; D003239:Connective Tissue Cells / Q000378:metabolism* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D000091344:Filaggrin Proteins; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D011233:Precipitin Tests; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012163:Retinal Detachment / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*
D017362:Cyclic AMP Response Element-Binding Protein; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D018808:Transcription Factor AP-1; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020928:Mitogen-Activated Protein Kinases