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Scott F. Geller, Geoffrey P. Lewis, Steven K. Fisher; FGFR1, Signaling, and AP-1 Expression after Retinal Detachment: Reactive Müller and RPE Cells. Invest. Ophthalmol. Vis. Sci. 2001;42(6):1363-1369.
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purpose. 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
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-κB 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.
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