FGFR1, signaling, and AP-1 expression after retinal detachment: reactive Müller and RPE cells

Invest Ophthalmol Vis Sci. 2001 May;42(6):1363-9.

Abstract

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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Cats
  • Connective Tissue Cells / metabolism*
  • Connective Tissue Cells / pathology
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Phosphorylation
  • Pigment Epithelium of Eye / metabolism*
  • Pigment Epithelium of Eye / pathology
  • Precipitin Tests
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Detachment / metabolism*
  • Retinal Detachment / pathology
  • Signal Transduction*
  • Transcription Factor AP-1 / biosynthesis*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • NF-kappa B
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Transcription Factor AP-1
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Mitogen-Activated Protein Kinases