Role of the low-affinity NGF receptor (p75) in survival of retinal bipolar cells

Eric M. Wexler, Oksana Berkovich, Scott Nawy

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

We have examined the role of neurotrophins in promoting survival of mammalian rod bipolar cells (RBC) in culture. Retinas taken from 8- to 10-day-old Long-Evans rats were dissociated and cultured in media supplemented with either nerve growth factor (NGF), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), or basic fibroblast growth factor (FGF-2). Survival was measured by the number of cells that were immunoreactive for α-, β-, γ-PKC, a bipolar cell-specific marker. Compared to untreated cultures, CNTF had no effect on RBC survival, while NGF and NT-3 increased survival only slightly. BDNF, however, increased survival by approximately 300%. Similar results were obtained with FGF-2. Both nerve growth factor (NGF) and an antibody (anti-REX) which interferes with binding to the 75-kD low-affinity neurotrophin receptor (p75(NTR)) eliminated BDNF-promoted survival, but had no effect on FGF-2-mediated survival. Interestingly, p75(NTR) was expressed by retinal glia (Muller cells), but not by the bipolar cells themselves, providing for the possibility that BDNF might induce Muller cells to produce a secondary factor, perhaps FGF-2, which directly rescues RBCs. In support of this hypothesis, an antibody that neutralizes FGF-2 attenuated the trophic effects of BDNF, and dramatically reduced survival in cultures with no added growth factors, indicating that there may be an endogenous source of FGF-2 that promotes survival of RBCs in culture. We suggest that BDNF increases production or release of FGF-2 by binding to p75(NTR) on Muller cells.

Original languageEnglish (US)
Pages (from-to)211-218
Number of pages8
JournalVisual Neuroscience
Volume15
Issue number2
DOIs
Publication statusPublished - Mar 1 1998

    Fingerprint

Keywords

  • Anti-REX
  • BDNF
  • Cell culture
  • FGF-2
  • Muller cells

ASJC Scopus subject areas

  • Physiology
  • Sensory Systems

Cite this