Microglia-Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration

Takayuki Harada, Chikako Harada, Shinichi Kohsaka, Etsuko Wada, Kazuhiko Yoshida, Shigeaki Ohno, Hiroshi Mamada, Kohichi Tanaka, Luis F. Parada, Keiji Wada

Research output: Contribution to journalArticle

314 Scopus citations

Abstract

Activation of microglia commonly occurs in response to a wide variety of pathological stimuli including trauma, axotomy, ischemia, and degeneration in the CNS. In the retina, prolonged or high-intensity exposure to visible light leads to photoreceptor cell apoptosis. In such a light-reared retina, we found that activated microglia invade the degenerating photoreceptor layer and alter expression of neurotrophic factors such as nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and glial cell line-derived neurotrophic factor (GDNF), Because these neurotrophic factors modulate secondary trophic factor expression in Müller glial cells, microglia-Müller glia cell interaction may contribute to protection of photoreceptors or increase photoreceptor apoptosis. In the present study, we demonstrate the possibility that such functional glia-glia interactions constitute the key mechanism by which microglia-derived NGF, brain-derived neurotrophic factor (BDNF), and CNTF indirectly influence photoreceptor survival, although the receptors for these neurotrophic factors are absent from photoreceptors, by modulating basic fibroblast growth factor (bFGF) and GDNF production and release from Müller glia. These observations suggest that microglia regulate the microglia-Müller glia-photoreceptor network that serves as a trophic factor-controlling system during retinal degeneration.

Original languageEnglish (US)
Pages (from-to)9228-9236
Number of pages9
JournalJournal of Neuroscience
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2002

Keywords

  • Glia-glia interaction
  • Glia-neuron interaction
  • Microglia
  • Müller glial cell
  • Neurotrophins
  • Photoreceptor
  • Retinal degeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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    Harada, T., Harada, C., Kohsaka, S., Wada, E., Yoshida, K., Ohno, S., Mamada, H., Tanaka, K., Parada, L. F., & Wada, K. (2002). Microglia-Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. Journal of Neuroscience, 22(21), 9228-9236. https://doi.org/10.1523/jneurosci.22-21-09228.2002