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The Journal of Neuroscience, November 1, 2002, 22(21):9228-9236
Microglia-Müller Glia Cell Interactions Control Neurotrophic Factor Production during Light-Induced Retinal Degeneration
Takayuki Harada1, 3, 4, 6, *, Chikako Harada1, 3, 4, 6, *, Shinichi Kohsaka2, Etsuko Wada1, Kazuhiko Yoshida3, Shigeaki Ohno3, Hiroshi Mamada4, Kohichi Tanaka4, 5, Luis F. Parada6, and Keiji Wada1 Departments of 1 Degenerative Neurological Diseases and 2 Neurochemistry, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan, 3 Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan, 4 Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan, 5 PRESTO, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan, and 6 Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133
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.
Key words: microglia; Müller glial cell; photoreceptor; neurotrophins; glia-glia interaction; glia-neuron interaction; retinal degeneration
* T.H. and C.H. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22219228-09$05.00/0
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