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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain-Derived Neurotrophic Factor / biosynthesis
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Brain-Derived Neurotrophic Factor / genetics
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Cell Movement / radiation effects
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Cells, Cultured
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Ciliary Neurotrophic Factor / biosynthesis
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Ciliary Neurotrophic Factor / genetics
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Disease Models, Animal
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Glial Cell Line-Derived Neurotrophic Factor
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Light / adverse effects*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microglia / metabolism
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Microglia / pathology
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Microglia / radiation effects
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Nerve Growth Factor / biosynthesis
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Nerve Growth Factor / genetics
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Nerve Growth Factors / biosynthesis*
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Nerve Growth Factors / genetics
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Neuroglia / metabolism*
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Neuroglia / pathology
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Neuroglia / radiation effects*
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Neurotrophin 3 / biosynthesis
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Photoreceptor Cells / pathology
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Photoreceptor Cells / radiation effects
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor / deficiency
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism
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Retina / pathology
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Retina / radiation effects
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Retinal Degeneration / metabolism*
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Retinal Degeneration / pathology
Substances
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Brain-Derived Neurotrophic Factor
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Ciliary Neurotrophic Factor
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Gdnf protein, mouse
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Gdnf protein, rat
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Glial Cell Line-Derived Neurotrophic Factor
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Nerve Growth Factors
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Neurotrophin 3
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RNA, Messenger
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor
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Nerve Growth Factor