TY - JOUR
T1 - Microglia-Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration
AU - Harada, Takayuki
AU - Harada, Chikako
AU - Kohsaka, Shinichi
AU - Wada, Etsuko
AU - Yoshida, Kazuhiko
AU - Ohno, Shigeaki
AU - Mamada, Hiroshi
AU - Tanaka, Kohichi
AU - Parada, Luis F.
AU - Wada, Keiji
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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.
AB - 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.
KW - Glia-glia interaction
KW - Glia-neuron interaction
KW - Microglia
KW - Müller glial cell
KW - Neurotrophins
KW - Photoreceptor
KW - Retinal degeneration
UR - http://www.scopus.com/inward/record.url?scp=0036850873&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036850873&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.22-21-09228.2002
DO - 10.1523/jneurosci.22-21-09228.2002
M3 - Article
C2 - 12417648
AN - SCOPUS:0036850873
SN - 0270-6474
VL - 22
SP - 9228
EP - 9236
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 21
ER -