Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration
Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration
复制标题
DOI：
10.1523/jneurosci.22-21-09228.2002
复制
发表时间：
2002-11-01
影响因子：
5.3
通讯作者：
Wada, K
中科院分区：
文献类型：
--
作者：
Harada, T;Harada, C;Wada, K
小胶质细胞的激活通常响应于多种病理刺激而发生，包括创伤、轴突切断、缺血和CNS中的变性。在视网膜中，长时间或高强度暴露于可见光导致感光细胞凋亡。在这样的光饲养的视网膜，我们发现，激活的小胶质细胞侵入退化的感光层，并改变神经营养因子，如神经生长因子（NGF），睫状神经营养因子（CNTF），和胶质细胞源性神经营养因子（GDNF）的表达。由于这些神经营养因子调节Muller神经胶质细胞中的二级营养因子表达，因此小胶质细胞-Muller神经胶质细胞相互作用可能有助于保护光感受器或增加光感受器凋亡。在本研究中，我们证明了这样的功能性胶质细胞-胶质细胞相互作用的可能性构成的关键机制，小胶质细胞源性神经生长因子，脑源性神经营养因子（BDNF），和CNTF间接影响感光细胞的生存，虽然这些神经营养因子的受体是不存在的光感受器，通过调节碱性成纤维细胞生长因子（bFGF）和GDNF的生产和释放穆勒胶质细胞。这些观察结果表明，小胶质细胞调节小胶质细胞-Muller胶质细胞-感光网络，该网络在视网膜变性期间充当营养因子控制系统。
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 Muller glial cells, microglia-Muller 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 Muller glia. These observations suggest that microglia regulate the microglia-Muller glia-photoreceptor network that serves as a trophic factor-controlling system during retinal degeneration.