Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany.
Ophthalmologica. 2012;227(1):1-19. doi: 10.1159/000328979. Epub 2011 Sep 15.
Virtually all pathogenic stimuli activate Müller cells. Reactive Müller cells exert protective and toxic effects on photoreceptors and neurons. They contribute to oxidative stress and glutamate toxicity due to malfunctions of glutamate uptake and glutathione synthesis. Downregulation of potassium conductance disrupts transcellular potassium and water transport, resulting in neuronal hyperexcitability and edema. Protective effects of reactive Müller cells include upregulation of adenosine 5'-triphosphate (ATP)-degrading ectoenzymes, which enhances the extracellular availability of the neuroprotectant adenosine, abrogation of the osmotic release of ATP, which might protect retinal ganglion cells from apoptosis, and the release of antioxidants and neurotrophic factors. The dedifferentiation of reactive Müller cells to progenitor-like cells might have an impact on future therapeutic approaches. A better understanding of the gliotic mechanisms will be helpful in developing efficient therapeutic strategies aiming at increased protective and regenerative properties and decreased toxicity of reactive Müller cells.
几乎所有的致病刺激都会激活 Müller 细胞。反应性 Müller 细胞对光感受器和神经元既有保护作用，也有毒性作用。它们会导致谷氨酸摄取和谷胱甘肽合成功能障碍，引起氧化应激和谷氨酸毒性。钾电导下调会破坏细胞间钾和水的转运，导致神经元过度兴奋和水肿。反应性 Müller 细胞的保护作用包括上调三磷酸腺苷（ATP）降解的外切酶，增加神经保护物质腺苷的细胞外可用性，阻断 ATP 的渗透释放，从而保护视网膜神经节细胞免于凋亡，以及释放抗氧化剂和神经营养因子。反应性 Müller 细胞向祖细胞样细胞的去分化可能会对未来的治疗方法产生影响。深入了解神经胶质细胞的激活机制，有助于开发有效的治疗策略，以提高反应性 Müller 细胞的保护和再生特性，降低其毒性。
