Influence of microglia on retinal progenitor cell turnover and cell replacement
Influence of microglia on retinal progenitor cell turnover and cell replacement
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DOI：
10.1038/eye.2008.380
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发表时间：
2009-10-01
期刊：
影响因子：
3.9
通讯作者：
Dick, A. D.
中科院分区：
文献类型：
--
作者：
Dick, A. D.
视网膜内的小胶质细胞不断被骨髓取代，是视网膜内常驻的髓源性细胞。在整个生命过程中，小胶质细胞的功能受到微环境的制约，微环境提供免疫调节来控制炎症，并使其能够正常发育，并在成年期维持正常的视网膜功能。在成年期，最近的证据支持视网膜继续替换细胞以保持最佳功能的观点。虽然在某些情况下，在损伤、变性或炎症后，仍然存在不可避免的视觉功能下降，这可以推断出细胞替代的缺陷，这种缺陷可以通过小胶质细胞激活影响视网膜祖细胞或募集祖细胞整合和分化的能力来解释。髓细胞的反应因损伤而异：很明显，在炎症期间，小胶质细胞和浸润的髓细胞的功能是由细胞因子环境调节的。事实上，在自身免疫实验模型中，调节髓细胞功能治疗性地抑制疾病，而在非炎症模型中，小胶质细胞对退行性变的过程几乎没有影响。髓细胞活化的程度可以帮助确定视网膜祖细胞的周转。视网膜祖细胞可以从成人视网膜中分离出来，尽管有限，但具有有丝分裂活性并能分化。分泌IL-6的小胶质细胞激活限制了祖细胞的周转和向有丝分裂后视网膜细胞分化的程度。这些实验数据表明，需要开发方法来补充正常的视网膜髓细胞功能，促进整合，无论是通过细胞移植还是通过鼓励视网膜祖细胞恢复视网膜功能。Eye (2009) 23, 1939-1945；doi: 10.1038 / eye.2008.380;2008年12月19日在网上发表
Microglia within the retina are continually replaced from the bone marrow and are the resident myeloid-derived cells within the retina. Throughout life, microglial function is conditioned by the microenvironment affording immunomodulation to control inflammation as well as functioning to enable normal development and, during adulthood, maintain normal retinal function. In adulthood, recent evidence supports the concept that the retina continues to replace cells to maintain optimal function. Although in some cases after injury, degeneration, or inflammation there remains an inextricable decline in visual function inferring a deficit in cell replacement, the deficit could be explained by microglial cell activation influencing the ability of either retinal progenitor cells or recruited progenitor cells to integrate and differentiate appropriately. Myeloid cell response differs depending on insult: it is evident that during inflammation microglia and the infiltrating myeloid cell function are conditioned by the cytokine environment. Indeed, modulating myeloid cell function therapeutically suppresses disease in experimental models of autoimmunity, whereas in non-inflammatory models microglia have little or no effect on the course of degeneration. The extent of myeloid activation can help determine retinal progenitor cell turnover. Retinal progenitor cells may be isolated from adult human retina, which, albeit limited, display mitotic activity and can differentiate. Microglial activation secreting IL-6 limits progenitor cell turnover and the extent to which differentiation to post-mitotic retinal cells occurs. Such experimental data illustrate the need to develop methods to replenish normal retinal myeloid cell function facilitating integration, either by cell transplantation or by encouraging retinal progenitor cells to recover retinal function. Eye (2009) 23, 1939-1945; doi:10.1038/eye.2008.380; published online 19 December 2008