Department of Clinical Sciences South Bristol, Academic Unit of Ophthalmology, University of Bristol, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.
Eye (Lond). 2009 Oct;23(10):1939-45. doi: 10.1038/eye.2008.380. Epub 2008 Dec 19.
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.
视网膜内的小胶质细胞不断从骨髓中产生，是视网膜内的固有髓样细胞。在整个生命周期中，小胶质细胞的功能受到微环境的调节，从而实现免疫调节以控制炎症，以及促进正常发育，并在成年期维持正常的视网膜功能。最近的证据表明，在成年期，视网膜继续替换细胞以维持最佳功能。尽管在某些情况下，损伤、变性或炎症后仍然存在视觉功能不可逆转的下降，暗示细胞替换不足，但这种不足可以通过小胶质细胞激活来解释，这会影响视网膜祖细胞或募集的祖细胞适当整合和分化的能力。髓样细胞反应因损伤而异：在炎症期间，小胶质细胞和浸润的髓样细胞的功能受到细胞因子环境的调节，这一点是显而易见的。事实上，通过调节髓样细胞的功能进行治疗可以抑制自身免疫实验模型中的疾病，而在非炎症模型中，小胶质细胞对变性过程几乎没有影响。髓样细胞激活的程度可以帮助确定视网膜祖细胞的更新。可以从成人视网膜中分离出视网膜祖细胞，尽管数量有限，但它们具有有丝分裂活性并可以分化。小胶质细胞激活分泌的 IL-6 限制了祖细胞的更新，以及向有丝分裂后视网膜细胞分化的程度。这些实验数据说明了需要开发方法来补充正常的视网膜髓样细胞功能，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。
