Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Glia. 2014 Dec;62(12):1943-54. doi: 10.1002/glia.22715. Epub 2014 Jul 2.
Neuroinflammation underlies a wide variety of pathological processes in the central nerve system (CNS). Although previous experimental and clinical studies indicate that activation of neuroinflammatory signaling occurs early in glaucoma, the mechanisms controlling microglia activation are still poorly defined. In the present study, we investigated the role of the chemokine receptor Cx3cr1 in microglia activation and retinal ganglion cell (RGC) death in an experimental mouse glaucoma model with transient elevation of intraocular pressure (IOP). We demonstrated that retinal microglia played a pathogenic role in RGC death. Conversely, pharmacological suppression of microglia activation by minocycline increased RGC survival. Moreover, we found that Cx3cr1 deficiency enhanced microglial neurotoxicity and subsequently induced more extensive RGC loss, suggesting that Cx3cr1 suppressed microglial activation under elevated IOP. Overall, these findings provided novel insight into the mechanisms by which Cx3cr1 modulated microglia activation under elevated IOP. Suppression of microglia activation might be a potential treatment for slowing down the course of the disease and for increasing RGC survival in glaucoma patients.
神经炎症是中枢神经系统（CNS）多种病理过程的基础。尽管先前的实验和临床研究表明，神经炎症信号的激活发生在青光眼的早期，但控制小胶质细胞激活的机制仍未得到明确界定。在本研究中，我们研究了趋化因子受体 Cx3cr1 在实验性小鼠青光眼模型（短暂性眼压升高）中小胶质细胞激活和视网膜神经节细胞（RGC）死亡中的作用。我们证明视网膜小胶质细胞在 RGC 死亡中起致病作用。相反，米诺环素抑制小胶质细胞激活的药理学作用增加了 RGC 的存活。此外，我们发现 Cx3cr1 缺陷增强了小胶质细胞的神经毒性，随后导致更广泛的 RGC 丢失，表明 Cx3cr1 在高眼压下抑制小胶质细胞激活。总的来说，这些发现为 Cx3cr1 调节高眼压下小胶质细胞激活的机制提供了新的见解。抑制小胶质细胞激活可能是减缓疾病进程和增加青光眼患者 RGC 存活的潜在治疗方法。
