Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fen Yang Road, Shanghai, 200031, People's Republic of China.
Inflammation. 2013 Feb;36(1):42-52. doi: 10.1007/s10753-012-9518-6.
Microglia-associated inflammation is closely related to the pathogenesis of retinal degenerative disorders. We have previously shown in vivo that naloxone protected photoreceptors from light-induced apoptosis possibly through inhibiting microglial activation. In this study, we attempted to explore the effect of lipopolysaccharide (LPS)-activated microglia on photoreceptor death and the influence of naloxone treatment using an in vitro retinal microglia and 661 W photoreceptor co-culture system. Immunofluorescent staining and ELISA measurements demonstrated that LPS activated microglia by changing the morphology and increasing the production of proinflammatory factors interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Flow cytometry analysis of annexin V/propidium iodide staining showed that LPS-activated microglia promoted the apoptosis of co-cultured 661 W photoreceptor cells. Naloxone inhibited microglial activation and decreased the release of IL-1beta and TNF-alpha but could not prevent photoreceptors from undergoing apoptosis. Considering the dual role of microglia-associated inflammation in both neurotoxicity and neuroprotection, modulating the function, rather than simply inhibiting their activation, might be a new therapeutic method for preventing photoreceptor degeneration.
小胶质细胞相关炎症与视网膜退行性疾病的发病机制密切相关。我们之前已经在体内证明，纳洛酮通过抑制小胶质细胞的激活来保护光感受器免受光诱导的细胞凋亡。在这项研究中，我们试图使用体外视网膜小胶质细胞和 661W 光感受器共培养系统来探索脂多糖（LPS）激活的小胶质细胞对光感受器死亡的影响以及纳洛酮治疗的影响。免疫荧光染色和 ELISA 测量表明，LPS 通过改变形态和增加促炎因子白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的产生来激活小胶质细胞。用 Annexin V/碘化丙啶染色的流式细胞术分析表明，LPS 激活的小胶质细胞促进了共培养的 661W 光感受器细胞的凋亡。纳洛酮抑制小胶质细胞的激活并减少 IL-1β和 TNF-α的释放，但不能阻止光感受器发生凋亡。考虑到小胶质细胞相关炎症在神经毒性和神经保护中的双重作用，调节其功能而不仅仅是抑制其激活可能是预防光感受器变性的一种新的治疗方法。
