Microglial Inhibition as a Therapeutic Strategy for Subretinal Hemorrhage

我们建立了一个视网膜下出血的小鼠模型，以表征出血后急性发作的炎症反应和光感受器退化。观察到小胶质细胞早在出血后6h就开始渗入视网膜外。伴随着感光细胞变性和细胞凋亡，炎性细胞逐渐聚集在外核层。应用小胶质细胞激活抑制剂米诺环素减少小胶质细胞趋化因子的表达，减少视网膜下出血后小胶质细胞的浸润和光感受器细胞的丢失 在活体内。视网膜下出血后出现炎症反应和光感受器萎缩，但反应程度和萎缩程度相似。 在C3缺乏和C3充足的小鼠之间，表明补体介导的过程的作用有限。我们的数据表明炎症反应在视网膜下出血中驱动光感受器细胞丢失中起作用，并提出抑制小胶质细胞可能在视网膜下出血的治疗中有益。

We created a mouse model of subretinal hemorrhage to characterize the inflammatory responses and photoreceptor degeneration that occur in the acute aftermath of hemorrhage. It was observed that microglial infiltration into the outer retina commences as early as 6 hours after hemorrhage. Inflammatory cells progressively accumulate in the outer nuclear layer concurrently with photoreceptor degeneration and apoptosis. Administration of minocycline, an inhibitor of microglial activation, decreased microglial expression of chemotactic cytokines in vitro and reduced microglial infiltration and photoreceptor cell loss after subretinal hemorrhage in vivo. Inflammatory responses and photoreceptor atrophy occurred after subretinal hemorrhage, however, the degree of response and atrophy were similar between C3-deficient and C3-sufficient mice, indicating a limited role for complement-mediated processes. Our data indicate a role for inflammatory responses in driving photoreceptor cell loss in subretinal hemorrhage, and it is proposed that microglial inhibition may be beneficial in the treatment of subretinal hemorrhage.