Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
National Clinical Research Center for Eye Disease, Shanghai, China.
Cell Death Dis. 2021 Oct 9;12(10):926. doi: 10.1038/s41419-021-03983-3.
Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.
光感受器死亡和神经退行性变是不可逆视力丧失的主要原因。小胶质细胞的炎症反应在神经退行性变过程中起着重要作用。在这项研究中,我们选择视网膜脱离作为光感受器变性的模型。我们发现肌球蛋白 1f 在视网膜脱离后上调,并且特异性表达在小胶质细胞中。肌球蛋白 1f 缺乏可通过抑制小胶质细胞激活来保护光感受器凋亡。小胶质细胞的消除可以消除肌球蛋白 1f 缺乏的保护作用。在 LPS 刺激后,肌球蛋白 1f 缺乏的小胶质细胞表现出 MAPK 和 AKT 途径的下调。我们的结果表明,肌球蛋白 1f 通过调节两条经典炎症途径在视网膜损伤和光感受器变性后的小胶质细胞诱导的神经炎症中发挥关键作用,从而降低炎症细胞因子的表达。肌球蛋白 1f 的敲除减少了免疫反应的强度并防止光感受器的细胞死亡,表明可以抑制肌球蛋白 1f 来防止视网膜脱离后视力下降。