Pharmacological Research Group, Basic Research Development Division, Rohto Pharmaceutical Co., Ltd., Kizugawa, Kyoto, Japan.
Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
J Ocul Pharmacol Ther. 2020 Jun;36(5):311-319. doi: 10.1089/jop.2019.0163. Epub 2020 May 5.
Photoreceptor degeneration is a major cause of blindness. Microglia are known to play key roles in the pathogenesis and progression of neural degeneration. We examined the possible use of apigenin, which is a naturally occurring flavonoid, for the treatment of photoreceptor degeneration through regulation of microglial activities. As analyses, BV2 and MG5 mouse microglia cell lines were stimulated in the presence or absence of apigenin, and their activation profile was examined. study was done using rd1 photoreceptor degeneration model, and apigenin was administered by intravitreal injection, and pathological feature was examined. Cell survival was not affected by apigenin in either BV2 and MG5. Apigenin suppressed lipopolysaccharide (LPS)-induced chemokine production in both BV2 and MG5 cells, but phagocytosis was suppressed in MG5 cells but not in BV2 cells. Apigenin inhibited LPS-induced M1 activation but could not drive microglia toward the M2 phenotype. Apigenin suppressed the expression of miR-155 in a dose-dependent manner. Furthermore, the Ets protein level was suppressed by treatment of BV2 cells with apigenin. When rd1 mice were treated with apigenin by intravitreal injection, the expression of inflammatory chemokines in the retina was reduced, and activation of microglia and Müller glia was suppressed. Furthermore, the thickness of the outer nuclear layer of the retina of rd1 mice was thicker in apigenin-treated retinas. Taken together, local administration of apigenin to the retina is a potential therapeutic treatment for photoreceptor degeneration, which involves downregulation of microglia in the retina when photoreceptors are damaged.
光感受器变性是失明的主要原因。已知小胶质细胞在神经变性的发病机制和进展中起关键作用。我们研究了天然存在的黄酮类化合物芹菜素通过调节小胶质细胞活性治疗光感受器变性的可能性。作为分析，在存在或不存在芹菜素的情况下刺激 BV2 和 MG5 小鼠小胶质细胞系，并检查其激活谱。这项研究使用 rd1 光感受器变性模型进行，通过玻璃体内注射给予芹菜素，并检查病理特征。细胞存活不受 BV2 和 MG5 中芹菜素的影响。芹菜素抑制 LPS 诱导的两种 BV2 和 MG5 细胞中的趋化因子产生，但吞噬作用在 MG5 细胞中受到抑制，而在 BV2 细胞中不受抑制。芹菜素抑制 LPS 诱导的 M1 激活，但不能使小胶质细胞向 M2 表型转变。芹菜素以剂量依赖的方式抑制 miR-155 的表达。此外，Ets 蛋白水平被芹菜素处理的 BV2 细胞抑制。当 rd1 小鼠通过玻璃体内注射用芹菜素治疗时，视网膜中炎症趋化因子的表达减少，小胶质细胞和 Muller 胶质细胞的激活受到抑制。此外，rd1 小鼠视网膜的外核层厚度在芹菜素处理的视网膜中较厚。综上所述，局部给予视网膜芹菜素是治疗光感受器变性的一种潜在治疗方法，当光感受器受损时，涉及视网膜中小胶质细胞的下调。
