Song Yifan, Wang Mengru, Zhao Suyan, Tian Yanjie, Zhang Chun
Department of Ophthalmology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Beijing, China.
Front Pharmacol. 2022 Sep 27;13:936632. doi: 10.3389/fphar.2022.936632. eCollection 2022.
Optic neuritis (ON), characterized by inflammation of the optic nerve and apoptosis of retinal ganglion cells (RGCs), is one of the leading causes of blindness in patients. Given that RGC, as an energy-intensive cell, is vulnerable to mitochondrial dysfunction, improving mitochondrial function and reducing oxidative stress could protect these cells. Matrine (MAT), an alkaloid derived from , has been shown to regulate immunity and protect neurons in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis and ON. However, the protective mechanism of MAT on RGCs is largely unknown. In this study, we show that MAT treatment significantly reduced the degree of inflammatory infiltration and demyelination of the optic nerve and increased the survival rate of RGCs. The expression of Sirtuin 1 (SIRT1), a member of an evolutionarily conserved gene family (sirtuins), was upregulated, as well as its downstream molecules Nrf2 and PGC-1α. The percentage of TOMM20-positive cells was also increased remarkably in RGCs after MAT treatment. Thus, our results indicate that MAT protects RGCs from apoptosis, at least in part, by activating SIRT1 to regulate PGC-1α and Nrf2, which, together, promote mitochondrial biosynthesis and reduce the oxidative stress of RGCs.
视神经炎（ON）以视神经炎症和视网膜神经节细胞（RGCs）凋亡为特征，是导致患者失明的主要原因之一。鉴于RGC作为一种能量消耗大的细胞，易受线粒体功能障碍影响，改善线粒体功能和减轻氧化应激可保护这些细胞。苦参碱（MAT）是一种从[植物名称缺失]中提取的生物碱，在实验性自身免疫性脑脊髓炎（EAE）这一多发性硬化症和视神经炎的动物模型中，已显示出调节免疫和保护神经元的作用。然而，MAT对RGCs的保护机制在很大程度上尚不清楚。在本研究中，我们发现MAT治疗显著降低了视神经的炎症浸润程度和脱髓鞘程度，并提高了RGCs的存活率。进化上保守的基因家族（沉默调节蛋白）成员沉默调节蛋白1（SIRT1）及其下游分子Nrf2和PGC-1α的表达上调。MAT处理后，RGCs中TOMM20阳性细胞的百分比也显著增加。因此，我们的结果表明，MAT至少部分地通过激活SIRT1来调节PGC-1α和Nrf2，从而保护RGCs免于凋亡，这两者共同促进线粒体生物合成并降低RGCs的氧化应激。
