Liu Jinfeng, Zhou Lina, Wu Xueping, Chen Zihang, Zheng Xiaofei, Wang Huajun, So Kwok Fai, Ma Lan, Wang Jiantao, Chiu Kin
Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, Shenzhen, China.
Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Front Pharmacol. 2024 Jul 3;15:1404119. doi: 10.3389/fphar.2024.1404119. eCollection 2024.
Murray (LR) known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the HO-challenged immortalized microglial (IMG) cell line . LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.
黑果枸杞(LR),又称“黑枸杞”或“黑狼杞”,在中草药中被广泛应用。黑果枸杞果实显示出其在治疗心脏损伤、实验性结肠炎、非酒精性脂肪性肝病、疲劳和衰老方面的抗氧化和/或抗炎活性。青光眼是不可逆失明的主要原因。除了眼压升高(IOP)外,氧化应激和神经炎症也被认为是青光眼发病机制的促成因素。本研究在激光诱导的慢性高眼压(COH)小鼠模型和DBA/2J小鼠品系中,研究了黑果枸杞水提取物(LRE)对受持续眼压升高威胁的视网膜神经节细胞(RGCs)的治疗效果。在过氧化氢(HO)刺激的永生化小胶质细胞(IMG)细胞系中进一步测试了LRE的抗氧化和抗炎作用。在两种模拟青光眼的模型中,口服LRE(2 g/kg)均能保留RGCs的功能并促进其存活。LRE降低了视网膜中8-羟基鸟苷(氧化应激标志物)的表达。LRE减少了COH小鼠视网膜中Iba-1+小胶质细胞的数量,但在DBA/2J小鼠中未减少。在mRNA水平上,LRE逆转了COH诱导的COH小鼠视网膜中HO-1和SOD-2的过表达。进一步的研究表明,LRE预处理IMG细胞可通过上调GPX-4、Prdx-5、HO-1和SOD-2显著降低H2O2诱导的氧化应激。我们的工作表明,每日口服LRE可能通过降低氧化应激和抑制视网膜中的小胶质细胞活化,用作预防/治疗剂来保护高眼压应激下的RGCs。