Inhibition of LOX-1 prevents inflammation and photoreceptor cell death in retinal degeneration
Inhibition of LOX-1 prevents inflammation and photoreceptor cell death in retinal degeneration
复制标题
抑制 LOX-1 可预防视网膜变性中的炎症和感光细胞死亡。
DOI：
10.1016/j.intimp.2020.106190
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发表时间：
2020-03-01
影响因子：
5.6
通讯作者：
Yang, Liu
中科院分区：
文献类型：
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作者：
Gao, Xinran;Zhu, Ruilin;Yang, Liu
目的：探讨凝集素样氧化低密度脂蛋白受体1（LOX-1）在视网膜变性中的表达及作用。方法：采用光照诱导BALB/c小鼠视网膜变性。 BV2细胞被LPS刺激激活。在光损伤 (LD) 或 LPS 刺激之前，用 LOX-1 中和抗体或聚肌苷酸 (Poly)（LOX-1 抑制剂）预处理视网膜或 BV2 细胞。通过实时RT-PCR、蛋白质印迹或ELISA检测视网膜或BV2细胞中LOX-1、TNF-α、IL-1β、CCL2和NF-κB的表达。对视网膜进行组织学分析。通过视网膜中的 TUNEL 测定或在小胶质细胞条件培养基中培养的 661W 细胞中通过流式细胞术评估感光细胞死亡。结果：LD 在 BALB/c 小鼠视网膜中诱导感光细胞死亡和 LOX-1 表达升高。 LOX-1中和抗体或PolyI预处理可显着降低LD引起的视网膜LOX-1、TNF-α、IL-1β、CCL2和p-NF-κB表达升高。 LOX-1中和抗体或Polyl对LOX-1的抑制显着减少了LD诱导的视网膜感光细胞死亡。 LPS 引起的 TNF-α、IL-1β 和 CCL2 水平升高可通过抑制 BV2 细胞中的 LOX-1 来下调。抑制LOX-1可降低小胶质细胞对光感受器的神经毒性。结论：光诱导的视网膜变性中LOX-1表达增加，抑制LOX1可防止视网膜变性中的炎症和光感受器细胞死亡，并降低小胶质细胞对光感受器的神经毒性。因此，LOX-1可以作为此类视网膜变性疾病的潜在治疗靶点。
Purpose: To explore the expression and role of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in retinal degeneration.Methods: The retinal degeneration of BALB/c mice was induced by light exposure. BV2 cells were activated by LPS stimulation. Retinas or BV2 cells were pretreated with LOX-1 neutralizing antibody or Polyinosinic acid (Polyl) (the inhibitor of LOX-1) before light damage (LD) or LPS stimulation. LOX-1, TNF-alpha, IL-1 beta, CCL2 and NF-kappa B expression were detected in retinas or BV2 cells by real-time RT-PCR, western blot or ELISA. Histological analyses of retinas were performed. Photoreceptor cell death was assessed by TUNEL assay in retinas or by flow cytometry in 661W cells cultured in microglia-conditioned medium.Results: Photoreceptor cell death and elevated expression of LOX-1 were induced by LD in retinas of BALB/c mice. LOX-1 neutralizing antibody or PolyI pretreatment significantly reduced the elevated expression of LOX-1, TNF-alpha, IL-1 beta, CCL2 and p-NF-kappa B caused by LD in retinas. Inhibition of LOX-1 by LOX-1 neutralizing antibody or Polyl significantly reduced photoreceptor cell death induced by LD in retinas. Elevated levels of TNF-alpha, IL-1 beta and CCL2 caused by LPS were down-regulated by inhibition of LOX-1 in BV2 cells. Inhibition of LOX-1 reduces microglial neurotoxicity on photoreceptors.Conclusions: LOX-1 expression is increased in light induced retinal degeneration, what's more, inhibition of LOX1 prevents inflammation and photoreceptor cell death in retinal degeneration and reduces microglial neurotoxicity on photoreceptors. Therefore, LOX-1 can be used as a potential therapeutic target for such retinal degeneration diseases.