Laboratory Evidence of Sustained Chronic Inflammatory Reaction in Retinitis Pigmentosa

Laboratory Evidence of Sustained Chronic Inflammatory Reaction in Retinitis Pigmentosa
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DOI:
10.1016/j.ophtha.2012.07.008
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发表时间:
2013-01-01
期刊:
影响因子:
13.7
通讯作者:
Ishibashi, Tatsuro
Ishibashi, Tatsuro
中科院分区:
医学1区
文献类型:
--
作者:
Yoshida, Noriko;Ikeda, Yasuhiro;Ishibashi, Tatsuro

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目的:研究视网膜色素变性(RP)动物模型RD10小鼠视网膜炎症反应的性质,以及抗氧化剂对视网膜炎症和感光细胞凋亡的影响。设计:实验研究。参与者和对照组:42只未经治疗的RD10小鼠,30只N-乙酰半胱氨酸(NAC)处理的RD10小鼠和20只C57BL/6小鼠作为对照。方法:采用实时定量聚合酶链式反应(RT-PCR)技术检测RD10小鼠视网膜炎症因子(促炎细胞因子和趋化因子)的表达水平。用抗氧化剂NAC治疗RD10小鼠,用免疫组织化学方法检测其对视网膜炎症和光感受器凋亡的影响。主要观察指标:实时荧光定量聚合酶链式反应和免疫组织化学。结果:在RD10小鼠视网膜变性过程中,发生了促炎症细胞因子和趋化因子表达增加、小胶质细胞激活和光感受器细胞凋亡的一系列事件。结论:持续的慢性炎症反应可能参与了RD10小鼠视网膜变性的发病机制,提示使用抗氧化剂干预眼部炎症反应可能是治疗RP患者的一种潜在的治疗方法。
Purpose: To study the nature of retinal inflammatory response in rd10 mice, an animal model of retinitis pigmentosa (RP), and to investigate the effect of an antioxidant on retinal inflammation and photoreceptor apoptosis.Design: Experimental study.Participants and Controls: This study included 42 untreated rd10 mice, 30 N-acetylcysteine (NAC)-treated rd10 mice, and 20 C57BL/6 mice as controls.Methods: Real-time polymerase chain reaction (PCR) was performed to evaluate the expression levels of inflammatory factors (proinflammatory cytokines and chemokines) in rd10 mouse retinas. Rd10 mice were treated with an antioxidant NAC, and its effect on retinal inflammation and photoreceptor apoptosis were examined by immunohistochemistry.Main Outcome Measures: Real-time PCR and immunohistochemistry.Results: We demonstrated sequential events involving increased expression of proinflammatory cytokines and chemokines, activation of microglia, and photoreceptor apoptosis during retinal degeneration of rd10 mice. Furthermore, antioxidant treatment with NAC prevented the photoreceptor cell death along with suppression of inflammatory factors and microglial activation.Conclusions: Sustained chronic inflammatory reaction may contribute to the pathogenesis of retinal degeneration in rd10 mice, suggesting interventions for ocular inflammatory reaction using antioxidants as a potential treatment for patients with RP.