Blockade of Adenosine A2A Receptor Protects Photoreceptors after Retinal Detachment by Inhibiting Inflammation and Oxidative Stress
Blockade of Adenosine A2A Receptor Protects Photoreceptors after Retinal Detachment by Inhibiting Inflammation and Oxidative Stress
复制标题
阻断腺苷 A2A 受体可通过抑制炎症和氧化应激来保护视网膜脱离后的感光细胞。
DOI：
10.1155/2020/7649080
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发表时间：
2020-07-03
影响因子：
--
通讯作者：
Shen, Xi
中科院分区：
文献类型：
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作者：
Gao, Sha;Li, Na;Shen, Xi
目的.腺苷A（2A）受体（A（2A）R）信号传导在一些视网膜损伤模型中具有神经保护作用，但其在视网膜脱离（RD）期间神经元存活中的作用尚不清楚。我们验证了A（2A）R拮抗剂ZM 241385通过抑制RD后视网膜炎症和氧化应激来预防感光细胞凋亡的假设。方法.将A（2A）R拮抗剂ZM 241385以3 mg/kg的剂量（i. p.）在创建RD之前2小时开始。用免疫荧光法评估A（2A）R表达、小胶质细胞增殖和反应性、胶质细胞酸性蛋白（GFAP）积累、IL-1 β表达和活性氧（ROS）产生。光感受器TUNEL法检测。结果视网膜脱离后A（2A）R表达明显增加，并在视网膜小胶质细胞和Muller细胞内聚集。A（2A）R拮抗剂ZM 241385有效抑制视网膜小胶质细胞增殖和反应性，降低Muller细胞GFAP上调和促炎细胞因子IL-1 β表达，抑制活性氧过量产生，从而减轻RD后光感受器细胞凋亡。结论. A（2A）R拮抗剂ZM 241385是RD小鼠模型中小胶质细胞增殖和反应性、神经胶质增生、神经炎症、氧化应激和感光细胞凋亡的有效抑制剂。这表明，A（2A）R阻断可能是一种重要的治疗策略，以保护光感受器在RD和其他CNS疾病，共享一个共同的病因。
Purpose. Adenosine A(2A) receptor (A(2A)R) signaling is neuroprotective in some retinal damage models, but its role in neuronal survival during retinal detachment (RD) is unclear. We tested the hypothesis that A(2A)R antagonist ZM241385 would prevent photoreceptor apoptosis by inhibiting retinal inflammation and oxidative stress after RD. Methods. The A(2A)R antagonist ZM241385 was delivered daily to C57BL/6J mice for three days at a dose (3 mg/kg, i.p.) starting 2 hours prior to creating RD. A(2A)R expression, microglia proliferation and reactivity, glial fibrillary acidic protein (GFAP) accumulation, IL-1 beta expression, and reactive oxygen species (ROS) production were evaluated with immunofluorescence. Photoreceptor TUNEL was analyzed. Results. A(2A)R expression obviously increased and accumulated in microglia and Muller cells in the retinas after RD. The A(2A)R antagonist ZM241385 effectively inhibited retinal microglia proliferation and reactivity, decreased GFAP upregulation and proinflammatory cytokine IL-1 beta expression of Muller cells, and suppressed ROS overproduction, resulting in attenuation of photoreceptor apoptosis after RD. Conclusions. The A(2A)R antagonist ZM241385 is an effective suppressor of microglia proliferation and reactivity, gliosis, neuroinflammation, oxidative stress, and photoreceptor apoptosis in a mouse model of RD. This suggests that A(2A)R blockade may be an important therapeutic strategy to protect photoreceptors in RD and other CNS diseases that share a common etiology.