Purpose. Adenosine A_2A receptor (A_2AR) 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_2AR antagonist ZM241385 would prevent photoreceptor apoptosis by inhibiting retinal inflammation and oxidative stress after RD. Methods. The A_2AR 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_2AR expression, microglia proliferation and reactivity, glial fibrillary acidic protein (GFAP) accumulation, IL-1β expression, and reactive oxygen species (ROS) production were evaluated with immunofluorescence. Photoreceptor TUNEL was analyzed. Results. A_2AR expression obviously increased and accumulated in microglia and Müller cells in the retinas after RD. The A_2AR antagonist ZM241385 effectively inhibited retinal microglia proliferation and reactivity, decreased GFAP upregulation and proinflammatory cytokine IL-1β expression of Müller cells, and suppressed ROS overproduction, resulting in attenuation of photoreceptor apoptosis after RD. Conclusions. The A_2AR 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_2AR blockade may be an important therapeutic strategy to protect photoreceptors in RD and other CNS diseases that share a common etiology.

中文翻译：

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腺苷 A2A 受体的阻断通过抑制炎症和氧化应激来保护视网膜脱离后的光感受器。

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。我们检验了 A _2AR拮抗剂 ZM241385 会通过抑制 RD 后的视网膜炎症和氧化应激来防止光感受器凋亡的假设。方法。A 2AR 拮抗剂 ZM241385 在产生 RD 前₂小时开始每天以剂量（3 mg/kg，ip）递送给 C57BL/6J 小鼠，持续三天。A _2AR表达、小胶质细胞增殖和反应性、胶质纤维酸性蛋白 (GFAP) 积累、IL-1 β用免疫荧光评估表达和活性氧（ROS）的产生。分析了光感受器 TUNEL。结果。RD 后视网膜的小胶质细胞和 Müller 细胞中的_2AR表达明显增加和积累。A 2AR 拮抗剂 ZM241385 有效抑制视网膜小胶质细胞的_增殖和反应性，降低 Müller 细胞的 GFAP 上调和促炎细胞因子 IL-1 β表达，并抑制 ROS 过度产生，导致 RD 后光感受器凋亡减弱。结论。A _2AR 拮抗剂 ZM241385 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 阻断可能是保护 RD 和其他具有共同病因的 CNS 疾病中的光感受器的重要治疗策略。