Adenosine A2A Receptor: A New Neuroprotective Target in Light-Induced Retinal Degeneration.
Adenosine A2A Receptor: A New Neuroprotective Target in Light-Induced Retinal Degeneration.
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DOI：
10.3389/fphar.2022.840134
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发表时间：
2022
影响因子：
5.6
通讯作者：
López-Costa JJ
中科院分区：
文献类型：
--
作者：
Soliño M;Larrayoz IM;López EM;Rey-Funes M;Bareiro M;Loidl CF;Girardi E;Martínez A;López-Costa JJ
连续光照会导致光感受器退化。这种光诱导视网膜变性的动物模型类似于人类视网膜外部退行性疾病的许多特征，例如年龄相关性黄斑变性。本工作旨在评价腺苷A2a受体的调节在光诱导视网膜变性模型中的潜在神经保护作用。SD大鼠右眼玻璃体内注射腺苷A2a受体激动剂CGS 21680或腺苷A2a受体拮抗剂SCH 58261。对侧眼分别注射不同的交通工具作为对照。对大鼠视网膜进行胶质纤维酸性蛋白(GFAP)免疫组织化学、末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)、Western blotting(WB)和定量逆转录聚合酶链式反应(qRT-PCR)检测。另一组大鼠接受视网膜电描记术的功能研究。CGS21680治疗组大鼠视网膜外核层凋亡核明显增多，视网膜GFAP免疫反应面积明显增加，但对WB和视网膜电流图结果无明显影响。定量逆转录聚合酶链式反应显示，CGS 21680可显著上调IL-1β的表达。相反，SCH 58261显著减少视网膜外核层和胶质纤维酸性蛋白免疫反应区的凋亡核。它还显著降低了GFAP和激活的caspase-3水平，并保留了视网膜功能，因为治疗眼显示出明显更大的a波和b波幅度和振荡电位。定量逆转录聚合酶链式反应显示，SCH 58261可显著降低肿瘤坏死因子α的表达。这些结果表明，在致病过程开始之前阻断A2A受体是具有神经保护作用的，因为它可以防止光诱导的视网膜损伤。A2A型受体拮抗剂在视网膜退行性疾病中的应用值得评价。
Continuous illumination induces the degeneration of photoreceptors. This animal model of light-induced retinal degeneration resembles many characteristics of human degenerative diseases of the outer retina, such as age-related macular degeneration. This work aimed to evaluate the potential neuroprotective effect of the modulation of adenosine A2A receptor in the model of light-induced retinal degeneration. Sprague-Dawley rats were intravitreally injected in the right eye with either CGS 21680, an adenosine A2A receptor agonist, or SCH 58261, an adenosine A2A receptor antagonist. Contralateral eyes were injected with respective vehicles as control. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h. Retinas were processed by glial fibrillary acidic protein (GFAP) immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique, Western blotting (WB), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Another group of rats was subjected to functional studies by electroretinography. Animals treated with CGS21680 showed a significant increase of apoptotic nuclei in the outer nuclear layer and a significant increase of GFAP immunoreactive area of the retinas but did not alter WB nor electroretinography results. qRT-PCR showed that CGS 21680 significantly increased the expression of interleukin-1β. On the opposite, SCH 58261 significantly decreased apoptotic nuclei in the outer nuclear layer and GFAP immunoreactive area of the retinas. It also significantly decreased GFAP and activated caspase-3 levels as measured by WB and preserved retinal function, as treated eyes showed significantly greater amplitudes of a- and b-waves and oscillatory potentials. qRT-PCR revealed that SCH 58261 significantly decreased the expression of tumor necrosis factor-α. These results show that the blockade of the A2A receptor before the start of the pathogenic process is neuroprotective, as it prevents light-induced retinal damage. The use of A2A receptor antagonists deserves to be evaluated in retinal degenerative diseases.
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影响因子：
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