Larsen A K, Osborne N N
Nuffield Laboratory of Ophthalmology, University of Oxford, United Kingdom.
Invest Ophthalmol Vis Sci. 1996 Dec;37(13):2603-11.
The aim of this study was to determine whether adenosinergic agents can be used to slow down the changes seen in the rat retina after ischemia-reperfusion.
Ischemia-reperfusion injury to the rat retina was induced by raising the intraocular pressure above the systolic blood pressure for 45 minutes, followed by reperfusion for 3 days. This insult caused a reduction of the b-wave of the electroretinogram (54% +/- 5%, n = 23) relative to the contralateral control retina, an expression of glial fibrillary acidic protein (GFAP) in the Müller cells, and an alteration in the "staining" pattern of the calretinin immunoreactivity. The normal two to three bands of calretinin immunoreactivity in the inner plexiform layer appeared as a single band. Elevation of the intraocular pressure for 60 minutes, followed by reperfusion of 2 weeks, caused a 40% reduction in the thickness of the inner nuclear and plexiform layers. No statistically significant changes in the other retinal layers were recorded.
When the adenosine deaminase inhibitor erythro-9-(2-hydroxyl-3-nonyl)adenine (EHNA) was injected into the eye just before ischemia, the ischemia-reperfusion changes in the b-wave and calretinin immunoreactivity were largely prevented. Similar results were observed when the adenosine A1 receptor agonist, R-N6-(2-phenylisopropyl)adenosine (R-PLA), was administered intraperitoneally just before ischemia. Injection of adenosine deaminase into the eye before ischemia seemed to potentiate the ischemia-reperfusion effect because the reduction of the b-wave was almost complete (8% +/- 4%, n = 6). The ischemia-reperfusion-induced expression of GFAP in the Müller cells was not reduced by any of the adenosinergic agents tested. This suggests that GFAP expression in the Müller cells is not related to a reduction in the b-wave. An injection of EHNA into the eye before ischemia reduced the thinning of the inner plexiform and nuclear retinal layers so that no significant difference between them and the control retinas existed. However, an injection of R-PIA just before ischemia did not reduce the thinning of the retinal layers in a statistically significant way, possibly because the R-PIA protective effect is less than that of EHNA and is difficult to detect when thickness of the retinal layers is measured. It may be necessary to use higher concentrations of R-PIA to observe a protective effect.
The combined data show that substances resulting in the activation of adenosine A1 receptors protect the retina against changes induced by ischemia-reperfusion.
本研究的目的是确定腺苷能药物是否可用于减缓大鼠视网膜缺血再灌注后的变化。
通过将眼压升高至收缩压以上45分钟，随后再灌注3天，诱导大鼠视网膜缺血再灌注损伤。这种损伤导致视网膜电图b波相对于对侧对照视网膜降低（54%±5%，n = 23），穆勒细胞中胶质纤维酸性蛋白（GFAP）表达，以及钙视网膜蛋白免疫反应性“染色”模式改变。在内网状层中正常的两到三条钙视网膜蛋白免疫反应带变为一条带。将眼压升高60分钟，随后再灌注2周，导致内核层和网状层厚度减少40%。其他视网膜层未记录到统计学上的显著变化。
在缺血前将腺苷脱氨酶抑制剂赤型-9-(2-羟基-3-壬基)腺嘌呤（EHNA）注入眼内，可在很大程度上预防b波和钙视网膜蛋白免疫反应性的缺血再灌注变化。在缺血前腹腔注射腺苷A1受体激动剂R-N6-(2-苯基异丙基)腺苷（R-PIA）时也观察到类似结果。在缺血前向眼内注射腺苷脱氨酶似乎会增强缺血再灌注效应，因为b波降低几乎完全（8%±4%，n = 6）。所测试的任何腺苷能药物均未降低缺血再灌注诱导的穆勒细胞中GFAP的表达。这表明穆勒细胞中GFAP的表达与b波降低无关。在缺血前向眼内注射EHNA可减少内网状层和视网膜核层的变薄，使其与对照视网膜之间不存在显著差异。然而，在缺血前注射R-PIA并没有以统计学上显著的方式减少视网膜层的变薄，可能是因为R-PIA的保护作用小于EHNA，并且在测量视网膜层厚度时难以检测到。可能需要使用更高浓度的R-PIA才能观察到保护作用。
综合数据表明，导致腺苷A1受体激活的物质可保护视网膜免受缺血再灌注诱导的变化。
