Kalisch Folke, Wurm Antje, Iandiev Ianors, Uckermann Ortrud, Dilsiz Nihat, Reichenbach Andreas, Wiedemann Peter, Bringmann Andreas
Paul Flechsig Institute of Brain Research, University of Leipzig Medical Faculty, 04109 Leipzig, Germany.
Exp Eye Res. 2006 Oct;83(4):962-71. doi: 10.1016/j.exer.2006.05.003. Epub 2006 Jun 19.
Atrial natriuretic peptide (ANP) is a regulator of the water and electrolyte content in the brain which also mediates cell volume homeostasis. Here, we determined whether the expression of ANP in the retina of the rat undergoes changes during ischemia-reperfusion, and whether ANP affects the osmotic swelling of Müller glial cells in postischemic retinas under hypotonic conditions. Transient retinal ischemia was induced by elevation of the intraocular pressure above systolic blood pressure for 1h. At 1 and 3 days after reperfusion, there was an increased content of ANP protein in the retina, as determined by Western blotting. The increase of the retinal ANP content was markedly reduced when triamcinolone acetonide (10 mM in 2 microl vehicle) was intravitreally injected before ischemia. ANP inhibited the osmotic swelling of Müller cell somata in retinal slices. The effect of ANP was mediated by activation of NP receptors expressed by retinal neurons which evoked a release of glutamate. The stimulation of metabotropic glutamate receptors expressed by Müller cells evoked an autocrine purinergic signaling mechanism that resulted in the opening of K(+) and Cl(-) channels; the ion efflux counteracted the osmotic swelling of Müller cells. It is concluded that the expression of ANP is transiently upregulated in the postischemic retina of the rat. The increased expression of ANP may represent a part of the retinal response to transient ischemia and may inhibit cytotoxic glial cell swelling.
心房利钠肽（ANP）是大脑中水电解质含量的调节剂，也介导细胞容积稳态。在此，我们确定大鼠视网膜中ANP的表达在缺血再灌注过程中是否发生变化，以及ANP是否影响低渗条件下缺血后视网膜中Müller胶质细胞的渗透性肿胀。通过将眼压升高至收缩压以上1小时诱导短暂性视网膜缺血。再灌注后1天和3天，通过蛋白质印迹法测定，视网膜中ANP蛋白含量增加。在缺血前玻璃体内注射曲安奈德（2微升溶媒中含10毫摩尔）时，视网膜ANP含量的增加明显减少。ANP抑制视网膜切片中Müller细胞胞体的渗透性肿胀。ANP的作用是通过激活视网膜神经元表达的NP受体介导的，该受体引起谷氨酸释放。对Müller细胞表达的代谢型谷氨酸受体的刺激引发了一种自分泌嘌呤能信号机制，导致K(+)和Cl(-)通道开放；离子外流抵消了Müller细胞的渗透性肿胀。结论是，大鼠缺血后视网膜中ANP的表达短暂上调。ANP表达的增加可能是视网膜对短暂性缺血反应的一部分，并且可能抑制细胞毒性胶质细胞肿胀。
