Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Exp Eye Res. 2012 Mar;96(1):116-23. doi: 10.1016/j.exer.2011.12.012. Epub 2011 Dec 20.
The purpose of this project was to investigate the effects of the mineralocorticoid receptor antagonist against retinal ischemia-reperfusion injury and identify the aldosterone/mineralocorticoid receptor (MR) system in the rat retina. Retinal ischemia was induced by increasing intraocular pressure to 130 mmHg. Rats were treated with the angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), MR antagonist (spironolactone), or aldosterone. Retinal damage was evaluated at 7 days after the ischemia by measuring the retinal thickness and the number of retinal ganglion cells. Pretreatment with candesartan, spironolactone, or candesartan and spironolactone significantly inhibited retinal ischemic injury. However, there was no protective effect against retinal ischemia-reperfusion injury provided by the combined aldosterone with candesartan treatment. Additionally, pretreatment with aldosterone alone also did not provide any neuroprotective effects against retinal ischemia-reperfusion injury. When rats were treated via local administration of aldosterone in the absence of ischemia, the number of retinal ganglion cells decreased while the retinal thickness remained unchanged. The present findings demonstrated the existence of a local aldosterone/MR system in the retina. Our results also demonstrated that an MR antagonist can attenuate subsequent ischemic damage in the rat retina.
本项目旨在研究盐皮质激素受体拮抗剂对视网膜缺血再灌注损伤的影响，并鉴定大鼠视网膜中的醛固酮/盐皮质激素受体 (MR) 系统。通过将眼内压升高至 130mmHg 来诱导视网膜缺血。用血管紧张素 II 型 1 型受体 (AT1-R) 拮抗剂 (坎地沙坦)、MR 拮抗剂 (螺内酯) 或醛固酮对大鼠进行处理。通过测量视网膜厚度和视网膜神经节细胞数量，在缺血后 7 天评估视网膜损伤。坎地沙坦、螺内酯或坎地沙坦和螺内酯预处理显著抑制了视网膜缺血性损伤。然而，醛固酮与坎地沙坦联合治疗对视网膜缺血再灌注损伤没有提供任何保护作用。此外，单独用醛固酮预处理对视网膜缺血再灌注损伤也没有提供任何神经保护作用。当大鼠在没有缺血的情况下局部给予醛固酮治疗时，视网膜神经节细胞数量减少，而视网膜厚度保持不变。这些发现表明在视网膜中存在局部醛固酮/MR 系统。我们的结果还表明，MR 拮抗剂可减轻大鼠视网膜随后的缺血损伤。
