Purpose Retinal ischemia-induced injury, such as diabetic retinopathy and retinal vein occlusion, remains a common cause of visual impairment and blindness in the world. In our previous study, we have demonstrated the renin-angiotensin system, which was widely known as a hormonal system that regulates blood pressure and water balance, was involved in the progression of retinal ischemia damage. By inhibiting the angiotensin II type 1 receptor (AT1-R), neuroprotection was achieved. The purpose of this study was to investigate the effect of the downstream products of aldosterone in retinal ischemia-induced injury.
Method Retinal ischemia was induced by elevating the intraocular pressure to 130 mmHg for 45 minutes. Rats were treated with AT1-R combined with aldosterone or not, or mineralocorticoid receptor (MR) antagonist (spironolactone). Seven days after ischemia, retinal damage was evaluated according to the thickness of retinal layers and the survival rate of retinal ganglion cell. Immunohistochemistry and western blot was done on normal retina and post-ischemia (6h, 12h, 24h) retina to detect the expression level and the localization of MR.
Results By assessing the thickness of retinal layers and counting the retinal ganglion cell number, significant neuroprotective effect was found in the ischemia group pretreated with 1mg/kg candesartan and the groups pretreated with spironolactone (10mg/kg and 100mg/kg). However, in the group combined candasartan with aldosterone, neuroprotective effect of candesartan was disappeared. The peak of expression of MR was 12 h after ischemia. According to the immunohistochemical results, the expression of MR was in RGC in normal retina. In contrast, 12 hours after ischemia, MR positive cell was found in RGC, IPL and INL.
Conclusion The present research demonstrates that the expression level of MR in retina increased significantly after ischemia injury. Neuroprotective effect can be achieved not only by inhibiting the production of aldosterone with ARB, but also by antagonizing MR. Taking these data in consideration, we make a conclusion that aldosterone has a deleterious role during ischemia damage. This may provide us a new therapeutic target for the treatment of the ocular diseases caused by ischemia. |
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