Fernandez Diego C, Bordone Melina P, Chianelli Mónica S, Rosenstein Ruth E
Departamento de Bioquímica Humana, Universidad de Buenos Aires, CEFyBO/CONICET, Buenos Aires, Argentina.
Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3922-30. doi: 10.1167/iovs.08-3344. Epub 2009 Apr 1.
Retinal ischemia may provoke blindness. There is no effective treatment against retinal ischemic damage. The authors investigated whether brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) protects the retina from ischemia-reperfusion damage.
Ischemia was induced by increasing intraocular pressure (120 mm Hg for 40 or 60 minutes). Five minutes after reperfusion, animals underwent 3, 7, or 10 cycles of 1-minute ischemia/1-minute reperfusion or 7 minutes of ischemia. In other experiments, seven ischemia-reperfusion cycles were applied 10, 30, and 60 minutes or 24 hours after ischemia. A group of animals received intraperitoneal injections of cycloheximide (CHX) 1 minute before or 6 hours after postconditioning. Seven or 14 days after ischemia, animals were subjected to electroretinography and histologic analysis.
Seven ischemia-reperfusion cycles applied 5 minutes after reperfusion afforded significant functional protection in eyes exposed to ischemia-reperfusion injury. A marked reduction in retinal thickness and an increase in Müller cell glial fibrillary acidic protein (GFAP) levels were observed in ischemic retinas, whereas postconditioning preserved retinal structure and reduced GFAP levels in Müller cells. Postconditioning initiated between 5 and 60 minutes after reperfusion protected against ischemic injury. Retinal protection depended on the number of ischemia-reperfusion cycles. One 7-minute pulse applied 5 minutes after ischemia induced significant protection against ischemic damage. Retinal protection induced by postconditioning was reversed by CHX (injected 1 minute before but not 6 hours after postconditioning).
These results indicate that postconditioning significantly protected retinal function and histology from ischemia-reperfusion injury through a mechanism that involved de novo synthesis of protein.
视网膜缺血可能导致失明。目前尚无针对视网膜缺血性损伤的有效治疗方法。作者研究了在再灌注开始时施加短暂间歇性缺血（即后处理）是否能保护视网膜免受缺血再灌注损伤。
通过升高眼压（120毫米汞柱，持续40或60分钟）诱导缺血。再灌注5分钟后，动物接受3、7或10个周期的1分钟缺血/1分钟再灌注或7分钟缺血。在其他实验中，在缺血后10、30、60分钟或24小时施加7个缺血再灌注周期。一组动物在进行后处理前1分钟或后处理后6小时腹腔注射环己酰亚胺（CHX）。缺血7或14天后，对动物进行视网膜电图和组织学分析。
再灌注5分钟后施加7个缺血再灌注周期，对遭受缺血再灌注损伤的眼睛提供了显著的功能保护。在缺血的视网膜中观察到视网膜厚度显著降低和Müller细胞胶质纤维酸性蛋白（GFAP）水平升高，而后处理保留了视网膜结构并降低了Müller细胞中的GFAP水平。再灌注后5至60分钟开始的后处理可防止缺血性损伤。视网膜保护取决于缺血再灌注周期的数量。缺血后5分钟施加一次7分钟的脉冲可诱导对缺血损伤的显著保护。后处理诱导的视网膜保护被CHX逆转（在进行后处理前1分钟注射，但在后处理后6小时注射则不会）。
这些结果表明，后处理通过涉及蛋白质从头合成的机制，显著保护了视网膜功能和组织学免受缺血再灌注损伤。
