Lafuente López-Herrera María P, Mayor-Torroglosa Sergio, Miralles de Imperial Jaime, Villegas-Pérez María P, Vidal-Sanz Manuel
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Campus de Espinardo, E-30.100 Espinardo, Murcia, Spain.
Exp Neurol. 2002 Dec;178(2):243-58. doi: 10.1006/exnr.2002.8043.
In adult rats we have induced retinal ischemia and investigated retrograde axonal transport in ganglion cells. The animals received in their left eyes, 1 h prior to ischemia, two 5-microl drops of saline or 0.5% brimonidine (BMD). Retinal ischemia was induced by transient ligature of the left ophthalmic vessels for 90 min. One hour or 1 week after ischemia, Fluorogold (FG) was applied to both superior colliculi, the animals were processed 1 week after FG application, and FG-labeled retinal ganglion cell (RGC) densities were estimated in the right control and left experimental retinas. In the left retinas of the saline-pretreated animals, RGC densities diminished to 39 or 30% of the densities found in their right control retinas, 7 or 14 days after ischemia, respectively. Because in a previous similar study in which FG was applied 7 days before ischemia, the percentages of FG-labeled RGCs were 54 and 48%, 7 and 14 days after ischemia, respectively, this suggests that retrograde axonal transport was impaired in some surviving RGCs. This was confirmed in an additional group of rats in which 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate was applied to both SCi 3 weeks before ischemia, and FG was applied to the intraorbitally cut optic nerve 9 days after ischemia and 5 days before euthanization. In the left retinas of the BMD-pretreated animals, RGC densities amounted to 90% of the RGC population 7 or 14 days after ischemia and were comparable to those obtained in their contralateral nonischemic retinas. Retinal ischemia causes RGC loss and induces alterations of retrograde axonal transport in a proportion of surviving RGCs. BMD rescues RGCs from ischemia-induced cell death and preserves retrograde axonal transport in surviving RGCs.
在成年大鼠中，我们诱导了视网膜缺血，并研究了神经节细胞中的逆行轴突运输。在缺血前1小时，给动物的左眼滴入两滴5微升的生理盐水或0.5%的溴莫尼定（BMD）。通过暂时结扎左眼部血管90分钟诱导视网膜缺血。缺血后1小时或1周，将荧光金（FG）注入双侧上丘，在注入FG后1周对动物进行处理，并估计右侧对照视网膜和左侧实验视网膜中FG标记的视网膜神经节细胞（RGC）密度。在生理盐水预处理动物的左侧视网膜中，缺血后7天或14天，RGC密度分别降至右侧对照视网膜中密度的39%或30%。因为在之前一项类似研究中，在缺血前7天注入FG，缺血后7天和14天，FG标记的RGC百分比分别为54%和48%，这表明在一些存活的RGC中逆行轴突运输受损。在另一组大鼠中得到了证实，在缺血前3周将1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐注入双侧上丘，在缺血后9天和安乐死前5天，将FG注入眶内切断的视神经。在BMD预处理动物的左侧视网膜中，缺血后7天或14天，RGC密度相当于RGC总数的90%，与对侧未缺血视网膜中的密度相当。视网膜缺血导致RGC丢失，并在一部分存活的RGC中诱导逆行轴突运输改变。BMD可使RGC免受缺血诱导的细胞死亡，并在存活的RGC中保留逆行轴突运输。
