Zhang Cheng, Guo Yan, Miller Neil R, Bernstein Steven L
Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
Brain Res. 2009 Apr 6;1264:67-75. doi: 10.1016/j.brainres.2008.12.075. Epub 2009 Jan 15.
Nonarteritic anterior ischemic optic neuropathy (NAION) results from isolated anterior optic nerve (ON)-axonal ischemia near the retina-optic nerve junction. We utilized a rodent model of NAION (rAION) to study the in vivo inflammatory response after pure axonal ischemic infarct. ON ischemia was generated using laser-coupled rose Bengal dye photoactivation, and the infarct localized using tetrazolium red and histology. ON inflammation was evaluated following infarct using extrinsic macrophage (ED1) and microglial (isolated Iba1) cell markers. In naive ONs, some ED1(+)/Iba1(+) cells, representing extrinsic macrophages, were present in intraretinal ON region, but not in the retroscleral (isolated ON) region. Numerous ED1(-)/Iba1(+) cells, likely representing intrinsic microglia, were present throughout the entire ON. One day post-stroke, slight increases in both ED1(+) and Iba1(+) cells were apparent in the eye region immediately surrounding the anterior ON. Three days post-stroke, there was marked infiltration and aggregates of ED1(+)/Iba1(+) cells, with axon structural disruption in the region of the ischemic infarct. ED1(+) and Iba1(+) cells were present in the portion of the ON surrounding the infarct, possibly representing a penumbral region similar to that seen in ischemic brain infarcts. Although ED1(+) cells decreased by 7-14 days post-stroke, large numbers of Iba1(+) cells persisted in the anterior ON. Similar to other CNS ischemic strokes, pure axonal ischemia results in the early recruitment of extrinsic macrophages to the ischemic region. Manipulation of the inflammatory response may be an important variable that could potentially improve visual outcome.
非动脉炎性前部缺血性视神经病变（NAION）是由视网膜 - 视神经交界处附近孤立的前部视神经（ON）轴突缺血所致。我们利用NAION的啮齿动物模型（rAION）来研究单纯轴突缺血性梗死之后的体内炎症反应。使用激光耦合孟加拉玫瑰红染料光激活产生ON缺血，并使用四氮唑红和组织学方法定位梗死灶。在梗死之后，使用外源性巨噬细胞（ED1）和小胶质细胞（分离的Iba1）细胞标志物评估ON炎症。在未受损的ON中，一些代表外源性巨噬细胞的ED1(+)/Iba1(+)细胞存在于视网膜内ON区域，但不存在于巩膜后（孤立的ON）区域。大量可能代表内源性小胶质细胞的ED1(-)/Iba1(+)细胞存在于整个ON中。中风后一天，紧邻前部ON的眼区域中ED1(+)和Iba1(+)细胞均有轻微增加。中风后三天，ED1(+)/Iba1(+)细胞出现明显浸润和聚集，缺血性梗死区域的轴突结构遭到破坏。ED1(+)和Iba1(+)细胞存在于梗死灶周围的ON部分，可能代表类似于缺血性脑梗死中所见的半暗带区域。尽管中风后7 - 14天ED1(+)细胞减少，但大量Iba1(+)细胞仍在前部ON中持续存在。与其他中枢神经系统缺血性中风相似，单纯轴突缺血导致外源性巨噬细胞早期募集至缺血区域。对炎症反应的调控可能是一个重要变量，有可能改善视觉预后。
