Lam Dawn, Jim Janey, To Eleanor, Rasmussen Carol, Kaufman Paul L, Matsubara Joanne
Southern California College of Optometry, Fullerton, CA, USA.
Mol Vis. 2009 Oct 31;15:2217-29.
To examine early cellular changes, including astrocyte reactivity and microglial activation, in the central nervous system (CNS) after unilateral optic nerve transection (ONT) or ocular hypertension (OHT) in monkeys.
Unilateral ONT or OHT was achieved in monkeys for periods ranging from two weeks to two months in duration. After intracardial perfusion, sections of the lateral geniculate nucleus (LGN) and visual cortex (V1) were examined by immunohistochemistry for glial fibrillary acidic protein (GFAP) and CD11b, a subunit of the complement 3 receptor and marker of macrophage and microglia cells (MAC-1). Alternate serial sections were evaluated by cytochrome oxidase (CO) histochemistry to assess metabolic activity.
Both ONT and OHT caused a reduction in metabolic activity in the treated eye layers of the LGN and V1. GFAP and MAC-1 immunoreactivities were elevated in spatial register with the treated eye layers of the LGN and V1 in ONT animals. In the OHT animals, GFAP, but not MAC-1, immunoreactivity was elevated in spatial register with the treated eye layers of LGN and V1. Thus, during the first weeks after OHT or ONT, loss of metabolic activity was accompanied by astrocyte and microglial activation in the ONT group and astrocyte activation in the OHT animals.
These results suggest that unilateral OHT or ONT triggers separate signaling pathways that promote differential activation of CNS glial populations. Astrocyte reactivity was present in all brains studied and demonstrates the loss of metabolic activity is accompanied by increased GFAP immunoreactivity. Microglial activation was only observed in ONT brains. The lack of microglial activation as late as two months following OHT may represent a time window for early treatment to prevent long-term neuronal loss in the CNS after OHT.
研究猴子单侧视神经横断（ONT）或高眼压（OHT）后中枢神经系统（CNS）早期的细胞变化，包括星形胶质细胞反应性和小胶质细胞活化。
在猴子中实现单侧ONT或OHT，持续时间为两周至两个月。心脏灌注后，通过免疫组织化学检测外侧膝状体核（LGN）和视觉皮层（V1）切片中的胶质纤维酸性蛋白（GFAP）和CD11b，CD11b是补体3受体的一个亚基，也是巨噬细胞和小胶质细胞（MAC-1）的标志物。通过细胞色素氧化酶（CO）组织化学评估交替的连续切片以评估代谢活性。
ONT和OHT均导致LGN和V1中受治疗眼层的代谢活性降低。在ONT动物中，LGN和V1的受治疗眼层在空间上对应的区域中，GFAP和MAC-1免疫反应性升高。在OHT动物中，LGN和V1的受治疗眼层在空间上对应的区域中，GFAP免疫反应性升高，但MAC-1免疫反应性未升高。因此，在OHT或ONT后的最初几周内，ONT组中代谢活性丧失伴随着星形胶质细胞和小胶质细胞活化，而OHT动物中仅伴有星形胶质细胞活化。
这些结果表明，单侧OHT或ONT触发了不同的信号通路，促进了中枢神经系统胶质细胞群的不同活化。在所研究的所有大脑中均存在星形胶质细胞反应性，表明代谢活性丧失伴随着GFAP免疫反应性增加。仅在ONT大脑中观察到小胶质细胞活化。OHT后长达两个月仍缺乏小胶质细胞活化可能代表了一个早期治疗的时间窗，以防止OHT后中枢神经系统长期神经元丢失。
