Thanos S, Pavlidis C, Mey J, Thiel H J
Department of Ophthalmology, University of Tübingen, School of Medicine, Germany.
Exp Eye Res. 1992 Jul;55(1):101-17. doi: 10.1016/0014-4835(92)90098-d.
The present work was undertaken to assess the fate of ganglion cell debris in the axotomized retina of adult rats and employed a new technique to label phagocytosing microglia via the internalized material. In the main experiment, transection axotomy was performed on the intraorbital segment of the optic nerve, and a fast-transported, vital fluorescent styryl dye (4Di-10ASP) was deposited at the ocular stump of the nerve in order to pre-label retrogradely the ganglion cells destined to die because of the axotomy. Optic nerve transection resulted in progressive degradation of ganglion cell axons, perikarya, and dendrites within the retina and in release of fluorescent material, which was then incorporated into cells identified as microglia. No other retinal cells stained, although astrocytes and Müller's cells also responded to neuron degeneration by accumulating glial fibrillary acidic protein. Incorporation of labelled material into microglia topo-chronologically paralleled the ganglion cell degeneration starting within the optic fibre layer (OFL) and proceeding towards the ganglion cell layer (GCL) and the inner plexiform layer (IPL) of the affected retina. Long-term labelling of microglia monitored up to 3 months after optic nerve transection indicated that labelled microglial cells persisted within the retina. Microglia displayed a strong territorial arrangement within the GCL and IPL, and staggered, bilaminated distribution in both layers. These studies directly prove that microglia in the retina can be transcellularly labelled during traumatic degeneration of ganglion cells. The findings suggest that microglial cells play an important role in axotomy-induced wound healing and removal of cell debris.
本研究旨在评估成年大鼠视神经切断后视网膜中神经节细胞碎片的命运，并采用一种新技术通过内化物质标记吞噬性小胶质细胞。在主要实验中，对视神经眶内段进行横断性轴突切断术，并将一种快速运输的活体荧光苯乙烯基染料（4Di-10ASP）沉积在神经的眼端，以便逆行预标记因轴突切断术而注定死亡的神经节细胞。视神经切断导致视网膜内神经节细胞轴突、胞体和树突逐渐退化，并释放荧光物质，这些物质随后被纳入被鉴定为小胶质细胞的细胞中。尽管星形胶质细胞和穆勒细胞也通过积累胶质纤维酸性蛋白对神经元变性做出反应，但没有其他视网膜细胞染色。标记物质纳入小胶质细胞的时间顺序与神经节细胞变性平行，神经节细胞变性从受影响视网膜的视神经纤维层（OFL）开始，向神经节细胞层（GCL）和内网状层（IPL）发展。视神经切断后长达3个月的小胶质细胞长期标记表明，标记的小胶质细胞持续存在于视网膜内。小胶质细胞在GCL和IPL内呈现出强烈的区域排列，并且在两层中呈交错的双层分布。这些研究直接证明，在神经节细胞创伤性变性过程中，视网膜中的小胶质细胞可以被跨细胞标记。研究结果表明，小胶质细胞在轴突切断术诱导的伤口愈合和细胞碎片清除中起重要作用。
