Pavlidis M, Fischer D, Thanos S
Department of Experimental Ophthalmology, School of Medicine, University of Münster, Germany.
Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2318-28.
Photoreceptor loss in the Royal College of Surgeons (RCS) rat deprives the retinal ganglion cells (RGCs) of sensory input, which could interfere with RGC physiology. Whether axonal and dendritic transport is altered, and whether RGCs retain their capacity to regenerate their axons, both in vivo and in culture, was ascertained.
The study was conducted at postnatal days (P) 30 (while most photoreceptors are still intact), P90 (photoreceptors being almost completely absent), and P180 (approximately 3 months after photoreceptor disappearance). RGCs were studied with retrograde transport of the fluorescent dye 4Di-10ASP. Dendritic transport was also studied with 4Di-10ASP that is transported from the cell bodies into the RGC dendrites. Regeneration of RGC axons in vivo was monitored in the grafting paradigm of replacing the cut optic nerve (ON) with a sciatic nerve (SN) piece. Cell counts were performed in retinal wholemounts. Axonal regrowth in vitro was assessed in organotypic cultures of retinal stripes.
Photoreceptor dystrophy did not adversely affect retrograde axonal transport but attenuated dendritic transport compared with the wild-type control rats. Axons of RGCs were able to regenerate if provided with a SN graft, and regeneration was observed to be similar between RCS and wild-type rats at P30 but differed significantly at P90 and P180. In addition to an age-dependent decline in the regenerative ability, seen also in control animals, the number of RCS RGCs able to regenerate declined drastically beginning at 3 months. It is plausible that the intraretinal reorganization, as a consequence of photoreceptor disappearance, interferes with the regenerative ability of the RGCs.
The findings suggest for the first time that diminution of photoreceptor sensory input does not induce detectable death of RGCs until P180, but that it attenuates certain ganglion cell functions like intraretinal dendritic transport and propensity for axonal regeneration.
皇家外科学院（RCS）大鼠的光感受器丧失剥夺了视网膜神经节细胞（RGCs）的感觉输入，这可能会干扰RGC的生理功能。本研究确定了轴突和树突运输是否改变，以及RGCs在体内和体外是否保留其轴突再生能力。
研究在出生后第30天（此时大多数光感受器仍完整）、第90天（光感受器几乎完全缺失）和第180天（光感受器消失后约3个月）进行。使用荧光染料4Di-10ASP的逆行运输来研究RGCs。还使用从细胞体运输到RGC树突中的4Di-10ASP来研究树突运输。在将切断的视神经（ON）用坐骨神经（SN）片段替代的移植模型中监测RGC轴突在体内的再生。在视网膜全层标本中进行细胞计数。在视网膜条带的器官型培养物中评估轴突在体外的再生。
与野生型对照大鼠相比，光感受器营养不良对逆行轴突运输没有不利影响，但减弱了树突运输。如果提供SN移植物，RGC的轴突能够再生，并且在第30天观察到RCS和野生型大鼠之间的再生相似，但在第90天和第180天有显著差异。除了在对照动物中也观察到的与年龄相关的再生能力下降外，能够再生的RCS RGC数量从3个月开始急剧下降。光感受器消失导致的视网膜内重组干扰RGC的再生能力似乎是合理的。
这些发现首次表明，直到第180天，光感受器感觉输入的减少才会诱导可检测到的RGC死亡，但它会减弱某些神经节细胞功能，如视网膜内树突运输和轴突再生倾向。
