Schaub Julie A, Kimball Elizabeth C, Steinhart Matthew R, Nguyen Cathy, Pease Mary E, Oglesby Ericka N, Jefferys Joan L, Quigley Harry A
Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, United States.
Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2765-2773. doi: 10.1167/iovs.17-21761.
To determine if retinal ganglion cell (RGC) axon loss in experimental mouse glaucoma is uniform in the optic nerve.
Experimental glaucoma was induced for 6 weeks with a microbead injection model in CD1 (n = 78) and C57BL/6 (B6, n = 68) mice. From epoxy-embedded sections of optic nerve 1 to 2 mm posterior to the globe, total nerve area and regional axon density (axons/1600 μm2) were measured in superior, inferior, nasal, and temporal zones.
Control eyes of CD1 mice have higher axon density and more total RGCs than control B6 mice eyes. There were no significant differences in control regional axon density in all mice or by strain (all P > 0.2, mixed model). Exposure to elevated IOP caused loss of RGC in both strains. In CD1 mice, axon density declined without significant loss of nerve area, while B6 mice had less density loss, but greater decrease in nerve area. Axon density loss in glaucoma eyes was not significantly greater in any region in either mouse strain (both P > 0.2, mixed model). In moderately damaged CD1 glaucoma eyes, and CD1 eyes with the greatest IOP elevation exposure, density loss differed by region (P = 0.05, P = 0.03, mixed model) with the greatest loss in the temporal and superior regions, while in severely injured B6 nerves superior loss was greater than inferior loss (P = 0.01, mixed model, Bonferroni corrected).
There was selectively greater loss of superior and temporal optic nerve axons of RGCs in mouse glaucoma at certain stages of damage. Differences in nerve area change suggest non-RGC responses differ between mouse strains.
确定实验性小鼠青光眼模型中视网膜神经节细胞(RGC)轴突在视神经中的丢失是否均匀。
通过微珠注射模型在CD1小鼠(n = 78)和C57BL/6(B6,n = 68)小鼠中诱导实验性青光眼6周。在眼球后方1至2毫米处的视神经环氧树脂包埋切片上,测量上、下、鼻、颞四个区域的总神经面积和区域轴突密度(轴突数/1600平方微米)。
CD1小鼠的对照眼比B6小鼠的对照眼具有更高的轴突密度和更多的RGC总数。所有小鼠或不同品系的对照区域轴突密度均无显著差异(所有P>0.2,混合模型)。眼压升高导致两个品系的RGC丢失。在CD1小鼠中,轴突密度下降,但神经面积无显著损失,而B6小鼠的密度损失较小,但神经面积减少更大。在任何一个小鼠品系中,青光眼眼中的轴突密度损失在任何区域均无显著差异(均P>0.2,混合模型)。在中度受损的CD1青光眼眼中,以及眼压升高暴露最大的CD1眼中,密度损失因区域而异(P = 0.05,P = 0.03,混合模型),颞侧和上侧区域损失最大,而在严重受损的B6神经中,上侧损失大于下侧损失(P = 0.01,混合模型,Bonferroni校正)。
在小鼠青光眼损伤的某些阶段,RGC的上侧和颞侧视神经轴突选择性地损失更大。神经面积变化的差异表明小鼠品系之间非RGC反应不同。