He Jiucheng, Bazan Haydee E P
Louisiana State University Health School of Medicine, New Orleans, Louisiana, United States 2Neuroscience Center of Excellence, Louisiana State University Health, New Orleans, Louisiana, United States 3Department of Ophthalmology, Louisiana State Universi.
Invest Ophthalmol Vis Sci. 2016 Feb;57(2):664-74. doi: 10.1167/iovs.15-18019.
To investigate the entire nerve architecture and content of the two main sensory neuropeptides in mouse cornea to determine if it is a good model with similarities to human corneal innervation.
Mice aged 1 to 24 weeks were used. The corneas were stained with neuronal-class βIII-tubulin, calcitonin gene-related peptide (CGRP), and substance P (SP) antibodies; whole-mount images were acquired to build an entire view of corneal innervation. To test the origin of CGRP and SP, trigeminal ganglia (TG) were processed for immunofluorescence. Relative corneal nerve fiber densities or neuron numbers were assessed by computer-assisted analysis.
Between 1 and 3 weeks after birth, mouse cornea was mainly composed of a stromal nerve network. At 4 weeks, a whorl-like structure (or vortex) appeared that gradually became more defined. By 8 weeks, anatomy of corneal nerves had reached maturity. Epithelial bundles converged into the central area to form the vortex. The number and pattern of whorl-like structures were different. Subbasal nerve density and nerve terminals were greater in the center than the periphery. Nerve fibers and terminals that were CGRP-positive were more abundant than SP-positive nerves and terminals. In trigeminal ganglia, the number of CGRP-positive neurons significantly outnumbered those positive for SP.
This is the first study to show a complete map of the entire corneal nerves and CGRP and SP sensory neuropeptide distribution in the mouse cornea. This finding shows mouse corneal innervation has many similarities to human cornea and makes the mouse an appropriate model to study pathologies involving corneal nerves.
研究小鼠角膜的整个神经结构以及两种主要感觉神经肽的含量，以确定其是否为与人类角膜神经支配相似的良好模型。
使用1至24周龄的小鼠。角膜用神经元类βIII-微管蛋白、降钙素基因相关肽（CGRP）和P物质（SP）抗体染色；采集整装图像以构建角膜神经支配的全貌。为了检测CGRP和SP的起源，对三叉神经节（TG）进行免疫荧光处理。通过计算机辅助分析评估相对角膜神经纤维密度或神经元数量。
出生后1至3周，小鼠角膜主要由基质神经网络组成。4周时，出现了一种螺旋状结构（或涡旋），并逐渐变得更加清晰。到8周时，角膜神经的解剖结构已达到成熟。上皮束汇聚到中心区域形成涡旋。螺旋状结构的数量和模式各不相同。基底膜下神经密度和神经末梢在中心比周边更多。CGRP阳性的神经纤维和末梢比SP阳性的神经和末梢更丰富。在三叉神经节中，CGRP阳性神经元的数量明显多于SP阳性神经元。
这是第一项展示小鼠角膜完整神经图谱以及CGRP和SP感觉神经肽分布的研究。这一发现表明小鼠角膜神经支配与人类角膜有许多相似之处，使小鼠成为研究涉及角膜神经的病理学的合适模型。
