Age-related changes in rat corneal epithelial nerve density
Age-related changes in rat corneal epithelial nerve density
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DOI：
10.1167/iovs.07-1324
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发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Marfurt, Carl F.
中科院分区：
文献类型：
--
作者：
Dvorscak, Lauren;Marfurt, Carl F.
目的.在动物模型中确定年龄对角膜上皮神经密度的影响。用抗全神经元标记物神经微管蛋白的抗血清对6、12、18和24月龄大鼠的角膜全标本进行免疫化学染色。使用连接在光学显微镜上的绘图管，从每个角膜标准化的1 mm（2）中央和外周区域中绘制上皮神经末梢和基底下神经。扫描图像，神经密度计算为神经占据每1 mm（2）区域的百分比。测量6月龄和24月龄动物基底下神经的直径。基底下神经漩涡进行了定性分析，参考位置，形态外观和方向性。6至24个月，上皮神经末梢密度下降约50%。下降率大致呈线性，中央和周边角膜相似。相比之下，基底下神经密度增加超过50%之间6和24个月的中央和周边角膜。角膜基底下神经的平均直径在6个月至24个月之间减少了约30%（0.384 μ m对0.271 μ m）。基底下神经涡的形态学表现和方向性在动物间表现出相当大的变异性，并且与年龄无关。大鼠角膜神经末梢密度随年龄的增加而降低，而角膜基底下神经密度随年龄的增加而增加。在大鼠角膜中观察到的与年龄相关的神经末梢密度损失与老年人中报告的角膜敏感性降低一致，并且可能有助于老年人干眼病的发病机制。
PURPOSE. To determine the effect of aging on corneal epithelial nerve density in an animal model.METHODS. Corneal whole mounts from rats aged 6, 12, 18, and 24 months were stained immunohistochemically with antisera against the pan-neuronal marker neurotubulin. Epithelial nerve terminals and subbasal nerves in standardized 1-mm(2) central and peripheral zones from each cornea were drawn using a drawing tube attached to a light microscope. Images were scanned, and nerve densities were calculated as the percentage of each 1-mm(2) area occupied by nerves. The diameters of subbasal nerves in 6- and 24-month old animals were measured. Subbasal nerve vortices were analyzed qualitatively with reference to location, morphologic appearance, and directionality.RESULTS. Epithelial nerve terminal density decreased by approximately 50% between 6 and 24 months. The rate of decline was roughly linear and similar in both central and peripheral cornea. In contrast, subbasal nerve density increased by more than 50% between 6 and 24 months in both central and peripheral cornea. The mean diameter of corneal subbasal nerves decreased approximately 30% (0.384 mu m vs. 0.271 mu m) between 6 and 24 months. The morphologic appearance and directionality of the subbasal nerve vortex demonstrated considerable interanimal variability and did not correlate with age.CONCLUSIONS. Rat corneal nerve terminal density decreases, but corneal subbasal nerve density increases, as a function of age. The age-related loss of nerve terminal density seen in the rat cornea is in keeping with the decreased corneal sensitivity reported in elderly humans and may contribute to the pathogenesis of dry eye disease in aged persons.