Yücel Y H, Kalichman M W, Mizisin A P, Powell H C, Weinreb R N
Glaucoma Center, Department of Ophthalmology, University of California, San Diego, USA.
J Glaucoma. 1999 Feb;8(1):38-45.
To assess relative changes in different tissue components of optic nerve and their relationship to nerve fiber loss in the experimental monkey model of glaucoma.
Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the right eye of eight monkeys (Macaca fascicularis). Both experimental right optic nerves and control left optic nerves were studied. Histomorphometric analysis was performed on optic nerve cross-sections using bright field microscopy with camera lucida. Cross-sectional areas of optic nerve tissue components were estimated by point counting. Nerve fiber density was estimated by unbiased random sampling. Nerve fiber number was calculated by multiplying nerve fiber density with neuroglial area.
Varying degrees of nerve fiber loss were seen in eight optic nerves with chronic IOP elevation. More than 50% nerve fiber loss was noted in four of eight experimental optic nerves. In these severely affected optic nerves, total optic nerve area was significantly decreased compared with control optic nerves. Among the optic nerve tissue components, only the ratio of myelinated fiber area to total optic nerve area was significantly decreased. The ratio of extraaxonal area to total optic nerve area was significantly increased, whereas the ratio of interfascicular septal area to total optic nerve area did not change significantly. For all optic nerves, differences in nerve fiber count between control and experimental optic nerves showed the strongest correlation with differences in myelinated fiber area, followed by differences in extraaxonal area and total optic nerve area.
This histomorphometric study suggests the validity of the experimental monkey model of glaucoma in studying changes occurring in the nonaxonal optic nerve tissue components in human glaucomatous optic neuropathy. Glial scar tissue area was significantly increased in optic nerves with severe glaucomatous damage. Although a decrease in total optic nerve area was observed, among the optic nerve tissue components only myelinated nerve fiber area decreased significantly. Myelinated nerve fiber area also showed the strongest association with nerve fiber loss in experimental glaucoma.
在青光眼实验性猴模型中评估视神经不同组织成分的相对变化及其与神经纤维丢失的关系。
通过激光小梁成形术使8只食蟹猴右眼眼压慢性升高。对实验性右侧视神经和对照左侧视神经均进行研究。使用带有绘图仪的明场显微镜对视神经横截面进行组织形态计量分析。通过点计数法估计视神经组织成分的横截面积。通过无偏随机抽样估计神经纤维密度。通过将神经纤维密度与神经胶质面积相乘计算神经纤维数量。
在8条眼压慢性升高的视神经中观察到不同程度的神经纤维丢失。8条实验性视神经中有4条神经纤维丢失超过50%。在这些严重受影响的视神经中,与对照视神经相比,视神经总面积显著减小。在视神经组织成分中,仅髓鞘化纤维面积与视神经总面积的比值显著降低。轴突外面积与视神经总面积的比值显著增加,而束间隔面积与视神经总面积的比值无显著变化。对于所有视神经,对照视神经和实验性视神经之间神经纤维数量的差异与髓鞘化纤维面积的差异相关性最强,其次是轴突外面积和视神经总面积的差异。
这项组织形态计量学研究表明青光眼实验性猴模型在研究人类青光眼性视神经病变中非轴突性视神经组织成分变化方面的有效性。在严重青光眼性损伤的视神经中,胶质瘢痕组织面积显著增加。尽管观察到视神经总面积减小,但在视神经组织成分中只有髓鞘化神经纤维面积显著减小。在实验性青光眼中,髓鞘化神经纤维面积也与神经纤维丢失的相关性最强。