Inman Denise M, Sappington Rebecca M, Horner Philip J, Calkins David J
Harborview Research & Training, Department of Neurosurgery, University of Washington, Seattle, Washington 98104, USA.
Invest Ophthalmol Vis Sci. 2006 Mar;47(3):986-96. doi: 10.1167/iovs.05-0925.
To investigate quantitatively the relationships between elevated intraocular pressure (IOP), axonal loss, and corneal thickness in the DBA/2 mouse model of glaucoma, to understand better how these factors contribute to disease progression.
IOP was measured with a handheld tonometer (Tono-Pen; Medtronic Solan, Jacksonville, FL) in 195 to 446 eyes of mice 2 to 10 months of age sampled from a colony of 400 DBA/2 mice. From a group of 24 eyes at 4, 9, and 10 months of age, correlations were determined between the density and number of RGC axons, corneal thickness, and IOP.
Mean IOP levels in the colony were 15 to 16 mm Hg at 2 months of age and rose almost linearly at a rate of 0.9 mm Hg/mo before reaching 22 to 23 mm Hg at 10 months. Both the density and number of axons decreased with increasing average lifetime IOP. IOP variation within age groups strongly correlated with density. Age-matched mice with lower mean IOP had greater preservation of axons in the optic nerve. Elevated IOP was accompanied by increased corneal thickness at the limbus. Surprisingly, corneal thickness was a strong predictor of axonal density (r2 = -0.75), regardless of age.
IOP increased with age in most, but not all, DBA/2 mice. In age-matched mice, differences in IOP corresponded to differences in axonal density and number. In young mice with elevated IOP, the loss of axons resembled that of older animals with similar IOP. Whether corneal thickness is a byproduct of elevated IOP remains unknown, but it may be useful as an index of optic nerve degeneration.
在DBA/2青光眼小鼠模型中定量研究眼内压(IOP)升高、轴突损失和角膜厚度之间的关系,以更好地理解这些因素如何促进疾病进展。
使用手持眼压计(Tono-Pen;美敦力索兰公司,佛罗里达州杰克逊维尔)测量从400只DBA/2小鼠群体中选取的2至10月龄小鼠的195至446只眼睛的眼压。在4、9和10月龄的24只眼睛中,确定视网膜神经节细胞(RGC)轴突的密度和数量、角膜厚度与眼压之间的相关性。
该群体中2月龄时平均眼压水平为15至16mmHg,在10月龄达到22至23mmHg之前几乎以0.9mmHg/月的速率呈线性上升。轴突的密度和数量均随平均寿命眼压的升高而降低。年龄组内的眼压变化与密度密切相关。平均眼压较低的年龄匹配小鼠的视神经中轴突保留得更好。眼压升高伴随着角膜缘处角膜厚度增加。令人惊讶的是,无论年龄如何,角膜厚度都是轴突密度的强预测指标(r2 = -0.75)。
大多数(但并非全部)DBA/2小鼠的眼压随年龄增长而升高。在年龄匹配的小鼠中,眼压差异对应于轴突密度和数量的差异。在眼压升高的年轻小鼠中,轴突损失类似于眼压相似的老年动物。角膜厚度是否是眼压升高的副产品尚不清楚,但它可能作为视神经退变的一个指标。