Dai Yi, Lindsey James D, Duong-Polk Xuandao, Nguyen Duy, Hofer Anthony, Weinreb Robert N
Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California 92093-0946, USA.
Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5749-53. doi: 10.1167/iovs.08-3367. Epub 2009 Sep 24.
Transgenic Col1a1(r/r) mice develop elevated intraocular pressure (IOP) with an open angle and progressive optic nerve axon loss. The present study was undertaken to evaluate aqueous outflow facility and its age dependence in these mice.
Homozygous B6;129S4-Col1a1(tm1Jae) mice and corresponding wild-type Col1a1(+/+) mice from 12 to 56 weeks of age were anesthetized, and IOP was measured with a microneedle. Outflow facility was determined by a two-level, constant-pressure infusion
Type I collagen, subunit alpha1 was assessed in sclera and choroid by Western blot analysis.
The mean IOP in 12- to 36-week-old transgenic Col1a1(r/r) mice was 25.1% higher than in control Col1a1(+/+) mice (P < 0.01), whereas the mean outflow facility was 25.4% lower than in control mice (P < 0.01). After this period, the mean IOP in 42- to 56-week-old transgenic mice returned to normal levels, whereas outflow facility increased by 36.0%. Over the 12- to 56-week study period, IOP and outflow facility in the transgenic mice were inversely correlated (r(2) = -0.702, P < 0.01). Collagen I alpha1 content was greater in 37- and 43-week-old transgenic mice than in age-matched wild-type control mice.
Outflow facility is reduced in transgenic Col1a1(r/r) mice with IOP elevation. The inverse correlation of IOP elevation to facility reduction indicates that increased resistance in the aqueous outflow pathway contributes to ocular hypertension in Col1a1(r/r) mice. These mice may be useful as a model for open-angle glaucoma, as well as for assessing the relationship between collagen type I metabolism and aqueous outflow.
转基因Col1a1(r/r)小鼠出现开角型眼压升高及进行性视神经轴突丢失。本研究旨在评估这些小鼠的房水流出易度及其年龄依赖性。
对12至56周龄的纯合B6;129S4-Col1a1(tm1Jae)小鼠和相应的野生型Col1a1(+/+)小鼠进行麻醉，用微针测量眼压。通过两级恒压灌注法测定流出易度。
通过蛋白质免疫印迹分析评估巩膜和脉络膜中的I型胶原α1亚基。
12至36周龄的转基因Col1a1(r/r)小鼠的平均眼压比对照Col1a1(+/+)小鼠高25.1%（P < 0.01），而平均流出易度比对照小鼠低25.4%（P < 0.01）。在此之后，42至56周龄转基因小鼠的平均眼压恢复到正常水平，而流出易度增加了36.0%。在12至56周的研究期间，转基因小鼠的眼压和流出易度呈负相关（r(2) = -0.702，P < 0.01）。37周和43周龄的转基因小鼠的I型胶原α1含量高于年龄匹配的野生型对照小鼠。
眼压升高的转基因Col1a1(r/r)小鼠的流出易度降低。眼压升高与流出易度降低的负相关表明房水流出途径阻力增加导致Col1a1(r/r)小鼠眼压升高。这些小鼠可能作为开角型青光眼的模型，以及用于评估I型胶原代谢与房水流出之间的关系。
