Ocular hypertension in mice with a targeted type I collagen mutation
Ocular hypertension in mice with a targeted type I collagen mutation
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DOI：
10.1167/iovs.02-0759
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
Weinreb, RN
中科院分区：
文献类型：
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作者：
Aihara, M;Lindsey, JD;Weinreb, RN
目的.目的评价I型胶原α 1亚基基因靶向突变转基因小鼠的眼内压（IOP）。麻醉纯合B6; 129-Cola 1（tm 1 Jae）小鼠和相应的野生型小鼠。然后将连接到压力传感器的充满流体的玻璃微针通过角膜插入前房以测量IOP。所有测量均在上午11：30至下午1：30之间进行。在出生后12、18、24和36周测量7只Colla 1（r/r）和8只相应的野生型Col 1a 1（+/+）雄性小鼠的IOP。在出生后7、12、18、24和36周测量另外5至24只Col 1a 1（r/r）小鼠的IOP。通过荧光化学法评估眼前节的结构和胶原I的分布。对照Col 1a 1（+/+）小鼠出生后12周和18周的平均IOP测量值（IOPc）相对恒定，分别为18.9 +/- 2.0和19.2 +/- 1.9 mm Hg。然后，平均IOP在24周和36周分别降至15.8 ± 0.8和16.2 ± 1.2 mm Hg。相比之下，转基因（Col 1a 1（r/r））小鼠的平均IOP测量值在12周时高出2.7 +/- 3.4 mm Hg，在24周时增加到最大值23.6 +/- 2.4 mm Hg。这两组平均IOP之间的差异逐渐增加，在36周龄时达到最大值4.8 mm Hg（30%），并且在24周龄和36周龄时与对照小鼠显著不同。在36周分析期间，未观察到Col 1a 1（r/r）小鼠的眼前节异常，并且未观察到Col 1a 1（r/r）和Col 1a 1（+/+）小鼠的眼前节外观存在差异。然而，Col 1a 1（r/r）小鼠巩膜和相关结构中的I型胶原免疫反应性高于Col 1a 1（+/+）小鼠。当额外Col 1a 1（r/r）小鼠的平均IOP测量值包括在这些测量值中时，每个年龄的平均IOP分别为16.7 +/- 0.8、21.8 +/- 3.9、23.2 +/- 2.8、23.5 +/- 2.4和22.1 +/- 3.6 mmHg。在18、24和36周时，Col 1a 1（r/r）小鼠的平均IOP分别显著高于Col 1a 1（+/+）小鼠21%、44%和36%（P < 0.05）。这些结果证明了具有靶向I型胶原突变的小鼠的高眼压，并表明IOP调节与纤维胶原周转之间存在关联。
PURPOSE. To evaluate intraocular pressure (IOP) in transgenic mice with a targeted mutation in the gene for the alpha1 subunit of Collagen type I.METHODS. Homozygous B6; 129-Cola1(tm1Jae) mice and corresponding wild-type mice were anesthetized. A fluid-filled glass microneedle connected to a pressure transducer was then inserted through the cornea into the anterior chamber to measure IOP. All measurements were made between 11:30 AM and 1:30 PM. The IOP of seven Colla1(r/r) and eight corresponding wild-type Col1a1(+/+) male mice was measured at 12, 18, 24, and 36 weeks after birth. The IOP of 5 to 24 additional Col1a1(r/r) mice was measured at 7, 12, 18, 24, and 36 weeks after birth. The structure of the anterior segment and the distribution of Collagen I were assessed by immunohistochemistry.RESULTS. Mean IOP measurements of the control Col1a1(+/+) mice (IOPc) at 12 and 18 weeks after birth were relatively constant at 18.9 +/- 2.0 and 19.2 +/- 1.9 mm Hg, respectively. Mean IOP then decreased to 15.8 +/- 0.8 and 16.2 +/- 1.2 mm Hg at 24 and 36 weeks, respectively. In contrast, mean IOP measurements in the transgenic (Col1a1(r/r)) mice was 2.7 +/- 3.4 mm Hg higher at 12 weeks and increased to a maximum of 23.6 +/- 2.4 mm Hg at 24 weeks. The difference between mean IOP in these two groups gradually increased to a maximum of 4.8 mm Hg (30%) at 36 weeks and was significantly different from the control mice at both 24 and 36 weeks of age. No anterior segment abnormality was observed in Col1a1(r/r) mice and no difference between the anterior segment appearance of Col1a1(r/r) and Col1a1(+/+) mice was observed throughout the 36-week analysis period. However, Collagen I immunoreactivity in sclera and associated structures was greater in Col1a1(r/r), mice than in Col1a1(+/+) mice. When the mean IOP measurements from the additional Col1a1(r/r) mice were included with these measurements, mean IOP at each age was 16.7 +/- 0.8, 21.8 +/- 3.9, 23.2 +/- 2.8, 23.5 +/- 2.4, and 22.1 +/- 3.6 nun Hg, respectively. Mean IOP in the Col1a1(r/r) mice was significantly higher than in the Col1a1(+/+) mice at 18, 24, and 36 weeks by 21%, 44%, and 36%, respectively (P < 0.05).CONCLUSIONS. These results demonstrate ocular hypertension in mice with a targeted type I collagen mutation and suggest there is an association between IOP regulation and fibrillar collagen turnover.