Aihara Makoto, Lindsey James D, Weinreb Robert N
Hamilton Glaucoma Center, University of California San Diego, La Jolla, California 92093, USA.
Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1581-5. doi: 10.1167/iovs.02-0759.
To evaluate intraocular pressure (IOP) in transgenic mice with a targeted mutation in the gene for the alpha1 subunit of collagen type I.
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 Col1a1(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.
Mean IOP measurements of the control Col1a1(+/+) mice (IOP(c)) 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 mm 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).
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.
评估I型胶原蛋白α1亚基基因发生靶向突变的转基因小鼠的眼压（IOP）。
将纯合的B6; 129-Cola1(tm1Jae)小鼠和相应的野生型小鼠麻醉。然后将连接压力传感器的充满液体的玻璃微针经角膜插入前房以测量眼压。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Col1a1(r/r)雄性小鼠和8只相应的野生型Col1a1(+/+)雄性小鼠的眼压。在出生后7、12、18、24和36周测量另外5至24只Col1a1(r/r)小鼠的眼压。通过免疫组织化学评估眼前节结构和I型胶原蛋白的分布。
出生后12周和18周时，对照Col1a1(+/+)小鼠的平均眼压测量值（IOP(c)）相对稳定，分别为18.9±2.0和19.2±1.9 mmHg。然后平均眼压在24周和36周时分别降至15.8±0.8和16.2±1.2 mmHg。相比之下，转基因（Col1a1(r/r)）小鼠在12周时的平均眼压测量值高2.7±3.4 mmHg，并在24周时最高升至23.6±2.4 mmHg。这两组的平均眼压差异在36周时逐渐增加至最大4.8 mmHg（30%），并且在24周和36周龄时与对照小鼠有显著差异。在Col1a1(r/r)小鼠中未观察到眼前节异常，并且在整个36周的分析期内未观察到Col1a1(r/r)和Col1a1(+/+)小鼠眼前节外观的差异。然而，Col1a1(r/r)小鼠巩膜和相关结构中的I型胶原蛋白免疫反应性比Col1a1(+/+)小鼠更强。当将另外的Col1a1(r/r)小鼠的平均眼压测量值纳入这些测量中时，各年龄的平均眼压分别为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，Col1a1(r/r)小鼠的平均眼压分别比Col1a1(+/+)小鼠高21%、44%和36%（P<0.05）。
这些结果证明I型胶原蛋白靶向突变的小鼠存在高眼压，并提示眼压调节与纤维状胶原蛋白周转之间存在关联。
