Ocular hypertension in mice with a targeted type I collagen mutation

被引:76
作者
Aihara, M [1 ]
Lindsey, JD [1 ]
Weinreb, RN [1 ]
机构
[1] Univ Calif San Diego, Hamilton Glaucoma Ctr, La Jolla, CA 92093 USA
关键词
D O I
10.1167/iovs.02-0759
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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.
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页码:1581 / 1585
页数:5
相关论文
共 25 条
[1]  
Aihara M, 2002, INVEST OPHTH VIS SCI, V43, P146
[2]  
Aihara M, 2001, INVEST OPHTH VIS SCI, V42, P2554
[3]  
ALEXANDER JP, 1991, INVEST OPHTH VIS SCI, V32, P172
[4]  
ANDO H, 1993, INVEST OPHTH VIS SCI, V34, P3541
[5]   Identification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation [J].
Balbín, M ;
Fueyo, A ;
Knäuper, V ;
López, JM ;
Alvarez, J ;
Sánchez, LM ;
Quesada, V ;
Bordallo, J ;
Murphy, G ;
López-Otín, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) :10253-10262
[6]  
Bradley JMB, 1998, INVEST OPHTH VIS SCI, V39, P2649
[7]   Matrix metalloproteinases and their inhibitors in aqueous humor [J].
Huang, SH ;
Adamis, AP ;
Wiederschain, DG ;
Shima, DT ;
Shing, Y ;
Moses, MA .
EXPERIMENTAL EYE RESEARCH, 1996, 62 (05) :481-489
[8]  
Kim JW, 2001, INVEST OPHTH VIS SCI, V42, P1514
[9]  
KRANE SM, 1999, MED INTELL UNIT, V10, P171
[10]   Hydrolysis of triple-helical collagen peptide models by matrix metalloproteinases [J].
Lauer-Fields, JL ;
Tuzinski, KA ;
Shimokawa, K ;
Nagase, H ;
Fields, GB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (18) :13282-13290