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Abstract #8576 Published in IGR 5-1
Ocular hypertension in mice with a targeted type I collagen mutation
Aihara M; Lindsey JD; Weinreb RNInvestigative Ophthalmology and Visual Science 2003; 44: 1581-1585
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 a.m. and 1:30 p.m.. 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 five to 24 additional Col1a1(r/r) mice was measured at seven, 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 (IOP(c)) at 12 and 18 weeks after birth were relatively constant at 18.9 ± 2.0 and 19.2 ± 1.9 mmHg, respectively. Mean IOP then decreased to 15.8 ± 0.8 and 16.2 ± 1.2 mmHg at 24 and 36 weeks, respectively. In contrast, mean IOP measurements in the transgenic (Col1a1(r/r)) mice was 2.7 ± 3.4 mmHg higher at 12 weeks and increased to a maximum of 23.6 ± 2.4 mmHg at 24 weeks. The difference between mean IOP in these two groups gradually increased to a maximum of 4.8 mmHg (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 mmHg, 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.
Dr. M. Aihara, Hamilton Glaucoma Center, University of California San Diego, La Jolla, CA 92093, USA
Classification:
1.2 Population genetics (Part of: 1 General aspects)
1.3 Pathogenesis (Part of: 1 General aspects)
5 Experimental glaucoma; animal models
