Ocular hypertension in mice with a targeted type I collagen mutation.
OBJECTIVE
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 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.


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 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).


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.
Aihara
Makoto
M
Hamilton Glaucoma Center, University of California San Diego, La Jolla, California 92093, USA.
Lindsey
James D
JD
Weinreb
Robert N
RN
D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000235:genetics*; D008297:Male; D020782:Matrix Metalloproteinases / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009798:Ocular Hypertension / Q000235:genetics* / Q000378:metabolism
D024042:Collagen Type I; D020782:Matrix Metalloproteinases