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Abstract #10738 Published in IGR 6-2
Optic nerve damage in mice with a targeted type I collagen mutation
Mabuchi F; Lindsey JD; Aihara M; Mackey MR; Weinreb RNInvestigative Ophthalmology and Visual Science 2004; 45: 1841-5
PURPOSE: Transgenic (Col1a1r/r) mice gradually develop elevated intraocular pressure (IOP) with open angles. The present study was undertaken to evaluate optic nerve axonal loss with time in these mice. METHODS: The IOP of transgenic (Col1a1r/r) mice and control wild-type (Col1a1+/+) mice was measured at 7, 12, 16, 24, 36, and 54 weeks of age using a microneedle method. Transgenic Col1a1r/r and control Col1a1+/+ mice at 24 and 54 weeks of age were randomly selected and their optic nerves were processed conventionally for electron microscopy. Optic nerve cross-sections were collected 300 micro m posterior to the globe. Low (200X) and high (10,000X) magnification images were collected systematically and were masked before analysis. For each nerve, cross-sectional area was measured in low magnification images, and axonal number was counted in high magnification images. RESULTS: Mean IOP of the transgenic Col1a1r/r mice was significantly higher than that of the control Col1a1+/+ mice at 16, 24, 36, and 54 weeks by 21%, 42%, 41%, and 33% respectively (P < 0.05). The mean axonal density and total axonal number in the transgenic Col1a1r/r mice at 54 weeks of age (n = 10) was significantly less than those in the control Col1a1+/+ mice at 24 weeks (n = 5) and 54 weeks (n = 5; P = 0.0081 and P = 0.020, respectively, analysis of variance, P < 0.05 for pair-wise comparisons). The mean axonal density and total axonal number in the transgenic Col1a1r/r mice at 54 weeks also were significantly less than in the transgenic Col1a1r/r mice at 24 weeks (n = 10). Mean axonal loss between 24 and 54 weeks of age in the transgenic Col1a1r/r mice was 28.7%. CONCLUSIONS: Transgenic Col1a1r/r mice develop sustained elevation of IOP and progressive optic nerve axon loss. This suggests that these mice may be useful as a mouse model of primary open angle glaucoma as well as for assessing the relationship between collagen type I metabolism and optic nerve axon loss.
Hamilton Glaucoma Center, University of California San Diego, La Jolla 92093-0946, USA.
Classification:
3.2 Electron microscopy (Part of: 3 Laboratory methods)
5 Experimental glaucoma; animal models