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Abstract #24946 Published in IGR 11-4
Outflow facility in mice with a targeted type I collagen mutation
Dai Y; Lindsey JD; Duong-Polk X; Nguyen D; Hofer A; Weinreb RNInvestigative Ophthalmology and Visual Science 2009; 50: 5749-5753
See also comment(s) by Douglas Rhee •
PURPOSE: Transgenic Col1a1(r/r) mice develop elevated intraocular pressure (IOP) with an open angle and progressive optic nerve axon loss. The present study was undertaken to evaluate aqueous outflow facility and its age dependence in these mice. METHODS: Homozygous B6;129S4-Col1a1(tm1Jae) mice and corresponding wild-type Col1a1(+/+) mice from 12 to 56 weeks of age were anesthetized, and IOP was measured with a microneedle. Outflow facility was determined by a two-level, constant-pressure infusion METHOD: Type I collagen, subunit alpha1 was assessed in sclera and choroid by Western blot analysis. RESULTS: The mean IOP in 12- to 36-week-old transgenic Col1a1(r/r) mice was 25.1% higher than in control Col1a1(+/+) mice (P < 0.01), whereas the mean outflow facility was 25.4% lower than in control mice (P < 0.01). After this period, the mean IOP in 42- to 56-week-old transgenic mice returned to normal levels, whereas outflow facility increased by 36.0%. Over the 12- to 56-week study period, IOP and outflow facility in the transgenic mice were inversely correlated (r(2) = -0.702, P < 0.01). Collagen I alpha1 content was greater in 37- and 43-week-old transgenic mice than in age-matched wild-type control mice. CONCLUSIONS: Outflow facility is reduced in transgenic Col1a1(r/r) mice with IOP elevation. The inverse correlation of IOP elevation to facility reduction indicates that increased resistance in the aqueous outflow pathway contributes to ocular hypertension in Col1a1(r/r) mice. These mice may be useful as a model for open-angle glaucoma, as well as for assessing the relationship between collagen type I metabolism and aqueous outflow.
Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California 92093-0946, USA.
Classification:
2.6.2.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics > 2.6.2 Outflow)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
