Outflow Facility in Mice With a Targeted Type I Collagen Mutation

Abstract

Purpose: : Col1a1 ^r/r mice gradually develop elevated intraocular pressure with open angle and progressive optic nerve axon loss. The present study was undertaken to evaluate aqueous outflow resistance with age in these mice.

Methods: : Homozygous B6;129S4-Col1a1^tm1Jae mice and corresponding wild-type Col1a1^+/+ mice from 12 to 56 weeks were anesthetized and intraocular pressure (IOP) was measured using a fluid-filled glass microneedle connected to a pressure transducer inserted through the cornea into the anterior chamber. A silicon tube was linked to the transducer measuring outflow volume. Outflow facility was determined based on a two- level constant pressure infusion method.

Results: : Mean IOP measurements in 12-36 week-old transgenic Col1a1^r/r (20.9±1.4 mmHg, n=25) was 25.1% higher than that of the control Col1a1^+/+ mice (16.7±1.5 mmHg, n=12, P<0.01). Mean outflow facility in 12-36 week-old transgenic Col1a1^r/rmice (0.0050±0.0008 µl/min per mmHg, n=25) was 25.4% lower than that of the control Col1a1^+/+ mice (0.0067±0.0010 µl/min per mmHg, n=12, P<0.01). Mean outflow facility of 42-56 week-old transgenic Col1a1^r/r (n=21) was 0.0068±0.0011 µl/min per mmHg while mean IOP reduced to 15.7±1.4 mmHg. There was significant correlation between the outflow facility and IOP in 12-56 week-old transgenic Col1a1^r/r (linear regression, r²=-0.702, P<0.01).

Conclusions: : Transgenic Col1a1^r/r with elevated IOP exhibit reduced outflow facility. The significant correlation of IOP elevation to facility reduction suggests that ocular hypertension of Col1a1^r/rmice reflects the increased resistance in the aqueous outflow pathway. These mice may be useful as an open angle glaucoma model as well as for assessing the relationship between collagen type I metabolism and aqueous outflow.

Keywords: aqueous • trabecular meshwork • ciliary body