IOVS Journal of Clinical Investigation
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(Investigative Ophthalmology and Visual Science. 2003;44:722-727.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-0386
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Noninvasive Assessment of Aqueous Humor Turnover in the Mouse Eye

Marcel Y. Avila,1 Claire H. Mitchell,1 Richard A. Stone,2 and Mortimer M. Civan1,3

1From the Departments of Physiology, 2Ophthalmology, and 3Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

PURPOSE. To develop a noninvasive test for monitoring changes in aqueous humor turnover in the mouse eye.

METHODS. After topical instillation of fluorescein, the rate of decay of fluorescence from aqueous humor and cornea was monitored in Black Swiss, C57 Bl6, and DBA 2J mice with a microscope equipped with epifluorescence and a charge-coupled device (CCD) camera.

RESULTS. The rate of decay of fluorescence was identical in right and left eyes over an approximately 70-minute measurement period. The rate of decay was similar in normal mice aged 2 and 18 months. Pilocarpine and latanoprost, known to enhance aqueous humor outflow in humans, accelerated the decay of fluorescence. Levobunolol, known to inhibit aqueous humor inflow in humans, slowed decay. Dimethylamiloride, an inhibitor of the Na+,H+ exchanger that is known to act on cultured cells of both the ciliary epithelium and trabecular meshwork and to lower mouse intraocular pressure (IOP), enhanced decay. DBA 2J mice, in which secondary glaucoma develops, displayed a slower decay of fluorescence at 18 months of age than age-matched unaffected animals.

CONCLUSIONS. Monitoring decay of fluorescence provides a noninvasive index of aqueous humor dynamics in the mouse eye that facilitates study of ocular hypotensive drugs and mouse models of glaucoma. Coupled with knowledge of IOP, it permits semiquantitative conclusions about the relative roles of aqueous humor inflow and outflow in conditions with altered IOP. Based on this approach, dimethylamiloride appears to lower mouse IOP primarily by enhancing outflow of aqueous humor.




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