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Justin A. Saunders, Rachel L. León, Matheson Harris, Harold J. Williams, Charles L. Rosen, Jason D. Huber, Jennifer A. Sivak; Development Of An Animal Model For The Study Of Keratoconjunctivitis Sicca. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3722.
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© ARVO (1962-2015); The Authors (2016-present)
To determine estrogenic effects on tear production and breakup time in aged, ovariectomized female rats following nine months of estrogen or placebo treatment.
Ovariectomy surgery: At 9 months of age, rats underwent ovariectomy or sham surgery. Ovaries were excised from rats in treatment Groups 1 and 2, but left intact in rats in Group 3. Subjects received either 17β-Estradiol or placebo treatment by subcutaneous pellet in a 90-day time release matrix (Innovative Research of America). Tear breakup time: 2 drops of fluorescein were instilled into 1 eye with a micropipette calibrated to 5µl. The eyelids were manually closed 5 times. The time lapse between the last blink and the first randomly distributed dry spot on the cornea using a portable slit lamp was recorded. The process was repeated 3 times for each subject. Modified Schirmer's test: Schirmer's test strips were cut to 1.67 mm (+/- 0.01 mm) width and folded at the 5 mm mark. Rats received 0.5 uL fluorescein onto the eye, then the eye was manually blinked 5 times, and the modified Schirmer's strip was placed in the upper fornix for 5 minutes for assessment of tear volume.
Tear breakup times using fluorescein. No significant differences were found between treatment groups and controls. Tear volume measured by a modified Schirmer’s test. Ovariectomized rats supplemented with placebo showed significantly increased volume of tears compared to sham-operated, placebo treated controls.
Our results do not suggest a significant difference exists in the tear breakup times of our treatment groups. This may relate to the anatomy of the rat lacrimal system, which contains two intraorbital and one extraorbital lacrimal gland, thereby providing several routes for tear production. Also, additional measures might be warranted in the delivery of maintenance anesthesia to reduce the eye’s exposure to a circulating gas. Our results do suggest chronic estrogen exposure decreases tear production in rats receiving a nine month course of estrogen versus placebo treatment. These findings confirm in an aged-animal model, that estrogen supplementation may play a causal role in decreased tear production by the lacrimal gland. In conclusion, these results indicate that aged, chronically estrogen-treated female rats may prove a suitable model for the study of KCS and its treatment.
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