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Dilek Dursun, Min Wang, Dagoberto Monroy, De-Quan Li, Balakrishna L. Lokeshwar, Michael E. Stern, Stephen C. Pflugfelder; A Mouse Model of Keratoconjunctivitis Sicca. Invest. Ophthalmol. Vis. Sci. 2002;43(3):632-638.
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purpose. To evaluate the effects of pharmacologic inhibition of aqueous tear
production and desiccating environmental stress on aqueous tear
production, tear clearance, corneal epithelial permeability, and
conjunctival epithelial morphology, proliferation, and conjunctival
goblet cell differentiation.
methods. Aqueous tear production was inhibited by applying transdermal
scopolamine (scop) patches to the depilated midtail of female MC, CBA
mice. Desiccating environmental stress was created by placing mice in a
hood with a continuous airflow blower. Aqueous tear production and
volume, tear clearance, and corneal barrier function were compared in
four experimental groups: untreated control mice, mice placed in the
blower hood, mice treated with a scop patch, and mice treated with a
scop patch and blower hood (scop patch + blower). Cotton threads were
used to evaluate aqueous tear production and volume. Tear clearance was
assessed by fluorometric measurement of collected tear fluid 15 minutes
after instillation of 1% sodium fluorescein. Corneal epithelial
barrier function was assessed by fluorometric measurement of
carboxyfluorescein uptake. Conjunctival morphology and goblet cell
density were evaluated in stained histologic sections. Conjunctival
epithelial proliferation was assessed by bromodeoxyuridine (BrdU)
results. Significant decreases in cotton thread wetting and tear clearance were
observed in mice treated with a scop patch (P <
0.001) or with a scop patch and blower desiccation
(P < 0.001), with a greater reduction in tear
clearance in the latter group. Significantly increased corneal
carboxyfluorescein uptake was noted in the scop patch group compared
with untreated mice (P = 0.05) and in the scop
patch + blower group compared with all the other groups
(P < 0.0001). Changes in conjunctival epithelial
morphology and a significant decrease in conjunctival goblet cell
density (P < 0.001) were observed in the scop
patch + blower group compared with the untreated control group. The
number of proliferating conjunctival epithelial cells was significantly
greater in the scop patch + blower group.
conclusions. Pharmacologic inhibition of tear production in mice is accompanied by
ocular surface epithelial changes resembling human keratoconjunctivitis
sicca (KCS) that are exacerbated by desiccating environmental stress.
Cholinergic stimulated tear production appears to be essential for
maintaining a healthy ocular surface.
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