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Cecil P. Moore, Jon B. McHugh, James G. Thorne, Thomas E. Phillips; Effect of Cyclosporine on Conjunctival Mucin in a Canine Keratoconjunctivitis Sicca Model. Invest. Ophthalmol. Vis. Sci. 2001;42(3):653-659.
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purpose. To test the hypothesis that beneficial effects of Cyclosporin A (CsA;
Sandimmune; Sandoz, Basel, Switzerland) in treating
keratoconjunctivitis sicca (KCS) include an effect on the
mucin-producing conjunctival goblet cells independent of CsA’s effect
methods. Keratoconjunctivitis sicca was induced bilaterally in six dogs after
removal of orbital and nictitans lacrimal glands. Two weeks after
induction of KCS, either 2% CsA or vehicle was applied twice daily to
each surgically altered eye until 6 weeks after KCS induction. Eyes of
three control dogs without surgically altered eyes were treated twice
daily with vehicle only. Incisional biopsy specimens of ventral fornix
conjunctiva were collected before gland removal (baseline) and at 2, 4,
and 6 weeks after KCS induction. At each sampling time, eyes were
photographed, and color images were subsequently graded for degree of
conjunctivitis and characteristics of ocular discharge. Intracellular
mucin stores in conjunctival epithelia were estimated using
computer-assisted morphometry of biopsy specimen cross sections, and
clinical and morphometric findings were correlated.
results. Lacrimal gland removal resulted in induction of KCS in dogs by 2 weeks,
with mean Schirmer tear test (STT) values of 5 mm/min or less occurring
in surgically altered eyes compared with STT values of 22.5 mm/min
before surgery and 22.9 mm/min in unaltered control eyes at 2 weeks. In
surgically altered eyes, STTs remained low during the 6-week study,
independent of topical treatment. Intracellular mucin stores were
quantified from conjunctival samples collected from each eye at
baseline and 2, 4, and 6 weeks. At 4 and 6 weeks (after 2 and 4 weeks
of topical treatment), intraepithelial mucin quantities were
significantly greater (P < 0.05) in CsA-treated
KCS eyes (14.4 and 13.1 μm2/μm, respectively)
compared with pretreatment KCS (7.4 μm2/μm)
eyes and vehicle-treated KCS eyes (7.3 and 8.5μ
m2/μm, respectively). KCS eyes treated with
CsA had lower conjunctivitis and ocular discharge scores than did
vehicle-treated KCS eyes.
conclusions. Topical 2% CsA restored in vivo conjunctival mucin stores to control
levels over a 4-week period, determined by computer-assisted
morphometry of sequential conjunctival biopsy specimens from eyes of
dogs with surgically induced KCS. Degree of conjunctivitis and severity
of mucus discharge were decreased in KCS eyes treated with CsA. Because
lacrimal tissues were removed from animals in this study, conjunctival
responses occurred independent of lacrimogenic effect(s). These results
indicate that restoration of conjunctival goblet cell mucin production,
i.e., the balance between synthesis and secretion of mucin
glycoproteins, may play an important role in the beneficial effect of
CsA in treating KCS.
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