Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model

PURPOSE. To test the hypothesis that beneficial effects of Cyclosporin A (C sA; Sandimmune; Sandoz, Basel, Switzerland) in treating keratoconjunctiviti s sicca (KCS) include an effect on the mucin-producing conjunctival goblet cells independent of CsA's effect on lacrimation. METHODS. Keratoconjunctivitis sicca was induced bilaterally in six dogs aft er removal of orbital and nictitans lacrimal glands. Two weeks after induct ion of KCS, either 2% CsA or vehicle was applied twice dairy to each surgic ally altered eye until 6 weeks after KCS induction. Eyes of three control d ogs without surgically altered eyes were treated twice daily with vehicle o nly. Incisional biopsy specimens of ventral fornix conjunctiva were collect ed before gland removal (baseline) and at 2, 4, and 6 weeks after KCS induc tion. At each sampling time, eyes were photographed, and color images were subsequently graded for degree of conjunctivitis and characteristics of ocu lar discharge. Intracellular mucin stores in conjunctival epithelia were es timated using computer-assisted morphometry of biopsy specimen cross sectio ns, and clinical and morphometric findings were correlated. RESULTS. Lacrimal gland removal resulted in induction of KCS in dogs by 2 w eeks, with mean Schirmer tear test (STT) values of 5 mm/min or less occurri ng in surgically altered eyes compared with STT values of 22.5 mm/min befor e surgery and 22.9 mm/min in unaltered control eyes at 2 weeks. In surgical ly altered eyes, STTs remained low during the 6-week study, independent of topical treatment. Intracellular mucin stores were quantified from conjunct ival 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 m ucin quantities were significantly greater (P < 0.05) in CsA-treated KCS ey es (14.4 and 13.1 <mu>m(2)/mum, respectively) compared with pretreatment KC S (7.4 mum(2)/mum) eyes and vehicle-treated KCS eyes (7.3 and 8.5 mum(2)/mu m, respectively). KCS eyes treated with CsA had lower conjunctivitis and oc ular discharge scores than did vehicle-treated KCS eyes. CONCLUSIONS. Topical 2% CsA restored in vivo conjunctival mucin stores to c ontrol levels over a 4-week period, determined by computer-assisted morphom etry of sequential conjunctival biopsy specimens from eyes of dogs with sur gically induced KCS. Degree of conjunctivitis and severity of mucus dischar ge were decreased in KCS eyes treated with CsA. Because lacrimal tissues we re removed from animals in this study, conjunctival responses occurred inde pendent of lacrimogenic effect(s). These results indicate that restoration of conjunctival goblet cell mucin production, i.e., the balance between syn thesis and secretion of mucin glycoproteins, may play an important role in the beneficial effect of CsA in treating KCS.