Investigating regulatory mechanisms of conjunctival mucin secretion is essential to developing new strategies for treating ocular surface mucin deficient diseases which are characterized by loss of conjunctival goblet cells (OGCs). Reduction or elimination of OGCs is consistently observed in chronic tear deficient diseases and is associated with mononuclear, primarily lymphocytic, inflammatory infiltrates supporting the premise that lymphocyte-mediated inflammatory events modulate the sustained full differentiation of conjunctival GCs. The investigators hypothesize that inflammatory suppression of OGCs in keratoconjunctivitis sicca (KCS) may be reversed by the immunomodulant cyclosporine A (CsA), independent of its tear stimulating effects. To test this hypothesis the investigators propose to use an experimental canine model of KCS since dogs have similar tear deficient diseases as humans, morphologic analogies exist between canine and human conjunctiva and surgically-inducted KCS is well-defined in the dog. In this revised proposal, the investigators plan to study the histochemical and morphometric effects of CsA, artificial tear (AT) and CsA+AT treatments on conjunctival mucin secretions in the canine KCS model. Two levels of experimental canine KCS will be created. Full-KCS will be induced by removing the orbital and nictitans lacrimal glands (OLG and NLG) and mild KCS will be induced by removing only the OLG. Sequential conjunctival samples will be collected and analyzed histochemically and morphometrically using conventional stains, lectin probes and by immunohistochemistry. Tear production and tear osmolarities will be measured and correlated with morphometric data. Results of this study will provide important pilot data on the effects of CsA on OGCs in KCS and should provide necessary insights for rational design of new and more extensive experiments on the immunoregulation of OGC mucin secretion.
