Cyclosporin A increases tear fluid secretion via release of sensory neurotransmitters and muscarinic pathway in mice

Cyclosporin A, an immunosuppressant, has the potential to increase tear flu id secretion through mechanisms which are not yet well understood. To gain insight into this question, we investigated the effect of cyclosporin A con taining eyedrops on lacrimation in normal mice. Topical application of 0.1% cyclosporin A eyedrops for 3 days significantly increased lacrimation. Thi s response was completely blocked by pre-exposure to 1% capsaicin. Immunohi stochemical analysis revealed that capsaicin treatment depleted substance P from the lacrimal gland. Furthermore, following 1% atropine treatment, whi ch completely blocks pilocarpine-stimulated (500 mu g kg(-1), i.p.) lacrima tion, application of 0.1% cyclosporin A eyedrops significantly increased la crimation. However, this increase was less than the response seen with 0.1% cyclosporin A in the absence of atropine. Interestingly, substance P-induc ed tear secretion was also partially inhibited in atropine treated mice. Th ese results suggest that cyclosporin A accelerates tear secretion by releas ing neurotransmitters from sensory nerve endings which interacts with the p arasympathetic nerves. (C) 1999 Academic Press.