Abstract
BackgroundTopical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown.Methods and FindingReb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment.ConclusionTopical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces.
Highlights
Sjogren’s syndrome (SS) is an autoimmune disease characterized by lymphocyte infiltration and destruction of the salivary and lacrimal glands [1]
Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces
We demonstrated the therapeutic effects of orally administered rebamipide (Reb), a mucosal protective agent, on autoimmune lesions in thymectomized NFS/sld mice, a murine model for SS [4]
Summary
Sjogren’s syndrome (SS) is an autoimmune disease characterized by lymphocyte infiltration and destruction of the salivary and lacrimal glands [1]. Many patients with SS suffer from keratoconjunctivitis due to severe dry eye. We demonstrated the therapeutic effects of orally administered rebamipide (Reb), a mucosal protective agent, on autoimmune lesions in thymectomized NFS/sld mice, a murine model for SS [4]. Reb had two potent effects including the immunosuppressive activity and the antiapoptotic activity in target cells [4]. Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjogren’s syndrome (SS). The effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown
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