Anti-Inflammatory Effects of Rebamipide Eyedrop Administration on Ocular Lesions in a Murine Model of Primary Sjögren's Syndrome

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.

Vision-related quality of life and psychological status in Chinese women with Sjogren’s syndrome dry eye: a case-control study

“…In patients with SSDE, chronic ocular inflammatory lesions involve injury to the epithelial cells of the conjunctiva and cornea. [10] As a result, ocular manifestations in SSDE are commonly more severe than in non-SSDE conditions [11, 12]. Patients with SSDE, who often continue to experience ocular symptoms despite extended use of palliative treatments, such as artificial tears, punctual occlusion, and acupuncture [13], may be prone to excessive medical behavior and high levels of mental stress.…”

Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2

“…Unfortunately, there is little data available in the literature about effects of rebamipide on IL-10. Arakaki et al (2014) reported rebamipide up-regulated IL-10 expression in eye lesions. However, in contrast to the results reported here, Aihara et al (1998) noted that rebamipide suppressed production of IL-10 (as well as of TNF and IL-1).…”

“…The drug is also effective as an anti-inflammatory agent and has been useful in the treatment of inflammatory diseases such as colitis (Kishimoto et al 2000) and mucositis (Kim et al 2015). This anti-inflammatory effect is associated with an inhibition of cytokine-mediated neutrophil infiltration, inhibition of reactive oxygen species (ROS) release (Sakurai et al 1998) and induction of IL-10 (Arakaki et al 2014). …”

“…Moreover, it has been reported that rebamipide induces expression of the PGE 2 receptors EP4 and EP2 in gastric mucosa (Suetsugu et al 2000). Rebamipide also processes an anti-inflammatory activity that may be related to its ability to inhibit nuclear factor (NF)-B signaling (Li et al 2015), suppression of release of IL-8, IL-1, IL-6 and TNF, reduction in expression of a marker of inflammatory cell infiltration, myeloperoxidase (Choe et al 2010;Fukuda et al 2014;Funahashi et al 2014), as well as induction of expression of IL-10 ( Arakaki et al 2014).…”

Pathological Analysis of Ocular Lesions in a Murine Model of Sjögren’s Syndrome

“…After fluorescein staining, the cornea was examined for corneal epithelial disorders using a slit-lamp microscope with a blue filter which was evaluated using a previously described method with modifications [11]. …”