JBP485 promotes tear and mucin secretion in ocular surface epithelia

Abstract

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES.

JBP485 promotes corneal epithelial wound healing

“…Our recent study showed that JBP485 promotes tear and mucin secretion in corneal and conjunctival cells 30 . Clinically, decreased secretion of tears sometimes makes corneal wound healing slow or intractable.…”

“…Albino Japanese rabbits were obtained from Kitayama Laboratories (Kyoto, Japan) and were maintained under pathogen-free conditions in the barrier facility. In vivo rabbit models of corneal wound closure were created as previously described 30 . Rabbits were anaesthetised with an intramuscular injection of ketamine hydrochloride (60 mg/kg of body mass; Daiichi Sankyo Propharma, Tokyo, Japan) and xylazine (5 mg/kg; Bayer Medical, Tokyo Japan) as well as with oxybuprocaine eye drop (Santen pharmaceutical company, Osaka, Japan).…”

Anti-inflammatory Effect of JBP485 on Dextran Sulfate Sodium-induced Colitis in Mice

“…In addition to such a mechanism, innate immunity also plays a role in humans. Interestingly, JBP485 promoted the expression and secretion of mucin in the conjunctival epithelium [17]. Mucin plays an important role to preserve gastrointestinal mucosal barrier against bacterial penetration, and therefore it could be possible that JBP485 protects the DSS-induced damage of the mucosal epithelial barrier by promoting the expression and secretion of mucin.…”

Topical Application of Apricot Kernel Extract Improves Dry Eye Symptoms in a Unilateral Exorbital Lacrimal Gland Excision Mouse

“…Mucins are transmembrane glycoproteins that are detected at the apical surface of all mucosal epithelial cells. They can be further classified as (a) secreted gel-forming mucins and (b) membrane-bound mucins [19]. Membrane-bound mucins have a single transmembrane domain including a large glycosylated extracellular domain, a helical transmembrane domain and a short cytoplasmic tail, and these mucins are expressed in the apical cell membranes of the epithelium [20].…”