ABSTRACT
Proper wound healing is vital for maintenance of corneal integrity and transparency. Corneal epithelial damage is one of the most frequently observed ocular disorders. Because clinical options are limited, further novel treatments are needed to improve clinical outcomes for this type of disease. In the present study, it was found that placental extract-derived dipeptide (JBP485) significantly increased the proliferation and migration of corneal epithelial cells (CECs). Moreover, JBP485 accelerated corneal epithelial wound healing in vivo without inflammation and neovascularization and was found to be effective for the treatment of corneal damage. These data indicate that JBP485 efficiently activates the viability of CECs and has potential as a novel treatment for various kinds of corneal epithelial disease.
Subject(s)
Epithelium, Corneal/drug effects , Epithelium, Corneal/pathology , Peptides, Cyclic/pharmacology , Wound Healing/drug effects , Animals , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Epithelial Cells/drug effects , Epithelial Cells/metabolism , RabbitsABSTRACT
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.
Subject(s)
Epithelium, Corneal/drug effects , Mucin 5AC/metabolism , Peptides, Cyclic/pharmacology , Animals , Cells, Cultured , Disease Models, Animal , Dry Eye Syndromes/metabolism , Dry Eye Syndromes/pathology , Epithelium, Corneal/metabolism , Galectin 3/genetics , Galectin 3/metabolism , Mice , Mucin-1/genetics , Mucin-1/metabolism , Mucin-4/genetics , Mucin-4/metabolism , Rabbits , Real-Time Polymerase Chain Reaction , Tears/metabolismABSTRACT
Severe ocular surface diseases (OSDs) with severe dry eye can be devastating and are currently some of the most challenging eye disorders to treat. To investigate the feasibility of using an autologous tissue-engineered cultivated nasal mucosal epithelial cell sheet (CNMES) for ocular surface reconstruction, we developed a novel technique for the culture of nasal mucosal epithelial cells expanded ex vivo from biopsy-derived human nasal mucosal tissues. After the protocol, the CNMESs had 4-5 layers of stratified, well-differentiated cells, and we successfully generated cultured epithelial sheets, including numerous goblet cells. Immunohistochemistry confirmed the presence of keratins 3, 4, and 13; mucins 1, 16, and 5AC; cell junction and basement membrane assembly proteins; and stem/progenitor cell marker p75 in the CNMESs. We then transplanted the CNMESs onto the ocular surfaces of rabbits and confirmed the survival of this tissue, including the goblet cells, up to 2 weeks. The present report describes an attempt to overcome the problems of treating severe OSDs with the most severe dry eye by treating them using tissue-engineered CNMESs to supply functional goblet cells and to stabilize and reconstruct the ocular surface. The present study is a first step toward assessing the use of tissue-engineered goblet-cell transplantation of nonocular surface origin for ocular surface reconstruction.
