Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals.
The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism.
Research Promotion Institute, Oita University, Oita, Japan.|Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
Akihiro
A
Higuchi
Department of Chemistry, Keio University, School of Medicine, Kanagawa, Japan.
Hiroyoshi
H
Inoue
Tokyo New Drug Research Laboratories, Kowa Co., Ltd., Tokyo, Japan.
Yoshio
Y
Kaneko
Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
Erina
E
Oonishi
Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
Kazuo
K
Tsubota
D000818:Animals; D065306:Corneal Injuries / Q000517:prevention & control*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000150:complications / Q000188:drug therapy*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism
D009883:Ophthalmic Solutions; D016566:Organoselenium Compounds; D011956:Receptors, Cell Surface; C038340:lactoferrin receptors; D007781:Lactoferrin