Development of New Pharmaceutical Candidates With Antioxidant Activity for the Treatment of Corneal Disorders

摘要

The ocular surface is continuously exposed to physical and chemical factors in the environment. Oxidative stress, which strongly affects the ocular surface, is caused by several factors, including ultraviolet irradiation, fine particles, and tobacco smoke. Oxidative stress is one of the pathogeneses for corneal disorders. Thus, corneal epithelium and tear fluid contain antioxidants and antioxidative enzymes to protect the cornea against oxidative stress. Because autologous serum eye drops are useful for the treatment of corneal disorders caused by dry eye, these eye drops are globally used as a therapeutic intervention in patients with dry eye. We investigated the serum components that exert antioxidative effects to clarify the mechanism of action for serum antioxidants on corneal epithelial cells and to apply these components as drugs for the treatment of corneal disorders. We found that selenoprotein P, a known selenium-transfer plasma glycoprotein, was secreted into the tear fluid to supply the corneal epithelium with selenium. Selenium participates in the regulation of oxidative stress in many tissues, including the cornea. We subsequently developed selenium compounds for application in eye drops and successfully prepared Se-COMP as a new candidate for the treatment of corneal disorders.