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    Glycoprotein and peptide eyedrops promote healing of epithelial defects

    Investigational therapies address underlying causes in pathophysiology of lesions

    Reviewed by Teruo Nishida, MD, DSc

    Investigational therapies based on fibronectin-integrin interactions can be effective treatment for non-healing corneal epithelial defects that are refractory-to-conventional management techniques, said Teruo Nishida, MD, DSc.

    The investigational therapies, which Dr. Teruo and colleagues have been using with success for many years, include autologous fibronectin eyedrops and eyedrops formulated with a fibronectin-derived peptide or with peptides derived from substance P plus insulin-like growth factor-1 (IGF-1).

    “There is an unmet need for medications to treat non-healing corneal epithelial defects,” said Dr. Nishida, professor emeritus, Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. “So development of these investigational eyedrops into commercially available medications with the cooperation of industry is an important goal.”

    Non-healing corneal epithelial defects are uncommon, he added. but an important problem because they can progress to stromal ulceration with resulting loss of vision.

    The investigational treatments were developed to target two causes for failure to heal--lack of an adequate scaffold for stimulating adhesion and migration of epithelial cells and presence of dysfunctional epithelial cells. The fibronectin eyedrops, which are derived from autologous plasma, provide an appropriate scaffold.

    PHSRN is a fibronectin-derived peptide that activates dysfunctional epithelial cells by increasing the expression of integrin proteins that constitute the fibronectin receptor. The combination of peptides derived from substance P and IGF-1, FGLM-amide and SSSR, respectively, shares the same mechanism as PHSRN.



    FGLM-amide and SSSR are used rather than the parent molecules based on preclinical research in which it was determined that they represented the minimum amino acid sequences for safely promoting corneal epithelial wound closure.

    “We have been using autologous fibronectin eyedrops for more than two decades,” said Dr. Nishida. “The FGLM-amide/SSSR and PHSRN eyedrops for more than one decade.”

    He presented a series of cases demonstrating their effectiveness.

    The cases included non-healing corneal epithelial defects that developed in patients who had herpetic keratitis, ocular surgery, or neurosurgery. The non-healing lesions had been present for between 1 and 2 months. Resurfacing occurred in all cases between 8 days and 6 weeks after initiating the peptide eyedrop treatments.

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