title: Potential New Modes of Treatment of Neurotrophic Keratopathy.
abstract: The cornea focuses external light onto the retina, a function for which it must be transparent and possess a smooth surface. Homeostasis of the corneal epithelium is regulated by various humoral factors present in the tear fluid and by neural factors derived from the trigeminal nerve. Neurotrophic keratopathy (NK) is characterized by corneal epithelial disorders that result from impairment of trigeminal nerve function and a consequent deficiency of neural factors. The ideal mode of treatment for this condition is the regeneration of damaged trigeminal nerve fibers, but such therapy is not currently available. In this review, we describe established and potential new treatments of NK. Our research demonstrated that a combination of the neurotransmitter substance P and insulin-like growth factor 1 (IGF-1) has a synergistic stimulatory effect on corneal epithelial migration in vitro and on corneal wound closure in vivo. Furthermore, we identified the minimal amino acid sequences of substance P and IGF-1 required for this synergistic action based on the assumption that the clinical application of peptides corresponding to these sequences would have fewer side effects compared with the full-length molecules. Combination of the substance P-derived peptide FGLM-amide and the IGF-1-derived peptide SSSR promoted corneal epithelial wound healing in patients with NK.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01756456.
authors.affiliation: *Department of Ophthalmology, Graduate School of Medicine, Yamaguchi University, Ube City, Japan; and †Department of Ophthalmology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yanai
authors.forename: Teruo
authors.initials: T
authors.lastname: Nishida
authors.forename: Tai-Ichiro
authors.initials: T
authors.lastname: Chikama
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Morishige
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamada
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
mesh_terms: D002986:Clinical Trials as Topic; D004357:Drug Synergism; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000627:therapeutic use*; D007634:Keratitis / Q000188:drug therapy* / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D013373:Substance P / Q000494:pharmacology / Q000627:therapeutic use*; D020433:Trigeminal Nerve Diseases / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D018377:Neurotransmitter Agents; D009883:Ophthalmic Solutions; D013373:Substance P; D007334:Insulin-Like Growth Factor I