phenylalanyl-glycyl-leucyl-methioninamide and Corneal-Diseases

The physiological roles of the cornea are to conduct external light into the eye, focus it, together with the lens, onto the retina, and to provide rigidity to the entire eyeball. Good vision thus requires maintenance of the transparency and proper refractive shape of the cornea. Although the cornea appears to be a relatively static structure, dynamic processes operate within and around the cornea at the tissue, cell, and molecular level. In this article, I review the mechanisms responsible for maintenance of corneal homeostasis as well as the development of new modes of treatment for various corneal diseases. I. The static cornea: structure and physiological functions. The cornea is derived from ectoderm, so that it can be considered as transparent skin. It is devoid of blood vessels and manifests the highest sensitivity in the entire body. The surface of the cornea is covered by tear fluid, which serves both as a lubricant and as a conduit for regulatory molecules. The cornea is also supplied with oxygen and various nutrients by the aqueous humor and a loop vascular system in addition to tear fluid. The cornea interacts with its surrounding tissues directly as well as indirectly through tear fluid or aqueous humor, with such interactions playing an important role in the regulation of corneal structure and functions. The resident cells of the cornea-epithelial cells, fibroblasts (keratocytes), and endothelial cells--also engage in mutual interactions through network systems. These interactions as well as those with infiltrated cells and regulation by nerves contribute to the maintenance of the normal structure and functions of the cornea as well as to the repair of corneal injuries. II. The dynamic cornea: maintenance of structure and functions by network systems. Developments in laser and computer technology have allowed observation of the cells and collagen fibers within the cornea. Furthermore, progress in cell and molecular biology has allowed characterization of dynamic network systems-including cell-cell and cell-extracellular matrix interactions as well as cytokines and neural factors-that contribute to the maintenance of corneal transparency and shape. III. Disruption of network systems: persistent corneal epithelial defects and corneal ulcer. Selection of the appropriate treatment for pathologic lesions of the cornea and the accompanying decrease in visual acuity requires localization of the lesion with regard to the epithelium, stroma, or endot

Topics: Annexin A5; Cornea; Corneal Diseases; Diterpenes; Drug Design; Epoxy Compounds; Fibronectins; Homeostasis; Humans; Matrix Metalloproteinases, Secreted; Oligopeptides; Ophthalmic Solutions; Phenanthrenes

The efficacy of eyedrops containing peptides based on substance P (FGLM-amide) and insulinlike growth factor-1 (SSSR) for prevention of superficial punctate keratopathy (SPK) after cataract surgery in individuals with type 2 diabetes was examined.. Twenty-nine patients (29 eyes) with diabetes were enrolled in a double-masked, prospective, randomized, placebo-controlled clinical study. They were randomly assigned to one of two groups that received eyedrops containing either FGLM-amide and SSSR (n = 14) or phosphate-buffered saline (n = 15) four times a day for 14 days starting 1 day after phacoemulsification. SPK scores (area, density, and combined area and density) were determined before as well as 1, 3, 7, and 14 days after surgery as main outcome measures.. SPK scores did not differ between the two groups before surgery or before initiation of treatment. At day 2 after treatment initiation, all SPK scores were significantly lower in the FGLM-amide/SSSR group than in the control group. The density score was also significantly lower in the former group at day 7 after surgery. All scores returned to preoperative levels by day 14 after surgery in both groups.. Eyedrops containing FGLM-amide and SSSR were effective for the prevention of SPK after cataract surgery in diabetic patients.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Corneal Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Epithelium, Corneal; Female; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Oligopeptides; Ophthalmic Solutions; Phacoemulsification; Postoperative Complications; Prospective Studies; Substance P; Treatment Outcome

Loss of corneal sensation results in the development of persistent corneal epithelial defects. The combination of a substance P-derived peptide (FGLM-amide) and an insulin-like growth factor-1 (IGF-1)-derived peptide (SSSR) stimulates rabbit corneal epithelial migration in vitro and rabbit corneal epithelial wound closure in vivo. The clinical efficacy of eye-drops containing FGLM-amide and SSSR for the treatment of persistent corneal epithelial defects in individuals with neurotrophic keratopathy was examined in a prospective open study.. Twenty-five consecutive patients (26 eyes) with persistent corneal epithelial defects associated with neurotrophic keratopathy were treated by administration of eye-drops containing FGLM-amide and SSSR. The course of epithelial healing was monitored by slit-lamp examination.. Epithelial defects resurfaced completely in 19 of the 26 eyes (73%) within 4 weeks after treatment initiation. Complete resurfacing of epithelial defects was apparent in 18 of 22 (82%) or in one of four (25%) eyes without or with limbal stem cell deficiency, respectively. No adverse effects of treatment were observed in any subject.. Eye-drops containing FGLM-amide and SSSR induced the rapid resurfacing of persistent epithelial defects in stem cell-positive individuals with neurotrophic keratopathy.

Topics: Adult; Aged; Aged, 80 and over; Cornea; Corneal Diseases; Drug Combinations; Epithelium, Corneal; Female; Humans; Limbus Corneae; Male; Middle Aged; Oligopeptides; Ophthalmic Solutions; Prospective Studies; Sensation Disorders; Stem Cells; Tears; Treatment Outcome; Visual Acuity; Wound Healing

Non-invasive confocal biomicroscopy revealed regeneration of corneal nerve fibres coincident with corneal epithelial healing in a patient with neurotrophic keratopathy.

Topics: Cornea; Corneal Diseases; Drug Therapy, Combination; Epithelium, Corneal; Humans; Insulin-Like Growth Factor I; Male; Microscopy, Confocal; Middle Aged; Nerve Regeneration; Oligopeptides; Visual Acuity

Topics: Corneal Diseases; Cranial Nerve Diseases; Drug Therapy, Combination; Epithelium, Corneal; Female; Humans; Insulin-Like Growth Factor I; Middle Aged; Oligopeptides; Paralysis; Trigeminal Nerve; Visual Acuity; Wound Healing