title: Effect of nafamostat on N-methyl-D-aspartate-induced retinal neuronal and capillary degeneration in rats.
abstract: We examined the effects of the serine protease inhibitor nafamostat mesilate on neuronal and vascular injury in rat retinas treated with N-methyl-D-aspartate (NMDA). The degree of neuronal degeneration was assessed by measuring the number of cells in the ganglion cell layer and the thickness of the inner plexiform layer. The degree of capillary degeneration was assessed by measuring the number of empty basement membrane sleeves that were left as remnants of the vessels. Significant neuronal and capillary degeneration was observed 7 d after a single intravitreal injection of NMDA into the eye. Both forms of degeneration were significantly prevented by simultaneous injection of nafamostat mesilate with NMDA. These results indicate that nafamostat mesilate affords protection against the neuro/vascular injury seen in NMDA-treated retinas. Nafamostat mesilate may be considered as a candidate for neuro/vascular protective interventions in retinal diseases associated with glutamate-induced excitotoxicity, such as glaucoma and diabetic retinopathy.
authors.affiliation: Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5–9–1 Shirokane, Minato-ku, Tokyo 108–8641, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.forename: Kaori
authors.initials: K
authors.lastname: Ueda
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000818:Animals; D001485:Basement Membrane; D001550:Benzamidines; D002196:Capillaries / Q000187:drug effects*; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000517:prevention & control; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects; D005901:Glaucoma / Q000139:chemically induced / Q000517:prevention & control; D018698:Glutamic Acid / Q000009:adverse effects*; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D058449:Intravitreal Injections; D008297:Male; D016202:N-Methylaspartate / Q000009:adverse effects; D009410:Nerve Degeneration / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012164:Retinal Diseases / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D055351:Retinal Neurons / Q000187:drug effects* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012720:Severity of Illness Index; D014652:Vascular Diseases / Q000517:prevention & control
chemical_list: D001550:Benzamidines; D018690:Excitatory Amino Acid Agonists; D006146:Guanidines; D018696:Neuroprotective Agents; D015842:Serine Proteinase Inhibitors; D018698:Glutamic Acid; D016202:N-Methylaspartate; C032855:nafamostat