Effect of Nafamostat on <i>N</i>-Methyl-<small>D</small>-aspartate-Induced Retinal Neuronal and Capillary Degeneration in Rats

  • Tsuda Yo
    Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University
  • Nakahara Tsutomu
    Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University
  • Ueda Kaori
    Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University
  • Mori Asami
    Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University
  • Sakamoto Kenji
    Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University
  • Ishii Kunio
    Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University

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  • Effect of Nafamostat on N-Methyl-D-aspartate-Induced Retinal Neuronal and Capillary Degeneration in Rats

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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.

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