May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Neuroprotective Effects of Calpain Inhibitor MDL 28170 in a Model of Intravitreal Excitotoxicity
Author Affiliations & Notes
  • M. Pallas
    Department of Ophthalmology, Otto von Guericke University, Magdeburg, Germany
  • C. Knop
    Department of Ophthalmology, Otto von Guericke University, Magdeburg, Germany
  • W. Behrens-Baumann
    Department of Ophthalmology, Otto von Guericke University, Magdeburg, Germany
  • C.K. Vorwerk
    Department of Ophthalmology, Otto von Guericke University, Magdeburg, Germany
  • Footnotes
    Commercial Relationships  M. Pallas, None; C. Knop, None; W. Behrens-Baumann, None; C.K. Vorwerk, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 110. doi:
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      M. Pallas, C. Knop, W. Behrens-Baumann, C.K. Vorwerk; Neuroprotective Effects of Calpain Inhibitor MDL 28170 in a Model of Intravitreal Excitotoxicity . Invest. Ophthalmol. Vis. Sci. 2003;44(13):110.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Traumatic or glaucomatous lesions of the optic nerve lead to a substantial loss of retinal ganglion cells (RGC). The involvement of an uncontrolled and prolonged calpain-mediated proteolysis has been suggested in the pathogenesis of neuronal cell death associated with excitotoxicity and ischemia. The present study was initiated to determine if calpain inhibitor MDL 28170 could reduce the loss of RGC in a model of acute excitotoxic stimulation of RGC. MDL 28170 has been shown to offer neuroprotective effects in cerebral ischemia and to protect cultured neurons from NMDA. Methods: Excitotoxic lesions were induced by intraocular injection of 20 nmol NMDA, an endogenous glutamate agonist. A second group received in addition intraperitoneal injections of MDL 28170 (50 mg per kg body weight in Dimethyl-sulfoxide) 0, 3 and 6 hours after the intraocular NMDA lesion. 7 days after the excitotoxic retinal damage, RGC were labeled with fluorogold. After additional 2 days eyes were enucleated and retinal whole mounts counted for fluorogold positive RGC. Results: RGC density in controls without lesion was 1855 ± 502 RGC/mm², whereas NMDA alone treated animals revealed a RGC survival of only 258 ± 121 RGC/mm². Animals treated with MDL 28170 resulted in a significant increase of the surviving RGC to 530 ± 355 RGC/mm². Controls with calpain inhibitor alone did not show any effect. Conclusions: The results demonstrate that the inhibition of calcium-activated neutral cysteine proteases by MDL 28170 may offer neuroprotective effects after an excitotoxic lesion.

Keywords: neuroprotection • ganglion cells • animal model 
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