December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
A Prodrug of a Selective Inhibitor of Inducible Nitric Oxide Synthase Is Neuroprotective In The Rat Model of Glaucoma
Author Affiliations & Notes
  • S-I Kawai
    Dept of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • S Das
    Dept of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • S Vora
    Dept of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • EN Gachie
    Dept of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • PT Manning
    The Pharmacia Corp St Louis MO
  • JR Connors
    The Pharmacia Corp St Louis MO
  • AH Neufeld
    Dept of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • Footnotes
    Commercial Relationships   S. Kawai, None; S. Das, None; S. Vora, None; E.N. Gachie, None; P.T. Manning, The Pharmacia Corp. F; J.R. Connors, The Pharmacia Corp. F; A.H. Neufeld, None. Grant Identification: NIH Grant EY12017
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2192. doi:
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      S-I Kawai, S Das, S Vora, EN Gachie, PT Manning, JR Connors, AH Neufeld; A Prodrug of a Selective Inhibitor of Inducible Nitric Oxide Synthase Is Neuroprotective In The Rat Model of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2192.

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

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Abstract

Abstract: : Purpose:We have previously presented data that indicates that nitric oxide neurotoxicity causes the optic neuropathy associated with glaucoma. To test the hypothesis that pharmacological inhibition of inducible nitric oxide synthase (NOS-2) will be useful for the treatment of the optic neuropathy associated with glaucoma, we have tested a selective and potent inhibitor of NOS-2 in a rat model of glaucoma. Methods:Unilateral, chronic, moderately elevated intraocular pressure was created in rats by cautery of three episcleral vessels. Rats were treated orally with L-N6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51), a prodrug of an inhibitor of inducible nitric oxide synthase. SC-51 was started at the time of episcleral vessel cautery or three months after episcleral vessel cautery. Retinal ganglion cells (RGCs) were retrogradely labeled with Fluoro-Gold. The loss of RGCs was quantitated as an indicator of glaucomatous damage. Results:At the end of seven months, rat eyes with chronic, moderately elevated intraocular pressure lost approximately 20,000 RGCs. Treatment with SC-51 over a seven months period completely prevented the loss of RGCs in eyes with chronic, moderately elevated intraocular pressure. When treatment with SC-51 was delayed and started after three months of chronic, moderately elevated intraocular pressure, further loss of RGCs was prevented. Treatment with SC-51 did not affect intraocular pressure, body weight or water drinking. Conclusion:Pharmacological neuroprotection with a selective and potent inhibitor of inducible nitric oxide synthase may be useful for the treatment of glaucoma.

Keywords: 489 neuroprotection • 415 ganglion cells • 491 nitric oxide 
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