April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Systemic Administration of Dextromethorphan Slows Cone Cell Death in an Animal Model of Retinitis Pigmentosa (RP)
Author Affiliations & Notes
  • K. Miki
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • A. Miki
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • S. Usui
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • P. A. Campochiaro
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  K. Miki, None; A. Miki, None; S. Usui, None; P.A. Campochiaro, None.
  • Footnotes
    Support  EY05951 from the NEI
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1377. doi:
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      K. Miki, A. Miki, S. Usui, P. A. Campochiaro; Systemic Administration of Dextromethorphan Slows Cone Cell Death in an Animal Model of Retinitis Pigmentosa (RP). Invest. Ophthalmol. Vis. Sci. 2010;51(13):1377.

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

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Abstract

Purpose: : Dextromethorphan (DM) is widely used as a cough-suppressant with an excellent safety profile. Recent studies have demonstrated that DM has a novel anti-oxidant effect as a NADPH oxidase inhibitor. We have previously demonstrated that cones die from oxidative damage in RP. In this study, we tested the effect of systemically administered DM in rd1+/+ mice.

Methods: : Rd1+/+

Results: : At P13, after intravenous injection of HDE, rd1+/+ mice treated with IP injections of 40mg/kg of DM had much less fluorescence in the retinal sections compared to those from vehicle-treated mice. At P25 with a stimulus intensity of 30cd-s/m2, mean photopic b-wave amplitudes of rd1+/+ mice treated with IP injections of 40mg/kg of DM were 24.5±4.4µV compared to 15.0±2.5µV in rd1+/+ mice treated with vehicle (p<0.05). At P25, mean cone cell density (cones/0.0529 mm2) was greater at 2 of 4 locations in the retinas of rd1+/+ mice given daily IP injections of 40 mg/kg of DME compared to vehicle-treated rd1+/+ mice (superior: 80.2±6.5 vs 59±3.6 (P<0.01), inferior: 67.6±6.8 vs 37±4.5 (P<0.01), temporal: 50.9±5.3 vs 45.2.±3.2, nasal 50.6±6.8 vs 40.6±6.6).

Conclusions: : Systemic treatment with DM, reduced superoxide radicals in the retina, preserves cone function, and reduces cone death in an animal model of RP.

Keywords: retinal degenerations: hereditary • oxidation/oxidative or free radical damage • retina 
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