April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Minocycline Synergizes With N-acetylcysteine To Improve Rat Retinal Function Following Ischemia
Author Affiliations & Notes
  • Daniel M. Rosenbaum
    Neurology,
    SUNY Downstate, Brooklyn, New York
  • Brian Saunders
    Neurology,
    SUNY Downstate, Brooklyn, New York
  • Frank C. Barone
    Neurology,
    SUNY Downstate, Brooklyn, New York
  • Jie Li
    Neurology,
    SUNY Downstate, Brooklyn, New York
  • Jin Zhou
    Neurology,
    SUNY Downstate, Brooklyn, New York
  • Samah G. Abdel Baki
    Physiology&Pharmacology,
    SUNY Downstate, Brooklyn, New York
  • Pearl S. Rosenbaum
    Opthalmology, Bronx-Lebanon Hospital Center, Bronx, New York
  • Peter J. Bergold
    Physiology&Pharmacology,
    SUNY Downstate, Brooklyn, New York
  • Footnotes
    Commercial Relationships  Daniel M. Rosenbaum, None; Brian Saunders, None; Frank C. Barone, None; Jie Li, None; Jin Zhou, None; Samah G. Abdel Baki, None; Pearl S. Rosenbaum, None; Peter J. Bergold, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2653. doi:
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      Daniel M. Rosenbaum, Brian Saunders, Frank C. Barone, Jie Li, Jin Zhou, Samah G. Abdel Baki, Pearl S. Rosenbaum, Peter J. Bergold; Minocycline Synergizes With N-acetylcysteine To Improve Rat Retinal Function Following Ischemia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2653.

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

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Abstract

Purpose: : Many individual drugs have failed clinical trials suggesting a role for drug combinations in CNS injury. Synergistic drug combinations provide an improved intervention strategy (e.g., regarding potency and safety). Recently we showed that Minocycline (MINO; anti-inflammatory antibiotic) synergizes with N-acetylcysteine (NAC; anti-oxidant amino acid) to improve cognition in rat traumatic brain injury (PLoS One. 5(8):e12490, 2010). Here we evaluate these drugs alone or together, compared to control saline (SAL) to determine if synergistic protection of the ischemic retina can be demonstrated.

Methods: : Retinal ischemia was produced in male Sprague Dawley rats. High intraocular pressure (120 mmHg) induced right eye retinal ischemia for 45 minutes. Electroretinograms (ERG) α- and β-waves were measured in each eye before ischemia and 7 days later. SAL (Vehicle; N=9), MINO (50 mg/kg; N=7), NAC (150 mg/kg; N=7) or MINO+NAC (same doses; N=12) was administered intraperitonially as 4 ml/kg one hour after ischemia. Retinal function was measured as percent normal eye ERG baseline wave response (i.e., calculated as post-wave ratio; post-ischemia eye/post-normal eye, to pre-wave ratio; pre-ischemia eye/pre-normal eye).

Results: : Following retinal ischemia, the ERG α-wave did not differ but ERG β-wave was decreased similarly in the SAL (17.4+4.5 %), MINO (28.8+8.1 %) and NAC (25.9+8.9 %) groups. In contrast, the MINO+NAC group increased ERG β-wave retinal function (53.2+24.9 %; only this group differed significantly from all other groups; p< 0.01). Thus, a clear synergistic protective effect was demonstrated for the MINO+NAC combination.

Conclusions: : These data demonstrate that post-ischemic administration of MINO+NAC act synergistically to protect the retina from functional injury. Since these drugs are already FDA-approved for uses other than brain injury, they provide a potential opportunity for combined intervention for CNS injury in the future.

Keywords: ischemia • antioxidants • inflammation 
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