April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Neuroprotective Effect of Amphiphilic Cholesterol-Based PBN Derivatives
Author Affiliations & Notes
  • I. Ranchon-Cole
    Biophysique des handicaps sensoriels, Universite d Auvergne, France, Clermont-Ferrand, France
    Laboratoire de Chimie Bioorganique et des Systèmes Moléculaires Vectoriels, Université d’Avignon et des pays de Vaucluse, France
  • F. Choteau
    Laboratoire de Chimie Bioorganique et des Systèmes Moléculaires Vectoriels, Université d’Avignon et des pays de Vaucluse, France
  • G. Durand
    Laboratoire de Chimie Bioorganique et des Systèmes Moléculaires Vectoriels, Université d’Avignon et des pays de Vaucluse, France
  • C. Cercy
    Biophysique des handicaps sensoriels, Universite d Auvergne, France, Clermont-Ferrand, France
  • M. Doly
    Biophysique des handicaps sensoriels, Universite d Auvergne, France, Clermont-Ferrand, France
  • B. Pucci
    Laboratoire de Chimie Bioorganique et des Systèmes Moléculaires Vectoriels, Université d’Avignon et des pays de Vaucluse, France
  • Footnotes
    Commercial Relationships  I. Ranchon-Cole, None; F. Choteau, None; G. Durand, None; C. Cercy, None; M. Doly, None; B. Pucci, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3882. doi:
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      I. Ranchon-Cole, F. Choteau, G. Durand, C. Cercy, M. Doly, B. Pucci; Neuroprotective Effect of Amphiphilic Cholesterol-Based PBN Derivatives. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3882.

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

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Abstract

Purpose: : Phenyl-N-tert-Butyl Nitrone (PBN) is a potent neuroprotective agent but PBN has to be used at a very high concentration. In order to reduce this concentration, , the PBN molecule has been attached to an amphiphilic cholesterol-based carrier to increase its bioavailability and to facilitate its intracellular uptake. The purpose of this study was to investigate the neuroprotective effect of these novel amphiphilic PBN derivatives.

Methods: : Wistar rats were raised in dim-cyclic light. At 49 days of age, they were dark-adapted overnight before being exposed for 24 hours to intense light. Sixteen hours before exposure, they were uninjected or injected with DMSO 2%, PBN (9 mM), LPBNCHOL (0.9 mM) or CHOLPBN (0.9 mM). Electroretinograms (ERG) were recorded before exposure and/or treatment, at 1 day (D1) and 15 days (D15) after exposure to the damaging light. Bmax (maximal b-wave amplitude) was calculated. After the last ERG, rats were sacrificed for morphometric analysis. Unexposed animals were processed in parallel.

Results: : In unexposed rats, DMSO2%, PBN, LPBNCHOL and CHOLPBN had no toxic effect on the retina. In DMSO treated retina, light-exposure induced a decrease of Bmax by 60% and a thinning of ONL by 47%. In PBN-exposed retina, light exposure had less effect than in DMSO ones. Bmax was only reduced by 20 % and the ONL by 11 %. In LPBNCHOL-exposed retina, Bmax was reduced by 35% and the ONL by 28 %. Finally in the same conditions, in CHOLPBN-exposed retina, light exposure had less effect than in DMSO, PBN or LPBNCHOL group. Bmax was reduced by 10% and the ONL by 6 %.

Conclusions: : LPBNCHOL and CHOLPBN are not toxic for the retina. They have a neuroprotective effect at a concentration 10 times lower than PBN, CHOLPBN being more potent than LPBNCHOL.

Keywords: antioxidants • neuroprotection • retina 
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