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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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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.
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.
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 %.
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.
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