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Single doses of all-trans-N-retinylacetamide slow down the ERG amplitude recovery after bleaching in rats

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Abstract

To assess the safety and to quantify the effects of a single application of all-trans-N-retinylacetamide on the rat retina measured by electroretinography (ERG). Brown Norway rats were assigned to either a control group (n = 13) or to one of the three groups treated with a single intra-peritoneal dose of all-trans-N-retinylacetamide: 20 (n = 8), 5 (n = 7), or 1 mg/kg (n = 8). Full-field ERGs were performed 7 days before (baseline) and 12 h after treatment. Intensity–response relationship of b-wave amplitudes were evaluated in dark-adapted conditions using white stimuli (0.000003–0.3 cd.s/m2). Fast dynamics of rod sensitivity was assessed by a paired-flash paradigm; recovery dynamics of b-wave amplitudes after bleaching was followed for 70 min. Light-adapted ERGs were recorded for cone evaluation. No effects were found on either dark-adapted sensitivity or on fast rod recovery. However, drug treatment at 5 and 20 mg/kg significantly delayed ERG amplitude recovery after bleaching: 60 min after bleaching the b-wave amplitude was 21 ± 9% (P < 0.05) and 66 ± 10% (P < 0.05), respectively, compared to baseline. Recovery rates returned to normal 8 weeks after treatment. There were no changes in light-adapted ERG in any group. Systemic administration of a single dose of the visual cycle modulator all-trans-N-retinylacetamide reversibly delayed recovery of dark-adapted ERG amplitudes after bleaching, leaving other functions unchanged. This finding could make the compound potentially useful in experimental conditions or in specific diseases where the visual cycle is involved, such as retinitis pigmentosa or age-related macular degeneration.

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Authors and Affiliations

  1. Centre for Ophthalmology, University of Tübingen, Schleichstr. 12–16, 72076, Tübingen, Germany

    Andre Messias, Eberhart Zrenner, Aneta Baryluk & Florian Gekeler

  2. School of Medicine of Ribeirão Preto, Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, USP, Ribeirão Preto, Brazil

    Andre Messias

  3. Acucela Inc., Bothell, WA, USA

    Radouil Tzekov, David McGee & Ryo Kubota

  4. Steinbeis Transfer Centre for Biomedical Optics and Function Testing (STC), Tübingen, Germany

    Eberhart Zrenner, Tobias Peters & Barbara Wilhelm

Authors
  1. Andre Messias
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  2. Eberhart Zrenner
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  3. Radouil Tzekov
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  4. David McGee
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  5. Tobias Peters
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  6. Barbara Wilhelm
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  7. Aneta Baryluk
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  8. Ryo Kubota
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  9. Florian Gekeler
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Correspondence to Andre Messias.

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Andre Messias and Eberhart Zrenner have equally contributed to this work.

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Messias, A., Zrenner, E., Tzekov, R. et al. Single doses of all-trans-N-retinylacetamide slow down the ERG amplitude recovery after bleaching in rats. Doc Ophthalmol 120, 165–174 (2010). https://doi.org/10.1007/s10633-009-9209-2

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  • DOI: https://doi.org/10.1007/s10633-009-9209-2

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