Single doses of all-trans-N-retinylacetamide slow down the ERG amplitude recovery after bleaching in rats.
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/m(2)). 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 + or - 9% (P < 0.05) and 66 + or - 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.
Messias
Andre
A
Centre for Ophthalmology, University of Tübingen, Schleichstr. 12-16, 72076, Tübingen, Germany. amessias@hotmail.com
Zrenner
Eberhart
E
Tzekov
Radouil
R
McGee
David
D
Peters
Tobias
T
Wilhelm
Barbara
B
Baryluk
Aneta
A
Kubota
Ryo
R
Gekeler
Florian
F
D000818:Animals; D003623:Dark Adaptation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008268:Macular Degeneration / Q000188:drug therapy; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D012172:Retinaldehyde / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D012174:Retinitis Pigmentosa / Q000188:drug therapy; D012176:Retinoids / Q000008:administration & dosage*; D013997:Time Factors; D014795:Visual Pathways / Q000187:drug effects
D012176:Retinoids; D012172:Retinaldehyde