title: The effects of taurine on vigabatrin, high light intensity and mydriasis induced retinal toxicity in the pigmented rat.
abstract: The overall purpose of this study was to establish a model that may be used for examining the effect of Vigabatrin-induced retinal toxicity in pigmented rats, and subsequently examine the possible effects of taurine on the retinal toxicity. In the first part of the study, pigmented Long Evans rats were subjected to combinations of induced mydriasis, low/high light intensities (40/2000 lx) and oral administration of near-MTD (Maximum Tolerated Dose) doses (200 mg/kg/day) of Vigabatrin for up to 6 weeks. The combination of mydriasis and high light intensity applied to Long Evans rats resulted in retinal damage that was increased by the administration of Vigabatrin. In the second part of the study Long Evans rats were subjected to combinations of induced mydriasis and high/low light intensity (40/2000 lx) while being orally administered low (30 mg/kg/day) or high (200 mg/kg/day) doses of Vigabatrin for up to 6 weeks. In addition, selected groups of animals were administered taurine via the drinking water (20 mg/ml), resulting in systemic taurine concentrations of approximately threefold the endogenous concentration. The combined results of the studies demonstrate that retinal damage can be induced in pigmented animals when combining mydriasis and high light intensity. Retinal damage was functionally evaluated by electroretinography (ERG), then confirmed by histopathology. While depending on mydriasis and high light intensity, administration of Vigabatrin increased the retinal toxicity and resulted in the formation of rosette-like structures in the retina in a dose-related manner. Administration of taurine did not alleviate the Vigabatrin-induced retinal toxicity, as demonstrated either functionally by ERG or morphologically, although systemic concentrations of 3-fold the endogenous levels were reached, and it was thus not possible to demonstrate a protective effect of taurine in these pigmented animals.
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: adar@lundbeck.com.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Rasmussen
authors.affiliation: WIL Research Europe-Lyon, Department of General Toxicology, 329 Impasse du Domaine Rozier, Les Oncins, 69210 Saint-Germain-Nuelles, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Truchot
authors.affiliation: WIL Research Europe-Lyon, Department of General Toxicology, 329 Impasse du Domaine Rozier, Les Oncins, 69210 Saint-Germain-Nuelles, France.
authors.forename: Nigel
authors.initials: N
authors.lastname: Pickersgill
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Zia Irene
authors.initials: ZI
authors.lastname: Thale
authors.affiliation: UPMC Universite Paris 06, UMR_S 968, Centre de Recherche-Institut de la Vision, 17 rue Moreau, 75012 Paris, France; Clinique Veterinaire Voltaire, Asnieres, France.
authors.forename: Serge G
authors.initials: SG
authors.lastname: Rosolen
authors.affiliation: WIL Research Europe-Lyon, Department of Pathology, 329 Impasse du Domaine Rozier, Les Oncins, 69210 Saint-Germain-Nuelles, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Botteron
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001285:Atropine / Q000633:toxicity; D004195:Disease Models, Animal; D004596:Electroretinography; D008297:Male; D015878:Mydriasis / Q000473:pathology; D009184:Mydriatics / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology*; D013654:Taurine / Q000633:toxicity*; D020888:Vigabatrin / Q000633:toxicity*
chemical_list: D000927:Anticonvulsants; D009184:Mydriatics; D013654:Taurine; D001285:Atropine; D020888:Vigabatrin
keywords: High light intensity; Long Evans; Mydriasis; Rat; Retina; Retinal toxicity; Taurine; Vigabatrin