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Role of Taurine Transporter in the Retinal Uptake of Vigabatrin

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Abstract

Vigabatrin (VGB) is a first-line drug used for treatment of infantile spasms. On therapeutic dose, VGB accumulates in the retina causing permanent peripheral visual field constriction. The mechanism involved in retinal accumulation of VGB is ambiguous. In the present study, mechanism of VGB transport into retina was evaluated. VGB uptake into retina was studied in vitro using human adult retinal pigment epithelial (ARPE-19) cells as a model for outer blood retinal barrier. The VGB cell uptake studies demonstrated saturation kinetics with Km value of 13.1 mM and uptake was significantly increased at pH 7.4 and hyperosmolar conditions indicating involvement of carrier-mediated Na+–Cl−-dependent transporter. In the presence of taurine transporter (TauT) substrates (taurine and GABA) and inhibitor guanidinoethyl sulfonate (GES), the uptake of VGB decreased significantly demonstrating contribution of TauT. The VGB retinal levels in rats were decreased by 1.5- and 1.3-folds on chronic administration of GES and taurine, respectively. In conclusion, this study demonstrated the TauT involvement in VGB uptake and accumulation in retina.

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Authors and Affiliations

  1. University of Mississippi, University, MS, 38677, USA

    Anitha Police, Vijay Kumar Shankar & S. Narasimha Murthy

  2. Institute for Drug Delivery & Biomedical Research, Bangalore, India

    S. Narasimha Murthy

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  1. Anitha Police
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  2. Vijay Kumar Shankar
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  3. S. Narasimha Murthy
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Correspondence to S. Narasimha Murthy.

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The animal study was conducted as per study protocol approved by the institutional animal ethical committee at the University of Mississippi, Mississippi 38677, USA.

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Police, A., Shankar, V.K. & Murthy, S.N. Role of Taurine Transporter in the Retinal Uptake of Vigabatrin. AAPS PharmSciTech 21, 196 (2020). https://doi.org/10.1208/s12249-020-01736-7

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