Wahiba Hadj-Saïd1, Nicolas Froger1, Ivana Ivkovic1, Manuel Jiménez-López2, Élisabeth Dubus1, Julie Dégardin-Chicaud1, Manuel Simonutti1, César Quénol1, Nathalie Neveux3, María Paz Villegas-Pérez2, Marta Agudo-Barriuso2, Manuel Vidal-Sanz2, Jose-Alain Sahel4, Serge Picaud1, Diego García-Ayuso2. 1. INSERM U968, Institut de la Vision, Paris, France 2Sorbonne Universités, UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, France 3CNRS UMR7210, Institut de la Vision, Paris, France. 2. Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca). 3. Service de Biochimie, Groupe Hospitalier Cochin - Hôtel-Dieu, Assistance Publique - Hôpitaux de Paris, Paris, France 6Laboratoire de Nutrition, EA 4466, Université Paris Descartes, Faculté de Pharmacie, Paris, France. 4. INSERM U968, Institut de la Vision, Paris, France 2Sorbonne Universités, UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, France 3CNRS UMR7210, Institut de la Vision, Paris, France 7CHNO des Quinze-Vingts, Paris, France 8Academie des Sciences, Paris, France 9Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.
Abstract
PURPOSE: Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S- and L- cones) in an animal model of induced taurine depletion. METHODS: We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their retinal distribution studied using isodensity maps. RESULTS: The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed. CONCLUSIONS: This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin+cones, L-opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.
PURPOSE:Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S- and L- cones) in an animal model of induced taurine depletion. METHODS: We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their retinal distribution studied using isodensity maps. RESULTS: The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed. CONCLUSIONS: This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin+cones, L-opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.
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