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Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion.
Invest Ophthalmol Vis Sci. 2016 09 01; 57(11):4692-703.IO

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Hadj-Saïd W
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.
Froger N
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.
Ivkovic I
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.
Jiménez-López M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Dubus É
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.
Dégardin-Chicaud J
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.
Simonutti M
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.
Quénol C
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.
Neveux N
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.
Villegas-Pérez MP
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Agudo-Barriuso M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Vidal-Sanz M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Sahel JA
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.
Picaud S
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.
García-Ayuso D
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).

MeSH

AnimalsCell CountDisease Models, AnimalElectroretinographyImmunohistochemistryMaleMiceMice, Inbred BALB CRetinal Cone Photoreceptor CellsRetinal DegenerationRetinal Ganglion CellsTaurineTomography, Optical Coherence

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27607415

Citation

Hadj-Saïd, Wahiba, et al. "Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion." Investigative Ophthalmology & Visual Science, vol. 57, no. 11, 2016, pp. 4692-703.
Hadj-Saïd W, Froger N, Ivkovic I, et al. Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion. Invest Ophthalmol Vis Sci. 2016;57(11):4692-703.
Hadj-Saïd, W., Froger, N., Ivkovic, I., Jiménez-López, M., Dubus, É., Dégardin-Chicaud, J., Simonutti, M., Quénol, C., Neveux, N., Villegas-Pérez, M. P., Agudo-Barriuso, M., Vidal-Sanz, M., Sahel, J. A., Picaud, S., & García-Ayuso, D. (2016). Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion. Investigative Ophthalmology & Visual Science, 57(11), 4692-703. https://doi.org/10.1167/iovs.16-19535
Hadj-Saïd W, et al. Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion. Invest Ophthalmol Vis Sci. 2016 09 1;57(11):4692-703. PubMed PMID: 27607415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion. AU - Hadj-Saïd,Wahiba, AU - Froger,Nicolas, AU - Ivkovic,Ivana, AU - Jiménez-López,Manuel, AU - Dubus,Élisabeth, AU - Dégardin-Chicaud,Julie, AU - Simonutti,Manuel, AU - Quénol,César, AU - Neveux,Nathalie, AU - Villegas-Pérez,María Paz, AU - Agudo-Barriuso,Marta, AU - Vidal-Sanz,Manuel, AU - Sahel,Jose-Alain, AU - Picaud,Serge, AU - García-Ayuso,Diego, PY - 2016/9/9/entrez PY - 2016/9/9/pubmed PY - 2017/5/27/medline SP - 4692 EP - 703 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 57 IS - 11 N2 - 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. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/27607415/Quantitative_and_Topographical_Analysis_of_the_Losses_of_Cone_Photoreceptors_and_Retinal_Ganglion_Cells_Under_Taurine_Depletion_ DB - PRIME DP - Unbound Medicine ER -