Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion.
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.



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.



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.



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.
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.
Wahiba
W
Hadj-Saïd
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.
Nicolas
N
Froger
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.
Ivana
I
Ivkovic
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Manuel
M
Jiménez-López
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.
Élisabeth
É
Dubus
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.
Julie
J
Dégardin-Chicaud
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.
Manuel
M
Simonutti
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.
César
C
Quénol
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.
Nathalie
N
Neveux
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
María Paz
MP
Villegas-Pérez
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Marta
M
Agudo-Barriuso
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Manuel
M
Vidal-Sanz
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.
Jose-Alain
JA
Sahel
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.
Serge
S
Picaud
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain and Instituto Murciano de Investigación Biosanitaria- Hospital Virgen de la Arrixaca (IMIB-Arrixaca).
Diego
D
García-Ayuso
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D004596:Electroretinography; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D013654:Taurine / Q000378:metabolism*; D041623:Tomography, Optical Coherence
D013654:Taurine