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Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells.

Gaucher D, Arnault E, Husson Z, Froger N, Dubus E, Gondouin P, Dherbécourt D, Degardin J, Simonutti M, Fouquet S, Benahmed MA, Elbayed K, Namer IJ, Massin P, Sahel JA, Picaud S - Amino Acids (2012)

Bottom Line: GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase.At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway.When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20 %) as the number of retinal ganglion cells (19 %).

View Article: PubMed Central - PubMed

Affiliation: INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France.

ABSTRACT
In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion cells were degenerating in parallel to cone photoreceptors. The aim of this study was to re-assess a classic mouse model of taurine deficiency following a treatment with guanidoethane sulfonate (GES), a taurine transporter inhibitor to determine whether retinal ganglion cells are also affected. GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase. At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway. A change in the autofluorescence appearance of the eye fundus was explained on histological sections by an increased autofluorescence of the retinal pigment epithelium. Although the general morphology of the retina was not affected, cell damages were indicated by the general increase in glial fibrillary acidic protein expression. When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20 %) as the number of retinal ganglion cells (19 %). An abnormal synaptic plasticity of rod bipolar cell dendrites was also observed in GES-treated mice. These results indicate that taurine deficiency can not only lead to photoreceptor degeneration but also to retinal ganglion cell loss. Cone photoreceptors and retinal ganglion cells appear as the most sensitive cells to taurine deficiency. These results may explain the recent therapeutic interest of taurine in retinal degenerative pathologies.

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The weight development is reduced in GES-treated mice. No difference in the mean weight is noted at the beginning of the study (week 0), between the treated group and the control group (SEM, n = 8, P > 0.05, Student’s t test). After 2 months of treatment, the mean weight of the GES-treated mice is significantly reduced (SEM, n = 8, P = 0,024, asterisk denotes Student’s t test)
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Fig2: The weight development is reduced in GES-treated mice. No difference in the mean weight is noted at the beginning of the study (week 0), between the treated group and the control group (SEM, n = 8, P > 0.05, Student’s t test). After 2 months of treatment, the mean weight of the GES-treated mice is significantly reduced (SEM, n = 8, P = 0,024, asterisk denotes Student’s t test)

Mentions: When mice were administered GES (1 %) in their drinking water, their taurine plasma level was significantly decreased at 1 month (GES group: 305.75 ± 27.13 μmol L−1, SEM, n = 8; control group: 770.62 ± 62.47 μmol L−1, SEM, n = 8, P < 0.001) and 2 months (GES group: 283.12 ± 15.35 μmol L−1, SEM, n = 8; control group: 681.5 ± 27.51 μmol L−1, SEM, n = 8, P < 0.001) (Fig. 1a). At that point, the weight development was also significantly reduced in GES-treated mice (GES group: 29.54 ± 0.28 g, SEM, n = 8; control group: 31.67 ± 0.51 g, SEM, n = 8, P = 0.024), while no difference was noted at the beginning of the study (GES group: 22.46 ± 0.38 g, SEM, n = 8; control group: 22.84 ± 0.21 g, SEM, n = 8, P > 0.05) (Fig. 2). Taurine retinal concentration was also reduced in GES mice from 1 month after GES treatment (GES group: 20.33 ± 3.42 nmol/mg, SEM, n = 8; control group: 30.51 ± 2.93 nmol mg, SEM, n = 8, P = 0.046) (Fig. 1b)Fig. 1


Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells.

Gaucher D, Arnault E, Husson Z, Froger N, Dubus E, Gondouin P, Dherbécourt D, Degardin J, Simonutti M, Fouquet S, Benahmed MA, Elbayed K, Namer IJ, Massin P, Sahel JA, Picaud S - Amino Acids (2012)

The weight development is reduced in GES-treated mice. No difference in the mean weight is noted at the beginning of the study (week 0), between the treated group and the control group (SEM, n = 8, P > 0.05, Student’s t test). After 2 months of treatment, the mean weight of the GES-treated mice is significantly reduced (SEM, n = 8, P = 0,024, asterisk denotes Student’s t test)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3472058&req=5

Fig2: The weight development is reduced in GES-treated mice. No difference in the mean weight is noted at the beginning of the study (week 0), between the treated group and the control group (SEM, n = 8, P > 0.05, Student’s t test). After 2 months of treatment, the mean weight of the GES-treated mice is significantly reduced (SEM, n = 8, P = 0,024, asterisk denotes Student’s t test)
Mentions: When mice were administered GES (1 %) in their drinking water, their taurine plasma level was significantly decreased at 1 month (GES group: 305.75 ± 27.13 μmol L−1, SEM, n = 8; control group: 770.62 ± 62.47 μmol L−1, SEM, n = 8, P < 0.001) and 2 months (GES group: 283.12 ± 15.35 μmol L−1, SEM, n = 8; control group: 681.5 ± 27.51 μmol L−1, SEM, n = 8, P < 0.001) (Fig. 1a). At that point, the weight development was also significantly reduced in GES-treated mice (GES group: 29.54 ± 0.28 g, SEM, n = 8; control group: 31.67 ± 0.51 g, SEM, n = 8, P = 0.024), while no difference was noted at the beginning of the study (GES group: 22.46 ± 0.38 g, SEM, n = 8; control group: 22.84 ± 0.21 g, SEM, n = 8, P > 0.05) (Fig. 2). Taurine retinal concentration was also reduced in GES mice from 1 month after GES treatment (GES group: 20.33 ± 3.42 nmol/mg, SEM, n = 8; control group: 30.51 ± 2.93 nmol mg, SEM, n = 8, P = 0.046) (Fig. 1b)Fig. 1

Bottom Line: GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase.At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway.When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20 %) as the number of retinal ganglion cells (19 %).

View Article: PubMed Central - PubMed

Affiliation: INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France.

ABSTRACT
In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion cells were degenerating in parallel to cone photoreceptors. The aim of this study was to re-assess a classic mouse model of taurine deficiency following a treatment with guanidoethane sulfonate (GES), a taurine transporter inhibitor to determine whether retinal ganglion cells are also affected. GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase. At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway. A change in the autofluorescence appearance of the eye fundus was explained on histological sections by an increased autofluorescence of the retinal pigment epithelium. Although the general morphology of the retina was not affected, cell damages were indicated by the general increase in glial fibrillary acidic protein expression. When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20 %) as the number of retinal ganglion cells (19 %). An abnormal synaptic plasticity of rod bipolar cell dendrites was also observed in GES-treated mice. These results indicate that taurine deficiency can not only lead to photoreceptor degeneration but also to retinal ganglion cell loss. Cone photoreceptors and retinal ganglion cells appear as the most sensitive cells to taurine deficiency. These results may explain the recent therapeutic interest of taurine in retinal degenerative pathologies.

Show MeSH
Related in: MedlinePlus