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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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Taurine deficiency induces cone photoreceptors loss in GES-treated mice. Retinal sections of control animal (b) and GES-treated mice (a) were stained with peanut lectin (a, b), Inner and outer segments of cone photoreceptors are absent in many points of the retina in GES mice, leaving optically empty spaces throughout the segments photoreceptors line (a). These spaces are not detected on control eyes sections (b). Even if present, the inner/outer segments of cone photoreceptors seem broken and not well lined up in the treated mice (a) whereas they are aligned in controls (b). Cone photoreceptors count revealed a decrease number of cells in the GES-treated mice (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer) (c)
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Fig7: Taurine deficiency induces cone photoreceptors loss in GES-treated mice. Retinal sections of control animal (b) and GES-treated mice (a) were stained with peanut lectin (a, b), Inner and outer segments of cone photoreceptors are absent in many points of the retina in GES mice, leaving optically empty spaces throughout the segments photoreceptors line (a). These spaces are not detected on control eyes sections (b). Even if present, the inner/outer segments of cone photoreceptors seem broken and not well lined up in the treated mice (a) whereas they are aligned in controls (b). Cone photoreceptors count revealed a decrease number of cells in the GES-treated mice (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer) (c)

Mentions: To further assess the nature of these retinal lesions, different cell types were stained or immunolabelled. When cone outer/inner segments were labelled with the peanut agglutinin lectin, they appeared more scattered in GES-treated animals (Fig. 7a, b). Their quantification along whole retinal sections indicated that the GES treatment induced a 20.4 % loss of cone outer/inner segments (Fig. 7c) (GES group: 0.140 ± 0.01 segments/μm, SEM, n = 8; control group: 0.176 ± 0.01 segments/μm, SEM, n = 8, P = 0.023). In some instances, a disorganization of the outer nuclear layer was also visible. When ON bipolar cell postsynaptic to photoreceptors were immunolabelled by a PKCα antibody (staining ON rod bipolar cells) and a Goα antibody (staining both rod and cone ON bipolar cells), numerous dendrites extending into the outer nuclear layer were observed and they were always co-immunolabelled identifying them as rod bipolar cells (Fig. 8). These observations indicated that rod bipolar cells undergo synaptic plasticity and formation of ectopic synapses in the outer nuclear layer.Fig. 7


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)

Taurine deficiency induces cone photoreceptors loss in GES-treated mice. Retinal sections of control animal (b) and GES-treated mice (a) were stained with peanut lectin (a, b), Inner and outer segments of cone photoreceptors are absent in many points of the retina in GES mice, leaving optically empty spaces throughout the segments photoreceptors line (a). These spaces are not detected on control eyes sections (b). Even if present, the inner/outer segments of cone photoreceptors seem broken and not well lined up in the treated mice (a) whereas they are aligned in controls (b). Cone photoreceptors count revealed a decrease number of cells in the GES-treated mice (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer) (c)
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Fig7: Taurine deficiency induces cone photoreceptors loss in GES-treated mice. Retinal sections of control animal (b) and GES-treated mice (a) were stained with peanut lectin (a, b), Inner and outer segments of cone photoreceptors are absent in many points of the retina in GES mice, leaving optically empty spaces throughout the segments photoreceptors line (a). These spaces are not detected on control eyes sections (b). Even if present, the inner/outer segments of cone photoreceptors seem broken and not well lined up in the treated mice (a) whereas they are aligned in controls (b). Cone photoreceptors count revealed a decrease number of cells in the GES-treated mice (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer) (c)
Mentions: To further assess the nature of these retinal lesions, different cell types were stained or immunolabelled. When cone outer/inner segments were labelled with the peanut agglutinin lectin, they appeared more scattered in GES-treated animals (Fig. 7a, b). Their quantification along whole retinal sections indicated that the GES treatment induced a 20.4 % loss of cone outer/inner segments (Fig. 7c) (GES group: 0.140 ± 0.01 segments/μm, SEM, n = 8; control group: 0.176 ± 0.01 segments/μm, SEM, n = 8, P = 0.023). In some instances, a disorganization of the outer nuclear layer was also visible. When ON bipolar cell postsynaptic to photoreceptors were immunolabelled by a PKCα antibody (staining ON rod bipolar cells) and a Goα antibody (staining both rod and cone ON bipolar cells), numerous dendrites extending into the outer nuclear layer were observed and they were always co-immunolabelled identifying them as rod bipolar cells (Fig. 8). These observations indicated that rod bipolar cells undergo synaptic plasticity and formation of ectopic synapses in the outer nuclear layer.Fig. 7

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