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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 retinal ganglion cells loss in GES-treated adult mice. Retinal sections of GES-treated mice (a) and control mice (b) were immunolabelled with antibodies directed to Brn-3A (a, b). Ganglion cells count showed a decrease in ganglion cell density in GES-treated mice as compared with controls (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (c). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer, IPL inner plexiform layer, RGCL retinal ganglion cell layer)
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Fig9: Taurine deficiency induces retinal ganglion cells loss in GES-treated adult mice. Retinal sections of GES-treated mice (a) and control mice (b) were immunolabelled with antibodies directed to Brn-3A (a, b). Ganglion cells count showed a decrease in ganglion cell density in GES-treated mice as compared with controls (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (c). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer, IPL inner plexiform layer, RGCL retinal ganglion cell layer)

Mentions: Then, retinal ganglion cells were immunolabelled with an antibody directed against the transcription factor Brn-3a, which labels more than 90 % of this cell population (Nadal-Nicolas et al. 2009). Again, GES-treated mice appeared to exhibit less retinal ganglion cells than control animals (Fig. 9a, b). The retinal ganglion cell quantification on whole retinal section indicated that the GES treatment led to a 19.3 % decrease in the density of retinal ganglion cell population (Fig. 9c) (GES group: 0.096 ± 0.003 cells/μm, SEM, n = 8; control group: 0.119 ± 0.009 cells/μm, SEM, n = 8, P = 0.027). As GES can be taken up by the taurine transporter (TauT) (Tachikawa et al. 2009) to eventually become toxic to neurones (Hiramatsu 2003), we verified that GES was not directly toxic to retinal ganglion cells. Thus, pure rat retinal ganglion cells were prepared as described previously (Fuchs et al. 2005) and kept in culture for 6 days in the presence of GES (1 mM). In fact, their number were increased by 19.8 ± 9.8 % (SEM, n = 9), but this difference was not statistically significant indicating thereby that GES is not toxic to retinal ganglion cells.Fig. 9


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 retinal ganglion cells loss in GES-treated adult mice. Retinal sections of GES-treated mice (a) and control mice (b) were immunolabelled with antibodies directed to Brn-3A (a, b). Ganglion cells count showed a decrease in ganglion cell density in GES-treated mice as compared with controls (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (c). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer, IPL inner plexiform layer, RGCL retinal ganglion cell layer)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3472058&req=5

Fig9: Taurine deficiency induces retinal ganglion cells loss in GES-treated adult mice. Retinal sections of GES-treated mice (a) and control mice (b) were immunolabelled with antibodies directed to Brn-3A (a, b). Ganglion cells count showed a decrease in ganglion cell density in GES-treated mice as compared with controls (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (c). Scale bars represent 25 μm (ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer, IPL inner plexiform layer, RGCL retinal ganglion cell layer)
Mentions: Then, retinal ganglion cells were immunolabelled with an antibody directed against the transcription factor Brn-3a, which labels more than 90 % of this cell population (Nadal-Nicolas et al. 2009). Again, GES-treated mice appeared to exhibit less retinal ganglion cells than control animals (Fig. 9a, b). The retinal ganglion cell quantification on whole retinal section indicated that the GES treatment led to a 19.3 % decrease in the density of retinal ganglion cell population (Fig. 9c) (GES group: 0.096 ± 0.003 cells/μm, SEM, n = 8; control group: 0.119 ± 0.009 cells/μm, SEM, n = 8, P = 0.027). As GES can be taken up by the taurine transporter (TauT) (Tachikawa et al. 2009) to eventually become toxic to neurones (Hiramatsu 2003), we verified that GES was not directly toxic to retinal ganglion cells. Thus, pure rat retinal ganglion cells were prepared as described previously (Fuchs et al. 2005) and kept in culture for 6 days in the presence of GES (1 mM). In fact, their number were increased by 19.8 ± 9.8 % (SEM, n = 9), but this difference was not statistically significant indicating thereby that GES is not toxic to retinal ganglion cells.Fig. 9

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