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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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Retinal cell function in GES-treated mice. Electroretinogram (ERG) response of a 10 cds m−2 scotopic flash light stimulus recorded in a control animal, and in GES mouse (a). Response of a 25 cds m−2 photopic flash light stimulus recorded in a control animal, and in GES mouse (b). Photopic ERG response to a 15-Hz flickers light stimulus in a control animal, and in GES mouse (c). Oscillary Potentials (Ops) isolated in a control, and a GES mouse (d). Quantification of scotopic and photopic ERG amplitudes in controls (n = 15), and GES-treated animals showing the significant decrease in standard flash and flickers photopic ERG amplitudes. (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (e)
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Fig3: Retinal cell function in GES-treated mice. Electroretinogram (ERG) response of a 10 cds m−2 scotopic flash light stimulus recorded in a control animal, and in GES mouse (a). Response of a 25 cds m−2 photopic flash light stimulus recorded in a control animal, and in GES mouse (b). Photopic ERG response to a 15-Hz flickers light stimulus in a control animal, and in GES mouse (c). Oscillary Potentials (Ops) isolated in a control, and a GES mouse (d). Quantification of scotopic and photopic ERG amplitudes in controls (n = 15), and GES-treated animals showing the significant decrease in standard flash and flickers photopic ERG amplitudes. (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (e)

Mentions: To determine whether the GES treatment and its consequent taurine plasma and retina level decrease induced retinal dysfunction, scotopic and photopic electroretinograms (ERGs) were performed on both treated and untreated animals. Scotopic ERG recordings were made in dark adapted animals (24 h of dark adaptation) with flashes of different light intensities (0.1, 1, 100, 1,000 and 10,000 mcds m−2). In these recordings, the first negative signal (a-wave) provides an in vivo measurement of rod photoreceptor light response dynamic whereas the consecutive positive signal (b-wave) is informative about the postsynaptic bipolar cells. Although cones can be activated at certain light intensities, these measurements are highly rod dominated. Mean a- (data not shown) and b-wave amplitudes of scotopic ERGs were always reduced in GES animals as compared with controls. However, the differences between the two groups were not statistically significant (t test, P > 0.05) (Fig. 3a, e). When oscillatory potentials informative of the third-order neurones, namely amacrine cells, were isolated with a more restrictive filtering of the ERG recordings, no significant difference could be detected (Fig. 3d, e). In contrast, when a background light was used to saturate rod photoreceptors, the response to an intense flash, the photopic ERG, showed a significant decrease in the GES group as compared with control mice (GES group: 97.61 ± 8.74 μV, SEM, n = 8; control group: 122.91 ± 7.44 μV, SEM, n = 15, P = 0.048). This difference indicated that the cone pathways (cones and their postsynaptic cells) have a functional deficit. Similarly, when a flickering light was applied at a frequency incompatible with the slow dynamic of the rod photoreceptor light response, we found that amplitude of the 15 Hz flicker response was also reduced confirming a dysfunction in the cone pathway (GES group: 6.46 ± 1.89 μV, SEM, n = 8; control group: 11.61 ± 1.44 μV, SEM, n = 15, P = 0.045) (Fig. 3b, c, e). These measurements indicated that GES treatment and its consecutive taurine depletion induce retinal dysfunction of the cone pathway in adult mice.Fig. 3


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)

Retinal cell function in GES-treated mice. Electroretinogram (ERG) response of a 10 cds m−2 scotopic flash light stimulus recorded in a control animal, and in GES mouse (a). Response of a 25 cds m−2 photopic flash light stimulus recorded in a control animal, and in GES mouse (b). Photopic ERG response to a 15-Hz flickers light stimulus in a control animal, and in GES mouse (c). Oscillary Potentials (Ops) isolated in a control, and a GES mouse (d). Quantification of scotopic and photopic ERG amplitudes in controls (n = 15), and GES-treated animals showing the significant decrease in standard flash and flickers photopic ERG amplitudes. (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (e)
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Fig3: Retinal cell function in GES-treated mice. Electroretinogram (ERG) response of a 10 cds m−2 scotopic flash light stimulus recorded in a control animal, and in GES mouse (a). Response of a 25 cds m−2 photopic flash light stimulus recorded in a control animal, and in GES mouse (b). Photopic ERG response to a 15-Hz flickers light stimulus in a control animal, and in GES mouse (c). Oscillary Potentials (Ops) isolated in a control, and a GES mouse (d). Quantification of scotopic and photopic ERG amplitudes in controls (n = 15), and GES-treated animals showing the significant decrease in standard flash and flickers photopic ERG amplitudes. (SEM, n = 8, P < 0.05, asterisk denotes Student’s t test) (e)
Mentions: To determine whether the GES treatment and its consequent taurine plasma and retina level decrease induced retinal dysfunction, scotopic and photopic electroretinograms (ERGs) were performed on both treated and untreated animals. Scotopic ERG recordings were made in dark adapted animals (24 h of dark adaptation) with flashes of different light intensities (0.1, 1, 100, 1,000 and 10,000 mcds m−2). In these recordings, the first negative signal (a-wave) provides an in vivo measurement of rod photoreceptor light response dynamic whereas the consecutive positive signal (b-wave) is informative about the postsynaptic bipolar cells. Although cones can be activated at certain light intensities, these measurements are highly rod dominated. Mean a- (data not shown) and b-wave amplitudes of scotopic ERGs were always reduced in GES animals as compared with controls. However, the differences between the two groups were not statistically significant (t test, P > 0.05) (Fig. 3a, e). When oscillatory potentials informative of the third-order neurones, namely amacrine cells, were isolated with a more restrictive filtering of the ERG recordings, no significant difference could be detected (Fig. 3d, e). In contrast, when a background light was used to saturate rod photoreceptors, the response to an intense flash, the photopic ERG, showed a significant decrease in the GES group as compared with control mice (GES group: 97.61 ± 8.74 μV, SEM, n = 8; control group: 122.91 ± 7.44 μV, SEM, n = 15, P = 0.048). This difference indicated that the cone pathways (cones and their postsynaptic cells) have a functional deficit. Similarly, when a flickering light was applied at a frequency incompatible with the slow dynamic of the rod photoreceptor light response, we found that amplitude of the 15 Hz flicker response was also reduced confirming a dysfunction in the cone pathway (GES group: 6.46 ± 1.89 μV, SEM, n = 8; control group: 11.61 ± 1.44 μV, SEM, n = 15, P = 0.045) (Fig. 3b, c, e). These measurements indicated that GES treatment and its consecutive taurine depletion induce retinal dysfunction of the cone pathway in adult mice.Fig. 3

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