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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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Autofluorescence in the retinal pigment epithelium (RPE). Autofluorescence at the RPE level was measured in four distinct areas on retinal sections along the dorso-ventral axis: dorso-peripheral (DP), dorso-central (DC), ventro-central (VC) and ventro-peripheral (VP). Dapi-labelled nuclei are shown in blue while grey levels correspond to the autoflorescence measured under a 556-nm excitation light. Scale bar represents 1 mm (a). Representative pictures of autofluorescence observed at the RPE level in one control and one GES-treated mouse in each area. Dapi-labelled nuclei correspond to choroid cells (C) and RPE cells (R). The corresponding autofluorescence measurement is represented on the graph at the right. Note the increase in autofluorescence observed in GES-treated animals at the RPE level. Horizontal axis corresponds to arbitrary units of autofluorescence and vertical axis corresponds to distance from RPE (μm). Scale bar represents 20 μm (b). Mean maximal values of autofluorescence at the RPE level according to retina area and treatment. Significant increase of autofluorescence in DP, DC and VP areas were found in GES mice (SEM, n = 8, P < 0.05, asterisk denotes Mann–Whitney test) (c)
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Fig5: Autofluorescence in the retinal pigment epithelium (RPE). Autofluorescence at the RPE level was measured in four distinct areas on retinal sections along the dorso-ventral axis: dorso-peripheral (DP), dorso-central (DC), ventro-central (VC) and ventro-peripheral (VP). Dapi-labelled nuclei are shown in blue while grey levels correspond to the autoflorescence measured under a 556-nm excitation light. Scale bar represents 1 mm (a). Representative pictures of autofluorescence observed at the RPE level in one control and one GES-treated mouse in each area. Dapi-labelled nuclei correspond to choroid cells (C) and RPE cells (R). The corresponding autofluorescence measurement is represented on the graph at the right. Note the increase in autofluorescence observed in GES-treated animals at the RPE level. Horizontal axis corresponds to arbitrary units of autofluorescence and vertical axis corresponds to distance from RPE (μm). Scale bar represents 20 μm (b). Mean maximal values of autofluorescence at the RPE level according to retina area and treatment. Significant increase of autofluorescence in DP, DC and VP areas were found in GES mice (SEM, n = 8, P < 0.05, asterisk denotes Mann–Whitney test) (c)

Mentions: Examination of eye fundi and angiographs were performed to look for macroscopic retinal changes, because this technique is classically used in clinical investigations to localize retinal lesions (Schmitz-Valckenberg et al. 2008). Fundi were normal in all animals. No cataract was present in the treated animals, which could have impaired the ERG recordings. No vascular damage was found on fluorescein angiographs in any animal. Interestingly, numerous peripheral autofluorescent round spots were observed in both groups. Surprisingly, their presence and number were decreased in GES-treated animals (Fig. 4a–d). To examine whether autofluorescence anomalies and retinal dysfunction were related to cellular damage, a histological examination on retinal sagittal sections was performed. Large fluorescent bodies were scattered throughout the retinal pigment epithelium in both GES-treated and control animals. The difference between the two groups appeared as an increase in the autofluorescence of the retinal pigment epithelium such that the fluorescent bodies offered less contrast in GES-treated mice (Fig. 4e–j). Furthermore, quantitative analysis of the retinal pigment epithelium in four distinct regions of the retina revealed that autofluorescence is not homogeneous along the retina (Fig. 5). In retinas of control and GES-treated mice, intensity was higher in the central region than in the periphery. The GES treatment greatly increased this autofluorescence at the periphery (seven to ninefold) and less in central areas (1.9- to 2-fold) (Fig. 5). This increase in autofluorescence was statistically significant in the dorso-peripheral area (GES group: 4.7 ± 1.9 AU, SEM, n = 8; control group: 0.5 ± 0.4 AU, SEM, n = 8, P = 0.029), the dorso-central area (GES group: 11.8 ± 1.3 AU, SEM, n = 8; control group: 5.9 ± 2.1 AU, SEM, n = 8, P = 0.04) and the ventro-peripheral area (GES group: 5.6 ± 1.5 AU, SEM, n = 8; control group: 0.8 ± 0.6 AU, SEM, n = 8, P = 0.029), but not in the ventro-central area (GES group: 9.9 ± 1.6 AU, SEM, n = 8; control group: 5.2 ± 2.4 AU, SEM, n = 8, P = 0.186).Fig. 4


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)

Autofluorescence in the retinal pigment epithelium (RPE). Autofluorescence at the RPE level was measured in four distinct areas on retinal sections along the dorso-ventral axis: dorso-peripheral (DP), dorso-central (DC), ventro-central (VC) and ventro-peripheral (VP). Dapi-labelled nuclei are shown in blue while grey levels correspond to the autoflorescence measured under a 556-nm excitation light. Scale bar represents 1 mm (a). Representative pictures of autofluorescence observed at the RPE level in one control and one GES-treated mouse in each area. Dapi-labelled nuclei correspond to choroid cells (C) and RPE cells (R). The corresponding autofluorescence measurement is represented on the graph at the right. Note the increase in autofluorescence observed in GES-treated animals at the RPE level. Horizontal axis corresponds to arbitrary units of autofluorescence and vertical axis corresponds to distance from RPE (μm). Scale bar represents 20 μm (b). Mean maximal values of autofluorescence at the RPE level according to retina area and treatment. Significant increase of autofluorescence in DP, DC and VP areas were found in GES mice (SEM, n = 8, P < 0.05, asterisk denotes Mann–Whitney test) (c)
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Fig5: Autofluorescence in the retinal pigment epithelium (RPE). Autofluorescence at the RPE level was measured in four distinct areas on retinal sections along the dorso-ventral axis: dorso-peripheral (DP), dorso-central (DC), ventro-central (VC) and ventro-peripheral (VP). Dapi-labelled nuclei are shown in blue while grey levels correspond to the autoflorescence measured under a 556-nm excitation light. Scale bar represents 1 mm (a). Representative pictures of autofluorescence observed at the RPE level in one control and one GES-treated mouse in each area. Dapi-labelled nuclei correspond to choroid cells (C) and RPE cells (R). The corresponding autofluorescence measurement is represented on the graph at the right. Note the increase in autofluorescence observed in GES-treated animals at the RPE level. Horizontal axis corresponds to arbitrary units of autofluorescence and vertical axis corresponds to distance from RPE (μm). Scale bar represents 20 μm (b). Mean maximal values of autofluorescence at the RPE level according to retina area and treatment. Significant increase of autofluorescence in DP, DC and VP areas were found in GES mice (SEM, n = 8, P < 0.05, asterisk denotes Mann–Whitney test) (c)
Mentions: Examination of eye fundi and angiographs were performed to look for macroscopic retinal changes, because this technique is classically used in clinical investigations to localize retinal lesions (Schmitz-Valckenberg et al. 2008). Fundi were normal in all animals. No cataract was present in the treated animals, which could have impaired the ERG recordings. No vascular damage was found on fluorescein angiographs in any animal. Interestingly, numerous peripheral autofluorescent round spots were observed in both groups. Surprisingly, their presence and number were decreased in GES-treated animals (Fig. 4a–d). To examine whether autofluorescence anomalies and retinal dysfunction were related to cellular damage, a histological examination on retinal sagittal sections was performed. Large fluorescent bodies were scattered throughout the retinal pigment epithelium in both GES-treated and control animals. The difference between the two groups appeared as an increase in the autofluorescence of the retinal pigment epithelium such that the fluorescent bodies offered less contrast in GES-treated mice (Fig. 4e–j). Furthermore, quantitative analysis of the retinal pigment epithelium in four distinct regions of the retina revealed that autofluorescence is not homogeneous along the retina (Fig. 5). In retinas of control and GES-treated mice, intensity was higher in the central region than in the periphery. The GES treatment greatly increased this autofluorescence at the periphery (seven to ninefold) and less in central areas (1.9- to 2-fold) (Fig. 5). This increase in autofluorescence was statistically significant in the dorso-peripheral area (GES group: 4.7 ± 1.9 AU, SEM, n = 8; control group: 0.5 ± 0.4 AU, SEM, n = 8, P = 0.029), the dorso-central area (GES group: 11.8 ± 1.3 AU, SEM, n = 8; control group: 5.9 ± 2.1 AU, SEM, n = 8, P = 0.04) and the ventro-peripheral area (GES group: 5.6 ± 1.5 AU, SEM, n = 8; control group: 0.8 ± 0.6 AU, SEM, n = 8, P = 0.029), but not in the ventro-central area (GES group: 9.9 ± 1.6 AU, SEM, n = 8; control group: 5.2 ± 2.4 AU, SEM, n = 8, P = 0.186).Fig. 4

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