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Stéphane Fouquet - One of the best experts on this subject based on the ideXlab platform.
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Phototoxic damage to Cone Photoreceptors can be independent of the visual pigment: the porphyrin hypothesis
Cell Death and Disease, 2020Co-Authors: Mélanie Marie, Valérie Forster, Stéphane Fouquet, Josealain Sahel, Pascal Berto, Coralie Barrau, Camille Ehrismann, Gilles Tessier, Serge PicaudAbstract:Lighting is rapidly changing with the introduction of light-emitting diodes (LEDs) in our homes, workplaces, and cities. This evolution of our optical landscape raises major concerns regarding phototoxicity to the retina since light exposure is an identified risk factor for the development of age-related macular degeneration (AMD). In this disease, Cone Photoreceptors degenerate while the retinal pigment epithelium (RPE) is accumulating lipofuscin containing phototoxic compounds such as A2E. Therefore, it remains unclear if the light-elicited degenerative process is initiated in Cones or in the RPE. Using purified Cone Photoreceptors from pig retina, we here investigated the effect of light on Cone survival from 390 to 510 nm in 10 nm steps, plus the 630 nm band. If at a given intensity (0.2 mW/cm²), the most toxic wavelengths are comprised in the visible-to-near-UV range, they shift to blue-violet light (425-445 nm) when exposing cells to a solar source filtered by the eye optics. In contrast to previous rodent studies, this Cone photoreceptor phototoxicity is not related to light absorption by the visual pigment. Despite bright flavin autofluorescence of Cone inner segment, excitation-emission matrix of this inner segment suggested that Cone phototoxicity was instead caused by porphyrin. Toxic light intensities were lower than those previously defined for A2E-loaded RPE cells indicating Cones are the first cells at risk for a direct light insult. These results are essential to normative regulations of new lighting but also for the prevention of human retinal pathologies since toxic solar light intensities are encountered even at high latitudes.
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Taurine deficiency damages retinal neurones: Cone Photoreceptors and retinal ganglion cells
Amino Acids, 2012Co-Authors: David Gaucher, Emilie Arnault, Zoé Husson, Nicolas Froger, Elisabeth Dubus, Pauline Gondouin, Diane Dherbecourt, Julie Degardin, Manuel Simonutti, Stéphane FouquetAbstract: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.
Christoph K. Hitzenberger - One of the best experts on this subject based on the ideXlab platform.
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temporal changes of human Cone Photoreceptors observed in vivo with slo oct
Biomedical Optics Express, 2011Co-Authors: Michael Pircher, Julia-sophie Kroisamer, Franz Felberer, Harald Sattmann, Erich Götzinger, Christoph K. HitzenbergerAbstract:In this study we use our previously introduced scanning laser ophthalmoscope (SLO) / transverse scanning optical coherence tomography (TS-OCT) instrument to investigate long term changes in Cone Photoreceptors. The instrument is capable to provide 3D information of the human Cone Photoreceptors with negligible eye motion artifacts due to an implemented 3D motion correction on a cellular level. This allows for an in vivo investigation of exactly the same location on the retina with cellular resolution over several days. Temporal changes in the backscattered intensity are observed and quantified within the junction between inner and outer segments of Cone Photoreceptors, the Cone outer segments, the end tips of Cone Photoreceptors and the retinal pigment epithelium. Furthermore, the length of individual Cone outer segments is measured and observed over time. We show, to the best of our knowledge for the first time, that bright reflection spots which are located within the outer segment of Cone Photoreceptors change their position when observed over extended time periods. The average measured bright reflection spot motion speed corresponds well to the expected Cone growth speed. We believe that this observation can be associated with the first direct in vivo imaging of the Cone renewal process.
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Temporal changes of human Cone Photoreceptors observed in vivo with SLO/OCT
Biomedical optics express, 2010Co-Authors: Michael Pircher, Julia-sophie Kroisamer, Franz Felberer, Harald Sattmann, Erich Götzinger, Christoph K. HitzenbergerAbstract:In this study we use our previously introduced scanning laser ophthalmoscope (SLO) / transverse scanning optical coherence tomography (TS-OCT) instrument to investigate long term changes in Cone Photoreceptors. The instrument is capable to provide 3D information of the human Cone Photoreceptors with negligible eye motion artifacts due to an implemented 3D motion correction on a cellular level. This allows for an in vivo investigation of exactly the same location on the retina with cellular resolution over several days. Temporal changes in the backscattered intensity are observed and quantified within the junction between inner and outer segments of Cone Photoreceptors, the Cone outer segments, the end tips of Cone Photoreceptors and the retinal pigment epithelium. Furthermore, the length of individual Cone outer segments is measured and observed over time. We show, to the best of our knowledge for the first time, that bright reflection spots which are located within the outer segment of Cone Photoreceptors change their position when observed over extended time periods. The average measured bright reflection spot motion speed corresponds well to the expected Cone growth speed. We believe that this observation can be associated with the first direct in vivo imaging of the Cone renewal process.
Cheryl M Craft - One of the best experts on this subject based on the ideXlab platform.
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Transgenic mice expressing Cre-recombinase specifically in M- or S-Cone Photoreceptors
Investigative ophthalmology & visual science, 2004Co-Authors: Masayuki Akimoto, Cheryl M Craft, E. Filippova, Philip J. Gage, Xuemei Zhu, Anand SwaroopAbstract:Purpose To establish lines of transgenic mice that express Cre-recombinase in M- or S-Cone Photoreceptors for generating Cone photoreceptor-specific (conditional) mutants. Methods Five kilobases of 5' upstream sequence of the mouse red-green (M) opsin gene or 0.5 kb of the mouse blue (S) opsin gene was cloned into a Cre-expression plasmid. Transgenic mice were generated and characterized, and appropriate lines were established. The Cre-transgenic mice were crossed with ROSA26-lacZ mice (containing floxed beta-galactosidase gene) and analyzed to determine Cre-recombinase activity. Results Immunofluorescence study showed successful targeting of Cre-recombinase expression to Cone Photoreceptors. Double staining with anti-Cre antibody and anti-M- or anti-S-opsin antibody revealed specificity of Cre expression in M-opsin- and/or S-opsin-positive Photoreceptors. Mating with ROSA26-lacZ mice demonstrated that Cre-recombinase was functionally active in M- or S-Cones. Conclusions Lines of transgenic mice that specifically express functional Cre-recombinase in M- or S-Cones were established in this study. Because mutations in several widely expressed genes lead to photoreceptor degeneration, these transgenic mice should be valuable in generating conditional mutants to investigate the function of various genes specifically in Cone Photoreceptors.
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Mouse Cone arrestin expression pattern: light induced translocation in Cone Photoreceptors.
Molecular Vision, 2002Co-Authors: Aimin Li, Bruce M. Brown, Shoji Osawa, Ellen R. Weiss, Cheryl M CraftAbstract:Abstract Arrestins are a superfamily of regulatory proteins that down-regulate activated and phosphorylated G-protein coupled receptors (GPCRs). Cone arrestin (CAR) is expressed in Cone Photoreceptors and pinealocytes and may contribute to the shutoff mechanisms associtated with high acuity color vision. To initiate a study of CAR's function in Cone phototransduction, the mouse CAR (mCAR) transcript and protein expression patterns are examined and in vitro binding assays are also presented. Tissue distribution of mCAR was determined by Northern and immunoblot analyses and its cellular localization identified by In situ hybridization and immunohistochemistry. The protein expression pattern of mCAR in the postnatal developmental and adult mouse retina was analyzed by immunoblotting in normal C57 and rd/rd mouse retinas. In vitro binding assays with in vitro translated arrestins were used to study the interaction of mCAR and mouse S-antigen (mSAG) with embryonic chicken outer segment (OS) membranes containing both rod and Cone opsins. MCAR has a high level of amino acid sequence identity with orthologous sequences reported for other species except the C-terminal region, which is highly conserved between mouse and rat but divergent in other species. MCAR is expressed exclusively in the retina and the pineal gland, and unique isoforms are expressed during postnatal development of the retina and the pineal gland. The postnatal developmental expression pattern of mCAR and mSAG in the rd/rd mouse retina parallels the generation and degeneration of the Cone and rod Photoreceptors in these mice. In situ and immunohistochemistry both reveal Cone-specific expression of mCAR in the retina. Immunofluorescent staining of retinal sections from dark-adapted or light-exposed mice suggests a light-dependent translocation of mCAR immunoreactivity from the Cone inner segments (CIS) and other parts of the cell body to the Cone outer segments (COS), similar to but not as dramatic as rod arrestin. In vitro binding assays show a small yet significant increase in binding of the full-length mCAR (mCARFL) to embryonic chicken OS membranes following light activation and phosphorylation of the opsins in the membranes. MCAR is expressed in retinal Cone Photoreceptors and the pineal gland. The light-dependent translocation of mCAR immunoreactivity and the increase of mCAR binding to light-activated, phosphorylated embryonic chicken OS membranes, compared to its binding to dark, unphosphorylated membranes, suggest the possibility that mCAR is involved in shutting off the phototransduction cascade in Cone Photoreceptors as rod arrestin does in rod Photoreceptors. However, prominent differences exist between rod arrestin and CAR, suggesting other functions for CAR.
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mouse Cone arrestin expression pattern light induced translocation in Cone Photoreceptors
Molecular Vision, 2002Co-Authors: Xuemei Zhu, Bruce M. Brown, Shoji Osawa, Ellen R. Weiss, Cheryl M CraftAbstract:PURPOSE Arrestins are a superfamily of regulatory proteins that down-regulate activated and phosphorylated G-protein coupled receptors (GPCRs). Cone arrestin (CAR) is expressed in Cone Photoreceptors and pinealocytes and may contribute to the shutoff mechanisms associtated with high acuity color vision. To initiate a study of CAR's function in Cone phototransduction, the mouse CAR (mCAR) transcript and protein expression patterns are examined and in vitro binding assays are also presented. METHODS Tissue distribution of mCAR was determined by Northern and immunoblot analyses and its cellular localization identified by In situ hybridization and immunohistochemistry. The protein expression pattern of mCAR in the postnatal developmental and adult mouse retina was analyzed by immunoblotting in normal C57 and rd/rd mouse retinas. In vitro binding assays with in vitro translated arrestins were used to study the interaction of mCAR and mouse S-antigen (mSAG) with embryonic chicken outer segment (OS) membranes containing both rod and Cone opsins. RESULTS MCAR has a high level of amino acid sequence identity with orthologous sequences reported for other species except the C-terminal region, which is highly conserved between mouse and rat but divergent in other species. MCAR is expressed exclusively in the retina and the pineal gland, and unique isoforms are expressed during postnatal development of the retina and the pineal gland. The postnatal developmental expression pattern of mCAR and mSAG in the rd/rd mouse retina parallels the generation and degeneration of the Cone and rod Photoreceptors in these mice. In situ and immunohistochemistry both reveal Cone-specific expression of mCAR in the retina. Immunofluorescent staining of retinal sections from dark-adapted or light-exposed mice suggests a light-dependent translocation of mCAR immunoreactivity from the Cone inner segments (CIS) and other parts of the cell body to the Cone outer segments (COS), similar to but not as dramatic as rod arrestin. In vitro binding assays show a small yet significant increase in binding of the full-length mCAR (mCARFL) to embryonic chicken OS membranes following light activation and phosphorylation of the opsins in the membranes. CONCLUSIONS MCAR is expressed in retinal Cone Photoreceptors and the pineal gland. The light-dependent translocation of mCAR immunoreactivity and the increase of mCAR binding to light-activated, phosphorylated embryonic chicken OS membranes, compared to its binding to dark, unphosphorylated membranes, suggest the possibility that mCAR is involved in shutting off the phototransduction cascade in Cone Photoreceptors as rod arrestin does in rod Photoreceptors. However, prominent differences exist between rod arrestin and CAR, suggesting other functions for CAR.
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Mouse Cone arrestin gene characterization: promoter targets expression to Cone Photoreceptors.
FEBS letters, 2002Co-Authors: Bo Ma, Sudha Babu, Jaji Murage, Barry E Knox, Cheryl M CraftAbstract:Cone arrestin (CAR) is a novel member of the arrestin superfamily expressed in retinal Cone Photoreceptors and the pineal gland. To understand the regulatory mechanisms controlling its Cone- and pineal-specific expression, and to facilitate further functional studies using gene knockout approaches, we characterized the genomic organization and the 5'-flanking region of the mouse CAR (mCAR) gene. The mCAR gene is comprised of 17 exons and 16 introns, encoding five alternatively spliced transcripts. A 215-bp proximal promoter fragment containing a TATA box, an Sp1 site and four Cone-rod homeobox-binding sites is sufficient to direct expression in cultured retinoblastoma cells and in Cone Photoreceptors and the pineal gland in transgenic Xenopus laevis.
Xincheng Yao - One of the best experts on this subject based on the ideXlab platform.
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functional optical coherence tomography enables in vivo physiological assessment of retinal rod and Cone Photoreceptors
Scientific Reports, 2015Co-Authors: Qiuxiang Zhang, Benquan Wang, Jeffrey D Messinger, Christine A Curcio, Xincheng YaoAbstract:Transient intrinsic optical signal (IOS) changes have been observed in retinal Photoreceptors, suggesting a unique biomarker for eye disease detection. However, clinical deployment of IOS imaging is challenging due to unclear IOS sources and limited signal-to-noise ratios (SNRs). Here, by developing high spatiotemporal resolution optical coherence tomography (OCT) and applying an adaptive algorithm for IOS processing, we were able to record robust IOSs from single-pass measurements. Transient IOSs, which might reflect an early stage of light phototransduction, are consistently observed in the photoreceptor outer segment almost immediately (<4 ms) after retinal stimulation. Comparative studies of dark- and light-adapted retinas have demonstrated the feasibility of functional OCT mapping of rod and Cone Photoreceptors, promising a new method for early disease detection and improved treatment of diseases such as age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage.
Serge Picaud - One of the best experts on this subject based on the ideXlab platform.
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Phototoxic damage to Cone Photoreceptors can be independent of the visual pigment: the porphyrin hypothesis
Cell Death and Disease, 2020Co-Authors: Mélanie Marie, Valérie Forster, Stéphane Fouquet, Josealain Sahel, Pascal Berto, Coralie Barrau, Camille Ehrismann, Gilles Tessier, Serge PicaudAbstract:Lighting is rapidly changing with the introduction of light-emitting diodes (LEDs) in our homes, workplaces, and cities. This evolution of our optical landscape raises major concerns regarding phototoxicity to the retina since light exposure is an identified risk factor for the development of age-related macular degeneration (AMD). In this disease, Cone Photoreceptors degenerate while the retinal pigment epithelium (RPE) is accumulating lipofuscin containing phototoxic compounds such as A2E. Therefore, it remains unclear if the light-elicited degenerative process is initiated in Cones or in the RPE. Using purified Cone Photoreceptors from pig retina, we here investigated the effect of light on Cone survival from 390 to 510 nm in 10 nm steps, plus the 630 nm band. If at a given intensity (0.2 mW/cm²), the most toxic wavelengths are comprised in the visible-to-near-UV range, they shift to blue-violet light (425-445 nm) when exposing cells to a solar source filtered by the eye optics. In contrast to previous rodent studies, this Cone photoreceptor phototoxicity is not related to light absorption by the visual pigment. Despite bright flavin autofluorescence of Cone inner segment, excitation-emission matrix of this inner segment suggested that Cone phototoxicity was instead caused by porphyrin. Toxic light intensities were lower than those previously defined for A2E-loaded RPE cells indicating Cones are the first cells at risk for a direct light insult. These results are essential to normative regulations of new lighting but also for the prevention of human retinal pathologies since toxic solar light intensities are encountered even at high latitudes.
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functional rescue of Cone Photoreceptors in retinitis pigmentosa
Graefes Archive for Clinical and Experimental Ophthalmology, 2013Co-Authors: Josealain Sahel, Serge Picaud, Thierry Leveillard, Deniz Dalkara, Katia Marazova, Avinoam B SafranAbstract:In the highly intricate retinal functional anatomy, connectivity and information processing, the photoreceptor cells play a crucial role. In most simple terms, the Photoreceptors rods and Cones detect the light and transduce it to the brain as electrical signals through a sophisticated network of neurons. Pathologies that affect the photoreceptor structure and function result in impaired vision. Photoreceptor degeneration due to gene mutations causes a large number of blinding disorders known as inherited retinal dystrophies (IRDs). IRDs affect approximately one in every 3,000 individuals and represent the most frequent inherited forms of human visual handicap [1]. Retinitis pigmentosa (RP), a genetic disease that features degeneration of both rod and Cone Photoreceptors is the most commonly inherited retinal degeneration, affecting approximately 1.5 million people worldwide [2]. Currently, there is no known effective treatment that can prevent or reverse the vision loss in RP.
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Postsynaptic response kinetics are controlled by a glutamate transporter at Cone Photoreceptors.
Journal of neurophysiology, 1998Co-Authors: Lubor Gaal, Robert E. Marc, Botond Roska, Serge Picaud, Frank S. WerblinAbstract:Gaal, Lubor, Botond Roska, Serge A. Picaud, Samuel M. Wu, Robert Marc, and Frank S. Werblin. Postsynaptic response kinetics are controlled by a glutamate transporter at Cone Photoreceptors. J. Neur...