The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Michalis Averof - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the genetically tractable crustacean Parhyale hawaiensis reveals the organisation of a sensory system for low-resolution vision Analysis of the genetically tractable crustacean Parhyale hawaiensis reveals the organisation of a sensory sys
BMC Biology, 2019Co-Authors: Ana Patricia Ramos, Ola Gustafsson, Nicolas Labert, Iris Salecker, Dan-eric Nilsson, Michalis AverofAbstract:Background: Arthropod eyes have diversified during evolution to serve multiple needs, such as finding mates, hunting prey and navigating in complex surroundings under varying light conditions. This diversity is reflected in the optical apparatus, Photoreceptors and neural circuits that underpin vision. Yet our ability to genetically manipulate the visual system to investigate its function is largely limited to a single species, the fruit fly Drosophila melanogaster. Here, we describe the visual system of Parhyale hawaiensis, an amphipod crustacean for which we have established tailored genetic tools. Results: Adult Parhyale have apposition-type compound eyes made up of ~50 ommatidia. Each ommatidium contains four Photoreceptor cells with large rhabdomeres (R1–4), expected to be sensitive to the polarisation of light, and one Photoreceptor cell with a smaller rhabdomere (R5). The two types of Photoreceptors express different opsins, belonging to families with distinct wavelength sensitivities. Using the cis-regulatory regions of opsin genes, we established transgenic reporters expressed in each Photoreceptor cell type. Based on these reporters, we show that R1–4 and R5 Photoreceptors extend axons to the first optic lobe neuropil, revealing striking differences compared with the Photoreceptor projections found in related crustaceans and insects. Investigating visual function, we show that Parhyale have a positive phototactic response and are capable of adapting their eyes to different levels of light intensity. Conclusions: We propose that the visual system of Parhyale serves low-resolution visual tasks, such as orientation and navigation, based on broad gradients of light intensity and polarisation. Optic lobe structure and Photoreceptor projections point to significant divergence from the typical organisation found in other malacostracan crustaceans and insects, which could be associated with a shift to low-resolution vision. Our study provides the foundation for research in the visual system of this genetically tractable species.
Johann Helmut Brandstätter - One of the best experts on this subject based on the ideXlab platform.
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The presynaptic active zone protein bassoon is essential for Photoreceptor ribbon synapse formation in the retina
Neuron, 2003Co-Authors: Oliver Dick, Susanne Tom Dieck, Wilko D Altrock, Josef Ammermüller, Eckart D Gundelfinger, Craig C Garner, Johann Helmut BrandstätterAbstract:The Photoreceptor ribbon synapse is a highly specialized glutamatergic synapse designed for the continuous flow of synaptic vesicles to the neurotransmitter release site. The molecular mechanisms underlying ribbon synapse formation are poorly understood. We have investigated the role of the presynaptic cytomatrix protein Bassoon, a major component of the Photoreceptor ribbon, in a mouse retina deficient of functional Bassoon protein. Photoreceptor ribbons lacking Bassoon are not anchored to the presynaptic active zones. This results in an impaired Photoreceptor synaptic transmission, an abnormal dendritic branching of neurons postsynaptic to Photoreceptors, and the formation of ectopic synapses. These findings suggest a critical role of Bassoon in the formation and the function of Photoreceptor ribbon synapses of the mammalian retina.
Michael Housset - One of the best experts on this subject based on the ideXlab platform.
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loss of otx2 in the adult retina disrupts retinal pigment epithelium function causing Photoreceptor degeneration
The Journal of Neuroscience, 2013Co-Authors: Michael Housset, Alexander Samuel, Mohamed Ettaiche, Alexis A Bemelmans, Francis Beby, Nathalie BillonAbstract:Photoreceptors are specialized neurons of the retina that receive nursing from the adjacent retinal pigment epithelium (RPE). Frequent in the elderly, Photoreceptor loss can originate from primary dysfunction of either cell type. Despite intense interest in the etiology of these diseases, early molecular actors of late-onset Photoreceptor degeneration remain elusive, mostly because of the lack of dedicated models. Conditional Otx2 ablation in the adult mouse retina elicits Photoreceptor degeneration, providing a new model of late-onset neuronal disease. Here, we use this model to identify the earliest events after Otx2 ablation. Electroretinography and gene expression analyses suggest a nonautonomous, RPE-dependent origin for Photoreceptor degeneration. This is confirmed by RPE-specific ablation of Otx2, which results in similar Photoreceptor degeneration. In contrast, constitutive Otx2 expression in RPE cells prevents degeneration of Photoreceptors in Otx2-ablated retinas. We use chromatin immunoprecipitation followed by massive sequencing (ChIP-seq) analysis to identify the molecular network controlled in vivo by Otx2 in RPE cells. We uncover four RPE-specific functions coordinated by Otx2 that underpin the cognate Photoreceptor degeneration. Many direct Otx2 target genes are associated with human retinopathies, emphasizing the significance of the model. Importantly, we report a secondary genetic response after Otx2 ablation, which largely precedes apoptosis of Photoreceptors, involving inflammation and stress genes. These findings thus provide novel general markers for clinical detection and prevention of neuronal cell death.
Katie Binley - One of the best experts on this subject based on the ideXlab platform.
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EIAV-Based Retinal Gene Therapy in the shaker1 Mouse Model for Usher Syndrome Type 1B: Development of
2016Co-Authors: Marisa Zallocchi, Katie Binley, Scott Ellis, Peter Widdowson, S Iqball, Michelle Kelleher, Julie Loader, James Miskin, Yatish Lad, You Wei PengAbstract:Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or Photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on Photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (Photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating a-transducin translocation in Photoreceptors in response to low light intensity levels, and protection from light induced Photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and Photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse Photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in Photoreceptor cell loss, and restoration of the a-transducin translocation threshold in the Photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues Photoreceptor phenotypes in the shaker
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eiav based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1b development of ushstat
PLOS ONE, 2014Co-Authors: Marisa Zallocchi, Katie Binley, Scott Ellis, Peter Widdowson, S Iqball, Vicky Scripps, Michelle Kelleher, Julie Loader, James Miskin, You Wei PengAbstract:Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or Photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on Photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (Photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in Photoreceptors in response to low light intensity levels, and protection from light induced Photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and Photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse Photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in Photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the Photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues Photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.
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Development of Photoreceptor‐specific promoters and their utility to investigate EIAV lentiviral vector mediated gene transfer to Photoreceptors
The journal of gene medicine, 2007Co-Authors: Marjorie Nicoud, S Iqball, Peter Gouras, Jian Kong, O. Kan, Stuart Naylor, Rando Allikmets, Katie BinleyAbstract:We wanted to investigate the ability of recombinant equine infectious anemia virus (EIAV) vectors to transduce Photoreceptor cells by developing a series of Photoreceptor-specific promoters that drive strong gene expression in Photoreceptor cells. Promoter fragments derived from the rhodopsin (RHO), the beta phosphodiesterase (PDE) and the retinitis pigmentosa (RP1) genes were cloned in combination with an enhancer element, derived from the interPhotoreceptor retinoid-binding protein gene (IRBP), into luciferase reporter plasmids. An in vitro transient reporter assay was carried out in the human Y-79 retinoblastoma cell line. The optimal promoters from this screen were then cloned into the recombinant EIAV vector for evaluation in vivo following subretinal delivery into mice. All promoters maintained a Photoreceptor-specific expression profile in vitro and the gene expression was further enhanced in combination with the IRBP enhancer. The use of IRBP-combined RHO or PDE promoters showed modest but exclusive expression in Photoreceptors following subretinal delivery to mice. By contrast an EIAV vector containing the cytomegalovirus (CMV) promoter drove reporter gene expression in both Photoreceptors and retinal pigment epithelium. It may be possible to use recombinant EIAV vectors containing Photoreceptor-specific promoters to drive therapeutic gene expression to treat a range of retinal degenerative diseases where the Photoreceptor cell is the primary disease target.
You Wei Peng - One of the best experts on this subject based on the ideXlab platform.
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EIAV-Based Retinal Gene Therapy in the shaker1 Mouse Model for Usher Syndrome Type 1B: Development of
2016Co-Authors: Marisa Zallocchi, Katie Binley, Scott Ellis, Peter Widdowson, S Iqball, Michelle Kelleher, Julie Loader, James Miskin, Yatish Lad, You Wei PengAbstract:Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or Photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on Photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (Photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating a-transducin translocation in Photoreceptors in response to low light intensity levels, and protection from light induced Photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and Photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse Photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in Photoreceptor cell loss, and restoration of the a-transducin translocation threshold in the Photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues Photoreceptor phenotypes in the shaker
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eiav based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1b development of ushstat
PLOS ONE, 2014Co-Authors: Marisa Zallocchi, Katie Binley, Scott Ellis, Peter Widdowson, S Iqball, Vicky Scripps, Michelle Kelleher, Julie Loader, James Miskin, You Wei PengAbstract:Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or Photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on Photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (Photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in Photoreceptors in response to low light intensity levels, and protection from light induced Photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and Photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse Photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in Photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the Photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues Photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.
