The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Dongsheng Duan - One of the best experts on this subject based on the ideXlab platform.
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adeno associated virus serotype 9 mediated retinal Outer Plexiform Layer transduction is mainly through the photoreceptors
Advances in Experimental Medicine and Biology, 2010Co-Authors: Keqing Zhang, Arkasubhra Ghosh, Dongsheng DuanAbstract:Due to its high ocular transduction, low immune clearance and capability to bypass the brain blood barrier, adeno-associated virus-9 (AAV9) has been regarded as a promising vector for retinal disease gene therapy. We recently demonstrated that AAV9 efficiently transduces the retinal Outer Plexiform Layer (OPL). The OPL consists of synapses formed between axons of the rod and cone photoreceptors (cell bodies in the Outer nuclear Layer, ONL) and dendrites of bipolar and horizontal cells (cell bodies in the inner nuclear Layer, INL). It is not clear whether AAV9 transduces the OPL through the photoreceptors in the ONL or through bipolar and horizontal cells in the INL. To map the subcelluar pathway(s) involved in AAV9-mediated OPL transduction, we delivered subretinally AAV9.CMV.eGFP, an AAV vector carrying the enhanced green fluorescent protein gene (eGFP, 1 × 1010 viral genome particles in microliter), to young (21-day-old) and adult (2- to 3-month-old) C57BL/6 mice. Four weeks after subretinal injection, eGFP expression was examined on retinal cryosections. PSD95 (postsynaptic density protein, a marker for photoreceptor terminals), CtBP2 (C-terminal binding protein 2, a marker for the photoreceptor synaptic ribbon), PKCalpha (protein kinase Cα, a marker for rod bipolar cells), and calbindin (a marker for horizontal cells) were localized by immunofluorescence staining. In AAV9 infected retina, eGFP expression was seen in the retinal pigment epithelia, photoreceptor inner segments, ONL, OPL, Muller cells in the INL, inner Plexiform Layer and ganglion cell Layer. Interestingly, eGFP expression co-localized with PSD95 and CtBP2, but not with PKCalpha and calbindin. Our results suggest that AAV9 transduces the photoreceptor side of the synapses in the OPL rather than the dendrites of bipolar and horizontal cells.
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adeno associated virus serotype 9 efficiently transduces the retinal Outer Plexiform Layer
Molecular Vision, 2009Co-Authors: Keqing Zhang, Arkasubhra Ghosh, Dongsheng DuanAbstract:Purpose Adeno-associated virus serotype-9 (AAV-9) is a promising gene delivery vector. In this study, we evaluated AAV-9 transduction in the mouse retina.
Keqing Zhang - One of the best experts on this subject based on the ideXlab platform.
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adeno associated virus serotype 9 mediated retinal Outer Plexiform Layer transduction is mainly through the photoreceptors
Advances in Experimental Medicine and Biology, 2010Co-Authors: Keqing Zhang, Arkasubhra Ghosh, Dongsheng DuanAbstract:Due to its high ocular transduction, low immune clearance and capability to bypass the brain blood barrier, adeno-associated virus-9 (AAV9) has been regarded as a promising vector for retinal disease gene therapy. We recently demonstrated that AAV9 efficiently transduces the retinal Outer Plexiform Layer (OPL). The OPL consists of synapses formed between axons of the rod and cone photoreceptors (cell bodies in the Outer nuclear Layer, ONL) and dendrites of bipolar and horizontal cells (cell bodies in the inner nuclear Layer, INL). It is not clear whether AAV9 transduces the OPL through the photoreceptors in the ONL or through bipolar and horizontal cells in the INL. To map the subcelluar pathway(s) involved in AAV9-mediated OPL transduction, we delivered subretinally AAV9.CMV.eGFP, an AAV vector carrying the enhanced green fluorescent protein gene (eGFP, 1 × 1010 viral genome particles in microliter), to young (21-day-old) and adult (2- to 3-month-old) C57BL/6 mice. Four weeks after subretinal injection, eGFP expression was examined on retinal cryosections. PSD95 (postsynaptic density protein, a marker for photoreceptor terminals), CtBP2 (C-terminal binding protein 2, a marker for the photoreceptor synaptic ribbon), PKCalpha (protein kinase Cα, a marker for rod bipolar cells), and calbindin (a marker for horizontal cells) were localized by immunofluorescence staining. In AAV9 infected retina, eGFP expression was seen in the retinal pigment epithelia, photoreceptor inner segments, ONL, OPL, Muller cells in the INL, inner Plexiform Layer and ganglion cell Layer. Interestingly, eGFP expression co-localized with PSD95 and CtBP2, but not with PKCalpha and calbindin. Our results suggest that AAV9 transduces the photoreceptor side of the synapses in the OPL rather than the dendrites of bipolar and horizontal cells.
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adeno associated virus serotype 9 efficiently transduces the retinal Outer Plexiform Layer
Molecular Vision, 2009Co-Authors: Keqing Zhang, Arkasubhra Ghosh, Dongsheng DuanAbstract:Purpose Adeno-associated virus serotype-9 (AAV-9) is a promising gene delivery vector. In this study, we evaluated AAV-9 transduction in the mouse retina.
Srinivas R Sadda - One of the best experts on this subject based on the ideXlab platform.
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ATYPICAL PERIPAPILLARY INNER RETINOSCHISIS IN STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS.
Retinal Cases & Brief Reports, 2017Co-Authors: Michael Javaheri, Srinivas R SaddaAbstract:PURPOSE: To describe an atypical presentation of a patient with stellate nonhereditary idiopathic foveomacular retinoschisis with peripapillary retinoschisis of multiple Layers. METHODS: Complete ophthalmic examination including dilated extended ophthalmoscopy, fluorescein angiography, optical coherence tomography, optical coherence tomography angiography, and wide-field fundus photography. RESULTS: A 36-year-old Chinese American woman with mild myopia and good visual acuity (20/20) exhibited macular splitting of the Outer Plexiform Layer on spectral domain optical coherence tomography with an attached hyaloid in her left eye. Peripheral spectral domain optical coherence tomography also demonstrated peripapillary and midperipheral inner retinoschisis, involving the Outer Plexiform Layer and inner retina. The right eye was unremarkable. The diagnosis of stellate nonhereditary idiopathic foveomacular retinoschisis was made because of a lack of other associated ocular conditions and no family history of retinoschisis. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis is a recently described and uncommon cause of foveomacular retinoschisis in myopic women with good visual acuity. Recent evidence suggests that peripheral imaging is key in identifying other findings, including midperipheral or peripapillary inner retinoschisis, involving the Outer Plexiform Layer and the inner retina. Our patient may represent a variant of stellate nonhereditary idiopathic foveomacular retinoschisis that can be characterized by multiLayer peripapillary retinoschisis.
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different phenotypes of the appearance of the Outer Plexiform Layer on optical coherence tomography
Graefes Archive for Clinical and Experimental Ophthalmology, 2013Co-Authors: Yanling Ouyang, Alexander C Walsh, Pearse A Keane, Florian M Heussen, Rajeev R Pappuru, Srinivas R SaddaAbstract:Purpose To present a selected case series of different phenotypes of the normal Outer Plexiform Layer (OPL) visualized by optical coherence tomography (OCT).
Arkasubhra Ghosh - One of the best experts on this subject based on the ideXlab platform.
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adeno associated virus serotype 9 mediated retinal Outer Plexiform Layer transduction is mainly through the photoreceptors
Advances in Experimental Medicine and Biology, 2010Co-Authors: Keqing Zhang, Arkasubhra Ghosh, Dongsheng DuanAbstract:Due to its high ocular transduction, low immune clearance and capability to bypass the brain blood barrier, adeno-associated virus-9 (AAV9) has been regarded as a promising vector for retinal disease gene therapy. We recently demonstrated that AAV9 efficiently transduces the retinal Outer Plexiform Layer (OPL). The OPL consists of synapses formed between axons of the rod and cone photoreceptors (cell bodies in the Outer nuclear Layer, ONL) and dendrites of bipolar and horizontal cells (cell bodies in the inner nuclear Layer, INL). It is not clear whether AAV9 transduces the OPL through the photoreceptors in the ONL or through bipolar and horizontal cells in the INL. To map the subcelluar pathway(s) involved in AAV9-mediated OPL transduction, we delivered subretinally AAV9.CMV.eGFP, an AAV vector carrying the enhanced green fluorescent protein gene (eGFP, 1 × 1010 viral genome particles in microliter), to young (21-day-old) and adult (2- to 3-month-old) C57BL/6 mice. Four weeks after subretinal injection, eGFP expression was examined on retinal cryosections. PSD95 (postsynaptic density protein, a marker for photoreceptor terminals), CtBP2 (C-terminal binding protein 2, a marker for the photoreceptor synaptic ribbon), PKCalpha (protein kinase Cα, a marker for rod bipolar cells), and calbindin (a marker for horizontal cells) were localized by immunofluorescence staining. In AAV9 infected retina, eGFP expression was seen in the retinal pigment epithelia, photoreceptor inner segments, ONL, OPL, Muller cells in the INL, inner Plexiform Layer and ganglion cell Layer. Interestingly, eGFP expression co-localized with PSD95 and CtBP2, but not with PKCalpha and calbindin. Our results suggest that AAV9 transduces the photoreceptor side of the synapses in the OPL rather than the dendrites of bipolar and horizontal cells.
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adeno associated virus serotype 9 efficiently transduces the retinal Outer Plexiform Layer
Molecular Vision, 2009Co-Authors: Keqing Zhang, Arkasubhra Ghosh, Dongsheng DuanAbstract:Purpose Adeno-associated virus serotype-9 (AAV-9) is a promising gene delivery vector. In this study, we evaluated AAV-9 transduction in the mouse retina.
Stephen Yazulla - One of the best experts on this subject based on the ideXlab platform.
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ultrastructural analysis of the glutamatergic system in the Outer Plexiform Layer of zebrafish retina
Journal of Chemical Neuroanatomy, 2009Co-Authors: Jan Klooster, Maarten Kamermans, Stephen YazullaAbstract:Abstract l -Glutamate, the photoreceptor neurotransmitter, depolarizes horizontal cells and OFF-bipolar cells by ionotropic receptors and hyperpolarizes ON-bipolar cells by metabotropic receptors. Despite extensive light microscopy on the distribution of glutamate receptors in zebrafish retina, there are little ultrastructural data. Given the importance of zebrafish in studies on the genetic manipulation of retinal development and function, precise data on the synaptic neurochemical organization of the zebrafish retina is needed. Immunohistochemical techniques were used to determine the ultrastructural localization of glutamate receptor subunits GluR2, GluR4, NMDA2B (NR2B) and mGluR1α in zebrafish Outer Plexiform Layer (OPL). These antibodies were chosen because of an apparent conservation of localization of GluR2, GluR4 and mGluR1α in the vertebrate OPL, while there is some support for NMDA receptors in the OPL. GluR2-immunoreactivity (IR) was in all horizontal cell dendrites that invaginated cone pedicles and rod spherules. Three arrangements of dendrites contained GluR-IR in rod spherules: classical-type with GluR2-IR on lateral horizontal cell dendrites, a butterfly-shaped horizontal cell dendrite, and a goblet-shaped dendrite, likely of bipolar cell origin. GluR4-IR was restricted to dendrites of OFF-bipolar cells that innervated rod and cone terminals. NR2B-IR was restricted to a subtype of cone ON-bipolar cell. mGluR1α-IR was restricted to ON mixed rod/cone (Mb) bipolar cells whose dendrites innervated rod and cone synaptic terminals. The presence of mGluR1α on Mb bipolar cell dendrites is consistent with a role in retrograde endocannabinoid suppression. The subunit composition of glutamate receptors should affect the kinetics and pharmacology of these cells to glutamate receptor activation.
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postsynaptic localization of gamma aminobutyric acid transporters and receptors in the Outer Plexiform Layer of the goldfish retina an ultrastructural study
The Journal of Comparative Neurology, 2004Co-Authors: Jan Klooster, Stephen Yazulla, Bob Nunes Cardozo, Maarten KamermansAbstract:The γ-aminobutyric acid (GABA)-ergic system in the Outer Plexiform Layer (OPL) of the goldfish retina was studied via light and electron immunohistochemistry. The subcellular distributions of immunoreactivity (-IR) of plasma membrane GABA transporters GAT2 and GAT3, the α1 and α3 subunits of the ionotropic GABAA receptor, and the ρ1 subunit of the ionotropic GABAC receptor were determined. The localization of the GAT2-IR and GAT3-IR to horizontal cell dendrites at the base of the cone synaptic complex was the main characteristic at the ultrastructural level. Very rarely, GAT2-IR and GAT3-IR were found in horizontal cell dendrites innervating rod spherules. α1-IR and α3-IR were seen in wide bands in the OPL, whereas ρ1-IR appeared as a narrow band in the OPL. Most α1-IR was intracellular in rod and cone terminals. Membrane-associated α1-IR was observed in cone pedicles but not in rod spherules; postsynaptic elements were also labeled. α3-IR was concentrated in the lateral elements of horizontal cell dendrites in cone pedicles. In contrast, ρ1-IR was found mainly on the spinules of the horizontal cell dendrites in cone pedicles. In addition, in another type of cone pedicle, ρ1-IR was found at the position of OFF-bipolar cell dendrites. α3-IR and ρ1-IR were rarely found in horizontal cell dendrites innervating rods. We suggest that two GABAergic pathways exist in the Outer retina— first, a GABAergic positive loop with GABA receptors mainly on the horizontal cell dendrites and spinules and, second, a GABAergic feedback pathway involving GABA receptors on cone pedicles and GABA transporters on horizontal cells and that this pathway presumably modulates feedback strength from horizontal cells to cones. J. Comp. Neurol. 474:58–74, 2004. © 2004 Wiley-Liss, Inc.
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Postsynaptic localization of gamma-aminobutyric acid transporters and receptors in the Outer Plexiform Layer of the goldfish retina: An ultrastructural study.
The Journal of Comparative Neurology, 2004Co-Authors: Jan Klooster, Stephen Yazulla, Bob Nunes Cardozo, Maarten KamermansAbstract:The gamma-aminobutyric acid (GABA)-ergic system in the Outer Plexiform Layer (OPL) of the goldfish retina was studied via light and electron immunohistochemistry. The subcellular distributions of immunoreactivity (-IR) of plasma membrane GABA transporters GAT2 and GAT3, the alpha1 and alpha3 subunits of the ionotropic GABA(A) receptor, and the rho1 subunit of the ionotropic GABA(C) receptor were determined. The localization of the GAT2-IR and GAT3-IR to horizontal cell dendrites at the base of the cone synaptic complex was the main characteristic at the ultrastructural level. Very rarely, GAT2-IR and GAT3-IR were found in horizontal cell dendrites innervating rod spherules. alpha1-IR and alpha3-IR were seen in wide bands in the OPL, whereas rho1-IR appeared as a narrow band in the OPL. Most alpha1-IR was intracellular in rod and cone terminals. Membrane-associated alpha1-IR was observed in cone pedicles but not in rod spherules; postsynaptic elements were also labeled. alpha3-IR was concentrated in the lateral elements of horizontal cell dendrites in cone pedicles. In contrast, rho1-IR was found mainly on the spinules of the horizontal cell dendrites in cone pedicles. In addition, in another type of cone pedicle, rho1-IR was found at the position of OFF-bipolar cell dendrites. alpha3-IR and rho1-IR were rarely found in horizontal cell dendrites innervating rods. We suggest that two GABAergic pathways exist in the Outer retina- first, a GABAergic positive loop with GABA receptors mainly on the horizontal cell dendrites and spinules and, second, a GABAergic feedback pathway involving GABA receptors on cone pedicles and GABA transporters on horizontal cells and that this pathway presumably modulates feedback strength from horizontal cells to cones
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localization of the ampa subunit glur2 in the Outer Plexiform Layer of goldfish retina
The Journal of Comparative Neurology, 2001Co-Authors: Jan Klooster, Keith M Studholme, Stephen YazullaAbstract:L-glutamate, the photoreceptor neurotransmitter, depolarizes horizontal cells and OFF bipolar cells by ionotropic AMPA-glutamate receptors. The AMPA-receptor subunit (GluR4) is localized to dendrites of OFF bipolar cells in goldfish retina. Here, we used immunohistochemical techniques to identify AMPA-receptor subunits on horizontal cell dendrites. A monoclonal antibody against rat GluR2, with high sequence homology to the recently cloned goldfish GluR2a receptor, was used for light- and electron-microscopical immunocytochemistry. Light- and dark-adapted retinas were analyzed, with no major difference in results. GluR2-immunoreactivity (IR) was restricted to a narrow band in the Outer Plexiform Layer, in which it appeared as bright dome-shaped structures amidst numerous puncta. At the ultrastructural level, GluR2-IR was found in horizontal cell dendrites that invaginated cones and rods. Dendrites of OFF bipolar cells were not labeled. GluR2-IR was present mostly in horizontal cell dendrites that were the lateral elements of the triad, rather than in dendrites that were the central elements. In light-adapted retinas, GluR2-IR was found in many horizontal cell spinules. GluR2-IR was observed, on occasion, in a mixed rod/cone (Mb) ON bipolar cell process that innervated rod spherules. Verification of the Mb ON bipolar cell was made by protein kinase C and metabotropic mGluR1α immunolabeling. The presence of GluR2-IR in lateral elements suggests that lateral horizontal cell dendrites are postsynaptic to cones rather than only sites of feedback inhibition. All horizontal cell types express the GluR2 subunit, uniquely differentiating themselves from OFF bipolar cells that express the GluR4 subunit. This differentiation most likely has a major influence on the glutamate pharmacology and response kinetics of these cell types to glutamate. J. Comp. Neurol. 441:155–167, 2001. © 2001 Wiley-Liss, Inc.
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glycinergic contacts in the Outer Plexiform Layer of the xenopus laevis retina characterized by antibodies to glycine gaba and glycine receptors
The Journal of Comparative Neurology, 1990Co-Authors: John F Smiley, Stephen YazullaAbstract:: Electrophysiological experiments have predicted a direct synaptic input from glycinergic interPlexiform cells (IPCs) to GABAergic horizontal cells in the Xenopus retina. However, previous ultrastructural studies failed to demonstrate this input. Here, we used three immunocytochemical approaches to investigate this issue. First, double-label postembedding immunocytochemistry with GABA- and glycine-like immunoreactivity (GABA-LI and glycine-LI) was used to study possible interactions of the glycinergic IPC with GABAergic horizontal cells. Processes postsynaptic to glycine-LI IPC terminals in the Outer Plexiform Layer (OPL) fell into two groups, small microtubule-filled processes and larger electron-lucent processes with sparse microtubules and occasional mitochondria. In no case did we find glycine-LI synapses onto GABA-LI cells or processes. Second, pre-embedding immunocytochemistry was used to label GABA-LI cells and processes in the OPL. GABA-LI was sparse in horizontal cell axons and more intense in horizontal cell somas and in small processes. In agreement with our first set of experiments, GABA-LI profiles did not receive input from conventional synapses. Third, we localized glycine-receptor-like immunoreactivity (GlyR-LI) to several types of apparent synapses in the OPL. As expected, it was found at IPC synapses. Unexpectedly, GlyR-LI was also subsynaptic at photoreceptor synapses onto second order neurons, both at ribbon and basal junction type synapses. At least some of the GlyR-LI photoreceptor synapses were from cones. Also, GlyR-LI was apposed to photoreceptors and to unidentified small diameter processes, where no other indication of synaptic input was evident. Because glycine-LI is not found in photoreceptors, we suggest that glycine receptors at photoreceptor synapses are stimulated by glycine that diffuses from other sites, possibly from IPCs. This interpretation is consistent with available physiological studies of glycinergic effects in this retina.
