The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Machelle T Pardue - One of the best experts on this subject based on the ideXlab platform.
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subretinal electrical stimulation preserves inner retinal function in RCS Rat retina
Molecular Vision, 2013Co-Authors: V T Ciavatta, Julie A Mocko, Machelle T PardueAbstract:PURPOSE: Previously, studies showed that subretinal electrical stimulation (SES) from a microphotodiode array (MPA) preserves electroretinography (ERG) b-wave amplitude and regional retinal structure in the Royal College of Surgeons (RCS) Rat and simultaneously upregulates Fgf2 expression. This preservation appears to be associated with the increased current produced when the MPA is exposed to ERG test flashes, as weekly ERG testing produces greater neuroprotection than biweekly or no testing. Using an infrared source to stimulate the MPA while avoiding potential confounding effects from exposing the RCS retina to high luminance white light, this study examined whether neuroprotective effects from SES increased with subretinal current in a dose-dependent manner. METHODS: RCS Rats (n=49) underwent subretinal implantation surgery at P21 with MPA devices in one randomly selected eye, and the other eye served as the control. Naive RCS Rats (n=25) were also studied. To increase SES current levels, implanted eyes were exposed to 15 min per session of flashing infrared light (IR) of defined intensity, frequency, and duty cycle. Rats were divided into four SES groups that received ERG testing only (MPA only), about 450 µA/cm2 once per week (Low 1X), about 450 µA/cm2 three times per week (Low 3X), and about 1350 µA/cm2 once per week (High 1X). One eye of the control animals was randomly chosen for IR exposure. All animals were followed for 4 weeks with weekly binocular ERGs. A subset of the eyes was used to measure retina Fgf2 expression with real-time reverse-transcription PCR. RESULTS: Eyes receiving SES showed significant preservation of b-wave amplitude, a- and b-wave implicit times, oscillatory potential amplitudes, and post-receptoral parameters (Vmax and log σ) compared to untreated eyes. All SES-treated eyes had similar preservation, regardless of increased SES from IR light exposure. SES-treated eyes tended to have greater retinal Fgf2 expression than untreated eyes, but Fgf2 expression did not increase with IR light. CONCLUSIONS: The larger post-receptoral responses (Vmax), greater post-receptoral sensitivity (logσ), and larger oscillatory potentials suggest SES-treated eyes maintained better inner retinal function than the opposite, untreated eyes. This suggests that in addition to preserving photoreceptors in RCS Rats, SES may also promote more robust signal transmission through the retinal network compared to the control eyes. These studies suggest that the protective effects of SES on RCS retinal function cannot be improved with additional subretinal current induction from the MPA, or the charge injection provided by ERG Ganzfeld flashes was not adequately mimicked by the flashing IR light used in this study.
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Effects of Subretinal Electrical Stimulation in Mer-KO Mice
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Julie A Mocko, V T Ciavatta, A. E. Faulkner, Machelle T PardueAbstract:Purpose. Subretinal electrical stimulation (SES) from microphotodiode arrays protects photoreceptors in the RCS Rat model of retinitis pigmentosa. The authors examined whether merkd mice, which share a Mertk mutation with RCS Rats, showed similar neuroprotective effects from SES.
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neuroprotection of photoreceptors in the RCS Rat after implantation of a subretinal implant in the superior or inferior retina
Advances in Experimental Medicine and Biology, 2006Co-Authors: Machelle T Pardue, M J Phillips, Alan Y Chow, B Hanzlicek, Sherry L BallAbstract:The artificial silicon retina (ASRTM) consists of an array of photodiodes on a silicon disk that responds to incident light in a gradient fashion (Peyman et al., 1998; Chow et al., 2001, 2002). This device is designed to be placed in the subretinal space and serve as a replacement for degeneRating photoreceptors. Two possible mechanisms for the ASR device to improve visual function include 1) direct activation of the remaining inner retinal neurons and subsequent activation of visual centers in the brain or 2) a delay in photoreceptor loss due to a neurotrophic effect from subretinal electrical stimulation. Initial results of ongoing FDA trials with the ASR device suggest that subretinal electrical stimulation could elicit a neurotrophic effect (Chow et al., 2004). Ten advanced retinitis pigmentosa (RP) patients implanted with the ASR device have increased central visual fields and improved visual acuity and color vision (Chow et al., 2004). These improvements cannot be easily explained by direct activation since the implant was placed 20° from the macula. To determine whether neuroprotection results from subretinal electrical stimulation, the RCS Rat model of RP was implanted with an ASR device. Subretinal implantation of an ASR device into the superior retina of the Royal College of Surgeons (RCS) Rat resulted in preservation of photoreceptors (Pardue et al., 2004). However, the RCS Rat is known to have delayed photoreceptor degeneRation in the superior region of the retina (LaVail and Battelle, 1975). To determine whether the superior retina is a “privileged” site in the RCS Rat, ASR devices were subretinally implanted in the superior and inferior retina.
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neuroprotective effect of subretinal implants in the RCS Rat
Investigative Ophthalmology & Visual Science, 2005Co-Authors: Machelle T Pardue, M J Phillips, Brian D Sippy, Sarah Webbwood, Alan Y Chow, Sherry L BallAbstract:PURPOSE. Retinal prosthetics have been designed to interface with the neural retina by electrically stimulating the remaining retinal circuits after photoreceptor degeneRation. However, the electrical stimulation provided by the subretinal implant may also stimulate neurotrophic factors that provide neuroprotection to the retina. This study was undertaken to determine whether electrical stimulation from a subretinal photodiodebased implant has a neuroprotective effect on photoreceptors in the RCS Rat, a model of photoreceptor degeneRation. METHODS. Eyes of RCS Rats were implanted with an active or inactive device or underwent sham surgery before photoreceptor degeneRation. Outer retinal function was assessed with electroretinogram (ERG) recordings weekly until 8 weeks after surgery, at which time retinal tissue was collected and processed for morphologic assessment, including photoreceptor cell counts and retinal layer thickness. RESULTS. At 4 to 6 weeks after surgery, the ERG responses in the active-implant eyes were 30% to 70% greater in b-wave amplitude than the responses from eyes implanted with inactive devices, those undergoing sham surgery, or the nonsurgical control eyes. At 8 weeks after surgery the ERG responses from active-implant eyes were not significantly different from the control groups. However, the number of photoreceptors in eyes implanted with the active or inactive device was significantly greater in the regions over and around the implant versus sham-surgical and nonsurgical control eyes. CONCLUSIONS. These results suggest that subretinal electrical stimulation provides temporary preservation of retinal function in the RCS Rat. In addition, implantation of an active or inactive device into the subretinal space causes morphologic preservation of photoreceptors in the RCS Rat until 8 weeks after surgery. Further studies are needed to determine whether the correlation of neuropreservation with subretinal implantation is due to electrical stimulation and/or a mechanical presence of the implant in the subretinal space. (Invest Ophthalmol Vis Sci. 2005;46:674‐682) DOI:10.1167/iovs.04-0515
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evaluation of inner retinal structure in the aged RCS Rat
Advances in Experimental Medicine and Biology, 2003Co-Authors: Sherry L Ball, B Hanzlicek, Melissa Blum, Machelle T PardueAbstract:In retinal diseases such as retinitis pigmentosa (RP), photoreceptors degeneRate while inner retinal layers are relatively spared. In these cases, it is thought that, if given a signal, the “healthy” inner retina would be capable of processing visual information in a somewhat normal fashion. Several laboRatories are testing treatments designed to replace lost photoreceptors by transplanting healthy retinal tissue (Woch et al., 2001; Coffey et al., 2002) or implanting a light sensitive prosthetic device (Chow et al., 2001; Zrenner et al., 1999) into the subretinal space. These stRategies will work only if the inner retina is intact and functional. Recent evidence in humans as well as rodent models of RP shows that, especially at later stages of disease progression, the inner retina begins to exhibit changes (Stone et al., 1992; Strettoi et al., 2002). Determining the nature of these changes is critical to understanding the disease process as well as developing treatments.
Laura Kowalczuk - One of the best experts on this subject based on the ideXlab platform.
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non viral gene therapy for gdnf production in RCS Rat the crucial role of the plasmid dose
Gene Therapy, 2012Co-Authors: Elodie Touchard, Peter Heiduschka, Marianne Berdugo, Laura KowalczukAbstract:Non-viral gene therapy for GDNF production in RCS Rat: the crucial role of the plasmid dose
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Non-viral gene therapy for GDNF production in RCS Rat: the crucial role of the plasmid dose
Gene Therapy, 2012Co-Authors: Elodie Touchard, Peter Heiduschka, Marianne Berdugo, Laura Kowalczuk, P Bigey, S Chahory, C Gandolphe, J-c Jeanny, F Behar-cohenAbstract:Glial cell line-derived neurotrophic factor (GDNF) is one of the candidate molecules among neurotrophic factors proposed for a potential treatment of retinitis pigmentosa (RP). It must be administered repeatedly or through sustained releasing systems to exert prolonged neuroprotective effects. In the dystrophic Royal College of Surgeon's (RCS) Rat model of RP, we found that endogenous GDNF levels dropped during retinal degeneRation time course, opening a therapeutic window for GDNF supplementation. We showed that after a single electrotransfer of 30 μg of GDNF-encoding plasmid in the Rat ciliary muscle, GDNF was produced for at least 7 months. Morphometric, electroretinographic and optokinetic analyses highlighted that this continuous release of GDNF delayed photoreceptors (PRs) as well as retinal functions loss until at least 70 days of age in RCS Rats. Unexpectedly, increasing the GDNF secretion level acceleRated PR degeneRation and the loss of electrophysiological responses. This is the first report: (i) demonstRating the efficacy of GDNF delivery through non-viral gene therapy in RP; (ii) establishing the efficacy of intravitreal administRation of GDNF in RP associated with a mutation in the retinal pigment epithelium; and (iii) warning against potential toxic effects of GDNF within the eye/retina.
Elodie Touchard - One of the best experts on this subject based on the ideXlab platform.
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non viral gene therapy for gdnf production in RCS Rat the crucial role of the plasmid dose
Gene Therapy, 2012Co-Authors: Elodie Touchard, Peter Heiduschka, Marianne Berdugo, Laura KowalczukAbstract:Non-viral gene therapy for GDNF production in RCS Rat: the crucial role of the plasmid dose
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Non-viral gene therapy for GDNF production in RCS Rat: the crucial role of the plasmid dose
Gene Therapy, 2012Co-Authors: Elodie Touchard, Peter Heiduschka, Marianne Berdugo, Laura Kowalczuk, P Bigey, S Chahory, C Gandolphe, J-c Jeanny, F Behar-cohenAbstract:Glial cell line-derived neurotrophic factor (GDNF) is one of the candidate molecules among neurotrophic factors proposed for a potential treatment of retinitis pigmentosa (RP). It must be administered repeatedly or through sustained releasing systems to exert prolonged neuroprotective effects. In the dystrophic Royal College of Surgeon's (RCS) Rat model of RP, we found that endogenous GDNF levels dropped during retinal degeneRation time course, opening a therapeutic window for GDNF supplementation. We showed that after a single electrotransfer of 30 μg of GDNF-encoding plasmid in the Rat ciliary muscle, GDNF was produced for at least 7 months. Morphometric, electroretinographic and optokinetic analyses highlighted that this continuous release of GDNF delayed photoreceptors (PRs) as well as retinal functions loss until at least 70 days of age in RCS Rats. Unexpectedly, increasing the GDNF secretion level acceleRated PR degeneRation and the loss of electrophysiological responses. This is the first report: (i) demonstRating the efficacy of GDNF delivery through non-viral gene therapy in RP; (ii) establishing the efficacy of intravitreal administRation of GDNF in RP associated with a mutation in the retinal pigment epithelium; and (iii) warning against potential toxic effects of GDNF within the eye/retina.
Sherry L Ball - One of the best experts on this subject based on the ideXlab platform.
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neuroprotection of photoreceptors in the RCS Rat after implantation of a subretinal implant in the superior or inferior retina
Advances in Experimental Medicine and Biology, 2006Co-Authors: Machelle T Pardue, M J Phillips, Alan Y Chow, B Hanzlicek, Sherry L BallAbstract:The artificial silicon retina (ASRTM) consists of an array of photodiodes on a silicon disk that responds to incident light in a gradient fashion (Peyman et al., 1998; Chow et al., 2001, 2002). This device is designed to be placed in the subretinal space and serve as a replacement for degeneRating photoreceptors. Two possible mechanisms for the ASR device to improve visual function include 1) direct activation of the remaining inner retinal neurons and subsequent activation of visual centers in the brain or 2) a delay in photoreceptor loss due to a neurotrophic effect from subretinal electrical stimulation. Initial results of ongoing FDA trials with the ASR device suggest that subretinal electrical stimulation could elicit a neurotrophic effect (Chow et al., 2004). Ten advanced retinitis pigmentosa (RP) patients implanted with the ASR device have increased central visual fields and improved visual acuity and color vision (Chow et al., 2004). These improvements cannot be easily explained by direct activation since the implant was placed 20° from the macula. To determine whether neuroprotection results from subretinal electrical stimulation, the RCS Rat model of RP was implanted with an ASR device. Subretinal implantation of an ASR device into the superior retina of the Royal College of Surgeons (RCS) Rat resulted in preservation of photoreceptors (Pardue et al., 2004). However, the RCS Rat is known to have delayed photoreceptor degeneRation in the superior region of the retina (LaVail and Battelle, 1975). To determine whether the superior retina is a “privileged” site in the RCS Rat, ASR devices were subretinally implanted in the superior and inferior retina.
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neuroprotective effect of subretinal implants in the RCS Rat
Investigative Ophthalmology & Visual Science, 2005Co-Authors: Machelle T Pardue, M J Phillips, Brian D Sippy, Sarah Webbwood, Alan Y Chow, Sherry L BallAbstract:PURPOSE. Retinal prosthetics have been designed to interface with the neural retina by electrically stimulating the remaining retinal circuits after photoreceptor degeneRation. However, the electrical stimulation provided by the subretinal implant may also stimulate neurotrophic factors that provide neuroprotection to the retina. This study was undertaken to determine whether electrical stimulation from a subretinal photodiodebased implant has a neuroprotective effect on photoreceptors in the RCS Rat, a model of photoreceptor degeneRation. METHODS. Eyes of RCS Rats were implanted with an active or inactive device or underwent sham surgery before photoreceptor degeneRation. Outer retinal function was assessed with electroretinogram (ERG) recordings weekly until 8 weeks after surgery, at which time retinal tissue was collected and processed for morphologic assessment, including photoreceptor cell counts and retinal layer thickness. RESULTS. At 4 to 6 weeks after surgery, the ERG responses in the active-implant eyes were 30% to 70% greater in b-wave amplitude than the responses from eyes implanted with inactive devices, those undergoing sham surgery, or the nonsurgical control eyes. At 8 weeks after surgery the ERG responses from active-implant eyes were not significantly different from the control groups. However, the number of photoreceptors in eyes implanted with the active or inactive device was significantly greater in the regions over and around the implant versus sham-surgical and nonsurgical control eyes. CONCLUSIONS. These results suggest that subretinal electrical stimulation provides temporary preservation of retinal function in the RCS Rat. In addition, implantation of an active or inactive device into the subretinal space causes morphologic preservation of photoreceptors in the RCS Rat until 8 weeks after surgery. Further studies are needed to determine whether the correlation of neuropreservation with subretinal implantation is due to electrical stimulation and/or a mechanical presence of the implant in the subretinal space. (Invest Ophthalmol Vis Sci. 2005;46:674‐682) DOI:10.1167/iovs.04-0515
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evaluation of inner retinal structure in the aged RCS Rat
Advances in Experimental Medicine and Biology, 2003Co-Authors: Sherry L Ball, B Hanzlicek, Melissa Blum, Machelle T PardueAbstract:In retinal diseases such as retinitis pigmentosa (RP), photoreceptors degeneRate while inner retinal layers are relatively spared. In these cases, it is thought that, if given a signal, the “healthy” inner retina would be capable of processing visual information in a somewhat normal fashion. Several laboRatories are testing treatments designed to replace lost photoreceptors by transplanting healthy retinal tissue (Woch et al., 2001; Coffey et al., 2002) or implanting a light sensitive prosthetic device (Chow et al., 2001; Zrenner et al., 1999) into the subretinal space. These stRategies will work only if the inner retina is intact and functional. Recent evidence in humans as well as rodent models of RP shows that, especially at later stages of disease progression, the inner retina begins to exhibit changes (Stone et al., 1992; Strettoi et al., 2002). Determining the nature of these changes is critical to understanding the disease process as well as developing treatments.
Marianne Berdugo - One of the best experts on this subject based on the ideXlab platform.
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non viral gene therapy for gdnf production in RCS Rat the crucial role of the plasmid dose
Gene Therapy, 2012Co-Authors: Elodie Touchard, Peter Heiduschka, Marianne Berdugo, Laura KowalczukAbstract:Non-viral gene therapy for GDNF production in RCS Rat: the crucial role of the plasmid dose
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Non-viral gene therapy for GDNF production in RCS Rat: the crucial role of the plasmid dose
Gene Therapy, 2012Co-Authors: Elodie Touchard, Peter Heiduschka, Marianne Berdugo, Laura Kowalczuk, P Bigey, S Chahory, C Gandolphe, J-c Jeanny, F Behar-cohenAbstract:Glial cell line-derived neurotrophic factor (GDNF) is one of the candidate molecules among neurotrophic factors proposed for a potential treatment of retinitis pigmentosa (RP). It must be administered repeatedly or through sustained releasing systems to exert prolonged neuroprotective effects. In the dystrophic Royal College of Surgeon's (RCS) Rat model of RP, we found that endogenous GDNF levels dropped during retinal degeneRation time course, opening a therapeutic window for GDNF supplementation. We showed that after a single electrotransfer of 30 μg of GDNF-encoding plasmid in the Rat ciliary muscle, GDNF was produced for at least 7 months. Morphometric, electroretinographic and optokinetic analyses highlighted that this continuous release of GDNF delayed photoreceptors (PRs) as well as retinal functions loss until at least 70 days of age in RCS Rats. Unexpectedly, increasing the GDNF secretion level acceleRated PR degeneRation and the loss of electrophysiological responses. This is the first report: (i) demonstRating the efficacy of GDNF delivery through non-viral gene therapy in RP; (ii) establishing the efficacy of intravitreal administRation of GDNF in RP associated with a mutation in the retinal pigment epithelium; and (iii) warning against potential toxic effects of GDNF within the eye/retina.
