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      Visual evoked potential in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation

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          Abstract

          Photoelectric dye-coupled polyethylene film, designated Okayama University type-retinal prosthesis or OUReP™, generates light-evoked surface electric potentials and stimulates neurons. The dye-coupled films or plain films were implanted subretinally in both eyes of 10 Royal College of Surgeons rats with hereditary retinal dystrophy at the age of 6 weeks. Visual evoked potentials in response to monocular flashing light stimuli were recorded from cranially-fixed electrodes, 4 weeks and 8 weeks after the implantation. After the recording, subretinal film implantation was confirmed histologically in 7 eyes with dye-coupled films and 7 eyes with plain films. The recordings from these 7 eyes in each group were used for statistical analysis. The amplitudes of visual evoked potentials in the consecutive time points from 125 to 250 ms after flash were significantly larger in the 7 eyes with dye-coupled film implantation, compared to the 7 eyes with plain film implantation at 8 weeks after the implantation ( P < 0.05, repeated-measure ANOVA). The photoelectric dye-coupled polyethylene film, as retinal prosthesis, gave rise to visual evoked potential in response to flashing light.

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          Interim results from the international trial of Second Sight's visual prosthesis.

          Mark S Humayun, Jessy Dorn, Lyndon da Cruz … (2012)
          This study evaluated the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in blind subjects with severe outer retinal degeneration. Single-arm, prospective, multicenter clinical trial. Thirty subjects were enrolled in the United States and Europe between June 6, 2007, and August 11, 2009. All subjects were followed up for a minimum of 6 months and up to 2.7 years. The electronic stimulator and antenna of the implant were sutured onto the sclera using an encircling silicone band. Next, a pars plana vitrectomy was performed, and the electrode array and cable were introduced into the eye via a pars plana sclerotomy. The microelectrode array then was tacked to the epiretinal surface. The primary safety end points for the trial were the number, severity, and relation of adverse events. Principal performance end points were assessments of visual function as well as performance on orientation and mobility tasks. Subjects performed statistically better with the system on versus off in the following tasks: object localization (96% of subjects), motion discrimination (57%), and discrimination of oriented gratings (23%). The best recorded visual acuity to date is 20/1260. Subjects' mean performance on orientation and mobility tasks was significantly better when the system was on versus off. Seventy percent of the patients did not have any serious adverse events (SAEs). The most common SAE reported was either conjunctival erosion or dehiscence over the extraocular implant and was treated successfully in all subjects except in one, who required explantation of the device without further complications. The long-term safety results of Second Sight's retinal prosthesis system are acceptable, and most subjects with profound visual loss perform better on visual tasks with system than without it. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            INHERITED RETINAL DYSTROPHY IN THE RAT

            John Dowling, Richard Sidman (1962)
            Retinal dystrophies, known in man, dog, mouse, and rat, involve progressive loss of photoreceptor cells with onset during or soon after the developmental period. Functional (electroretinogram), chemical (rhodopsin analyses) and morphological (light and electron microscopy) data obtained in the rat indicated two main processes: (a) overproduction of rhodopsin and an associated abnormal lamellar tissue component, (b) progressive loss of photoreceptor cells. The first abnormality recognized was the appearance of swirling sheets or bundles of extracellular lamellae between normally developing retinal rods and pigment epithelium; membrane thickness and spacing resembled that in normal outer segments. Rhodopsin content reached twice normal values, was present in both rods and extracellular lamellae, and was qualitatively normal, judged by absorption maximum and products of bleaching. Photoreceptors attained virtually adult form and ERG function. Then rod inner segments and nuclei began degenerating; the ERG lost sensitivity and showed selective depression of the a-wave at high luminances. Outer segments and lamellae gradually degenerated and rhodopsin content decreased. No phagocytosis was seen, though pigment cells partially dedifferentiated and many migrated through the outer segment-debris zone toward the retina. Eventually photoreceptor cells and the b-wave of the ERG entirely disappeared. Rats kept in darkness retained electrical activity, rhodopsin content, rod structure, and extracellular lamellae longer than litter mates in light.
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              Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer.

              Satoko Narikawa, Eriko Sugano, Makoto Tamai … (2007)
              To investigate whether the channelopsin-2 (Chop2) gene would restore visual responses in 10-month-old dystrophic Royal College of Surgeons (aged RCS; rdy/rdy) rats, the authors transferred the Chop2 gene into the retinal cells of aged RCS rats using the adenoassociated virus (AAV) vector. The N-terminal fragment (residues 1-315) of Chop2 was fused to a fluorescent protein, Venus, in frame at the end of the Chop2 coding fragment. The viral vector construct (AAV-Chop2V) for the expression of the Chop2V in the retina was made by subcloning into an adenoassociated virus vector, including the CAG promoter. To evaluate the expression profile of Chop2V in the retina, the rats were killed and the eyes were removed and fixed with 4% paraformaldehyde in 0.1 M phosphate-buffered saline. Retinal wholemount specimens and cryosections were made. Under anesthetized conditions, electrodes for the recording of visually evoked potentials (VEPs) were implanted onto the visual cortex in aged-RCS (rdy/rdy) rats. AAV-Chop2V vectors were then injected into the vitreous cavity of the left eyes. As a control, AAV-Venus vectors were applied to the right eyes. VEPs were evoked by the flash of a blue, white, or red light-emitting diode (LED) and were recorded from the visual cortex of the rats at various time points after the AAV vector injection. Chop2V fluorescence was predominantly observed in retinal ganglion cells (RGCs). Some fluorescence was observed in the inner nuclear layer and the inner plexiform layer neurites. A tendency of recovery was observed in the VEPs of aged RCS (rdy/rdy) rats after the AAV-Chop2V injection but not after the AAV-Venus injection. The visual response of AAV-Chop2V-injected aged RCS (rdy/rdy) rats was less sensitive to the blue LED flash than that of nondystrophic RCS (+/+) rats. The AAV-Chop2V-injected aged RCS (rdy/rdy) rats were insensitive to the red LED flash, which evoked a robust VEP in the RCS (+/+) rats. The visual response of aged RCS (rdy/rdy) rats was partially restored by transduction of the Chop2 gene through AAV into the inner retinal neurons, mainly RGCs. These results suggest that the transduction of Chop2 would provide a new strategy to treat some retinitis pigmentosa (RP) symptoms independent of their etiology.
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                Author and article information

                Contributors
                Toshihiko Matsuo:
                ORCID: http://orcid.org/0000-0001-6570-0030
                +81-86-235-7297 , matsuot@cc.okayama-u.ac.jp
                Tetsuya Uchida: +81-86-251-8103 , tuchida@cc.okayama-u.ac.jp
                Journal
                Journal ID (nlm-ta): J Artif Organs
                Journal ID (iso-abbrev): J Artif Organs
                Title: Journal of Artificial Organs
                Publisher: Springer Japan (Tokyo )
                ISSN (Print): 1434-7229
                ISSN (Electronic): 1619-0904
                Publication date (Electronic): 8 February 2017
                Publication date PMC-release: 8 February 2017
                Publication date (Print): 2017
                Volume: 20
                Issue: 2
                Pages: 158-165
                Affiliations
                [1 ]ISNI 0000 0001 1302 4472, GRID grid.261356.5, Ophthalmology, , Okayama University Medical School and Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, ; Okayama, Japan
                [2 ]ISNI 0000 0001 1302 4472, GRID grid.261356.5, Medical Neurobiology, , Okayama University Medical School and Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, ; Okayama, Japan
                [3 ]ISNI 0000 0001 1302 4472, GRID grid.261356.5, Polymer Materials Science, , Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology, ; Okayama, Japan
                Author information
                http://orcid.org/0000-0001-6570-0030
                Article
                Publisher ID: 943
                DOI: 10.1007/s10047-016-0943-4
                PMC ID: 5446846
                PubMed ID: 28181076
                SO-VID: 1fcba7b6-e775-497e-81e4-fe6fde580345
                Copyright © © The Author(s) 2017
                History
                Date received : 9 May 2016
                Date accepted : 16 December 2016
                Funding
                Funded by: Ministry of Health, Labor and Welfare of Japan
                Award ID: a grant for Health and Labor Sciences
                Award Recipient :
                Categories
                Subject: Original Article
                Custom metadata
                issue-copyright-statement © The Japanese Society for Artificial Organs 2017

                Keywords: retinal prosthesis,photoelectric dye,rcs rat,visual evoked potential,retinitis pigmentosa
                Data availability:
                Keywords: retinal prosthesis, photoelectric dye, rcs rat, visual evoked potential, retinitis pigmentosa

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