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      Visual evoked potential in rabbits’ eyes with subretinal implantation by vitrectomy of Okayama University-type retinal prosthesis (OUReP TM)

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          Abstract

          Okayama University-type retinal prosthesis (OUReP TM) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. This study aims to test surgical feasibility for subretinal film implantation and to examine functional durability of films in subretinal space. Dye-coupled films were implanted subretinally by vitrectomy in the right eye of normal white rabbits: 8 rabbits for 1 month and 8 rabbits for 6 months. The implanted films were removed by vitrectomy in 4 of these 8 rabbits in 1-month or 6-month implantation group. The films were also implanted in 4 rhodopsin-transgenic retinal dystrophic rabbits. Visual evoked potential was measured before film implantation as well as 1 or 6 months after film implantation, or 1 month after film removal. The films were successfully implanted in subretinal space of retinal detachment induced by subretinal fluid injection with a 38G polyimide tip. The retina was reattached by fluid-air exchange in vitreous cavity, retinal laser coagulation, and silicone oil injection. The ratios of P 2 amplitudes of visual evoked potential in the implanted right eye over control left eye did not show significant changes between pre-implantation and post-implantation or post-removal (paired t-test). In Kelvin probe measurements, 4 pieces each of removed films which were implanted for 1 or 6 months showed proportional increase of surface electric potential in response to increasing light intensity. The film implantation was safe and implanted films were capable of responding to 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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            Retinal remodeling in the Tg P347L rabbit, a large-eye model of retinal degeneration.

            C Watt, Yanhua Lin, S. M Shaw … (2011)
            Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photoreceptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies. Copyright © 2011 Wiley-Liss, Inc.
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              Generation of a transgenic rabbit model of retinal degeneration.

              Yasuo Tano, Yuji Nishizawa, Shinji Ueno … (2009)
              To generate a transgenic (Tg) rabbit model of retinal degeneration and to characterize the pattern of degeneration by using histology and electrophysiology. Rhodopsin Pro347Leu Tg rabbits were generated by BAC transgenesis. Tg rabbits were identified by Southern blot analysis, and the expression levels were measured by quantitative RT-PCR. Retinal histology was examined by light and electron microscopy and immunohistochemistry. Retinal function was assessed by full-field electroretinograms (ERGs). Six lines of Tg rabbits were generated, and two lines with higher levels of expression showed rod-dominant progressive retinal degeneration. Retinal histology indicated a marked regional variation in the loss of photoreceptors with the central retina more severely affected than the peripheral retina. The characteristics of the ERGs of transgenic rabbits indicated that the rod components of the ERGs were reduced to only 5% by 48 weeks, whereas the cone components remained at 35% in the wild-type at the same time point. The retinal ultrastructure of Tg rabbits showed a large number of small vesicles that accumulated in the extracellular space of the photoreceptors. To the best of the authors' knowledge, this is the first rabbit model of progressive retinal degeneration. Because rabbits have large eyes and are easy to handle and breed, they will provide a useful animal model for the study of the pathophysiology of and new treatments for retinal degeneration.
              Article 0 comments Cited 25 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Vet Med Sci
                Journal ID (iso-abbrev): J. Vet. Med. Sci
                Journal ID (publisher-id): JVMS
                Title: The Journal of Veterinary Medical Science
                Publisher: The Japanese Society of Veterinary Science
                ISSN (Print): 0916-7250
                ISSN (Electronic): 1347-7439
                Publication date (Electronic): 01 January 2018
                Publication date (Print): February 2018
                Volume: 80
                Issue: 2
                Pages: 247-259
                Affiliations
                [1) ]Ophthalmology, Okayama University Medical School and Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama-shi, Okayama 700-8558, Japan
                [2) ]Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology, Okayama-shi, Okayama 700-8530, Japan
                [3) ]Ina Research, Inc., Ina-shi, Nagano 399-4501, Japan
                [4) ]Kurashiki University of Science and the Arts, Kurashiki-shi, Okayama 712-8505, Japan
                Author notes
                [* ]Correspondence to: Matsuo, T.: matsuot@ 123456cc.okayama-u.ac.jp
                Article
                Publisher ID: 17-0422
                DOI: 10.1292/jvms.17-0422
                PMC ID: 5836760
                PubMed ID: 29311491
                SO-VID: da6cb57c-070b-4d3c-9af1-b7cf4e60f8db
                Copyright © ©2018 The Japanese Society of Veterinary Science
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/ )

                History
                Date received : 01 August 2017
                Date accepted : 19 December 2017
                Categories
                Subject: Surgery
                Subject: Full Paper

                Keywords: dye-coupled thin film retinal prosthesis,rabbit,retinal dystrophy (retinitis pigmentosa),visual evoked potential,vitrectomy
                Data availability:
                Keywords: dye-coupled thin film retinal prosthesis, rabbit, retinal dystrophy (retinitis pigmentosa), visual evoked potential, vitrectomy

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