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      Photoelectric Dye Used for Okayama University-Type Retinal Prosthesis Reduces the Apoptosis of Photoreceptor Cells

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          Abstract

          Purpose: Our previous study demonstrated that photoelectric dye-coupled polyethylene film (Okayama University-type retinal prosthesis), which was implanted in subretinal space of the eyes of Royal College of Surgeons (RCS) rats, prevented retinal neurons from apoptotic death. In this study, we aimed to examine whether photoelectric dye itself would protect retinal neurons from apoptosis in RCS rats.

          Methods: RCS rats received intravitreous injection of different concentrations of the dye in the left eye and housed under a 12-h light–dark cycle. Saline injection in the right eye served as control. In addition, RCS rats with dye injection were kept in 24-h daily dark condition. Sections were processed for terminal deoxynucleotidyl transferase-mediated fluorescein-conjugated-dUTP nick-end-labeling (TUNEL) assay and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and protein kinase Cα (PKCα).

          Results: The number of TUNEL-positive cells significantly decreased in the retina of dye-injected eyes compared with those in saline-injected eyes ( P = 0.0001, 2-factor analysis of variance [ANOVA]), under 12-h light–dark cycle. Significant decrease of TUNEL-positive cells was noted in the retina of rats with dye injection compared with those with saline injection, kept under 24-h dark condition ( P = 0.0001, 2-factor ANOVA). Immunoreactive area for GFAP decreased significantly in the retina of dye-injected eyes compared with that in controls ( P = 0.0001, 2-factor ANOVA), whereas immunoreactive area for PKCα increased significantly in the retina of dye-injected eyes compared with that in controls ( P = 0.01, 2-factor ANOVA).

          Conclusions: Photoelectric dye inhibits apoptotic death of photoreceptor cells in RCS rats and downregulates GFAP expression in retinal Müller cells. Photoelectric dye may be a candidate agent for neuroprotection in retinitis pigmentosa and other retinal diseases.

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          Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000).

          L F Eng, R Ghirnikar, Y. Lee (2000)
          It is now well established that the glial fibrillary acidic protein (GFAP) is the principal 8-9 nm intermediate filament in mature astrocytes of the central nervous system (CNS). Over a decade ago, the value of GFAP as a prototype antigen in nervous tissue identification and as a standard marker for fundamental and applied research at an interdisciplinary level was recognized (Raine, 135). As a member of the cytoskeletal protein family, GFAP is thought to be important in modulating astrocyte motility and shape by providing structural stability to astrocytic processes. In the CNS of higher vertebrates, following injury, either as a result of trauma, disease, genetic disorders, or chemical insult, astrocytes become reactive and respond in a typical manner, termed astrogliosis. Astrogliosis is characterized by rapid synthesis of GFAP and is demonstrated by increase in protein content or by immunostaining with GFAP antibody. In addition to the major application of GFAP antisera for routine use in astrocyte identification in the CNS, the molecular cloning of the mouse gene in 1985 has opened a new and rich realm for GFAP studies. These include antisense, null mice, and numerous promoter studies. Studies showing that mice lacking GFAP are hypersensitive to cervical spinal cord injury caused by sudden acceleration of the head have provided more direct evidence for a structural role of GFAP. While the structural function of GFAP has become more acceptable, the use of GFAP antibodies and promoters continue to be valuable in studying CNS injury, disease, and development.
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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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              Photovoltaic restoration of sight with high visual acuity

              Henri Lorach, Georges Goetz, Richard JP Smith … (2015)
              Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We demonstrate that subretinal arrays with 70 μm photovoltaic pixels provide highly localized stimulation, with electrical and visual receptive fields of comparable sizes in rat retinal ganglion cells. Similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies, adaptation to static images and non-linear spatial summation. In rats with retinal degeneration, these photovoltaic arrays provide spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in pigmented rats. Ease of implantation of these wireless and modular arrays, combined with their high resolution opens the door to functional restoration of sight.
              Article 0 comments Cited 145 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Ocul Pharmacol Ther
                Journal ID (iso-abbrev): J Ocul Pharmacol Ther
                Journal ID (publisher-id): jop
                Title: Journal of Ocular Pharmacology and Therapeutics
                Publisher: Mary Ann Liebert, Inc. (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                ISSN (Print): 1080-7683
                ISSN (Electronic): 1557-7732
                Publication date (Print): 01 April 2017
                Publication date (Electronic): 01 April 2017
                Publication date PMC-release: 01 April 2017
                Volume: 33
                Issue: 3
                Pages: 149-160
                Affiliations
                [ 1 ]Department of Ophthalmology, Okayama University Medical School and Graduate School of Medicine , Dentistry, and Pharmaceutical Sciences, Okayama City, Japan.
                [ 2 ]Department of Medical Neurobiology, Okayama University Medical School and Graduate School of Medicine , Dentistry, and Pharmaceutical Sciences, Okayama City, Japan.
                [ 3 ]Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology , Okayama City, Japan.
                Author notes
                Address correspondence to: Dr. Toshihiko Matsuo, Department of Ophthalmology, Okayama University Medical School and Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 2–5-1 Shikata-cho, Okayama City 700-8558, Japan

                E-mail: matsuot@ 123456cc.okayama-u.ac.jp
                Article
                Publisher ID: 10.1089/jop.2016.0093
                DOI: 10.1089/jop.2016.0093
                PMC ID: 5385417
                PubMed ID: 28085534
                SO-VID: 30f934b1-e0cd-4ca7-9d69-2bc0b49379ee
                Copyright © © Shihui Liu, et al., 2017; Published by Mary Ann Liebert, Inc.
                License:

                This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                Date received : 11 July 2016
                Date accepted : 08 December 2016
                Page count
                Figures: 9, References: 34, Pages: 12
                Categories
                Subject: Original Articles

                Keywords: apoptosis,drug,retina,gfap,pkcα,photoreceptors
                Data availability:
                Keywords: apoptosis, drug, retina, gfap, pkcα, photoreceptors

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