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      Is Open Access

      Effectiveness of Ripasudil, a Rho-Associated Coiled/Coil-Containing Protein Kinase Inhibitor, in Improving Retinoschisis and Cystic-Like Foveal Cavities in Eyes with X-Linked Retinoschisis

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          Abstract

          This is the first reported case of a successful resolution of cystic-like foveal cavities in eyes with X-linked juvenile retinoschisis (XLRS) treated with topical ripasudil hydrochloride hydrate, a Rho-associated coiled/coil-containing protein kinase (ROCK) inhibitor. A chart review was performed on 1 patient to collect all relevant clinical information and the optical coherence tomographic (OCT) images. A healthy 18-year-old young man presented with bilateral visual disturbances. The patient was diagnosed with XLRS from the spoke-wheel pattern around the macula, negative electroretinograms, and retinoschisis with cystic-like foveal cavities in the OCT images. Significant reductions of the retinoschisis and cystic-like cavities were observed after treatment with topical ripasudil. This is the first case of XLRS that had a resolution of cystic-like foveal cavities after topical ripasudil, a ROCK inhibitor. Since many XLRS patients have a worsening of their visual acuities due to the progressive nature of retinoschisis and cystic-like foveal cavities, topical ripasudil offers a potential treatment option.

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          Most cited references17

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          X linked retinoschisis.

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            Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure.

            Deleterious mutations in RS1 encoding retinoschisin are associated with X-linked juvenile retinoschisis (RS), a common form of macular degeneration in males. The disorder is characterized by a negative electroretinogram pattern and by a splitting of the inner retina. To gain further insight into the function of the retinoschisin protein and its role in the cellular pathology of RS, we have generated knockout mice deficient in Rs1h, the murine ortholog of the human RS1 gene. We show that pathologic changes in hemizygous Rs1h(-/Y) male mice are evenly distributed across the retina, apparently contrasting with the macula-dominated features in human. Similar functional anomalies in human and Rs1h(-/Y) mice, however, suggest that both conditions are a disease of the entire retina affecting the organization of the retinal cell layers as well as structural properties of the retinal synapse.
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              Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells.

              To examine the biochemical properties, cell expression, and localization of RS1, the product of the gene responsible for X-linked juvenile retinoschisis. Rs1h mRNA expression was measured from the eyes of wild-type and rd/rd mice by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Specific antibodies raised against the N terminus of RS1 were used as probes to examine the properties and distribution of RS1 in retina, retinal cell cultures, and transfected COS-1 cells by Western blot analysis and immunofluorescence microscopy. Rs1h mRNA expression was detected in the retina of postnatal day (P)11 and adult CD1 mice, but not homozygous rd/rd mice by Northern blot analysis. However, Rs1h expression was detected in rd/rd mice by RT-PCR. RS1 migrated as a single 24-kDa polypeptide under disulfide-reducing conditions and a larger complex (>95 kDa) under nonreducing conditions in the membrane fraction of retinal tissue homogenates and transfected COS-1 cells. RS1 antibodies specifically stained rod and cone photoreceptors and most bipolar cells, but not Müller cells, ganglion cells, or the inner limiting membrane of adult and developing retina as revealed in double-labeling studies. RS1 antibodies also labeled retinal bipolar cells of photoreceptorless mice and retinal bipolar cells grown in cell culture. RS1 is expressed and assembled in photoreceptors of the outer retina and bipolar cells of the inner retina as a disulfide-linked oligomeric protein complex. The secreted complex associates with the surface of these cells, where it may function as a cell adhesion protein to maintain the integrity of the central and peripheral retina.
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                Author and article information

                Journal
                Case Rep Ophthalmol
                Case Rep Ophthalmol
                COP
                Case Reports in Ophthalmology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1663-2699
                May-Aug 2020
                6 August 2020
                6 August 2020
                : 11
                : 2
                : 411-417
                Affiliations
                Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan
                Author notes
                *Masahiko Sugimoto, Department of Ophthalmology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan), sugmochi@ 123456clin.medic.mie-u.ac.jp
                Article
                cop-0011-0411
                10.1159/000509261
                7506235
                200ef4f4-b60f-415a-ab6e-15431cbd185f
                Copyright © 2020 by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 17 April 2020
                : 6 June 2020
                : 2020
                Page count
                Figures: 2, References: 21, Pages: 7
                Categories
                Case Report

                cystic-like foveal cavities,retinoschisis,rho-associated coiled/coil-containing protein kinase inhibitor,ripasudil hydrochloride hydrate,x-linked retinoschisis

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