DOCSLIB.ORG

Molecular Insights Into PCARE-Associated Retinal Disease Julio César Corral Serrano 2018-13

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Molecular Insights Into PCARE-Associated Retinal Disease Julio César Corral Serrano 2018-13 PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/197551 Please be advised that this information was generated on 2021-09-28 and may be subject to change. Molecular insights into Molecular insights into PCARE PCARE- associated -associated retinal disease retinal disease Julio César Corral Serrano 2018-13 RIMLS Julio César Corral Serrano Molecular insights into PCARE-associated retinal disease Julio César Corral Serrano This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 317472 (EyeTN). The work presented in this thesis was carried out within the Radboud Institute for Molecular Life Sciences (RIMLS). The publication of this thesis was financially supported by the Radboud University Nijmegen, the Stichting Blindenhulp, the Landelijke Stichting voor Blinden en Slechtzienden, the Stichting Ooglijders and the Rotterdamse Stichting Blindenbelangen. ISBN: 978-94-6380-031-0 Cover and chapter covers designed by M. Eugenia Castejón Lorite Print and cover adaptation by Proefschrift Maken, proefschriftmaken.nl © Julio César Corral Serrano, 2018 No part of this book may be reproduced or transmitted, in any form or by any means, without written permission of the author or the publisher holding the copyright of the published articles. Molecular insights into PCARE-associated retinal disease Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. dr. J.H.J.M. van Krieken, volgens besluit van het college van decanen in het openbaar te verdedigen op maandag 3 december 2018 om 12.30 uur precies door Julio César Corral Serrano geboren op 17 oktober 1989 te Madrid, Spanje Promotoren Dr. Rob W.J. Collin Prof. dr. ir. Ronald Roepman Copromotor Dr. Alejandro Garanto Manuscriptcommissie Prof. dr. Anneke I. den Hollander Prof. dr. Colin A. Johnson (University of Leeds, Verenigd Koninkrijk) Prof. dr. Nine V.A.M. Knoers (Rijksuniversiteit Groningen) Paranimfen Daniel Lôpo Polla Laura Lorés de Motta Marc Pauper Molecular insights into PCARE-associated retinal disease Doctoral Thesis to obtain the degree of doctor from Radboud University Nijmegen on the authority of the Rector Magnificus prof. dr. J.H.J.M. van Krieken, according to the decision of the Council of Deans to be defended in public on Monday, December 3, 2018 at 12:30 hours by Julio César Corral Serrano Born on October 17, 1989 in Madrid, Spain Supervisors Dr. Rob W.J. Collin Prof. dr. ir. Ronald Roepman Co-supervisor Dr. Alejandro Garanto Doctoral thesis committee Prof. dr. Anneke I. den Hollander Prof. dr. Colin A. Johnson (University of Leeds, UK) Prof. dr. Nine V.A.M. Knoers (University of Groningen) Paranymphs Daniel Lôpo Polla Laura Lorés de Motta Marc Pauper a Popó Table of contents List of abbreviations .................................................................................................................... 11 Chapter 1 General introduction ........................................................................................... 17 Chapter 2 The photoreceptor-specific protein PCARE interacts with WASF3 to deploy a ciliary actin dynamics module ................................................................ 59 Chapter 3 Clinical and genetic overview of PCARE-associated retinal disease ..................... 101 Chapter 4 C2orf71a/pcare1 is important for photoreceptor outer segment morphogenesis and visual function in zebrafish ................................................. 119 Chapter 5 Generation and transcriptome analysis of PCARE-deficient iPSC-derived photoreceptor-like cells ................................................................. 143 Chapter 6 Generation and characterization of an adeno-associated virus (AAV) vector containing full-length PCARE cDNA ....................................... 171 Chapter 7 General discussion ............................................................................................. 191 Summary .................................................................................................................................. 213 Samenvatting ............................................................................................................................ 216 Resumen ................................................................................................................................... 220 Data management ..................................................................................................................... 225 Acknowledgements ................................................................................................................... 227 List of publications .................................................................................................................... 231 Curriculum vitae ........................................................................................................................ 233 RIMLS Portfolio ......................................................................................................................... 235 List of abbreviations * Stop codon 3D Three-dimensional aa Amino acid AAV Adeno-associated virus ABCA4 ATP binding cassette subfamily A member 4 ACTN1 α-actinin ad Autosomal dominant ar Autosomal recessive AON Antisense oligonucleotide Arp2/3 Actin-related protein 2/actin-related protein 3 Ax Axoneme BB Basal body BBS Bardet-Biedl syndrome bGHpA Bovine growth hormone polyadenylation signal BODIPY Boron-dipyrromethene C2ORF71 Chromosome 2 open reading frame 71 CaP Calyceal processes Cap Capsid gene CC Connecting cilium CCT Chaperonin containing TCP-1 CD Cone dystrophy CEN3 Centrin-3 CEP250 Centrosomal protein 250 kDa CEP290 Centrosomal protein 290 kDa cDNA Complementary deoxyribonucleic acid cGMP Cyclic guanosine monophosphate CHM Choroideremia CJ Connecting junctions CR Ciliary rootlet CRD Cone-rod dystrophy CRISPR Clustered regularly interspaced short palindromic repeat CRX Cone-rod homeobox CP Ciliary pocket 11 DA Distal appendages dC Daughter centriole DCTN2 Dynactin subunit 2 DNA Deoxyribonucleic acid dpf Days post fertilization dup Duplication ENA/VASP Enabled/vasodilator-stimulated phosphoprotein ER Endoplasmic reticulum ESC Embryonic stem cell FBS Fetal bovine serum FDA US Food and drug administration FL Fiber links Gli Glioma-associated oncogene GMP Guanosine monophosphate GT335 Polyglutamylated tubulin HDR Homology-directed repair HEK293T Human embryonic kidney 293T hpf Hours post fertilization hTERT RPE-1 Human telomerase-immortalized retinal pigmented epithelial-1 IFT Intraflagellar transport IFT57 Intraflagellar transport 57 kDa ins Insertion iPSC Induced pluripotent stem cell IRD Inherited retinal disease IS Inner segment ITR Inverted terminal repeat JBS Joubert syndrome kb Kilobase kDa Kilodalton KIF17 Kinesin family member 17 LCA Leber congenital amaurosis LCA5 Leber congenital amaurosis 5 LIMA1 LIM domain and actin binding 1 MI Mitochondria 12 mIMCD-3 Mouse inner medullary collecting duct-3 MKS Meckel-Gruber syndrome mpf Months post fertilization mRNA Messenger ribonucleic acid MT Microtubules NHEJ Non-homologous end joining NR Neural retina OFD1 Oral-facial-digital syndrome 1 OS Outer segment PCARE Photoreceptor cilium actin regulator PCM1 Pericentriolar material 1 PDE Phosphodiesterase PolyA Polyadenylation signal PRA Progressive retinal atrophy PRPH2 Peripherin 2 rd Retinal degeneration Rep Replication gene RHO Rhodopsin RK Rhodopsin kinase RNA Ribonucleic acid RNA-Seq RNA sequencing ROM1 Retinal outer segment membrane protein 1 RP Retinitis Pigmentosa RP1 Retinitis Pigmentosa 1 RP1L1 Retinitis Pigmentosa 1-Like 1 RP2 Retinitis Pigmentosa 2 RP54 Retinitis pigmentosa type 54 RPE Retinal pigment epithelium RPGR Retinitis Pigmentosa GTPase Regulator RPGRIP1L RPGR-interacting protein 1-like protein SA Sub-distal appendages Shh Sonic hedgehog SPATA7 Spermatogenesis associated 7 ST Synaptic terminal 13 SV40 Simian vacuolating virus 40 intron TAP Tandem affinity purification TZ Transition zone USH2A Usher syndrome type IIa WASF3 Wiskott-Aldrich syndrome protein family member 3 WAVE WASP-family verprolin-homologous protein family WPRE Woodchuck hepatitis virus (WHP) post-transcriptional regulatory element WRC WAVE regulatory complex Y2H Yeast two-hybrid YL Y-linkers 14 15 Chapter 1 General introduction CHAPTER 1 “We were born into a mystery, one that has haunted us since at least as long as we've been human.” (Quote from Cosmos: A Spacetime Odyssey, 2014, s01e03). Our world is filled with an infinite amount of colors and shapes. Sight enables us to perceive actions, while vision allows us to make assessments about those actions. Animals have been sensing brightness for a very long time. ‘’The ‘race’ between predator and prey and the need ‘to see’ and ‘to be seen’ or ‘not to be seen’ were drivers for the origin and subsequent evolution of efficient visual systems’’ (quote from Schoenemann et al., 2017).1 The oldest eye recorded dates from the Cambrian period, about 530 million years ago, and belongs to a hard-shelled species, the trilobite.1 The first light-sensing cell would have evolved much earlier, and since then, evolution of light-sensing organs has come a long way. In this introductory chapter, we will give a general overview of the process of human vision and
Load more

Recommended publications
  • Primary Cilia in Energy Balance Signaling and Metabolic Disorder
    BMB Rep. 2015; 48(12): 647-654 BMB www.bmbreports.org Reports Invited Mini Review Primary cilia in energy balance signaling and metabolic disorder Hankyu Lee, Jieun Song, Joo Hyun Jung & Hyuk Wan Ko* College of Pharmacy, Dongguk University, Goyang 10326, Korea Energy homeostasis in our body system is maintained by bal- complex, due to many confounding genetics and environ- ancing the intake and expenditure of energy. Excessive accu- mental factors equivocally affecting the progress of the disease. mulation of fat by disrupting the balance system causes over- Moreover, metabolic disorders are interrelated diseases exem- weight and obesity, which are increasingly becoming global plified by the association of obesity with insulin resistance, health concerns. Understanding the pathogenesis of obesity fo- leading to development of type II diabetes (2). Genetic factors cused on studying the genes related to familial types of for obesity are poorly understood, and recent progress by ge- obesity. Recently, a rare human genetic disorder, ciliopathy, nome-wide association studies support the notion of polygenic links the role for genes regulating structure and function of a features of obesity which suggests that multiple genes, tissues cellular organelle, the primary cilium, to metabolic disorder, and pathways contribute to the disease (3, 4). Intriguing subset obesity and type II diabetes. Primary cilia are microtubule of genes associated with obesity cause a dysfunction of pri- based hair-like membranous structures, lacking motility and mary cilia, which results in a rare pleiotropic human disorder functions such as sensing the environmental cues, and trans- called ciliopathy (5, 6). Primary cilia are microtubule based ducing extracellular signals within the cells.
    [Show full text]
  • CADTH ISSUES in EMERGING HEALTH TECHNOLOGIES Informing Decisions About New Health Technologies
    CADTH ISSUES IN EMERGING HEALTH TECHNOLOGIES Informing Decisions About New Health Technologies Issue Mar 171 2018 Gene Therapy: An Overview of Approved and Pipeline Technologies CADTH ISSUES IN EMERGING HEALTH TECHNOLOGIES 1 Authors: Alison Sinclair, Saadul Islam, Sarah Jones Cite as: Gene therapy: an overview of approved and pipeline technologies. Ottawa: CADTH; 2018 Mar. (CADTH issues in emerging health technologies; issue 171). Acknowledgments: Louis de Léséleuc, Jeff Mason, Teo Quay, Joanne Kim, Lesley Dunfield, Eftyhia Helis, Iryna Magega, Jane Hurge ISSN: 1488-6324 (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy- makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While CADTH has taken care to ensure that the information prepared by it in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect.
    [Show full text]
  • EYE DISEASES July 15-17, 2019
    International Conference on EYE DISEASES July 15-17, 2019 Venue Sonesta Fort Lauderdale Beach 999 N Fort Lauderdale Beach Blvd Fort Lauderdale, FL Exhibitor Day-1 | Monday July 15, 2019 Keynote Talks Vascular Basement Membrane Thickening in Diabetic Retinopathy Sayon Roy Boston University School of Medicine, Boston, MA Biography Dr. Sayon Roy is a Professor of Medicine and Ophthalmology in Department Ophthalmology, Boston University. He completed his B.S. and M.S. from University of Kalyani, India. He received his PhD from Boston University. Dr. Roy’s seminal work has identified several genes in the retina that are abnormally expressed in diabetic retinopathy. His pioneering work has led to novel gene modulatory techniques in retinal vascular cells using antisense oligonucleotides via intravitreal injection. Dr. Roy has received numerous awards including the American Diabetes Association Research Award for the commitment and dedication towards the fight against diabetes, the 2006 Mentor of the Year Award from Boston University, and the 2008 Innovative Award from the Juvenile Diabetes Research Foundation Does Genomics Play a Role in Diabetic Retinopathy? Arup Das1, Sampath Kumar Rangasamy2, Finny Monickaraj1, David Duggan2, Nicholas Schork2 and Paul McGuire1 1University of New Mexico School of Medicine, Albuquerque, NM 2 Translational and Genomics Research Institute, NM Abstract Genetic risk factors play an important role in the development and progression of diabetic retinopathy (DR). Using a well- defined, clinical phenotype, we have examined the role of rare genetic variants in DR progression, or protection by undertaking whole exome sequencing (WES). We performed WES analysis on two cohorts of patients selected from Diabetic Retinopathy Genomics (DRGen) study population.
    [Show full text]
  • Luxturna Voretigene Neparvovec Rzyl Molina Clinical Policy
    Subject: Luxturna (Voretigene neparvovec-rzyl) Original Effective Date: 7/10/2018 Policy Number: MCP-318 Revision Date(s): Review Date(s): 7/10/2018 DISCLAIMER This Molina Clinical Policy (MCP) is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this MCP document and provide the directive for all Medicare members. SUMMARY OF EVIDENCE/POSITION This policy addresses the coverage of Luxturna (Voretigene neparvovec-rzyl), a one-time gene therapy product indicated for the treatment of individuals with confirmed bi-allelic RPE65 mutation-associated retinal dystrophy, when appropriate criteria are met.
    [Show full text]
  • Générique Obésités De Causes Rares
    Protocole National de Diagnostic et de Soins (PNDS) Générique Obésités de causes rares Centre de Référence des maladies rares PRADORT Syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du comportement alimentaire 19 JUILLET 2021 Partie 2 – Argumentaire Cet argumentaire a été élaboré par le Centre de Référence du Syndrome de PRAder-Willi et autres Obésités Rares avec Troubles du comportement alimentaire (PRADORT) . Il a servi de base à l’élaboration du PNDS : Obésités de causes rares. Le PNDS est téléchargeable sur le site de l’HAS, le site du centre de référence PRADORT et le site de la filière DEFISCIENCES CRMR PRADORT 19/07/2021 DéfiScience Filière de santé maladies rares neurdéveloppement 1 Sommaire Liste des abréviations ........................................................................................3 Préambule ........................................................................................................4 Méthode de travail 4 Argumentaire ....................................................................................................5 1.1 Recherche documentaire 5 1.1.1 Base de données et nombre de références 5 1.1.2 Critères de sélection des articles 6 1.2 Sélection des articles 7 1.2.1 Recommandations HAS 7 1.2.2 Articles 10 Annexe 1. Liste des participants ........................................................................108 Annexe 2. Adresses et Coordonnées .................................................................110 Références bibliographiques .............................................................................111
    [Show full text]
  • Luxturna, INN-Voretigene Neparvovec
    20 September 2018 EMA/CHMP/700911/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report Luxturna International non-proprietary name: voretigene neparvovec Procedure No. EMEA/H/C/004451/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 6 1.1. Submission of the dossier ...................................................................................... 6 1.2. Steps taken for the assessment of the product ......................................................... 7 2. Scientific discussion ................................................................................ 9 2.1. Problem statement ............................................................................................... 9 2.1.1. Disease or condition ........................................................................................... 9 2.1.2. Epidemiology .................................................................................................... 9 2.1.3. Biologic features ...............................................................................................
    [Show full text]
  • Clinical Guideline Luxturna (Voretigene Neparvovec-Rzyl)
    Clinical Guideline Guideline Number: CG060, Ver. 1 Luxturna (voretigene neparvovec-rzyl) Disclaimer Clinical guidelines are developed and adopted to establish evidence-based clinical criteria for utilization management decisions. Oscar may delegate utilization management decisions of certain services to third-party delegates, who may develop and adopt their own clinical criteria. Clinical guidelines are applicable to certain plans. Clinical guidelines are applicable to members enrolled in Medicare Advantage plans only if there are no criteria established for the specified service in a Centers for Medicare & Medicaid Services (CMS) national coverage determination (NCD) or local coverage determination (LCD) on the date of a prior authorization request. Services are subject to the terms, conditions, limitations of a member’s policy and applicable state and federal law. Please reference the member’s policy documents (e.g., Certificate/Evidence of Coverage, Schedule of Benefits) or contact Oscar at 855-672-2755 to confirm coverage and benefit conditions. Summary Luxturna was the first in vivo (within living cells) gene therapy approved by the FDA in December 2017 for children and adults with rare inherited vision disorders caused by mutated RPE65 gene. For individuals who have mutations in both copies of the RPE65 gene, they cannot make proteins in the eye that convert light, which leads to partial or total vision loss. Luxturna is delivered as a single-dose, subretinal injection in each eye that works by targeting these mutations to create proteins again for light detection. Subretinal injection occurs after complete vitrectomy; therefore members first must receive a pars plana vitrectomy. Definitions “Gene therapy” is a technique that replaces a mutated gene with a healthy gene, inactivates a mutated gene, or introduces a new gene that helps fight against diseases and disorders.
    [Show full text]
  • Gene Therapy for Inherited Retinal Diseases
    1278 Review Article on Novel Tools and Therapies for Ocular Regeneration Page 1 of 13 Gene therapy for inherited retinal diseases Yan Nuzbrokh1,2,3, Sara D. Ragi1,2, Stephen H. Tsang1,2,4 1Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA; 2Jonas Children’s Vision Care, New York, NY, USA; 3Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, NY, USA; 4Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, USA Contributions: (I) Conception and design: All authors; (II) Administrative support: SH Tsang; (III) Provision of study materials or patients: SH Tsang; (IV) Collection and assembly of data: All authors; (V) Manuscript writing: All authors; (VI) Final approval of manuscript: All authors. Correspondence to: Stephen H. Tsang, MD, PhD. Harkness Eye Institute, Columbia University Medical Center, 635 West 165th Street, Box 212, New York, NY 10032, USA. Email: [email protected]. Abstract: Inherited retinal diseases (IRDs) are a genetically variable collection of devastating disorders that lead to significant visual impairment. Advances in genetic characterization over the past two decades have allowed identification of over 260 causative mutations associated with inherited retinal disorders. Thought to be incurable, gene supplementation therapy offers great promise in treating various forms of these blinding conditions. In gene replacement therapy, a disease-causing gene is replaced with a functional copy of the gene. These therapies are designed to slow disease progression and hopefully restore visual function. Gene therapies are typically delivered to target retinal cells by subretinal (SR) or intravitreal (IVT) injection.
    [Show full text]
  • 2018 Celebration of Research
    UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE 2018 Celebration of Research Welcome from the Dean The annual University of Florida College of Medicine Celebration of Research affords me the opportunity to say Thank You. Thank you for the late nights, the papers written and reviewed, the grant proposals that have been funded and those that will be resubmitted, the patience that you have shown with the varied hurdles placed in the pathway of research. But most importantly, thank you for the passion that you employ to move the boundary of science knowledge forward. Your research vision and the work of your research teams are appreciated and valued. The discoveries and inventions that result from the basic, translational, population and clinical research at our university are transforming medicine. Thank you for your dedication to creating a healthier future for all. The College of Medicine stands proudly behind your efforts. Michael L. Good, MD Dean, UF College of Medicine Celebration of Research 3 POSTER SESSION & RECEPTION Monday, February 19, 2018 5:30pm – 8:30pm Stephen C. O’Connell Center Slow down and smell the roses The 2018 Celebration is already here. Where did the year go? 2017 was indeed another remarkable year of continued growth and progress for research within the College of Medicine, and 2018 is already off to a great start. We have all been running and seem a bit out of breath. Now it is time to slow down and appreciate the breadth and depth of the College of Medicine’s research endeavors and recognize how our research is directed at fundamental, timely, and significant areas of human health.
    [Show full text]
  • First Gene Therapy Fda-Approved for An
    s FEATURE FIRST GENE THERAPY FDA-APPROVED FOR AN INHERITED RETINAL DISEASE The approval has stimulated research into gene therapies for other IRDs. BY MEGHAN J. DEBENEDICTIS, MS, LGC, MED, AND ALEKSANDRA V. RACHITSKAYA, MD he idea of gene therapy has been for clustered regularly interspaced short Scientists and companies have discussed in the medical litera- palindromic repeats) could allow edit- spent decades perfecting the use ture since as early as the 1970s. In ing of one or several sites within the of vectors for genetic material and 1972, Friedman and Roblin pro- mammalian genome.5 identifying ways to deliver them to posed that it was theoretically The most common type of gene increase therapeutic efficacy and possibleT to introduce “good” DNA to therapy is replacement gene therapy, treatment duration. Early investiga- replace defective DNA.1 Over the years, which involves replacing a mutated tions used viruses that delivered a number of gene therapy clinical trials gene that causes disease with a genes to every cell in the body, which emerged in efforts to treat genetic dis- healthy copy of that gene. It is first triggered a massive immune response eases of inborn errors of metabolism, necessary to identify the causative that could lead to organ failure. More all with varying degrees of success. mutated gene. This technology recently designed vectors deliver The basic principle of gene therapy works best in autosomal recessive specific genes to specific cells. is to put corrective genetic material biallelic disease with loss-of-function into cells to treat genetic disease. mutations. A vector is then created TARGET: IRDS Several gene therapy approaches, to carry a wild-type copy of the With the eye’s unique immunologic including replacement gene therapy, gene into the cell of interest.
    [Show full text]
  • Gene Therapy for Inherited Retinal Dystrophy, 2.04.144
    MEDICAL POLICY – 2.04.144 Gene Therapy for Inherited Retinal Dystrophy BCBSA Ref. Policy: 2.04.144 Effective Date: Mar. 1, 2021 RELATED MEDICAL POLICIES: Last Revised: Feb. 18, 2021 None Replaces: 8.01.536 Select a hyperlink below to be directed to that section. POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | HISTORY ∞ Clicking this icon returns you to the hyperlinks menu above. Introduction The retina is found at the back of the eye. It is made up of several layers. One of these layers contains cells called rods and cones. The rods and cones are stimulated when light enters our eyes. They convert the light energy into chemicals, which then create an electrical signal. The optic nerve sends the electrical signal to the brain. Many steps are required for this process to work correctly. One of these steps involves a protein called RPE65. This protein helps make some of the chemical changes that happen in the retina. A specific gene tells the body how to make this protein. If that gene is not normal, the protein cannot be made. The person without this protein will have visual problems called retinal dystrophy and can become blind, even at an early age. Changes in the RPE65 gene are rare. A new treatment uses an engineered virus to insert a healthy copy of the gene into the retinal cells. This treatment requires a genetic test to confirm the specific type of retinal dystrophy. Treatment also requires a specific amount of healthy retina to be available. This policy describes when this treatment may be considered medically necessary.
    [Show full text]
  • Copyrighted Material
    1 Index Note: Page numbers in italics refer to figures, those in bold refer to tables and boxes. References are to pages within chapters, thus 58.10 is page 10 of Chapter 58. A definition 87.2 congenital ichthyoses 65.38–9 differential diagnosis 90.62 A fibres 85.1, 85.2 dermatomyositis association 88.21 discoid lupus erythematosus occupational 90.56–9 α-adrenoceptor agonists 106.8 differential diagnosis 87.5 treatment 89.41 chemical origin 130.10–12 abacavir disease course 87.5 hand eczema treatment 39.18 clinical features 90.58 drug eruptions 31.18 drug-induced 87.4 hidradenitis suppurativa management definition 90.56 HLA allele association 12.5 endocrine disorder skin signs 149.10, 92.10 differential diagnosis 90.57 hypersensitivity 119.6 149.11 keratitis–ichthyosis–deafness syndrome epidemiology 90.58 pharmacological hypersensitivity 31.10– epidemiology 87.3 treatment 65.32 investigations 90.58–9 11 familial 87.4 keratoacanthoma treatment 142.36 management 90.59 ABCA12 gene mutations 65.7 familial partial lipodystrophy neutral lipid storage disease with papular elastorrhexis differential ABCC6 gene mutations 72.27, 72.30 association 74.2 ichthyosis treatment 65.33 diagnosis 96.30 ABCC11 gene mutations 94.16 generalized 87.4 pityriasis rubra pilaris treatment 36.5, penile 111.19 abdominal wall, lymphoedema 105.20–1 genital 111.27 36.6 photodynamic therapy 22.7 ABHD5 gene mutations 65.32 HIV infection 31.12 psoriasis pomade 90.17 abrasions, sports injuries 123.16 investigations 87.5 generalized pustular 35.37 prepubertal 90.59–64 Abrikossoff
    [Show full text]