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RPE65 Antibody Order 021-34695924 Orders@Ab-Mart.Com Support 400-6123-828 50Ul Support1@Ab-Mart.Com 100 Ul √ √ Web

TD13248 RPE65 Antibody Order 021-34695924 [email protected] Support 400-6123-828 50ul [email protected] 100 uL √ √ Web www.ab-mart.com.cn Description: Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. Catalyzes the cleavage and isomerization of all- trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore. Essential for the production of 11-cis retinal for both rod and cone photoreceptors. Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT (By similarity). Uniprot:Q16518 Alternative Names： All-trans-retinyl-palmitate hydrolase; LCA 2; LCA2; Leber congenital amaurosis; mRPE 65; mRPE65; p63; rd 12; rd12; Retinal pigment epithelium specific 61 kDa protein; Retinal pigment epithelium specific 65 kDa protein; Retinal pigment epithelium specific protein; Retinal pigment epithelium specific protein 65kDa; Retinal pigment epithelium-specific 65 kDa protein; Retinitis pigmentosa 20; Retinoid isomerohydrolase; Retinol isomerase; RP 20; RP20; RPE 65; RPE65; RPE65_HUMAN; sRPE 65; sRPE65; Specificity: RPE65 Antibody detects endogenous levels of total RPE65. Reactivity:Human, Mouse, Rat Source:Rabbit Mol.Wt.: 60kD; 61kDa(Calculated). Storage Condition: Store at -20 °C. Stable for 12 months from date of receipt. Application: WB 1:1000-1:2000；IHC/IF 1:50-1:500.

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RPE65 Mutant Dog/ Leber Congenital Amaurosis
Rpe65 mutant dogs Pde6A mutant dogs Cngb1 mutant dogs rAAV RPE65 Mutant Dog/ Leber Congenital Amaurosis Null mutation in Rpe65 retinal function (ERG & dim light vision) Failure of 11-cis retinal supply to photoreceptors (visual cycle) Retina only slow degeneration (S-cones and area centralis degeneration – variable) RPE lipid inclusions 8 Mo 3.5 yr The Visual (Retinoid) Cycle retinal pigment All-trans-retinol epithelium (Vitamin A) RPE65 11-cis-retinal Visual pigments All-trans-retinal rod and cone outer segments All-trans-retinol Gene supplementation therapy for RPE65 Leber Congenital Amaurosis Initial trials in dogs – very successful Outcome in humans Some improvement in visual function Appears to not preserve photoreceptors in longer term Questions Is there preservation of photoreceptors? Why is outcome in humans not so successful? Does RPE65 Gene Therapy Preserve Photoreceptors? Rpe65-/- dogs: Early loss of S-cones Slow LM cone loss Very slow rod loss Exception – region of high density of photoreceptors – rapid loss Gene therapy preservation of photoreceptors Limitations to Human Functional Rescue and Photoreceptor Preservation Hypothesis The dose of gene therapy delivered is a limiting factor for the efficacy of treatment Specific aim To compare the clinical efficacy and the levels of expression of RPE65 protein and the end product of RPE65 function (11-cis retinal) of various doses of RPE65 gene therapy in Rpe65 -/- dogs Methods Tested total dose of 8x108 to 1x1011 vg/eye ERG Scotopic b wave Vision testing % correct choice RPE65 protein expression Dose of gene therapy +/+ 8x108 4x109 2x1010 1x1011 RPE65 GAPDH RPE65 protein expression RPE65/DAPI/ autofluorescence Chromophore levels 11-cis retinal levels undetectable In Rpe65 -/- All-trans retinal Chromophore vs clinical outcomes Scotopic b wave r2 = 0.91 p < 0.0001 Vision testing % correct choice r2 = 0.58 p = 0.02 RPE65 gene expression Human vs.
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Mouse Mutants As Models for Congenital Retinal Disorders
Experimental Eye Research 81 (2005) 503–512 www.elsevier.com/locate/yexer Review Mouse mutants as models for congenital retinal disorders Claudia Dalke*, Jochen Graw GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, D-85764 Neuherberg, Germany Received 1 February 2005; accepted in revised form 1 June 2005 Available online 18 July 2005 Abstract Animal models provide a valuable tool for investigating the genetic basis and the pathophysiology of human diseases, and to evaluate therapeutic treatments. To study congenital retinal disorders, mouse mutants have become the most important model organism. Here we review some mouse models, which are related to hereditary disorders (mostly congenital) including retinitis pigmentosa, Leber’s congenital amaurosis, macular disorders and optic atrophy. q 2005 Elsevier Ltd. All rights reserved. Keywords: animal model; retina; mouse; gene mutation; retinal degeneration 1. Introduction Although mouse models are a good tool to investigate retinal disorders, one should keep in mind that the mouse Mice suffering from hereditary eye defects (and in retina is somehow different from a human retina, particular from retinal degenerations) have been collected particularly with respect to the number and distribution of since decades (Keeler, 1924). They allow the study of the photoreceptor cells. The mouse as a nocturnal animal molecular and histological development of retinal degener- has a retina dominated by rods; in contrast, cones are small ations and to characterize the genetic basis underlying in size and represent only 3–5% of the photoreceptors. Mice retinal dysfunction and degeneration. The recent progress of do not form cone-rich areas like the human fovea.
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Eyegene® Envisioning Cures for Rare Inherited Eye Disorders
eyeGENE® Envisioning cures for rare inherited eye disorders What is eyeGENE®? eyeGENE®, also known as the National Ophthalmic Disease Genotyping and Phenotyping Network, was launched by the National Eye Institute (NEI) in 2006 to facilitate research into the causes and mechanisms of rare inherited eye diseases and the development of treatments and cures. A public- private partnership, the eyeGENE® Network is a collaboration among the U.S. federal government, eye health providers across the U.S. and Canada, certified molecular diagnostic laboratories, private industry, and the vision research community. eyeGENE® components include a patient registry, a curated genotype/phenotype data repository, and a DNA biorepository. How is eyeGENE® funded? eyeGENE® is funded by federal support through the NEI, a part of the National Institutes of Health (NIH). NIH is the nation’s medical research agency. What does eyeGENE® do? eyeGENE® connects scientists studying rare eye disease with people who have a rare inherited eye disease and want to participate in clinical research. While rare eye diseases collectively affect thousands of people, each individual disease affects relatively few people. Finding adequate numbers of people with specific mutations to study and participate in clinical trials can be challenging. Patients with rare conditions often have difficulty finding clinicians with relevant expertise. Why study genes? ® Identifying disease genes can lead to eyeGENE Participants by Leading breakthrough therapies. For example, in the Diagnoses (>100) 1990s, researchers linked a gene called RPE65 to the blinding eye disease Leber congenital amaurosis (LCA). In 2008, clinical trials funded by the NEI and others showed that RPE65 gene therapy could improve the vision of people with LCA caused by this genetic mutation.
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RPE65-Related Retinal Dystrophy: Mutational and Phenotypic Spectrum in 45
medRxiv preprint doi: https://doi.org/10.1101/2021.01.19.21249492; this version posted January 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . TITLE: RPE65-related retinal dystrophy: mutational and phenotypic spectrum in 45 affected patients. AUTHORS: Lopez-Rodriguez R1*, Lantero E1*, Blanco-Kelly F1, Avila-Fernandez A1, Martin Merida I1, del Pozo-Valero M1, Perea-Romero I1, Zurita O1, Jiménez-Rolando B2, Swafiri ST1, Riveiro-Alvarez R1, Trujillo-Tiebas MJ1, Carreño Salas E2, García- Sandoval B2, Corton M1* and Ayuso C1* 1 Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital- Universidad Autónoma de Madrid (IIS-FJD, UAM), Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. 2 Department of Ophthalmology, Fundación Jiménez Díaz University Hospital (FJD), Madrid, Spain. *These authors contributed equally to this work CORRESPONDING AUTHOR: Carmen Ayuso (CA), MD, PhD Department of Genetics Fundación Jiménez Díaz University Hospital Av. Reyes Católicos nº 2. 28040 Madrid, Spain [email protected] NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 1 medRxiv preprint doi: https://doi.org/10.1101/2021.01.19.21249492; this version posted January 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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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.
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SPK-RPE65 Gene Therapy for Inherited Retinal Dystrophies Due to Mutations in the RPE65 Gene
Horizon Scanning Research January 2016 & Intelligence Centre SPK-RPE65 gene therapy for inherited retinal dystrophies due to mutations in the RPE65 gene LAY SUMMARY Inherited retinal dystrophies are a group of eye diseases caused by one or more abnormal genes (or ‘mutations’). These diseases all eventually lead to blindness, and at the moment there is no treatment This briefing is that either slows this down or improves sight after it has been lost. based on information available at the time Mutations in the RPE65 gene is one cause of inherited retinal of research and a dystrophies, particularly a condition called Leber’s congenital limited literature amaurosis, which leads to blindness in childhood. SPK-RPE65 is a search. It is not gene therapy that could treat mutations in the RPE65 gene, and may intended to be a improve the sight of people with an inherited retinal dystrophy caused definitive statement by these mutations. SPK-RPE65 is injected directly into the eye by a on the safety, surgeon. efficacy or effectiveness of the SPK-RPE65 is currently being studied to see how well it works and health technology whether it is safe to use. If SPK-RPE65 is licensed for use in the UK, it covered and should will be the first treatment available for people with this type of inherited not be used for retinal dystrophy. commercial purposes or commissioning NIHR HSRIC ID: 10177 without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health.
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Voretigene Neparvovec for Biallelic RPE65-Mediated Retinal Disease: Effectiveness, Value, and Value-Based Price Benchmarks
Voretigene Neparvovec for Biallelic RPE65-Mediated Retinal Disease: Effectiveness, Value, and Value-Based Price Benchmarks Background and Scope July 10, 2017 Background: Inherited retinal diseases (IRDs) are a cause of childhood blindness.1 IRDs are caused by many different mutations, and with the development and availability of genetic testing over the last decade, the responsible mutations have been identified for an increasing number of these conditions.2-4 Effective treatments to reverse IRDs or slow their progression have generally been unavailable. RPE65 (retinal pigment epithelium-specific 65 kDa protein; retinoid isomerohydrolase) is an enzyme found in the retinal pigment epithelium. It plays a critical role in the regeneration of light-reacting proteins in the retina, and thus is required for vision.5 The RPE65 protein is encoded by the gene RPE65; mutations in RPE65 can result in absent production (null alleles) or reduced production (hypomorphic alleles) of the protein.6 A number of different IRDs are caused by mutations in RPE65. We heard from experts that the phenotypic distinctions among the RPE65-associated IRDs likely reflect the amount of remaining RPE65 activity. Among IRDs caused by mutations affecting both copies of RPE65 (biallelic mutations), Leber congenital amaurosis type 2 (LCA2), a subset of Leber congenital amaurosis (LCA), is the most common.7 Children with LCA are typically severely visually impaired or blind at birth. However, in at least some individuals with LCA2, vision deteriorates later in life; all affected individuals are blind by young adulthood.7 It is estimated that approximately 3,700 individuals in the United States have LCA; of these, up to 16% are estimated to have LCA2.7 Thus, approximately 600 individuals with LCA2 could be candidates for gene therapy aimed at treating biallelic RPE65 mutations.
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A Cross-Sectional and Longitudinal Study of Retinal Sensitivity in RPE65-Associated Leber Congenital Amaurosis
Clinical and Epidemiologic Research A Cross-Sectional and Longitudinal Study of Retinal Sensitivity in RPE65-Associated Leber Congenital Amaurosis Neruban Kumaran,1,2 Gary S. Rubin,1,2 Angelos Kalitzeos,1,2 Kaoru Fujinami,1–4 James W. B. Bainbridge,1,2 Richard G. Weleber,5 and Michel Michaelides1,2 1UCL Institute of Ophthalmology, University College London, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom 3National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan 4Keio University, School of Medicine, Tokyo, Japan 5Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States Correspondence: Michel Michae- PURPOSE. RPE65-associated Leber congenital amaurosis (RPE65-LCA) is an early-onset severe lides, UCL Institute of Ophthalmolo- retinal dystrophy associated with progressive visual field loss. Phase I/II and III gene therapy gy, 11-43 Bath Street, London, EC1V trials have identified improved retinal sensitivity but little is known about the natural history 9EL, UK; of retinal sensitivity in RPE65-LCA. [email protected]. METHODS. A total of 19 subjects (aged 9 to 23 years) undertook monocular full-field static Submitted: January 24, 2018 Accepted: May 22, 2018 perimetry of which 13 subjects were monitored longitudinally. Retinal sensitivity was measured as mean sensitivity (MS) and volumetrically quantified (in decibel-steradian) using Citation: Kumaran N, Rubin GS, Kalit- visual field modeling and analysis software for the total (VTOT), central 308 (V30) and central zeos A, et al. A cross-sectional and 158 (V ) visual field. Correlation was evaluated between retinal sensitivity and age, best- longitudinal study of retinal sensitivity 15 in RPE65-associated Leber congenital corrected visual acuity (BCVA), contrast sensitivity, vision-related quality of life, and genotype.
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Leber Congenital Amaurosis
Leber congenital amaurosis Authors: Doctors Bart P Leroy1 and Sharola Dharmaraj2 Creation date: November 2003 Scientific Editor: Professor Jean-Jacques de Laey 1Dept of Ophthalmology & Ctr for Medical Genetics, Ghent University Hospital, Ghent, Belgium 2Johns Hopkins Center for Hereditary Eye Diseases, Wilmer Eye Institute, Baltimore, MD, USA Abstract Key words Disease name /synonyms Definition / Diagnostic criteria Differential diagnosis Etiology Clinical description Diagnostic methods Epidemiology Genetic counseling Prenatal diagnosis Management including treatment Unresolved questions References Abstract Leber congenital amaurosis (LCA) is a retinal dystrophy and/or dysplasia of prenatal onset. About 10 to 20% of blind children are thought to suffer from LCA, which makes it one of the frequent causes of childhood blindness. It is thought to account for 5% of inherited retinal disease. Affected children fail to fix and follow due to little or no retinal sensitivity to visual stimuli. Electroretinography shows either no or very reduced retinal function. Fundus examination in the first months of life is frequently normal, but later chorioretinal atrophy with intraretinal pigment migration becomes apparent. In some patients, a macular puched-out lesion is present. Patients have nystagmus and frequently poke their eyes. LCA is inherited as an autosomal recessive trait in the large majority of patients, with only a limited number of cases with autosomal dominant inheritance described. LCA is genetically heterogeneous, and, to date, mutations have been identified in six different genes known to be associated with LCA: AIPL1, CRB1, CRX, GUCY2D, RPE65 and RPGRIP1. At least another three additional loci have been linked to the condition. Although therapy is not currently available, encouraging results have been obtained with gene therapy in a dog model for this disease.
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NEI 50 Years of Advance in Vision Research
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A Strong and Highly Significant QTL on Chromosome 6 That Protects The
A Strong and Highly Significant QTL on Chromosome 6 that Protects the Mouse from Age-Related Retinal Degeneration Michael Danciger,1 Jessica Lyon,1 Danielle Worrill,1 Matthew M. LaVail,2 and Haidong Yang2 PURPOSE. BALB/cByJ (C) albino mice have significantly more etiology. Many studies have attempted to determine environ- retinal degeneration as they age than C57BL/6J-c2J (B6) albinos. mental risk factors that may be associated with AMD, but only To discover the genetic loci that influence age-related retinal smoking has been consistently demonstrated to be one of them degeneration (ARD), a quantitative genetics study was per- (for reviews, see 6–9). In contrast, twin studies and population- formed with 8-month-old progeny from an intercross between based familial aggregate studies have made it clear that genes these two strains. play a significant role in AMD. 10–13 It is also clear that AMD is 14,15 METHODS. The thickness of the outer nuclear layer of the retina a complex genetic disorder, one that first appears most was used as the quantitative trait. A genome-wide scan was commonly in elderly individuals, typically in those older than performed with 86 genetic markers at an average distance of 50 years. Because of the age of onset, informative family ped- 15.7 cM. Map Manager QTX was used to analyze the data. igrees of the size needed to identify genetic loci are difficult to find. Only one such locus (with a LOD score of 3.0) has been RESULTS. Three highly significant quantitative trait loci (QTLs) reported.16 Identifying AMD genetic loci with family-based were detected on mouse chromosomes (Chrs) 6, 10, and 16.
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RPE65 Gene RPE65, Retinoid Isomerohydrolase
RPE65 gene RPE65, retinoid isomerohydrolase Normal Function The RPE65 gene provides instructions for making a protein that is essential for normal vision. The RPE65 protein is produced in a thin layer of cells at the back of the eye called the retinal pigment epithelium (RPE). This cell layer supports and nourishes the retina, which is the light-sensitive tissue that lines the back of the eye. The RPE65 protein is involved in a multi-step process called the visual cycle, which converts light entering the eye into electrical signals that are transmitted to the brain. When light hits photosensitive pigments in the retina, it changes a molecule called 11- cis retinal (a form of vitamin A) to another molecule called all-trans retinal. This conversion triggers a series of chemical reactions that create electrical signals. The RPE65 protein then helps convert all-trans retinal back to 11-cis retinal so the visual cycle can begin again. Health Conditions Related to Genetic Changes Leber congenital amaurosis More than 30 mutations in the RPE65 gene have been found to cause Leber congenital amaurosis. Mutations in this gene account for 6 to 16 percent of all cases of this condition. RPE65 gene mutations lead to a partial or total loss of RPE65 protein function. As a result, all-trans retinal cannot be converted back to 11-cis retinal, and excess all-trans retinal builds up in the retinal pigment epithelium. These abnormalities block the visual cycle, which leads to severe visual impairment beginning very early in life. Fundus albipunctatus MedlinePlus Genetics provides information about Fundus albipunctatus Retinitis pigmentosa MedlinePlus Genetics provides information about Retinitis pigmentosa Other disorders Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1 More than 20 mutations in the RPE65 gene have been identified in people with another eye disorder called retinitis pigmentosa.
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