Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that lead to the gradual loss of vision in and around the macular area. There are no treatments for patients suffering from bestrophinopathies, and no measures can be taken to prevent visual deterioration in those who have inherited disease-causing mutations. Bestrophinopathies are caused by mutations in the Bestrophin1 gene (BEST1), a protein found exclusively in the retinal pigment epithelial (RPE) cells of the eye. Mutations in BEST1 affect the function of the RPE leading to the death of overlying retinal cells and subsequent vision loss. The pathogenic mechanisms arising from BEST1 mutations are still not fully understood, and it is not clear how mutations in BEST1 lead to diseases with distinct clinical features. This chapter discusses BEST1, the use of model systems to investigate the effects of mutations and the potential to investigate individual bestrophinopathies using induced pluripotent stem cells.
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BEST1 VARIANT ASSOCIATED WITH AN ATYPICAL MACULAR AND PERIPHERAL RETINAL PHENOTYPE.
Retin Cases Brief Rep
January 2025
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Purpose: Best vitelliform macular dystrophy is an inherited macular dystrophy associated with over 250 pathogenic variants of the Bestrophin-1 ( BEST1 ) gene. Although several types of lesions of best vitelliform macular dystrophy are well-described, reports of phenotypic variations associated with rare genetic variants are limited.
Methods: This was a retrospective case series performed in 2021 at a tertiary eye care center.
Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications.
J Transl Med
November 2024
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Ion channels in retinal pigment epithelial (RPE) cells are crucial for retinal health and vision functions. Defects in such channels are intricately associated with the development of various retinopathies that cause blindness. Human pluripotent stem cells (hPSC)-derived RPE cells, including those from human-induced pluripotent stem cells (hiPSC) and human embryonic stem cells (hESC), have been used as in vitro models for investigating pathogenic mechanisms and screening potential therapeutic strategies for retinopathies.
View Article and Find Full Text PDFAccelerated maturation of ARPE-19 cells for the translational assessment of gene therapy.
FASEB J
September 2024
Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
The human retinal pigment epithelium (RPE) cell line ARPE-19 is widely used as an alternative to primary RPE despite losing many features of primary RPE. We aimed to determine whether a combination of RPE-specific laminin (LN) and nicotinamide (NAM) could improve ARPE-19 redifferentiation to resemble mature RPE and improve the assessment of RPE-specific gene therapy strategies. ARPE-19 cells were propagated on tissue culture plastic supplemented with NAM and human recombinant LN521-coating.
View Article and Find Full Text PDFDetection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing.
Curr Med Sci
April 2024
Department of Senior Ophthalmology, the Third Medical Center of PLA General Hospital, Beijing, 100853, China.
Article Synopsis
- This study focuses on autosomal recessive bestrophinopathy (ARB), a retinal disease linked to mutations in the BEST1 gene, leading to visual loss and retinal degeneration in affected individuals.
- Researchers used advanced sequencing techniques, specifically Pacific Biosciences' SMRT sequencing and Sanger sequencing, to identify two new mutations in the BEST1 gene from two Chinese families with ARB.
- The findings demonstrate the effectiveness of third-generation sequencing for detecting genetic mutations, expanding the knowledge of BEST1 mutations in the Chinese population and emphasizing its potential for future genetic studies.
Gene therapy in bestrophinopathies: Insights from preclinical studies in preparation for clinical trials.
Saudi J Ophthalmol
December 2023
Department of Ophthalmic Genetics, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, United States of America.
Article Synopsis
- The gene in question encodes bestrophin-1, an ion channel found in the retinal pigment epithelium, which is crucial for eye health.
- Pathogenic variants of this gene can lead to a group of inherited retinal diseases known as bestrophinopathies, characterized by progressive vision loss and identifiable subretinal features.
- These diseases may be targeted for gene therapy, with strategies varying depending on the type of mutation, including gene augmentation for loss-of-function mutations and a combination of gene silencing and augmentation for toxic gain-of-function mutations.
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