What Should a Clinician Know to be Prepared for the Advent of Treatment of Retinal Dystrophies?

2008 ◽  
pp. 85-94 ◽  
Author(s):  
Alan C. Bird
Keyword(s):  
Retinal Dystrophies

scholarly journals NRL S50T mutation and the importance of ‘founder effects’ in inherited retinal dystrophies

2000 ◽  
Vol 8 (10) ◽  
pp. 783-787 ◽  
Author(s):  
David AR Bessant ◽  
Annette M Payne ◽  
Catherine Plant ◽  
Alan C Bird ◽  
Anand Swaroop ◽  
...  
Keyword(s):  
Founder Effects ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies

scholarly journals Bestrophinopathies: perspectives on clinical disease, Bestrophin-1 function and developing therapies

2021 ◽  
Vol 13 ◽  
pp. 251584142199719
Author(s):  
Simranjeet Singh Grewal ◽  
Joseph J. Smith ◽  
Amanda-Jayne F. Carr
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
Underlying Disease ◽  
Incomplete Penetrance ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
High Acuity ◽  
Induced Pluripotent

Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that typically affect the macular region, an area synonymous with central high acuity vision. This spectrum of disorders is caused by mutations in bestrophin1 ( BEST1), a protein thought to act as a Ca2+-activated Cl- channel in the retinal pigment epithelium (RPE) of the eye. Although bestrophinopathies are rare, over 250 individual pathological mutations have been identified in the BEST1 gene, with many reported to have various clinical expressivity and incomplete penetrance. With no current clinical treatments available for patients with bestrophinopathies, understanding the role of BEST1 in cells and the pathological pathways underlying disease has become a priority. Induced pluripotent stem cell (iPSC) technology is helping to uncover disease mechanisms and develop treatments for RPE diseases, like bestrophinopathies. Here, we provide a comprehensive review of the pathophysiology of bestrophinopathies and highlight how patient-derived iPSC-RPE are being used to test new genomic therapies in vitro.

scholarly journals Carbon Dot Nanoparticles: Exploring the Potential Use for Gene Delivery in Ophthalmic Diseases

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 935
Author(s):  
Manas R. Biswal ◽  
Sofia Bhatia
Keyword(s):  
Gene Delivery ◽  
Therapeutic Option ◽  
Retinal Dystrophy ◽  
Retinal Cells ◽  
Adeno Associated Virus ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Efficient Gene ◽  
New Type ◽  
Viral Nanoparticles

Ocular gene therapy offers significant potential for preventing retinal dystrophy in patients with inherited retinal dystrophies (IRD). Adeno-associated virus (AAV) based gene transfer is the most common and successful gene delivery approach to the eye. These days, many studies are using non-viral nanoparticles (NPs) as an alternative therapeutic option because of their unique properties and biocompatibility. Here, we discuss the potential of carbon dots (CDs), a new type of nanocarrier for gene delivery to the retinal cells. The unique physicochemical properties of CDs (such as optical, electronic, and catalytic) make them suitable for biosensing, imaging, drug, and gene delivery applications. Efficient gene delivery to the retinal cells using CDs depends on various factors, such as photoluminescence, quantum yield, biocompatibility, size, and shape. In this review, we focused on different approaches used to synthesize CDs, classify CDs, various pathways for the intake of gene-loaded carbon nanoparticles inside the cell, and multiple studies that worked on transferring nucleic acid in the eye using CDs.

scholarly journals Assessing photoreceptor status in retinal dystrophies: from high resolution imaging to functional vision

2021 ◽  
Author(s):  
José-Alain Sahel ◽  
Kate Grieve ◽  
Chloé Pagot ◽  
Colas Authié ◽  
Saddek Mohand-Said ◽  
...  
Keyword(s):  
High Resolution ◽  
High Resolution Imaging ◽  
Retinal Dystrophies ◽  
Resolution Imaging ◽  
Functional Vision

scholarly journals Nutraceutical Supplementation Ameliorates Visual Function, Retinal Degeneration, and Redox Status in rd10 Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1033
Author(s):  
Lorena Olivares-González ◽  
Sheyla Velasco ◽  
Isabel Campillo ◽  
David Salom ◽  
Emilio González-García ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Antioxidant Properties ◽  
Photoreceptor Cells ◽  
Redox Status ◽  
Inherited Retinal Dystrophies ◽  
Stress Markers ◽  
Retinal Dystrophies ◽  
Progressive Degeneration ◽  
Light Stimuli

Background: Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive degeneration of photoreceptor cells. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In this study, we investigated the effect of a mixture of nutraceuticals with antioxidant properties (NUT) on retinal degeneration in rd10 mice, a model of RP. Methods: NUT was orally administered to rd10 mice from postnatal day (PD) 9 to PD18. At PD18 retinal function and morphology were examined by electroretinography (ERG) and histology including TUNEL assay, immunolabeling of microglia, Müller cells, and poly ADP ribose polymers. Retinal redox status was determined by measuring the activity of antioxidant enzymes and some oxidative stress markers. Gene expression of the cytokines IL-6, TNFα, and IL-1β was assessed by real-time PCR. Results: NUT treatment delayed the loss of photoreceptors in rd10 mice partially preserving their electrical responses to light stimuli. Moreover, it ameliorated redox status and reduced inflammation including microglia activation, upregulation of cytokines, reactive gliosis, and PARP overactivation. Conclusions: NUT ameliorated retinal functionality and morphology at early stages of RP in rd10 mice. This formulation could be useful as a neuroprotective approach for patients with RP in the future.

scholarly journals Founder Effect of a c.828+3A>T Splice Site Mutation in Peripherin 2 (PRPH2) Causing Autosomal Dominant Retinal Dystrophies

2015 ◽  
Vol 133 (5) ◽  
pp. 511 ◽  
Author(s):  
Suma P. Shankar ◽  
David G. Birch ◽  
Richard S. Ruiz ◽  
Dianna K. Hughbanks-Wheaton ◽  
Lori S. Sullivan ◽  
...  
Keyword(s):  
Splice Site ◽  
Founder Effect ◽  
Autosomal Dominant ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Retinal Dystrophies

scholarly journals Genotype-Phenotype Correlations in RP1-Associated Retinal Dystrophies: A Multi-Center Cohort Study in JAPAN

2021 ◽  
Vol 10 (11) ◽  
pp. 2265
Author(s):  
Kei Mizobuchi ◽  
Takaaki Hayashi ◽  
Noriko Oishi ◽  
Daiki Kubota ◽  
Shuhei Kameya ◽  
...  
Keyword(s):  
Age At Onset ◽  
Japanese Patients ◽  
Clinical Findings ◽  
Cone Dystrophy ◽  
Element Insertion ◽  
Retinal Dystrophies ◽  
Whole Exome ◽  
Novel Variants ◽  
Alu Element ◽  
Frequent Variant

Background: Little is known about genotype–phenotype correlations of RP1-associated retinal dystrophies in the Japanese population. We aimed to investigate the genetic spectrum of RP1 variants and provide a detailed description of the clinical findings in Japanese patients. Methods: In total, 607 patients with inherited retinal diseases were examined using whole-exome/whole-genome sequencing (WES/WGS). PCR-based screening for an Alu element insertion (c.4052_4053ins328/p.Tyr1352AlafsTer9) was performed in 18 patients with autosomal-recessive (AR)-retinitis pigmentosa (RP) or AR-cone dystrophy (COD)/cone-rod dystrophy (CORD), including seven patients with heterozygous RP1 variants identified by WES/WGS analysis, and 11 early onset AR-RP patients, in whom no pathogenic variant was identified. We clinically examined 25 patients (23 families) with pathogenic RP1 variants, including five patients (five families) with autosomal-dominant (AD)-RP, 13 patients (11 families) with AR-RP, and seven patients (seven families) with AR-COD/CORD. Results: We identified 18 pathogenic RP1 variants, including seven novel variants. Interestingly, the Alu element insertion was the most frequent variant (32.0%, 16/50 alleles). The clinical findings revealed that the age at onset and disease progression occurred significantly earlier and faster in AR-RP patients compared to AD-RP or AR-COD/CORD patients. Conclusions: Our results suggest a genotype–phenotype correlation between variant types/locations and phenotypes (AD-RP, AR-RP, and AR-COD/CORD), and the Alu element insertion was the most major variant in Japanese patients with RP1-associated retinal dystrophies.

scholarly journals Telegenetics for inherited retinal diseases in the COVID-19 environment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ahmad Al-Moujahed ◽  
Aarushi Kumar ◽  
Teja Chemudupati ◽  
Stephen H. Tsang ◽  
Vinit B. Mahajan
Keyword(s):  
Genetic Testing ◽  
Diagnostic Tests ◽  
Family Counseling ◽  
Retinal Diseases ◽  
Clinical Testing ◽  
Medical Genetic ◽  
Retinal Dystrophies ◽  
Number Of Patients ◽  
Virtual Visits ◽  
Main Components

AbstractInherited retinal diseases (IRDs) are visually debilitating conditions that affect families worldwide. They require extensive clinical testing, examination, and patient and family counseling, which are frequently accomplished over single-day extended clinic visits. However, the COVID-19 pandemic has limited the number of patients and staff allowed in clinics, leading to interruptions in care. We therefore developed telehealth management protocols for complete or hybrid virtual visits. The three main components of our telegenetics approach included reviewing the diagnostic tests results remotely, in-person or virtual video visits with a retina specialist, and virtual genetic testing using saliva kits. During the first 5 months of the program, telegenetic care was provided for 80 patients, including 3 international patients, and a spectrum of retinal dystrophies were diagnosed and managed. In conclusion, telegenetic virtual visits ensure continuity of care while reducing patient and provider exposure to SARS-CoV-2 and may continue and expand into other medical genetic conditions long after the pandemic.

scholarly journals Genotypes Predispose Phenotypes—Clinical Features and Genetic Spectrum of ABCA4-Associated Retinal Dystrophies

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1421
Author(s):  
Yu-Chi Sung ◽  
Chang-Hao Yang ◽  
Chung-May Yang ◽  
Chao-Wen Lin ◽  
Ding-Siang Huang ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Degeneration ◽  
Medical Center ◽  
Fundus Autofluorescence ◽  
Genetic Diagnosis ◽  
Common Disease ◽  
Genetic Characteristics ◽  
Retinal Dystrophies ◽  
High Prevalence ◽  
Abca4 Gene

The ABCA4 gene is one of the most common disease-causing genes of inherited retinal degeneration. In this study, we report different phenotypes of ABCA4-associated retinal dystrophies in the Taiwanese population, its clinical progression, and its relationship with genetic characteristics. Thirty-seven subjects were recruited and all patients underwent serial ophthalmic examinations at a single medical center. Fundus autofluorescence (FAF) images were quantified for clinical evaluation, and panel-based next-generation sequencing testing was performed for genetic diagnosis. Visual preservation, disease progression, and genotype–phenotype correlation were analyzed. In this cohort, ABCA4-associated retinal degeneration presented as Stargardt disease 1 (STGD1, 62.16%), retinitis pigmentosa (32.43%), and cone-rod dystrophy (5.41%). STGD1 could be further divided into central and dispersed types. In each phenotype, the lesion areas quantified by FAF increased with age (p < 0.01) and correlated with poorer visual acuity. However, three patients had the foveal sparing phenotype and had relatively preserved visual acuity. Forty-two ABCA4 variants were identified as disease-causing, with c.1804C>T (p.Arg602Trp) the most frequent (37.84%). Patients with a combination of severe/null variants could have more extensive phenotypes, such as arRP and dispersed STGD1. This is the first cohort study of ABCA4-associated retinal degeneration in Taiwan with wide spectrums of both genotypic and phenotypic characteristics. An extremely high prevalence of c.1804C>T, which has not been reported in East Asia before, was noted. The extensiveness of retinal involvement might be regarded as a spectrum of ABCA4-associated retinal dystrophies. Different types of genetic variations could lead to distinctive phenotypes, according to the coding impact of variants.

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