Reviewing the Role of Ultra-Widefield Imaging in Inherited Retinal Dystrophies

Inherited retinal dystrophies are an assorted group of rare diseases that collectively account for the major cause of visual impairment of genetic origin worldwide. Besides clinically, these vision loss disorders present a high genetic and allelic heterogeneity. To date, over 250 genes have been associated to retinal dystrophies with reported causative variants of every nature (nonsense, missense, frameshift, splice-site, large rearrangements, and so forth). Except for a fistful of mutations, most of them are private and affect one or few families, making it a challenge to ratify the newly identified candidate genes or the pathogenicity of dubious variants in disease-associated loci. A recurrent option involves altering the gene in in vitro or in vivo systems to contrast the resulting phenotype and molecular imprint. To validate specific mutations, the process must rely on simulating the precise genetic change, which, until recently, proved to be a difficult endeavor. The rise of the CRISPR/Cas9 technology and its adaptation for genetic engineering now offers a resourceful suite of tools to alleviate the process of functional studies. Here we review the implementation of these RNA-programmable Cas9 nucleases in culture-based and animal models to elucidate the role of novel genes and variants in retinal dystrophies.

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Inherited Retinal Dystrophies: The role of gene expression regulators

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2015.02.007 ◽

2015 ◽

Vol 61 ◽

pp. 115-119 ◽

Cited By ~ 4

Author(s):

Marianthi Karali ◽

Sandro Banfi

Keyword(s):

Gene Expression ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies

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

European Journal of Human Genetics ◽

10.1038/sj.ejhg.5200538 ◽

2000 ◽

Vol 8 (10) ◽

pp. 783-787 ◽

Cited By ~ 7

Author(s):

David AR Bessant ◽

Annette M Payne ◽

Catherine Plant ◽

Alan C Bird ◽

Anand Swaroop ◽

...

Keyword(s):

Founder Effects ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies

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

Therapeutic Advances in Ophthalmology ◽

10.1177/2515841421997191 ◽

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.

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

Nanomaterials ◽

10.3390/nano11040935 ◽

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.

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

Antioxidants ◽

10.3390/antiox10071033 ◽

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.

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Combined Genetic and High-Throughput Strategies for Molecular Diagnosis of Inherited Retinal Dystrophies

PLoS ONE ◽

10.1371/journal.pone.0088410 ◽

2014 ◽

Vol 9 (2) ◽

pp. e88410 ◽

Cited By ~ 21

Author(s):

Marta de Castro-Miró ◽

Esther Pomares ◽

Laura Lorés-Motta ◽

Raul Tonda ◽

Joaquín Dopazo ◽

...

Keyword(s):

Molecular Diagnosis ◽

High Throughput ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies

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Novel mobility test to assess functional vision in patients with inherited retinal dystrophies

Clinical and Experimental Ophthalmology ◽

10.1111/ceo.13022 ◽

2017 ◽

Vol 46 (3) ◽

pp. 247-259 ◽

Cited By ~ 34

Author(s):

Daniel C Chung ◽

Sarah McCague ◽

Zi-Fan Yu ◽

Satha Thill ◽

Julie DiStefano-Pappas ◽

...

Keyword(s):

Mobility Test ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies ◽

Functional Vision

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Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

Scientific Reports ◽

10.1038/s41598-021-98677-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Atta Ur Rehman ◽

Neda Sepahi ◽

Nicola Bedoni ◽

Zeinab Ravesh ◽

Arash Salmaninejad ◽

...

Keyword(s):

Disease Genes ◽

Homozygous State ◽

Traditional Practice ◽

Genomic Variants ◽

Mutational Spectrum ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies ◽

Whole Exome ◽

Human Disorders ◽

Generation Sequencing

AbstractInherited retinal dystrophies (IRDs) constitute one of the most heterogeneous groups of Mendelian human disorders. Using autozygome-guided next-generation sequencing methods in 17 consanguineous pedigrees of Iranian descent with isolated or syndromic IRD, we identified 17 distinct genomic variants in 11 previously-reported disease genes. Consistent with a recessive inheritance pattern, as suggested by pedigrees, variants discovered in our study were exclusively bi-allelic and mostly in a homozygous state (in 15 families out of 17, or 88%). Out of the 17 variants identified, 5 (29%) were never reported before. Interestingly, two mutations (GUCY2D:c.564dup, p.Ala189ArgfsTer130 and TULP1:c.1199G > A, p.Arg400Gln) were also identified in four separate pedigrees (two pedigrees each). In addition to expanding the mutational spectrum of IRDs, our findings confirm that the traditional practice of endogamy in the Iranian population is a prime cause for the appearance of IRDs.

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