Michael E. Cheetham
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View article: Adenine base editor correction of pathogenic variations associated with inherited retinal dystrophy in patient iPSC and retinal organoids
Adenine base editor correction of pathogenic variations associated with inherited retinal dystrophy in patient iPSC and retinal organoids Open
Inherited retinal dystrophies (IRDs) are a group of incurable, genetically heterogeneous diseases that cause progressive degeneration of the retina, leading to the loss of vision. Genome editing technologies offer a powerful prospect for m…
View article: Preventing light-induced toxicity in a new mouse model of sector retinitis pigmentosa caused by Rhodopsin M39R variant
Preventing light-induced toxicity in a new mouse model of sector retinitis pigmentosa caused by Rhodopsin M39R variant Open
Retinitis Pigmentosa (RP) is an inherited retinal dystrophy characterised by the progressive loss of rod photoreceptors. Sector RP is a form of RP where degeneration originates in the inferior retina, mainly influenced by light exposure. O…
View article: Stargardt's Connected Research Network Inaugural Meeting: Landscape Review and Horizon Scanning of Stargardt Disease
Stargardt's Connected Research Network Inaugural Meeting: Landscape Review and Horizon Scanning of Stargardt Disease Open
This Stargardt's Connected Research Network initiative outlines a multistakeholder engagement model to discuss ongoing research and emerging treatments for Stargardt disease, a condition with promising therapeutic developments.
View article: <i>RHO</i>-Associated Retinitis Pigmentosa: Genetics, Phenotype, Natural History, Functional Assays, and Animal Model – In Preparation for Clinical Trials
<i>RHO</i>-Associated Retinitis Pigmentosa: Genetics, Phenotype, Natural History, Functional Assays, and Animal Model – In Preparation for Clinical Trials Open
RHO-associated RP encompasses a wide phenotypic spectrum with distinct genetic subtypes influencing disease severity and progression. These findings provide critical insights for patient counseling, identifying clinical endpoints, particip…
View article: Investigation of ABCA4 Missense Variants and Potential Small Molecule Rescue in Retinal Organoids
Investigation of ABCA4 Missense Variants and Potential Small Molecule Rescue in Retinal Organoids Open
These data highlight that retinal organoids are an exquisite model to investigate pathogenic variants in ABCA4 and test small compounds for translation to the human retina.
View article: Antisense oligonucleotide allele-specific targeting of EFEMP1 in a patient-derived model of Doyne honeycomb retinal dystrophy
Antisense oligonucleotide allele-specific targeting of EFEMP1 in a patient-derived model of Doyne honeycomb retinal dystrophy Open
Doyne honeycomb retinal dystrophy is an incurable juvenile macular dystrophy that leads to visual impairment by early to mid-adulthood. It is an autosomal dominant disorder caused by a c.1033T>C, p.Arg345Trp variant in EFEMP1 , and is char…
View article: CRISPRa-Mediated Increase of OPA1 Expression in Dominant Optic Atrophy
CRISPRa-Mediated Increase of OPA1 Expression in Dominant Optic Atrophy Open
Dominant Optic Atrophy (DOA) is the most common inherited optic neuropathy and presents as gradual visual loss caused by the loss of retinal ganglion cells (RGCs). Over 60% of DOA cases are caused by pathogenic variants in the OPA1 gene, w…
View article: Digitalizing English-language CT Interpretation for Positive Haemorrhage Evaluation Reporting: the DECIPHER study
Digitalizing English-language CT Interpretation for Positive Haemorrhage Evaluation Reporting: the DECIPHER study Open
Objectives Identifying whether there is a traumatic intracranial bleed (ICB+) on head CT is critical for clinical care and research. Free text CT reports are unstructured and therefore must undergo time-consuming manual review. Existing ar…
View article: Lost in communication: How Müller glia cells fail to maintain retinal integrity in USH1C retinal organoids
Lost in communication: How Müller glia cells fail to maintain retinal integrity in USH1C retinal organoids Open
Usher syndrome type 1, caused by pathogenic variants in the USH1C gene, leads to congenital deafness and progressive retinal degeneration resulting in vision loss. While auditory deficits can be compensated by cochlea implants and hearing …
View article: Preventing light-induced toxicity in a new mouse model of rhodopsin sector retinitis pigmentosa
Preventing light-induced toxicity in a new mouse model of rhodopsin sector retinitis pigmentosa Open
Retinitis Pigmentosa (RP) is an inherited retinal dystrophy characterized by the progressive loss of rod photoreceptors. Sector RP is a form of RP, where degeneration originates in the inferior retina, mainly influenced by light exposure. …
View article: A novel recurrent <i>ARL3</i> variant c.209G &gt; A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models
A novel recurrent <i>ARL3</i> variant c.209G > A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models Open
Inherited retinal dystrophies (IRDs) are characterized by their high clinical and genetic heterogeneity. Despite significant advances in the identification of genes associated with IRDs, many individuals and families still have not receive…
View article: Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids
Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids Open
Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report the use of gene editing to generate isogenic …
View article: Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids
Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids Open
Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report the use of gene editing to generate isogenic …
View article: Disruption of mitochondrial homeostasis and permeability transition pore opening in OPA1 iPSC-derived retinal ganglion cells
Disruption of mitochondrial homeostasis and permeability transition pore opening in OPA1 iPSC-derived retinal ganglion cells Open
Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterised by the selective loss of retinal ganglion cells (RGCs). Over 60% of DOA cases are caused by pathogenic variants in the OPA1 gene, which encodes a dyn…
View article: Specificity and diversity of <i>Klebsiella pneumoniae</i> phage-encoded capsule depolymerases
Specificity and diversity of <i>Klebsiella pneumoniae</i> phage-encoded capsule depolymerases Open
Klebsiella pneumoniae is an opportunistic pathogen with significant clinical relevance. K. pneumoniae-targeting bacteriophages encode specific polysaccharide depolymerases with the ability to selectively degrade the highly varied protectiv…
View article: Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach
Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach Open
Introduction Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topolo…
View article: Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping
Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping Open
UK Research and Innovation, Moorfields Eye Charity, Fight for Sight, Medical Research Council, NIHR BRC at Moorfields Eye Hospital and UCL Institute of Ophthalmology, Grantová Agentura České Republiky, Univerzita Karlova v Praze, the Natio…
View article: Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant
Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant Open
Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree …
View article: Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease
Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease Open
Fuchs endothelial corneal dystrophy (FECD) is an age-related cause of vision loss, and the most common repeat expansion-mediated disease in humans characterised to date. Up to 80% of European FECD cases have been attributed to expansion of…
View article: A Proximity Complementation Assay to Identify Small Molecules That Enhance the Traffic of ABCA4 Misfolding Variants
A Proximity Complementation Assay to Identify Small Molecules That Enhance the Traffic of ABCA4 Misfolding Variants Open
ABCA4-related retinopathy is the most common inherited Mendelian eye disorder worldwide, caused by biallelic variants in the ATP-binding cassette transporter ABCA4. To date, over 2200 ABCA4 variants have been identified, including missense…
View article: Tissue-Specific Dynamics of<i>TCF4</i>Triplet Repeat Instability Revealed by Optical Genome Mapping
Tissue-Specific Dynamics of<i>TCF4</i>Triplet Repeat Instability Revealed by Optical Genome Mapping Open
Here, we demonstrate the utility of optical genome mapping (OGM) to interrogate the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (termed CTG18.1) and gain novel insights into the tissue-specific nature…
View article: A proximity complementation assay to identify small molecules that enhance the traffic of ABCA4 misfolding variants
A proximity complementation assay to identify small molecules that enhance the traffic of ABCA4 misfolding variants Open
ABCA4-related-retinopathy is the most common inherited Mendelian eye disorder worldwide, caused by biallelic variants in the ATP-binding cassette transporter ABCA4. To date, over 2,200 ABCA4 variants have been identified, including missens…
View article: Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity
Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity Open
Blindness poses a growing global challenge, with approximately 26% of cases attributed to degenerative retinal diseases. While gene therapy, optogenetic tools, photosensitive switches, and retinal prostheses offer hope for vision restorati…
View article: Investigating the synaptic mechanisms of the spread of wild type and P301S 1N4R human tau in in vitro and in vivo models
Investigating the synaptic mechanisms of the spread of wild type and P301S 1N4R human tau in in vitro and in vivo models Open
Background Tau aggregates propagate across functionally connected neuronal networks in tauopathies as Alzheimer’s disease. However, the mechanisms underlying this process are poorly understood. Different studies showed that tau release is …