Retinal dystrophins and the retinopathy of Duchenne muscular dystrophy

Barboni, Mirella Telles Salgueiro; Joachimsthaler, Anneka; Roux, Michel J.; Nagy, Zoltán Zsolt; Ventura, Dora Fix; Rendón, Álvaro; Kremers, Jan; Vaillend, Cyrille

doi:10.1016/j.preteyeres.2022.101137

Cited by 4 publications

(1 citation statement)

References 284 publications

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“…Some forms of congenital myopathy result in eye muscle weakness and ophthalmoparesis and are particularly amenable to study via the optokinetic response ( Jungbluth et al, 2018 ). Dystroglycanopathies and, to a lesser extent, DMD are linked to retinal deficits due to the critical role of the dystrophin-glycoprotein complex in photoreceptor synapse function ( Barboni et al, 2022 ; Hagedorn et al, 2023 ; Jahncke and Wright, 2023 ). These have not been extensively studied in the zebrafish, but lighting conditions and shifts in light-dark cycles could affect experimental outcomes as zebrafish have defined circadian rhythms ( Wolter and Svoboda, 2020 ; Pintos et al, 2023 ).…”

Section: Standards For Phenotypic Endpoints and Outcome Measures For ...mentioning

confidence: 99%

Standardization of zebrafish drug testing parameters for muscle diseases

Karuppasamy,

English,

Henry

et al. 2024

Disease Models &Amp; Mechanisms

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Skeletal muscular diseases predominantly affect skeletal and cardiac muscle, resulting in muscle weakness, impaired respiratory function and decreased lifespan. These harmful outcomes lead to poor health-related quality of life and carry a high healthcare economic burden. The absence of promising treatments and new therapies for muscular disorders requires new methods for candidate drug identification and advancement in animal models. Consequently, the rapid screening of drug compounds in an animal model that mimics features of human muscle disease is warranted. Zebrafish are a versatile model in preclinical studies that support developmental biology and drug discovery programs for novel chemical entities and repurposing of established drugs. Due to several advantages, there is an increasing number of applications of the zebrafish model for high-throughput drug screening for human disorders and developmental studies. Consequently, standardization of key drug screening parameters, such as animal husbandry protocols, drug compound administration and outcome measures, is paramount for the continued advancement of the model and field. Here, we seek to summarize and explore critical drug treatment and drug screening parameters in the zebrafish-based modeling of human muscle diseases. Through improved standardization and harmonization of drug screening parameters and protocols, we aim to promote more effective drug discovery programs.

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Section: Standards For Phenotypic Endpoints and Outcome Measures For ...mentioning

confidence: 99%

Standardization of zebrafish drug testing parameters for muscle diseases

Karuppasamy,

English,

Henry

et al. 2024

Disease Models &Amp; Mechanisms

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Systemic Treatment of Body‐Wide Duchenne Muscular Dystrophy Symptoms

Konieczny

2024

Clin Pharma and Therapeutics

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Duchenne muscular dystrophy (DMD) is a fatal X‐linked disease that leads to premature death due to the loss of dystrophin. Current strategies predominantly focus on the therapeutic treatment of affected skeletal muscle tissue. However, certain results point to the fact that with successful treatment of skeletal muscle, DMD‐exposed latent phenotypes in tissues, such as cardiac and smooth muscle, might lead to adverse effects and even death. Likewise, it is now clear that the absence of dystrophin affects the function of the nervous system, and that this phenotype is more pronounced when shorter dystrophins are absent, in addition to the full‐length dystrophin that is present predominantly in the muscle. Here, I focus on the systemic aspects of DMD, highlighting the ubiquitous expression of the dystrophin gene in human tissues. Furthermore, I describe therapeutic strategies that have been tested in the clinic and point to unresolved questions regarding the function of distinct dystrophin isoforms, and the possibility of current therapeutic strategies to tackle phenotypes that relate to their absence.

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IPSC derived cardiac fibroblasts of DMD patients show compromised actin microfilaments, metabolic shift and pro-fibrotic phenotype

Soussi,

Savchenko,

Rovina

et al. 2023

Biol Direct

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Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy caused by mutations in the dystrophin gene. We characterized which isoforms of dystrophin were expressed by human induced pluripotent stem cell (hiPSC)-derived cardiac fibroblasts obtained from control and DMD patients. Distinct dystrophin isoforms were observed; however, highest molecular weight isoform was absent in DMD patients carrying exon deletions or mutations in the dystrophin gene. The loss of the full-length dystrophin isoform in hiPSC-derived cardiac fibroblasts from DMD patients resulted in deficient formation of actin microfilaments and a metabolic switch from mitochondrial oxidation to glycolysis. The DMD hiPSC-derived cardiac fibroblasts exhibited a dysregulated mitochondria network and reduced mitochondrial respiration, with enhanced compensatory glycolysis to sustain cellular ATP production. This metabolic remodeling was associated with an exacerbated myofibroblast phenotype and increased fibroblast activation in response to pro fibrotic challenges. As cardiac fibrosis is a critical pathological feature of the DMD heart, the myofibroblast phenotype induced by the absence of dystrophin may contribute to deterioration in cardiac function. Our study highlights the relationship between cytoskeletal dynamics, metabolism of the cell and myofibroblast differentiation and provides a new mechanism by which inactivation of dystrophin in non-cardiomyocyte cells may increase the severity of cardiopathy.

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Retinal dystrophins and the retinopathy of Duchenne muscular dystrophy

Cited by 4 publications

References 284 publications

Standardization of zebrafish drug testing parameters for muscle diseases

Standardization of zebrafish drug testing parameters for muscle diseases

Systemic Treatment of Body‐Wide Duchenne Muscular Dystrophy Symptoms

IPSC derived cardiac fibroblasts of DMD patients show compromised actin microfilaments, metabolic shift and pro-fibrotic phenotype

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