Extracellular vesicle therapy for retinal diseases

Mead, Ben; Tomarev, Stanislav I.

doi:10.1016/j.preteyeres.2020.100849

Cited by 93 publications

(88 citation statements)

References 117 publications

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“…In addition to replacement and neurotrophic mechanisms based on stem/progenitor cells, the latest studies have focused on extracellular exosomes secreted by stem cells as a potential therapy for RD. Several studies have identified that some types of MSCs secrete exosomes (MSC-Exo), mainly adipose, bone marrow and umbilical MSCs 45 . Exosomes are cell-derived nanovesicles that have low toxicity, low risk of immunological rejection, exquisite target-homing specificity and potential for drug/gene delivery 115 .…”

Section: Stem Cell-derived Exosomes For Rd Treatmentmentioning

confidence: 99%

“…Exosomes are cell-derived nanovesicles that have low toxicity, low risk of immunological rejection, exquisite target-homing specificity and potential for drug/gene delivery 115 . Accordingly, exosome-based therapy is gaining research attention for multiple diseases throughout the body 45 . For instance, scientists have found that MSC-Exo has a prominent therapeutic effect in central nervous system diseases, such as stroke 116,117 , Alzheimer's disease 118 and spinal cord injury 119 .…”

Section: Stem Cell-derived Exosomes For Rd Treatmentmentioning

confidence: 99%

“…More recently, it has been discovered that many types of stem cells, e.g., adipose, bone marrow and umbilical MSCs, can secrete multifunctional exosomes that have low risk of toxicity and immunological rejection, and hold substantial potential for immunotherapy and drug delivery by transmitting numerous biomolecules to specific cells [41][42][43][44] . This implies that stem cells will gain additional traction as a promising treatment for RD due to the advantages of their secreted nanoscale exosomes 45 . A previous review has described in detail the present basic experiments and rationale behind stem/progenitor cellbased transplantation for treatment of RD 46 .…”

Section: Introductionmentioning

confidence: 99%

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Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials

Wang

Tang

2020

Cell Death Dis

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Retinal degeneration (RD) is one of the dominant causes of irreversible vision impairment and blindness worldwide. However, the current effective therapeutics for RD in the ophthalmologic clinic are unclear and controversial. In recent years, extensively investigated stem/progenitor cells—including retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stromal cells (MSCs)—with proliferation and multidirectional differentiation potential have presented opportunities to revolutionise the ultimate clinical management of RD. Herein, we provide a comprehensive overview on the progression of clinical trials for RD treatment using four types of stem/progenitor cell-based transplantation to replace degenerative retinal cells and/or to supplement trophic factors from the aspects of safety, effectiveness and their respective advantages and disadvantages. In addition, we also discuss the emerging role of stem cells in the secretion of multifunctional nanoscale exosomes by which stem cells could be further exploited as a potential RD therapy. This review will facilitate the understanding of scientists and clinicians of the enormous promise of stem/progenitor cell-based transplantation for RD treatment, and provide incentive for superior employment of such strategies that may be suitable for treatment of other diseases, such as stroke and ischaemia–reperfusion injury.

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Section: Stem Cell-derived Exosomes For Rd Treatmentmentioning

confidence: 99%

Section: Stem Cell-derived Exosomes For Rd Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials

Wang

Tang

2020

Cell Death Dis

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“…They are considered signaling mediators between cells due to their capability of transporting and delivering proteins, mRNA, miRNA, and lipids. EV are gaining attraction as a candidate treatment for ocular diseases and have already been tested in many retinal damage models, such as glaucoma, retinal ischemia, autoimmune uveitis, and diabetic retinopathy, with promising results (Mead and Tomarev, 2020). Interestingly, it is becoming evident that the miRNA component of EV plays a relevant contribution to the protective action of EV.…”

Section: Microrna-based Approachesmentioning

confidence: 99%

Mutation-Independent Therapies for Retinal Diseases: Focus on Gene-Based Approaches

et al. 2020

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Gene therapy is proving to be an effective approach to treat or prevent ocular diseases ensuring a targeted, stable, and regulated introduction of exogenous genetic material with therapeutic action. Retinal diseases can be broadly categorized into two groups, namely monogenic and complex (multifactorial) forms. The high genetic heterogeneity of monogenic forms represents a significant limitation to the application of gene-specific therapeutic strategies for a significant fraction of patients. Therefore, mutation-independent therapeutic strategies, acting on common pathways that underly retinal damage, are gaining interest as complementary/alternative approaches for retinal diseases. This review will provide an overview of mutation-independent strategies that rely on the modulation in the retina of key genes regulating such crucial degenerative pathways. In particular, we will describe how gene-based approaches explore the use of neurotrophic factors, microRNAs (miRNAs), genome editing and optogenetics in order to restore/prolong visual function in both outer and inner retinal diseases. We predict that the exploitation of gene delivery procedures applied to mutation/gene independent approaches may provide the answer to the unmet therapeutic need of a large fraction of patients with genetically heterogeneous and complex retinal diseases.

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“…including for the treatment of neurodegenerative diseases (Sarko andMcKinney 2017, Mead andTomarev 2020). However, their use for the treatment of retinal degenerations is largely in its infancy (reviewed in (Mead and Tomarev 2020). Hajrasouliha et.…”

Section: Exosomes As Mediators Of Phototransductionmentioning

confidence: 99%

Extracellular vesicles and their miRNA cargo in retinal health and degeneration: mediators of homeostasis, and vehicles for targeted gene therapy

Wooff

Cioanca

Chu-Tan

et al. 2020

Preprint

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Photoreceptor cell death and inflammation are known to occur progressively in retinal degenerative diseases, however the molecular mechanisms underlying these biological processes are largely unknown. Exosomes are essential mediators of cell-to-cell communication with emerging roles in the modulation of immune responses. Exosomes encapsulate and transfer nucleic acids, including microRNA (miRNA), to recipient cells which in disease may result in dysfunctional immune responses and a loss of homeostatic regulation. In this work we investigated the role of retinal exosomes in both the healthy and degenerating retina. Isolated exosomes from normal retinas were characterized using dynamic light scattering, transmission electron microscopy and western blotting, and quantified across 5 days of photo-oxidative damage-induced degeneration using nanotracking analysis. Small RNAseq was used to characterize the miRNA cargo of retinal exosomes isolated from healthy and damaged retinas. Finally, the effect of exosome inhibition on cell-to-cell miRNA transfer and immune modulation was conducted using systemic daily administration of exosome inhibitor GW4869 and in situ hybridization of exosome-abundant miRNA, miR-124-3p. Electroretinography and immunohistochemistry was performed to assess functional and morphological changes to the retina as a result of exosome depletion.

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Extracellular vesicle therapy for retinal diseases

Cited by 93 publications

References 117 publications

Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials

Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials

Mutation-Independent Therapies for Retinal Diseases: Focus on Gene-Based Approaches

Extracellular vesicles and their miRNA cargo in retinal health and degeneration: mediators of homeostasis, and vehicles for targeted gene therapy

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