Recent advances of exosomes in immune-mediated eye diseases

Li, Na; Zhao, Lu; Wei, Yankai; Ea, Vicki; Nian, Hong; Wei, Ruihua

doi:10.1186/s13287-019-1372-0

Cited by 67 publications

(55 citation statements)

References 120 publications

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“…Exosomes, the smallest EV fraction (40–200 nm in diameter) ( Théry et al, 2002 ; Vella et al, 2017 ; Hessvik and Llorente, 2018 ; Słomka et al, 2018 ), in particular, have recently been implicated in the pathogenesis of retinal degenerative diseases. These include Age-Related Macular Degeneration (AMD) ( Wang et al, 2009 ; Klingeborn et al, 2017 ; Hsu et al, 2018 ; Li et al, 2019 ), Diabetic Retinopathy ( Huang et al, 2018 ), and Retinitis Pigmentosa ( Vidal-Gil et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Small-Medium 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

Front. Cell. Neurosci.

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Photoreceptor cell death and inflammation are known to occur progressively in retinal degenerative diseases such as age-related macular degeneration (AMD). However, the molecular mechanisms underlying these biological processes are largely unknown. Extracellular vesicles (EV) are essential mediators of cell-to-cell communication with emerging roles in the modulation of immune responses. EVs, including exosomes, encapsulate and transfer microRNA (miRNA) to recipient cells and in this way can modulate the environment of recipient cells. Dysregulation of EVs however is correlated to a loss of cellular homeostasis and increased inflammation. In this work we investigated the role of isolated retinal small-medium sized EV (s-mEV) which includes exosomes in both the healthy and degenerating retina. Isolated s-mEV 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 s-mEV 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 s-mEV-abundant miRNA, miR-124-3p. Electroretinography and immunohistochemistry was performed to assess functional and morphological changes to the retina as a result of GW4869-induced exosome depletion. Results demonstrated an inverse correlation between s-mEV concentration and photoreceptor survivability, with a decrease in s-mEV numbers following degeneration. Small RNAseq revealed that s-mEVs contained uniquely enriched miRNAs in comparison to in whole retinal tissue, however, there was no differential change in the s-mEV miRNAnome following photo-oxidative damage. Exosome inhibition via the use of GW4869 was also found to exacerbate retinal degeneration, with reduced retinal function and increased levels of inflammation and cell death demonstrated following photo-oxidative damage in exosome-inhibited mice. Further, GW4869-treated mice displayed impaired translocation of photoreceptor-derived miR-124-3p to the inner retina during damage. Taken together, we propose that retinal s-mEV and their miRNA cargo play an essential role in maintaining retinal homeostasis through immune-modulation, and have the potential to be used in targeted gene therapy for retinal degenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Small-Medium 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

Front. Cell. Neurosci.

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“…To conclude, this study demonstrates a simple yet effective peptide modality that is capable of stimulating both cell motility and exosome biogenesis in corneal epithelium, mediated through Lacritin biology. As exosomes mediate cellular communication, signaling, and immune modulation, the biological and therapeutic effects of both exosomes and LP-A96 in the context of dry eye diseases (DED) [ 40 , 41 ] will greatly advance our knowledge towards the pathophysiology of DED and aid in providing a better way to improve daily lives of DED patients.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium

Lee

Edman

Laurie

et al. 2020

IJMS

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Lacripep is a therapeutic peptide derived from the human tear protein, Lacritin. Lacripep interacts with syndecan-1 and induces mitogenesis upon the removal of heparan sulfates (HS) that are attached at the extracellular domain of syndecan-1. The presence of HS is a prerequisite for the syndecan-1 clustering that stimulates exosome biogenesis and release. Therefore, syndecan-1-mediated mitogenesis versus HS-mediated exosome biogenesis are assumed to be mutually exclusive. This study introduces a biosynthesized fusion between Lacripep and an elastin-like polypeptide named LP-A96, and evaluates its activity on cell motility enhancement versus exosome biogenesis. LP-A96 activates both downstream pathways in a dose-dependent manner. HCE-T cells at high confluence treated with 1 μM LP-A96 enhanced cell motility equipotent to Lacripep. However, cells at low density treated with 1 μM LP-A96 generated a 210-fold higher number of exosomes compared to those treated at low density with Lacripep. As monovalent Lacripep is capable of enhancing cell motility but not exosome biogenesis, activation of exosome biogenesis by LP-A96 not only suggests its utility as a novel molecular tool to study the Lacritin biology in the corneal epithelium but also implies activity as a potential therapeutic peptide that can further improve ocular surface health through the induction of exosomes.

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“…It was concluded that MSC-Exo effects were partly due to the polarization of the lacrimal macrophage as well as the responses of Treg and Th2 by NF-kB signaling pathways. Thus, MSC-Exos may be useful in the treatment of dry eye [113]. Experimental autoimmune uveoretinitis (EAU) could be effectively resolved by the use of bone marrow-derived MSC-Exos [114].…”

Section: Therapeutic Potential Of Exosomes In Autoimmune Diseasementioning

confidence: 99%

Biogenesis, Biologic Function and Clinical Potential of Exosomes in Different Diseases

et al. 2020

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Exosomes are extracellular vesicles (EVs) belonging to the nanovesicles family that function as signaling molecules between cells. After their first description in the late 1960s, interest in their potential as a research target has steadily increased. They are small secreted organelles with a single membrane that are well enriched in lipids, proteins, nucleic acids, and glycoconjugates. Exosomes take part in a larger communication network in which cells communicate between one another by DNA shuttling, proteins, RNA, and membrane-bound factors. The machinery of protein quality control occurs through the process termed “exosome biogenesis”. Furthermore, the pathway involved in intercellular movement of vesicles is vital in various aspects of human health and diseases. Due to their inherent properties, exosomes are currently being developed as potential therapeutic agents in a wide range of diseases including infectious and non-infectious diseases. Exosomes and other EVs sourced from Mesenchymal stem cells (MSCs) have been shown in different studies to possess therapeutic effects in diverse disease models either in vivo or in vitro. Some mechanisms and/or pathways that MSC-derived exosomes use to illustrate their therapeutic effect against some diseases have also been summarized. This review aims to highlight the recent findings and potential therapeutic application of exosomes in different diseases such as autoimmune, cardiovascular, obesity, neural, soft tissues, bone, and cartilage.

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Recent advances of exosomes in immune-mediated eye diseases

Cited by 67 publications

References 120 publications

Small-Medium Extracellular Vesicles and Their miRNA Cargo in Retinal Health and Degeneration: Mediators of Homeostasis, and Vehicles for Targeted Gene Therapy

Small-Medium Extracellular Vesicles and Their miRNA Cargo in Retinal Health and Degeneration: Mediators of Homeostasis, and Vehicles for Targeted Gene Therapy

Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium

Biogenesis, Biologic Function and Clinical Potential of Exosomes in Different Diseases

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