Emerging Role of Exosomes in Retinal Diseases

Zhang, Zhengyu; Mugisha, Aime; Fransisca, Silvia; Liu, Qing-Huai; Hu, Zizhong

doi:10.3389/fcell.2021.643680

Cited by 25 publications

(33 citation statements)

References 110 publications

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“…Quantification of EVs, identification of particle size distribution and of EV tetraspanin expression profiles may elucidate molecular pathogenesis of eye diseases and have future clinical application. The expression profiles of common tetraspanin markers, including CD63, CD81 and CD9 were defined ( Klingeborn et al, 2017 ; Kowal et al, 2016 ; Zhang et al, 2016 ) but whether these tetraspanins are expressed on AH-derived EVs remains unclear. In this pilot study, we evaluated 27 AH samples from 24 eyes of 19 patients with four different types of pediatric eye diseases: congenital cataract (CAT), congenital glaucoma (GLC), pediatric retinal disease (PRD) and retinoblastoma (Rb).…”

Section: Introductionmentioning

confidence: 99%

Single vesicle analysis of aqueous humor in pediatric ocular diseases reveals eye specific CD63‐dominant subpopulations

Peng

Sirivolu

et al. 2022

J of Extracellular Bio

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Aqueous humor (AH), the clear fluid in front of the eye, maintains the pressure and vitality of ocular tissues. This fluid is accessible via the clear cornea which enables use of AH as a liquid biopsy source of biomarkers for intraocular disease. Extracellular vesicles are detectable in the AH and small extracellular vesicles (sEVs) are present in the AH from adults. However, EVs in AH from pediatric eyes in vivo have never previously been explored. We know very little about the heterogeneity of AH EV populations in ocular disease. Twenty-seven processing-free AH samples from 19 patients across four different pediatric ocular diseases were subjected to Nanoparticle Tracking Analysis (NTA) and Single Particle-Interferometric Reflectance Imaging Sensor (SP-IRIS) analysis. NTA demonstrated the concentration of AH EV/EPs is 3.11 × 10 9 -1.38 × 10 10 particles/ml; the majority sized 76.8-103 nm. SP-IRIS revealed distinct patterns of tetraspanin expression of AH sEVs. An enriched mono-CD63+ sEV subpopulation identified in AH indicates this is a potential AH-specific biomarker. In the setting of retinoblastoma there was a more heterogeneous population of sEVs which normalized with treatment. This suggests a potential clinical application of direct measurement of sEV subpopulations in AH samples to monitor successful tumor response to therapy.

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Section: Introductionmentioning

confidence: 99%

Single vesicle analysis of aqueous humor in pediatric ocular diseases reveals eye specific CD63‐dominant subpopulations

Peng

Sirivolu

et al. 2022

J of Extracellular Bio

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“…Although MVs and exosomes are structurally similar, there are still some differences in the size and cellular origin. Exosomes are the smallest vesicles released by the fusion of multivesicular bodies containing intraluminal vesicles with the plasma membrane, and possess pleiotropic biological functions on retinal vessels, including modulation of vascular homeostasis, immune activation, and angiogenesis [ 2 , 30 , 31 , 32 ]. MVs are heterogeneous vesicles originating from multiple sources, such as selective outward pinching of the plasma membrane to membrane shedding and/or vesicles resulting from cell death [ 3 ].…”

Section: Resultsmentioning

confidence: 99%

Differences in the Quantity and Composition of Extracellular Vesicles in the Aqueous Humor of Patients with Retinal Neovascular Diseases

et al. 2021

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Extracellular vesicles (EVs) are secreted by various cells in the body fluid system and have been found to influence vessel formation and inflammatory responses in a variety of diseases. However, which EVs and their subtypes are involved in vascular retinal diseases is still unclear. Therefore, the aim of this study was to explore the particle distribution of EVs in retinal neovascular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, and central retinal vein occlusion. The aqueous humor was harvested from 20 patients with different retinal neovascular diseases and six patients with cataracts as the control group. The particle distribution was analyzed using nanoparticle tracking analysis (NTA) and transmitting electron microscopy (TEM). The results revealed that the disease groups had large amounts of EVs and their subtypes compared to the control group. After isolating exosomes, a higher expression of CD81+ exosomes was shown in the disease groups using flow cytometry. The exosomes were then further classified into three subtypes of exomeres, small exosomes, and large exosomes, and their amounts were shown to differ depending on the disease type. To the best of our knowledge, this is the first study to elucidate the dynamics of EVs in retinal neovascular diseases using clinical cases. Our findings demonstrated the possible functionality of microvesicles and exosomes, indicating the potential of exosomes in the diagnosis and therapy of retinal neovascular diseases.

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“…Exosomes, shed by various cell type, can exist extensively in body fluid; in the eye, they can exist in tears, aqueous humor, vitreous humor, and blood. 47,48 During the past decade, exosomes have emerged as a promising field in biomedical research as biomarkers for diagnosing diseases 19,49,50 or participants in cell-to-cell communication through receptor-ligand interactions. In ocular diseases, Ragusa et al previously performed miRNA sequencing on vitreal exosomes from uveal melanoma patients who underwent ocular enucleation.…”

Section: Discussionmentioning

confidence: 99%

Müller glia-derived exosomal miR-9-3p promotes angiogenesis by restricting sphingosine-1-phosphate receptor S1P1 in diabetic retinopathy

Liu

Yang

et al. 2022

Molecular Therapy - Nucleic Acids

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Diabetic retinopathy is a heterogeneous retinal degenerative disease with the microvascular dysfunction being recognized as a hallmark of the advanced stage. In this study, we demonstrated that exosomes collected from the vitreous humor of proliferative diabetic retinopathy patients promoted proliferation, migration and tube formation ability of primary human retinal endothelial cells via its elevated miR-9-3p expression level. Müller glia cells were further recognized as the sole source of the aberrantly expressed miR-9-3p, and both in vitro and in vivo experiments validated that Müller glia-derived exosomes aggravate vascular dysfunction under high glucose. Mechanistically, exosomal miRNA-9-3p was transferred to retinal endothelial cells and bound to the sphingosine-1-phosphate receptor S1P 1 coding sequence, which subsequently activated VEGFR2 phosphorylation and internalization in the presence or absence of exogenous VEGF-A. We successfully orchestrated the dynamic crosstalk between retinal Müller glia cells and endothelial cells in pathological condition, which may provide a novel biomarker or promising therapeutic agents for the treatment of diabetic retinopathy.

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Emerging Role of Exosomes in Retinal Diseases

Cited by 25 publications

References 110 publications

Single vesicle analysis of aqueous humor in pediatric ocular diseases reveals eye specific CD63‐dominant subpopulations

Single vesicle analysis of aqueous humor in pediatric ocular diseases reveals eye specific CD63‐dominant subpopulations

Differences in the Quantity and Composition of Extracellular Vesicles in the Aqueous Humor of Patients with Retinal Neovascular Diseases

Müller glia-derived exosomal miR-9-3p promotes angiogenesis by restricting sphingosine-1-phosphate receptor S1P1 in diabetic retinopathy

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