Lymphocytic microparticles suppress retinal angiogenesis via targeting Müller cells in the ischemic retinopathy mouse model

Purpose Advances in mass spectrometry have provided new insights into the role of metabolomics in the etiology of several diseases. Studies on retinopathy of prematurity (ROP), for example, overlooked the role of metabolic alterations in disease development. We employed comprehensive metabolic profiling and gold-standard metabolic analysis to explore major metabolites and metabolic pathways, which were significantly affected in early stages of pathogenesis toward ROP. Methods This was a multicenter, retrospective, matched-pair, case-control study. We collected plasma from 57 ROP cases and 57 strictly matched non-ROP controls. Non-targeted ultra-high-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS) was used to detect the metabolites. Machine learning was employed to reveal the most affected metabolites and pathways in ROP development. Results Compared with non-ROP controls, we found a significant metabolic perturbation in the plasma of ROP cases, which featured an increase in the levels of lipids, nucleotides, and carbohydrate metabolites and lower levels of peptides. Machine leaning enabled us to distinguish a cluster of metabolic pathways (glycometabolism, redox homeostasis, lipid metabolism, and arginine pathway) were strongly correlated with the development of ROP. Moreover, the severity of ROP was associated with the levels of creatinine and ribitol; also, overactivity of aerobic glycolysis and lipid metabolism was noted in the metabolic profile of ROP. Conclusions The results suggest a strong correlation between metabolic profiling and retinal neovascularization in ROP pathogenesis. These findings provide an insight into the identification of novel metabolic biomarkers for the diagnosis and prevention of ROP, but the clinical significance requires further validation.

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“… 87 An emerging body of evidence has shown that Müller cells are the predominant source of VEGF. 14 , 88 …”

Section: Discussionmentioning

confidence: 99%

“… 13 In oxygen-induced retinopathy (OIR) models of proliferative retinopathy, relative hypoxia induces high levels of VEGF-A production, causing uncontrolled vessel growth. 14 The metabolic needs of photoreceptors regulate this process. Photoreceptor metabolic alterations can control pathological angiogenesis.…”

mentioning

confidence: 99%

Comparative Analysis Reveals Novel Changes in Plasma Metabolites and Metabolomic Networks of Infants With Retinopathy of Prematurity

Yang

Luo

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…The reduced pathological retinal neovascularization has also been observed in a mouse model of OIR after intravitreal injection of LMPs. Specifically, LMPs inhibit the proliferation of Müller cells and decrease VEGF expression, thereby attenuating the infiltration of proangiogenic macrophages 122 . A study by Yang et al 123 analyzed the expression profiling of RNAs in LMPs and found selective enrichment of miR-18a, which inhibited retinal neovascularization in both in vitro and in vivo models of OIR.…”

Section: Ev-based Therapy In Drmentioning

confidence: 99%

Emerging role of extracellular vesicles in diabetic retinopathy

Zhu,

Huang,

Sun

et al. 2024

Theranostics

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Diabetic retinopathy (DR), a complex complication of diabetes mellitus (DM), is a leading cause of adult blindness. Hyperglycemia triggers DR, resulting in microvascular damage, glial apoptosis, and neuronal degeneration. Inflammation and oxidative stress play crucial roles during this process. Current clinical treatments for DR primarily target the advanced retinal disorder but offer limited benefits with inevitable side effects. Extracellular vesicles (EVs) exhibit unique morphological features, contents, and biological properties and can be found in cell culture supernatants, various body fluids, and tissues. In DR, EVs with specific cargo composition would induce the reaction of receptor cell once internalized, mediating cellular communication and disease progression. Increasing evidence indicates that monitoring changes in EV quantity and content in DR can aid in disease diagnosis and prognosis. Furthermore, extensive research is investigating the potential of these nanoparticles as effective therapeutic agents in preclinical models of DR. This review explores the current understanding of the pathological effects of EVs in DR development, discusses their potential as biomarkers and therapeutic strategies, and paves the way for further research and therapeutic advancements.

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“…Exosomes have also been researched substantially as a therapeutic tool in various other retinal diseases including diabetic retinopathy (Safwat et al, 2018;Li et al, 2021), glaucoma (Mead et al, 2018a, b) and retinopathy of prematurity (Xu et al, 2019;Cai et al, 2021). In addition, there are also various ongoing clinical trials including on dry eye and diabetes that show great promise in regenerative cell-free therapy and that exosome treatment is not far from reach.…”

Section: Exosome Therapy In Other Retinal Diseasesmentioning

confidence: 99%

Extracellular vesicles as a potential therapeutic for age-related macular degeneration

Mead¹,

Chow²

2023

Neural Regen Res

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Age-related macular degeneration is a major global cause of central visual impairment and severe vision loss. With an aging population, the already immense economic burden of costly anti-vascular endothelial growth factor treatment is likely to increase. In addition, current conventional treatment is only available for the late neovascular stage of age-related macular degeneration, and injections can come with potentially devastating complications, introducing the need for more economical and riskfree treatment. In recent years, exosomes, which are nano-sized extracellular vesicles of an endocytic origin, have shown immense potential as diagnostic biomarkers and in the therapeutic application, as they are bestowed with characteristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells. Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases; however, exosomes as a potential therapy for several retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically. This article will focus on the limited literature available on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures, as well as briefly identify future research directions. Current literature on exosome therapy using agerelated macular degeneration rodent models includes laser retinal injury, N-methyl-N-nitrosourea, and royal college of surgeon models, which mimic inflammatory and degenerative aspects of agerelated macular degeneration. These have shown promising results in preserving retinal function and morphology, as well as protecting photoreceptors from apoptosis. Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cytokines, mRNAs, and proteins involved in photoreceptor degeneration pathways to exert a therapeutic effect. Various findings have also opened exciting prospects for the involvement of cargo components in remedial effects on the damaged macula or retina.

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Lymphocytic microparticles suppress retinal angiogenesis via targeting Müller cells in the ischemic retinopathy mouse model

Cited by 7 publications

References 66 publications

Comparative Analysis Reveals Novel Changes in Plasma Metabolites and Metabolomic Networks of Infants With Retinopathy of Prematurity

Comparative Analysis Reveals Novel Changes in Plasma Metabolites and Metabolomic Networks of Infants With Retinopathy of Prematurity

Emerging role of extracellular vesicles in diabetic retinopathy

Extracellular vesicles as a potential therapeutic for age-related macular degeneration

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