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Recent advances of exosomes in age-related macular degeneration

FRONTIERS IN PHARMACOLOGY (2023)

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Article Cell Biology

Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD

Urvi Gupta et al.

Summary: In dry age-related macular degeneration, increased LCN2 levels lead to pathological changes in retinal pigmented epithelial cells, which are known to drive dry AMD pathology. By regulating autophagy and ferroptosis activities, LCN2 is involved in the development of AMD and provides a potential therapeutic strategy.

AUTOPHAGY (2023)

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Review Cell Biology

Autophagy in age-related macular degeneration

Kai Kaarniranta et al.

Summary: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the aging population. The progression of AMD is characterized by atrophic alterations in the retinal pigment epithelium and the formation of lipofuscin and deposits. Chronic oxidative stress, protein aggregation, and inflammation may contribute to the development of AMD.

AUTOPHAGY (2023)

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Calpain-2 Facilitates Autophagic/Lysosomal Defects and Apoptosis in ARPE-19 Cells and Rats Induced by Exosomes from RPE Cells under NaIO3 Stimulation

Shuaishuai Zhang et al.

Oxidative Medicine and Cellular Longevity (2023)

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Article Ophthalmology

Role of tear exosomes in the spread of herpes simplex virus type 1 in recurrent herpes simplex keratitis

Huiying Huang et al.

Summary: This study found that tear exosomes are abundant in tear fluids and may be involved in the recurrence of herpes simplex keratitis (HSK). Additionally, the study confirmed that herpes simplex virus type 1 (HSV-1) genes can be transferred between cells through the exosomal pathway, providing new insights for the clinical intervention, treatment, and drug discovery for recurrent HSK.

EYE (2023)

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Article Ophthalmology

Exosomal MicroRNA Profiling in Vitreous Humor Derived From Pathological Myopia Patients

Jie You et al.

Summary: This study explores the possible relations between the composition of microRNA in vitreous exosomes of patients with pathologic myopia (PM) and the progression of myopic maculopathy. The results indicate that vitreous exosomal miR-143-3p and miR-145-5p may participate in the development of myopic maculopathy, and these microRNAs are related to the insulin resistance pathway. Therefore, they can be considered biomarkers for patients with PM and may represent alarming signals of myopic maculopathy deterioration.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2023)

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Review Ophthalmology

Review of gene therapies for age-related macular degeneration

Arshad M. Khanani et al.

Summary: Gene therapies aim to deliver therapeutic substances to specific tissues and have been explored as potential treatments for chronic diseases requiring lifelong care. In ocular gene therapy, retinal diseases are particularly important due to their high prevalence and the challenge of properly delivering therapies to the target tissue.

EYE (2022)

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Review Biochemistry & Molecular Biology

Exosomes as a new frontier of cancer liquid biopsy

Dan Yu et al.

Summary: Liquid biopsy, a revolutionary strategy for cancer diagnosis and prognosis prediction, uses minimally invasive detection through biofluids such as blood, saliva, and urine. Exosomes, a subset of extracellular vesicles, play a crucial role in intercellular communication and are considered as potential biomarkers in liquid biopsy. However, the lack of high-quality separation and component analysis methods has limited the further clinical application of exosomes.

MOLECULAR CANCER (2022)

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Review Ophthalmology

The role of dark adaptation in understanding early AMD

Ian J. Murray et al.

Summary: This paper discusses the current knowledge on how AMD affects DA, focusing on molecular mechanisms, psychophysical issues, and the relationship between slowed DA and early AMD morphological abnormalities. Despite historical challenges, DA is considered useful in assessing photoreceptor pigment regeneration; new technological developments and mathematical algorithms show potential in improving analysis of the DA curve. Identifying a satisfactory endpoint for evaluating future AMD therapeutic strategies is crucial, with functional changes like those in DA showing promise.

PROGRESS IN RETINAL AND EYE RESEARCH (2022)

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MicroRNA regulation of critical retinal pigment epithelial functions

Samuel W. Du et al.

Summary: MicroRNAs are short, evolutionarily conserved noncoding RNAs that are critical for controlling normal cellular physiology. Recent research has highlighted their role in supporting retina function through regulating RPE activities. They have potential applications as therapeutics and biomarkers for visual diseases.

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Intraocular Exosomes in Eye Diseases

Hui Zhang et al.

Summary: This article reviews the latest advances of intraocular exosomes in the research of several eye diseases and discusses their roles in pathological processes.

CURRENT MOLECULAR MEDICINE (2022)

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Article Pharmacology & Pharmacy

Novel and investigational therapies for wet and dry age-related macular degeneration

Aira Sarkar et al.

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Therapeutic Potential of Exosomes Derived from Adipose Tissue-Sourced Mesenchymal Stem Cells in the Treatment of Neural and Retinal Diseases

Carl Randall Harrell et al.

Summary: AT-MSC-Exos are potential therapeutic agents for neural and retinal diseases by delivering neurotrophins, immunoregulatory factors, and pro-angiogenic miRNAs to alleviate inflammation and promote cell survival.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Chemistry, Multidisciplinary

Inflammation-Stimulated MSC-Derived Small Extracellular Vesicle miR-27b-3p Regulates Macrophages by Targeting CSF-1 to Promote Temporomandibular Joint Condylar Regeneration

Yufei Liu et al.

Summary: Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have been extensively studied. When MSCs are exposed to an inflammatory environment, they release more functional factors to regulate the inflammatory microenvironment and promote tissue regeneration. Inflammatory-stimulated sEVs show enhanced functions in cell proliferation, migration, and macrophage polarization. In vivo experiments demonstrate that modified sEVs have significant therapeutic effects on temporomandibular joint regeneration.

SMALL (2022)

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Review Chemistry, Multidisciplinary

Exosome Processing and Characterization Approaches for Research and Technology Development

James J. Lai et al.

Summary: Exosomes, as extracellular vesicles, have potential as disease biomarkers and therapeutic agents. However, manufacturing high-quality exosomes is challenging due to the lack of standardized practices and reference materials. This review compares exosome processing and characterization methods, recommends exosome workflows, and provides an introduction to exosomes, including their properties and roles in biological processes and disease progression. It also summarizes ongoing clinical trials.

ADVANCED SCIENCE (2022)

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Review Chemistry, Multidisciplinary

Exosomes: Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake

Ilgin Kimiz-Gebologlu et al.

Summary: This review discusses the general properties and biological functions of exosomes, as well as their potential in drug delivery systems. It provides an overview of methods for large-scale production, isolation, and drug loading of exosomes, and investigates the current challenges and potential directions in this emerging field of drug delivery.

JOURNAL OF CONTROLLED RELEASE (2022)

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Review Biochemistry & Molecular Biology

Recent Advances in Age-Related Macular Degeneration Therapies

Marie Fabre et al.

Summary: Age-related macular degeneration (AMD) is a common eye disease that leads to blindness in elderly people. This review provides an overview of the disease mechanism and progression, and discusses the current treatment options and drugs.

MOLECULES (2022)

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Article Biochemistry & Molecular Biology

Oxidative stress-induced lncRNA CYLD-AS1 promotes RPE inflammation via Nrf2/miR-134-5p/NF-κB signaling pathway

Han Du et al.

Summary: This study identified a novel oxidative stress-related long noncoding RNA (lncRNA) named CYLD-AS1, which showed increased expression in retinal pigment epithelium (RPE) cells during oxidative stress. Depletion of CYLD-AS1 promoted cell proliferation and mitochondrial function and protected RPE cells against oxidative damage. CYLD-AS1 regulated the expression of NRF2 and NF-kappa B signaling pathway members, which are related to oxidative stress and inflammation. These effects were mediated by the interaction with miR-134-5p. Exosomes secreted by CYLD-AS1 knockdown RPE cells had a lower proinflammatory effect compared to control cells.

FASEB JOURNAL (2022)

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Review Biochemistry & Molecular Biology

Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer

Qing-Fang Han et al.

Summary: This review systematically summarizes recent progress in understanding the mechanisms of exosome biogenesis in cancer and highlights pharmacological targeting of exosome biogenesis as a promising therapeutic strategy.

MOLECULAR CANCER (2022)

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Article Medicine, General & Internal

Proteomic Profiling of Aqueous Humor Exosomes from Age-related Macular Degeneration Patients

Ching-Yao Tsai et al.

Summary: This study examined the exosomal protein profile of patients with age-related macular degeneration (AMD) and found significant differences in the exosomal proteins between AMD patients and controls. The exosomal proteins in AMD patients were enriched in the lipoprotein metabolic process. Additionally, the study observed a decrease in the amount of two proteins in AMD patients receiving anti-VEGF therapy with longer treatment duration.

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES (2022)

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Review Ophthalmology

Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities

Priyatham S. Mettu et al.

Summary: This review explores the pathobiology, clinical manifestations, and treatment approaches for incomplete response to anti-VEGF therapy in NVAMD patients, focusing on persistent disease activity (PDA) and suboptimal vision recovery (SVR). Findings suggest that patients with high-flow CNV lesions are more prone to PDA, while poor vision recovery may be associated with dysfunction in photoreceptor synaptic function in the neurosensory retina.

PROGRESS IN RETINAL AND EYE RESEARCH (2021)

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Review Oncology

Anti-VEGF and Other Novel Therapies for Neovascular Age-Related Macular Degeneration: An Update

Mariacristina Parravano et al.

Summary: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness in older adults. The prognosis for neovascular AMD has improved with the introduction of biological drugs with antiangiogenic properties. Several molecules have been approved for AMD treatment, including those targeting vascular endothelial growth factor (VEGF).

BIODRUGS (2021)

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Article Biochemistry & Molecular Biology

Tear-Derived Exosome Proteins Are Increased in Patients with Thyroid Eye Disease

Jeong-Sun Han et al.

Summary: This study analyzed the exosomal proteins in tear fluids (TF) from patients with Thyroid eye disease (TED) and found that specific proteins were significantly increased in TED patients compared to control subjects. Orbital fibroblasts exposed to TF exosomes from TED patients showed higher levels of inflammatory cytokine production, suggesting a potential key role of these specific proteins in TED pathogenesis.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Medicine, Research & Experimental

Docosahexaenoic acid reverses the promoting effects of breast tumor cell-derived exosomes on endothelial cell migration and angiogenesis

Parisa Ghaffari-Makhmalbaf et al.

Summary: The research demonstrates that DHA treatment can inhibit angiogenesis of breast cancer cells by altering the exosomal miRNA contents from pro-angiogenic to anti-angiogenic properties.

LIFE SCIENCES (2021)

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Article Biochemical Research Methods

Isolation and characterization of extracellular vesicle subpopulations from tissues

Rossella Crescitelli et al.

Summary: This study presents a protocol for isolating multiple EV subpopulations directly from tissues, including enzymatic treatment, ultracentrifugation, density separation, electron microscopy characterization, etc., which can be completed in 22 hours. The approach can be applied to tissues such as human melanoma metastases and can be adopted by researchers experienced with cell culture and EV isolation.

NATURE PROTOCOLS (2021)

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Article Cell & Tissue Engineering

Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial-mesenchymal transition by targeting HOXC6

Dongli Li et al.

Summary: This study revealed that exosomal miR-27b derived from hucMSCs could reverse the EMT process induced by TGF-beta 2 by inhibiting HOXC6, suggesting the potential therapeutic role of the exosomal miR-27b/HOXC6 axis in ameliorating subretinal fibrosis.

STEM CELL RESEARCH & THERAPY (2021)

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News Item Medicine, General & Internal

Progress in FDA's Review of Millions of Tobacco Products

Rebecca Voelker

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Article Biochemistry & Molecular Biology

Exosome-mediated mRNA delivery in vivo is safe and can be used to induce SARS-CoV-2 immunity

Shang Jui Tsai et al.

Summary: Exosomes can be used as a promising delivery vehicle for functional mRNA, demonstrating efficient delivery to human cells and potential for clinical applications.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Review Oncology

Exosome-based liquid biopsies in cancer: opportunities and challenges

W. Yu et al.

Summary: Liquid biopsy in cancer research has seen significant progress, with efforts focused on utilizing circulating tumor cells, circulating tumor DNA, and extracellular vesicles like exosomes. Exosomes, as part of the intercellular communication system, carry tumor-derived materials and can serve as stable biomarkers for early detection and monitoring of cancer.

ANNALS OF ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

The complement system in age-related macular degeneration

Angela Armento et al.

Summary: Age-related macular degeneration (AMD) is a complex disease with genetic, aging, and lifestyle factors all playing a role in its onset and progression. Therapeutic attempts targeting the complement system have not been successful, highlighting the complexity of AMD beyond genetic factors.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

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Article Ophthalmology

Transcriptomics analysis of Ccl2/Cx3cr1/Crb1rd8 deficient mice provides new insights into the pathophysiology of progressive retinal degeneration

Anna Badia et al.

Summary: Chronic oxidative stress and immune dysregulation play crucial roles in the pathogenesis of most retinal degenerative diseases, including age-related macular degeneration. The DKOrd8 mouse model demonstrates early changes in the retina, such as photoreceptor atrophy and pigment alterations, leading to impaired retinal function. Transcriptomic analysis revealed significant differential expression of genes related to oxidative stress and neuronal function, emphasizing the relevance of these processes in pathological retinal degeneration.

EXPERIMENTAL EYE RESEARCH (2021)

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Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

Takuto Chiba et al.

Summary: miR-17 similar to miR-92 is dynamically regulated in renal endothelial cells after renal IRI and plays a role in the pathogenesis of AKI. Endothelial-specific miR-17 similar to miR-92 knockout exacerbates renal IRI, promoting renal tubular injury, reducing renal blood flow, and increasing oxidative stress in the kidneys. miR-17 similar to miR-92 is critical in the angiogenic response after renal IRI, and treatment with miR-18a and miR-19b mimics can mitigate the damage.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

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Umbilical Mesenchymal Stem Cell-Derived Exosome-Encapsulated Hydrogels Accelerate Bone Repair by Enhancing Angiogenesis

Yuntong Zhang et al.

Summary: Repairing large bone defects remains a major challenge for orthopedic surgeons, but this study demonstrates a promising strategy using umbilical MSC-derived exosomes in combination with hyaluronic acid hydrogel and nanohydroxyapatite/poly-epsilon-caprolactone scaffolds to enhance bone regeneration in rats. The exosomes were found to promote angiogenesis and potentially regulate it through the miR-21/NOTCH1/DLL4 signaling axis.

ACS APPLIED MATERIALS & INTERFACES (2021)

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Article Cell Biology

Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors

Miguel Flores-Bellver et al.

Summary: The study shows that extracellular vesicles secreted by RPE cells are enriched in proteins associated with AMD pathophysiology, exhibiting distinctive directional secretion modes under homeostatic conditions and differential modulation in response to AMD stressors. This suggests a finely-tuned mechanism regulating the secretion of drusen-associated proteins via EVs.

JOURNAL OF EXTRACELLULAR VESICLES (2021)

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Review Cell Biology

A brief history of nearly EV-erything - The rise and rise of extracellular vesicles

Yvonne Couch et al.

Summary: Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space, serving as a complex cell-to-cell communication mechanism that transfers functional cargo and influences biological processes, with deregulation in disease. The field of EVs has grown exponentially over the past two decades with an organized community, but still faces key challenges.

JOURNAL OF EXTRACELLULAR VESICLES (2021)

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Age-related macular degeneration

Monika Fleckenstein et al.

Summary: Age-related macular degeneration (AMD) is the leading cause of legal blindness in the industrialized world, with a complex pathophysiology involving aging, environmental factors, and genetic susceptibility leading to photoreceptor degeneration and drusen formation. Tailoring therapeutics to specific phenotypes and stages may be crucial for preventing irreversible vision loss in the future.

NATURE REVIEWS DISEASE PRIMERS (2021)

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Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications

Xiao-Huan Tang et al.

Summary: Exosomes, a subpopulation of the tumour microenvironment (TME), are crucial for intercellular communication and are enriched with noncoding RNAs that play important roles in the tumorigenesis, progression, and drug resistance of gastric cancer (GC). Regulating exosomal ncRNAs levels could potentially serve as therapeutic targets for GC treatment.

MOLECULAR CANCER (2021)

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Exosome-inflammasome crosstalk and their roles in inflammatory responses

Chadanat Noonin et al.

Summary: The inflammasome is a complex of proteins in the cytoplasm of cells activated by infectious and non-infectious stimuli, while exosomes are extracellular vesicles that play important roles in intercellular communication. The review discusses the interaction between exosomes and inflammasomes in inflammatory responses, highlighting the effects of inflammasome activation on exosomal secretion. Additionally, it explores the dual effects of exosomes on inhibiting and promoting inflammasome activation, and provides insights into the therapeutic potential of exosomes in human diseases.

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Cardiac telocytes inhibit cardiac microvascular endothelial cell apoptosis through exosomal miRNA-21-5p-targeted cdip1 silencing to improve angiogenesis following myocardial infarction

Zhaofu Liao et al.

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