Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

Autor: Hernandez BJ; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA., Skiba NP; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA., Plössl K; Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany., Strain M; Duke Molecular Physiology Institute, Department of Medicine, Duke University, Durham, NC 27710, USA., Liu Y; Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA., Grigsby D; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA., Kelly U; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA., Cady MA; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA., Manocha V; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA., Maminishkis A; Ophthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA., Watkins T; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.; Current address: Office of Animal Welfare Assurance, Duke Animal Care and Use Program, Duke University, Durham, NC 27710, USA., Miller SS; Ophthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA., Ashley-Koch A; Duke Molecular Physiology Institute, Department of Medicine, Duke University, Durham, NC 27710, USA., Stamer WD; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA., Weber BHF; Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany.; Institute of Clinical Human Genetics, University Hospital Regensburg, 93053 Regensburg, Germany., Bowes Rickman C; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.; Department of Cell Biology, Duke University, Durham, NC 27710, US., Klingeborn M; Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.; Current address: McLaughlin Research Institute, Great Falls, MT 59405, USA.
Jazyk: angličtina
Zdroj: Journal of extracellular biology [J Extracell Biol] 2023 Oct; Vol. 2 (10). Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1002/jex2.116
Abstrakt: The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD).
Competing Interests: Declaration of Interest Statement We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
Databáze: MEDLINE
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