Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy
Abstract
Remodeling senescent blood vessels: The retina is a thin layer of nervous tissue at the back of the eye that transforms light into neuronal signals. The retina is essential for vision and is supported by networks of blood vessels. In diabetic retinopathy, a common cause of vision loss, these microvessels degenerate and regrow in an aberrant manner. Such degeneration and regrowth can compromise the functioning of retinal nerve cells. Binet et al. observed that, after rapid proliferation, vascular endothelial cells in diseased blood vessels engaged molecular pathways linked to cellular senescence (see the Perspective by Podrez and Byzova). Senescent vascular units summoned an inflammatory response in which neutrophils extruded neutrophil extracellular traps onto diseased vessels to remodel them. This endogenous repair mechanism promoted the elimination of senescent blood vessels and could lead to beneficial vascular remodeling. Science , this issue p. eaay5356 ; see also p. 919
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Certain cytokines such as IL-1β and IL-6 have clearly emerged as key to promoting inflammaging.
“Certain cytokines, such as IL-1β and IL-6, have clearly emerged as key to promoting inflammaging.83,229–232”
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In aged organisms, senescent cells can contribute to a variety of age-related pathologies, including pulmonary fibrosis, biliary liver damage, arteriosclerosis, retinopathy, osteoarthritis, dementia and diabetes mellitus.
“In aged organisms, senescent cells can contribute to a variety of age- related pathologies, including pulmonary fibrosis, biliary liver damage, arteriosclerosis, retinopathy, osteoarthritis, dementia and diabetes mellitus 13-19 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [19]
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Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration
Yu, Q., Walters, H. E., Pasquini, G., Pal Singh, S., Lachnit, M., Oliveira, C. R., León-Periñán, D., Petzold, A., Kesavan, P., Subiran Adrados, C., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.09.009 · Cited by 52 · see citing works
- Authors
- Binet, F., Cagnone, G., Crespo-Garcia, S., Hata, M., Neault, M., Dejda, A., Wilson, A. M., Buscarlet, M., Mawambo, G. T., Howard, J. P., Diaz-Marin, R., Parinot, C., Guber, V., Pilon, F., Juneau, R., Laflamme, R., Sawchyn, C., Boulay, K., Leclerc, S., Abu-Thuraia, A., Côté, J.-F., Andelfinger, G., Rezende, F. A., Sennlaub, F., Joyal, J.-S., Mallette, F. A., & Sapieha, P.
- Affiliations
- Hôpital Maisonneuve-Rosemont (CA)
- Departments of Pediatrics and
- Departments of Ophthalmology and
- Biochemistry and Molecular Medicine, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec H1T 2M4, Canada.
- Montreal Clinical Research Institute (CA)
- Inserm (FR)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Corresponding author
- Joyal, Jean-Sébastien
- Mallette, Frédérick A.
- Sapieha, Przemyslaw
- ORCID
- Binet, François
- Cagnone, Gael
- Crespo-Garcia, Sergio
- Hata, Masayuki
- Neault, Mathieu
- Dejda, Agnieszka
- Wilson, Ariel M.
- Buscarlet, Manuel
- Mawambo, Gaelle Tagne
- Diaz-Marin, Roberto
- Parinot, Celia
- Guber, Vera
- Pilon, Frédérique
- Juneau, Rachel
- Laflamme, Rémi
- Sawchyn, Christina
- Boulay, Karine
- Leclerc, Severine
- Abu-Thuraia, Afnan
- Côté, Jean-François
- Andelfinger, Gregor
- Sennlaub, Florian
- Joyal, Jean-Sébastien
- Mallette, Frédérick A.
- Sapieha, Przemyslaw
- Venue
- Science
- Published
- 2020-08-21
- Volume
- 369
- Issue
- 6506
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3061354765
- Cited by
- 283
- References
- 86
- Citations by year
- 2026: 42 · 2025: 48 · 2024: 70 · 2023: 40 · 2022: 40 · 2021: 38 · 2020: 5
- FWCI
- 11.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund (1012321.01)
- Heart and Stroke Foundation of Canada (G-16-00014658)
- Canadian Diabetes Association (DI-3-18-5444-PS)
- Canadian Institutes of Health Research (#353770, MOP-133442, 141956, PJ2-169643, GER-163050)
- Banque Nationale Research Excellence Chair in Cardiovascular Genetics
- Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-06743, RGPIN-2017-05227, 418637)
- Fonds de Recherche du Québec - Santé (284059)
- Mitacs (IT09472)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- neutrophil extracellular traps, NETosis, diabetic retinopathy, proliferative diabetic retinopathy, vascular aging, vascular remodeling, sterile inflammation, neutrophils, ischemic retinopathy, retinal fibrosis
- MeSH terms
- Aging, Animals, Diabetic Retinopathy, Disease Models, Animal, Humans, Inflammation, Mice, Inbred C57BL, Neutrophils, Retinal Vessels, Cellular Senescence, Endothelial Cells, Mice, Extracellular Traps
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