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Media type:
E-Article
Title:
Immunosenescence in Choroidal Neovascularization (CNV)
:
Transcriptional Profiling of Naïve and CNV-Associated Retinal Myeloid Cells during Aging
Contributor:
Schlecht, Anja
[Author];
Thien, Adrian
[Author];
Wolf, Julian
[Author];
Prinz, Gabriele
[Author];
Agostini, Hansjürgen
[Author];
Schlunck, Günther
[Author];
Wieghofer, Peter
[Author];
Boneva, Stefaniya
[Author];
Lange, Clemens
[Author]
imprint:
Basel: MDPI, [2024]
Published in:International Journal of Molecular Sciences ; 22, (2021)
Description:
Immunosenescence is considered a possible factor in the development of age-related maculardegeneration and choroidal neovascularization (CNV). However, age-related changes of myeloidcells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are illdefined.In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting fromsix-week (young) and two-year-old (old) Cx3cr1GFP/+ mice, both during physiological aging andlaser-induced CNV development. High-throughput RNA-sequencing was performed to define theage-dependent transcriptional differences in MCs during physiological aging and CNV development,complemented by immunohistochemical characterization and the quantification of MCs, as well asCNV size measurements. These analyses revealed that myeloid cells change their transcriptionalprofile during both aging and CNV development. In the steady state, senescent MCs demonstratedan upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14,as well as the downregulation of microglial signature genes. During CNV formation, aged myeloidcells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitantwith significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparisonto young mice. Future studies need to clarify whether this observation is an epiphenomenon or acausal relationship to determine the role of immunosenescence in CNV formation.