Immunosenescence in choroidal neovascularization (CNV) - transcriptional profiling of naïve and CNV-associated retinal myeloid cells during aging

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Abstract: Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1GFP/+ mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an 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 myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: International journal of molecular sciences. - 22, 24 (2021) , 13318, ISSN: 1422-0067

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2022

Creator: Schlecht, Anja
Thien, Adrian
Wolf, Julian
Prinz, Gabriele
Agostini, Hansjürgen
Schlunck, Günther
Wieghofer, Peter
Boneva, Stefaniya
Lange, Clemens

DOI: 10.3390/ijms222413318

URN: urn:nbn:de:bsz:25-freidok-2235207

Rights: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:40 AM CEST

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2022

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