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 illdefined.
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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89479 |
| Date | 02 February 2024 |
| Creators | Schlecht, Anja, Thien, Adrian, Wolf, Julian, Prinz, Gabriele, Agostini, Hansjürgen, Schlunck, Günther, Wieghofer, Peter, Boneva, Stefaniya, Lange, Clemens |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 13318 |
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