TY  - JOUR
A1  - Schlecht, Anja
A1  - Thien, Adrian
A1  - Wolf, Julian
A1  - Prinz, Gabriele
A1  - Agostini, Hansjürgen
A1  - Schlunck, Günther
A1  - Wieghofer, Peter
A1  - Boneva, Stefaniya
A1  - Lange, Clemens
T1  - Immunosenescence in choroidal neovascularization (CNV) — Transcriptional profiling of naïve and CNV-associated retinal myeloid cells during aging
JF  - International Journal of Molecular Sciences
N2  - 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) Cx3cr1\(^{GFP/+}\) 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.
KW  - age-related macular degeneration (AMD)
KW  - choroidal neovascularization (CNV)
KW  - aging
KW  - immunosenescence
KW  - microglia
KW  - myeloid cells
KW  - RNA-sequencing
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284342
SN  - 1422-0067
VL  - 22
IS  - 24
ER  -