Immunosenescence in Choroidal Neovascularization (CNV)-Transcriptional Profiling of Naïve and CNV-Associated Retinal Myeloid Cells during Aging

• Published in: International journal of molecular sciences 2021-12, Vol.22 (24), p.13318
• Main Authors: Schlecht, Anja, Thien, Adrian, Wolf, Julian, Prinz, Gabriele, Agostini, Hansjürgen, Schlunck, Günther, Wieghofer, Peter, Boneva, Stefaniya, Lange, Clemens
• Format: Article
• Language: English
• Subjects: Age; Aging; Aging (artificial); Aging - genetics; Aging - metabolism; Aging - pathology; Angiogenesis; Animals; Cell cycle; Cell growth; Cell proliferation; Chemotaxis; Choroidal Neovascularization - genetics; Choroidal Neovascularization - metabolism; Choroidal Neovascularization - pathology; CX3CR1 protein; CXCL13 protein; Down-Regulation; Flow cytometry; Fluorescence; Gene expression; Gene Expression Profiling; Immune system; Immunosenescence; Lasers; Lasers - adverse effects; Macrophages; Macular degeneration; Macular Degeneration - genetics; Macular Degeneration - metabolism; Macular Degeneration - pathology; Mice; Mice, Transgenic; Microglia; Myeloid cells; Myeloid Cells - metabolism; Myeloid Cells - pathology; Ontology; Pathogenesis; Phase transitions; Physiology; Retina; Retina - metabolism; Retina - pathology; Transcription; Vascularization
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222413318

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, -positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) 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 , as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as and 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.