@article{SchlechtWolfBonevaetal.2022,
  author    = {Schlecht, Anja and Wolf, Julian and Boneva, Stefaniya and Prinz, Gabriele and Braunger, Barbara M. and Wieghofer, Peter and Agostini, Hansj{\"u}rgen and Schlunck, G{\"u}nther and Lange, Clemens},
  title     = {Transcriptional and distributional profiling of microglia in retinal angiomatous proliferation},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {7},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23073443},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284072},
  year      = {2022},
  abstract  = {Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution of MG and MAC to the myeloid cell pool at RAP sites and their exact functions remain unknown. In this study, we combined a microglia-specific reporter mouse line with a mouse model for RAP to identify the contribution of MG and MAC to myeloid cell accumulation at RAP and determined the transcriptional profile of MG using RNA sequencing. We found that MG are the most abundant myeloid cell population around RAP, whereas MAC are rarely, if ever, associated with late stages of RAP. RNA sequencing of RAP-associated MG showed that differentially expressed genes mainly contribute to immune-associated processes, including chemotaxis and migration in early RAP and proliferative capacity in late RAP, which was confirmed by immunohistochemistry. Interestingly, MG upregulated only a few angiomodulatory factors, suggesting a rather low angiogenic potential. In summary, we showed that MG are the dominant myeloid cell population at RAP sites. Moreover, MG significantly altered their transcriptional profile during RAP formation, activating immune-associated processes and exhibiting enhanced proliferation, however, without showing substantial upregulation of angiomodulatory factors.},
  language  = {en}
}
@article{SchlechtThienWolfetal.2021,
  author    = {Schlecht, Anja and Thien, Adrian and Wolf, Julian and Prinz, Gabriele and Agostini, Hansj{\"u}rgen and Schlunck, G{\"u}nther and Wieghofer, Peter and Boneva, Stefaniya and Lange, Clemens},
  title     = {Immunosenescence in choroidal neovascularization (CNV) — Transcriptional profiling of na{\"i}ve and CNV-associated retinal myeloid cells during aging},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {24},
  issn      = {1422-0067},
  doi       = {10.3390/ijms222413318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284342},
  year      = {2021},
  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) 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.},
  language  = {en}
}