TY  - JOUR
A1  - Schlecht, Anja
A1  - Wolf, Julian
A1  - Boneva, Stefaniya
A1  - Prinz, Gabriele
A1  - Braunger, Barbara M.
A1  - Wieghofer, Peter
A1  - Agostini, Hansjürgen
A1  - Schlunck, Günther
A1  - Lange, Clemens
T1  - Transcriptional and distributional profiling of microglia in retinal angiomatous proliferation
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - AMD
KW  - Mactel 2
KW  - macular neovascularization
KW  - MNV type 3
KW  - retinal angiomatous proliferation
KW  - RAP
KW  - microglia
KW  - RNA sequencing
KW  - Cx3cr1
KW  - CreERT2
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284072
SN  - 1422-0067
VL  - 23
IS  - 7
ER  -