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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89596 |
| Date | 07 February 2024 |
| Creators | Schlecht, Anja, Wolf, Julian, Boneva, Stefaniya, Prinz, Gabriele, Braunger, Barbara M., Wieghofer, Peter, Agostini, Hansjürgen, Schlunck, Günther, 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 | 3443 |
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