@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{GrassmannFritscheKeilhaueretal.2012,
  author    = {Grassmann, Felix and Fritsche, Lars G. and Keilhauer, Claudia N. and Heid, Iris M. and Weber, Bernhard H. F.},
  title     = {Modelling the Genetic Risk in Age-Related Macular Degeneration},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {5},
  doi       = {10.1371/journal.pone.0037979},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131315},
  pages     = {e37979},
  year      = {2012},
  abstract  = {Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95\% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95\% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95\% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5\% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2\% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9\% and a specificity of 99.9\% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4\% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2\% of individuals in the two lowest GRS categories which represent almost 50\% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.},
  language  = {en}
}