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 - TY - JOUR A1 - Schlecht, Anja A1 - Thien, Adrian A1 - Wolf, Julian A1 - Prinz, Gabriele A1 - Agostini, Hansjürgen A1 - Schlunck, Günther A1 - Wieghofer, Peter A1 - Boneva, Stefaniya A1 - Lange, Clemens T1 - Immunosenescence in choroidal neovascularization (CNV) — Transcriptional profiling of naïve and CNV-associated retinal myeloid cells during aging JF - International Journal of Molecular Sciences N2 - 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. KW - age-related macular degeneration (AMD) KW - choroidal neovascularization (CNV) KW - aging KW - immunosenescence KW - microglia KW - myeloid cells KW - RNA-sequencing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284342 SN - 1422-0067 VL - 22 IS - 24 ER - TY - JOUR A1 - Mages, Michelle A1 - Shojaa, Mahdieh A1 - Kohl, Matthias A1 - Stengel, Simon von A1 - Becker, Clemens A1 - Gosch, Markus A1 - Jakob, Franz A1 - Kerschan-Schindl, Katharina A1 - Kladny, Bernd A1 - Klöckner, Nicole A1 - Lange, Uwe A1 - Middeldorf, Stefan A1 - Peters, Stefan A1 - Schoene, Daniel A1 - Sieber, Cornel C. A1 - Tholen, Reina A1 - Thomasius, Friederike E. A1 - Uder, Michael A1 - Kemmler, Wolfgang T1 - Exercise effects on Bone Mineral Density in men JF - Nutrients N2 - In contrast to postmenopausal women, evidence for a favorable effect of exercise on Bone Mineral Density (BMD) is still limited for men. This might be due to the paucity of studies, but also to the great variety of participants and study characteristics that may dilute study results. The aim of the present systematic review and meta-analysis was to evaluate the effect of exercise on BMD changes with rational eligibility criteria. A comprehensive search of six electronic databases up to 15 March 2021 was conducted. Briefly, controlled trials ≥6 months that determined changes in areal BMD in men >18 years old, with no apparent diseases or pharmacological therapy that relevantly affect bone metabolism, were included. BMD changes (standardized mean differences: SMD) of the lumbar spine (LS) and femoral neck (FN) were considered as outcomes. Twelve studies with 16 exercise and 12 control groups were identified. The pooled estimate of random-effect analysis was SMD = 0.38, 95%-CI: 0.14–0.61 and SMD = 0.25, 95%-CI: 0.00–0.49, for LS and FN, respectively. Heterogeneity between the trials was low–moderate. Funnel plots and rank and regression correlation tests indicate evidence for small study publication bias for LS but not FN-BMD. Subgroup analyses that focus on study length, type of exercise and methodologic quality revealed no significant difference between each of the three categories. In summary, we provided further evidence for a low but significant effect of exercise on BMD in men. However, we are currently unable to give even rough exercise recommendations for male cohorts. KW - Bone Mineral Density KW - exercise KW - men KW - overview Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250247 SN - 2072-6643 VL - 13 IS - 12 ER -