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  - Bohnert, Simone
A1  - Georgiades, Kosmas
A1  - Monoranu, Camelia-Maria
A1  - Bohnert, Michael
A1  - Büttner, Andreas
A1  - Ondruschka, Benjamin
T1  - Quantitative evidence of suppressed TMEM119 microglial immunohistochemistry in fatal morphine intoxications
JF  - International Journal of Legal Medicine
N2  - The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2. We could document the lowest density of TMEM119-positive cells in MOR deaths with highly significant differences to the control densities in all three regions investigated. In ETH and METH deaths, the expression of TMEM119 was comparable to cell densities in controls. The results indicate that the immunoreaction in brain tissue is different in these groups depending on the drug type used for abuse.
KW  - immunohistochemistry
KW  - drug abuse
KW  - forensic neuropathology
KW  - neuroinflammation
KW  - neurotoxicity
KW  - microglia
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266934
SN  - 1437-1596
VL  - 135
IS  - 6
ER  -