A5005610340- Retinal Development and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Diseases and Treatments
- interferon and immune responses
- Immune Response and Inflammation
- Photoreceptor and optogenetics research
- Immune cells in cancer
- Ocular Disorders and Treatments
- Retinal and Optic Conditions
- Genomics and Rare Diseases
- RNA regulation and disease
- Retinopathy of Prematurity Studies
- Genetic and Kidney Cyst Diseases
- Ubiquitin and proteasome pathways
- Lysosomal Storage Disorders Research
- Hemoglobinopathies and Related Disorders
- Mitochondrial Function and Pathology
- Folate and B Vitamins Research
- Amino Acid Enzymes and Metabolism
- Ocular Diseases and Behçet’s Syndrome
- Cellular transport and secretion
- Phagocytosis and Immune Regulation
- Glaucoma and retinal disorders
- Neuroscience and Neuropharmacology Research
- MicroRNA in disease regulation
University of Cologne
2013-2025
University Hospital Cologne
2015-2020
Bayer (Germany)
2016-2019
University of Regensburg
2008-2013
Institute of Human Genetics
2010
The translocator protein (18 kDa) (TSPO) is a mitochondrial expressed on reactive glial cells and biomarker for gliosis in the brain. TSPO ligands have been shown to reduce neuroinflammation several mouse models of neurodegeneration. Here, we analyzed expression human retinal microglia studied effects ligand XBD173 microglial functions. analyses were performed retinoschisin-deficient retinas retinas. Lipopolysaccharide (LPS)-challenged BV-2 treated with shRNAs vitro pro-inflammatory markers...
Approximately 98% of mammalian DNA is noncoding, yet we understand relatively little about the function this enigmatic portion genome. The cis-regulatory elements that control gene expression reside in noncoding regions and can be identified by mapping binding sites tissue-specific transcription factors. Cone-rod homeobox (CRX) a key factor photoreceptor differentiation survival, but its vivo targets are largely unknown. Here, used chromatin immunoprecipitation with massively parallel...
Abstract Background Luteolin, a plant derived flavonoid, exerts variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen nitrogen species. Luteolin also shows potent anti-inflammatory by inhibiting nuclear factor kappa B (NFkB) signaling in immune cells. To better understand the immuno-modulatory effects this important we performed genome-wide expression analysis pro-inflammatory challenged microglia treated luteolin conducted...
Abstract Background Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, component tumeric, alleviates pro-inflammatory activities these by inhibiting nuclear factor kappa B (NFkB) signaling. To study immuno-modulatory effects curcumin on transcriptomic level, DNA-microarray analyses were performed resting and LPS-challenged microglial after short-term treatment curcumin. Methods Resting LPS-activated...
Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The polymorphism rs10490924 ARMS2 gene highly associated with AMD and linked to an indel mutation (del443ins54), latter inducing mRNA instability. At present, function protein, exact cellular sources retina biological consequences are unclear. Recombinant was expressed Pichia pastoris, protein functions were studied regarding cell surface binding complement activation human serum using...
Report22 December 2016Open Access Transparent process Polysialic acid blocks mononuclear phagocyte reactivity, inhibits complement activation, and protects from vascular damage in the retina Marcus Karlstetter Laboratory for Experimental Immunology of Eye, Department Ophthalmology, University Cologne, Germany Therapeutic Research Group Bayer Pharma AG, Wuppertal, Search more papers by this author Jens Kopatz Institute Reconstructive Neurobiology, Hospital Bonn, Alexander Aslanidis Anahita...
Microgliosis is a common phenomenon in neurodegenerative disorders, including retinal dystrophies. To identify candidate genes involved microglial activation, we used DNA-microarray analysis of microglia from wild-type and retinoschisin-deficient (Rs1h(-/Y)) mice, prototypic model for inherited degeneration. Thereby, cloned novel 76 aa protein encoding microglia/macrophage-restricted whey acidic (WAP) termed activated microglia/macrophage WAP domain (AMWAP). The gene consists three exons...
Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative lysosomal storage disorders characterized by vision loss, mental and motor deficits, spontaneous seizures. Neuropathological analyses autopsy material from NCL patients animal models revealed brain atrophy closely associated with glial activity. Earlier reports also noticed loss retinal cells reactive gliosis in some forms NCL. To study this phenomenon detail, we analyzed the ocular phenotype CLN6nclf mice, an established...
Mutations in the FAM161A gene were previously identified as cause for autosomal-recessive retinitis pigmentosa 28. To study effects of Fam161a dysfunction vivo, we generated gene-trapped Fam161aGT/GT mice with a disruption its C-terminal domain essential protein–protein interactions. We confirmed absence full-length protein retina using western blots and showed weak expression truncated by immunohistochemistry. Histological analyses demonstrated that photoreceptor segments disorganized young...
PurposePart of the hidden genetic variation in heterogeneous conditions such as inherited retinal diseases (IRDs) can be explained by copy-number variations (CNVs). Here, we explored genomic landscape IRD genes listed RetNet to identify and prioritize those susceptible CNV formation.MethodsRetNet underwent an assessment features occurrence Database Genomic Variants literature. CNVs identified cohort were characterized using targeted locus amplification (TLA) on extracted...
Microglia reactivity is a hallmark of neurodegenerative diseases. We have previously identified activated microglia/macrophage whey acidic protein (AMWAP) as counter-regulator pro-inflammatory response. Here, we studied its mechanisms action with focus on toll-like receptor (TLR) and nuclear factor κB (NFκB) signaling.Recombinant AMWAP was produced in Escherichia coli HEK293 EBNA cells purified by affinity chromatography. uptake fluorescent labeling, microglia markers were measured qRT-PCR...
Inherited retinal dystrophies (iRDs) are a group of genetically and clinically heterogeneous conditions resulting from mutations in over 250 genes. Here, homozygosity mapping whole-exome sequencing (WES) consanguineous family revealed homozygous missense mutation, c.973C>T (p.His325Tyr), RCBTB1. In affected individuals, it was found to segregate with retinitis pigmentosa (RP), goiter, primary ovarian insufficiency, mild intellectual disability. Subsequent analysis WES data different cohorts...
Significant association signals from genome-wide studies (GWAS) point to genomic regions of interest. However, for most loci the causative genetic variant remains undefined. Determining expression quantitative trait (eQTL) in a disease relevant tissue is an excellent approach zoom on disease- or trait-associated and hitherto mechanisms. To this end, we explored regulation gene healthy retina (n = 311) generated largest cis-eQTL data set available date. Genotype- RNA-Seq underwent rigorous...
In this study the retinal transcriptome was investigated during development of experimental autoimmune uveoretinitis (EAU) in mice. EAU induced by immunizing B10.RIII mice with human interphotoreceptor retinoid binding protein (hIRBP) 161–180 peptide. Genome-wide transcriptional profiles (day 7, 14 or 21 after immunization) and control retinas were generated using DNA-microarrays bioinformatic data mining. Microglia-associated transcripts identified. Quantitative real-time polymerase chain...
Purpose.: We studied associations of genetic polymorphisms in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) nonagenarians with macular degeneration (AMD). Methods.: This case-control study comprised 2737 persons (1204 controls, 1433 AMD cases), including 166 (52 114 cases). Single nucleotide (SNPs) the genes ARMS2 CFH were determined. Risk scores computed by multiple logistic regression analysis, environmental risk factors (smoking, hypertension, body mass...
Abstract The aim of this study was to unravel the molecular pathogenesis an unusual retinitis pigmentosa (RP) phenotype observed in a Turkish consanguineous family. Homozygosity mapping revealed two candidate genes, SAMD7 and RHO . A homozygous mutation c.448G > A, p.E150K found affected siblings, while no coding mutations were identified. Interestingly, four non-coding variants genomic regions relevant for binding retinal transcription factor CRX (CRX-bound regions, CBRs) these siblings....
Inherited retinal diseases are mainly caused by mutations in genes that highly expressed photoreceptors of the retina. The majority these is under control transcription factor Cone rod homeobox (Crx), acts as a master photoreceptors. Using genome-wide chromatin immunoprecipitation dataset highlights all potential vivo targets Crx, we have identified novel sterile alpha motif (SAM) domain containing protein, Samd7. mRNA Expression Samd7 was confined to late postnatal and adult mouse retina...