A5007334692- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Histone Deacetylase Inhibitors Research
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- bioluminescence and chemiluminescence research
- Signaling Pathways in Disease
- RNA regulation and disease
- Connexins and lens biology
- Nuclear Receptors and Signaling
- Biomarkers in Disease Mechanisms
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Free Radicals and Antioxidants
- Drug-Induced Ocular Toxicity
- Multiple Sclerosis Research Studies
- Renal Transplantation Outcomes and Treatments
- Cerebrovascular and genetic disorders
- Photochromic and Fluorescence Chemistry
- Acute Myocardial Infarction Research
- Telomeres, Telomerase, and Senescence
- Adenosine and Purinergic Signaling
University of Tübingen
2014-2025
STZ eyetrial
2010-2019
Ophthalmic Research Institute of Australia
2016
Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine
2015
Telethon Foundation
2008
Telethon Institute Of Genetics And Medicine
2007-2008
Laboratory of Molecular Genetics
2005
Cell death in neurodegenerative diseases is often thought to be governed by apoptosis; however, an increasing body of evidence suggests the involvement alternative cell mechanisms neuronal degeneration. We studied retinal neurodegeneration using 10 different animal models, covering all major groups hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho S334ter, P23H, Cnga3 cpfl1, Rpe65 KO), investigating metabolic processes relevant for forms death. show that apoptosis plays only a minor...
Significance Development of treatments for hereditary degeneration the retina (RD) is hampered by vast genetic heterogeneity this group diseases and delivery drug to an organ protected blood–retina barrier. Here, we present approach treatment different types RD, combining innovative therapy with a liposomal system that facilitates into retina. Using animal models RD show pharmacological preserved both viability cells in as well retinal function. Thus, our study provides avenue development...
The rd1 natural mutant is one of the first and probably most commonly studied mouse model for retinitis pigmentosa (RP), a severe frequently blinding human retinal degeneration. In several decades research, link between increase in photoreceptor cGMP levels extremely rapid cell death gave rise to number hypotheses. Here, we provide clear evidence that presence cyclic nucleotide gated (CNG) channels outer segment membrane key rod loss. Cngb1−/−× double mutants devoid regular CNG channels, are...
Abstract Retinitis pigmentosa (RP) defines a group of inherited degenerative retinal diseases causing progressive loss photoreceptors. To this day, RP is still untreatable and rational treatment development will require thorough understanding the underlying cell death mechanisms. Methylation DNA base cytosine by methyltransferases (DNMTs) an important epigenetic factor regulating gene expression, differentiation, death, survival. Previous studies suggested involvement mechanisms in RP,...
Inherited retinal degeneration affecting both rod and cone photoreceptors constitutes one of the leading causes blindness in developed world. Such is at present untreatable, underlying neurodegenerative mechanisms are unknown, even though certain genetic have been established. The rd1 mouse best characterized animal models for photoreceptor degeneration, whereas cpfl1 a recently discovered model cell death. Because affected by functionally similar mutations phosphodiesterase 6 genes,...
Mutations in the PDE6A gene can cause rod photoreceptors degeneration and blinding disease retinitis pigmentosa (RP). While a number of pathogenic mutations have been described, little is known about their impact on compound heterozygous situations potential interactions different disease-causing alleles. Here, we used novel mouse model for Pde6a R562W mutation combination with an existing line carrying V685M to generate V685M/R562W animals, exactly homologous case human RP. We compared...
Cone photoreceptor cell death as it occurs in certain hereditary retinal diseases is devastating, with the affected patients suffering from a loss of accurate and colour vision. Regrettably, these cone are still untreatable to date. Thus, identification substances able block or restrain primary importance. We studied neuroprotective effects histone deacetylase inhibitor, Trichostatin A (TSA), mouse model inherited, degeneration (cpfl1). show that HDAC inhibition protects cpfl1 cones vitro,...
Abstract Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and, ultimately blindness. In RP, a vast number mutations perturb structure function rod photoreceptors, while cones remain initially unaffected. Extensive advanced stages disease triggers cone by mechanism that is still largely unknown. Here, we show secondary animal models for RP associated with increased activity histone deacetylates...
Abstract The rd2 mouse model, characterized by a mutation in the Prph2 gene, exhibits abnormal development of photoreceptor outer segments, resulting progressive retinal degeneration. While correlation between poly-ADP-ribose polymerase (PARP) activity and degeneration rod photoreceptors is established specific mechanism driving cone this model remains unclear. Furthermore, it yet to be determined whether inhibiting PARP can effectively impede context. We demonstrated that inhibitors...
Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays key role in the visual transduction cascade rod and cone photoreceptors. Each type of photoreceptor utilizes discrete catalytic inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. degradation cyclic guanosine-3',5'-monophosphate at specifically tuned rates kinetics. Recently, human PDE6H gene was identified as novel locus for autosomal recessive (incomplete) color blindness. However, three different classes cones...
Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death poorly understood, consequently, there no treatments available. Previous studies suggest central role calcium (Ca2+) homeostasis deficits photoreceptor degeneration; however, direct evidence this is scarce physiological measurements Ca2+ degenerating mammalian lacking....
Retinitis pigmentosa (RP) is one of the leading causes visual handicap in world population and characterized by high genetic heterogeneity. The study disease mechanisms development efficient therapeutic approaches have mostly relied on availability animal models for this condition, so far. Nevertheless, little information available about RNA expression profiles RP genes human retina. An atlas 34 known murine retinas was generated to overcome lack information.Appropriate templates were...
Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death the light-sensing cone and rod photoreceptors. Despite individual IRDs (Inherited disease) being rare, collectively, they affect up to 1:2000 people worldwide, causing significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses Pde6ccpfl1 mouse model achromatopsia, cone-specific loss IRD disease), investigate potential...
Infiltration of macrophages into the central nervous system and activation microglia are hallmarks multiple sclerosis its animal model-experimental autoimmune encephalomyelitis (EAE). Cell death in EAE has been demonstrated as an essential mechanism local regulation inflammatory reaction, but also one major factors contributing to destruction tissue. The focus this study was on detection cell among ED1(+) cells (macrophages/activated microglia) spinal cord Dark Agouti rats at peak EAE....
Abstract Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision ultimately blindness. In RP, a vast number mutations perturb structure function rod photoreceptors while cones remain initially unaffected. follows secondarily due increased oxidative stress, inflammation, structural nutritional support provided by rods. Here, we show that secondary cone animal models for RP was associated with an activity...
We present a mathematical algorithm for the analysis of electrophoretic patterns resulting from arbitrarily primed PCR profiling. The is based on established procedures applied to digital images gel patterns. includes (a) transformation image into matrix form, (b) identification every lane as set columns that are further mathematically processed, (c) averaging corresponding lanes define representatives, (d) elimination "smiling" bands, (e) solving problem offset, and (f) removal background....
Abstract Retinal diseases caused by cone photoreceptor cell death are devastating as the patients experiencing loss of accurate and color vision. Understanding mechanisms identification key players therein could provide new treatment options. We studied neuroprotective effects a histone deacetylase inhibitor, Trichostatin A (TSA), in mouse model inherited, primary degeneration ( cpfl1 ). show that HDAC inhibition protects cones vitro , retinal explant cultures. More importantly, vivo single...