A5031356690- Retinal Development and Disorders
- Retinal Diseases and Treatments
- PARP inhibition in cancer therapy
- Photoreceptor and optogenetics research
- Connexins and lens biology
- Calcium signaling and nucleotide metabolism
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Microtubule and mitosis dynamics
- Adenosine and Purinergic Signaling
- Extracellular vesicles in disease
- Histone Deacetylase Inhibitors Research
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Drug-Induced Ocular Toxicity
- interferon and immune responses
- MicroRNA in disease regulation
- Phosphodiesterase function and regulation
- Mosquito-borne diseases and control
- Sirtuins and Resveratrol in Medicine
- Free Radicals and Antioxidants
- Advanced Fluorescence Microscopy Techniques
- Retinal and Optic Conditions
- bioluminescence and chemiluminescence research
University of Tübingen
2011-2025
STZ eyetrial
2009-2023
Harran University
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...
Purpose.: Spectral domain optical coherence tomography (SD-OCT) allows cross-sectional visualization of retinal structures in vivo. Here, the authors report efficacy a commercially available SD-OCT device to study mouse models degeneration. Methods.: C57BL/6 and BALB/c wild-type mice three different hereditary degeneration (Rho −/−, rd1, RPE65 −/−) were investigated using confocal scanning laser ophthalmoscopy (cSLO) for en face imaging structures. Histology was performed correlate...
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...
Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes blindness in developed world. RP is at present untreatable and underlying neurodegenerative mechanisms are unknown, even though genetic often established. Acetylation deacetylation histones, carried out by histone acetyltransferases (HATs) deacetylases (HDACs), respectively, affects cellular division, differentiation, death survival. We found acetylation histones probably...
Retinitis pigmentosa (RP) is a heterogeneous group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness. Many human cases are caused by mutations in the rhodopsin gene. An important question regarding RP pathology whether different genetic defects trigger same or cell death mechanisms. To answer this question, we analysed photoreceptor degeneration P23H S334ter transgenic rats carrying that affect protein folding sorting respectively. We found strong...
For most neurodegenerative diseases the precise duration of an individual cell's death is unknown, which obstacle when counteractive measures are being considered. To address this, we used rd1 mouse model for retinal neurodegeneration, characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor triggered high cyclic guanosine-mono-phosphate (cGMP) levels. Using cellular data on cGMP accumulation, cell death, survival, created mathematical models to simulate temporal development...
Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation enzymes belonging to the poly-ADP-ribose polymerase (PARP) was shown be involved photoreceptor degeneration human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated exact relevance predominant isoform - PARP1 cell death using knock-out (KO) mice. In vivo ex morphological...
Abstract The enzyme poly-ADP-ribose-polymerase (PARP) mediates DNA-repair and rearrangements of the nuclear chromatin. Generally, PARP activity is thought to promote cell survival in recent years a number inhibitors have been clinically developed for cancer treatment. Paradoxically, also connected many diseases including untreatable blinding disease Retinitis Pigmentosa (RP), where appears drive pathogenesis photoreceptor loss. We tested efficacy three different prevent loss rd1 mouse model...
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 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...
Abstract Retinitis Pigmentosa is a group of inherited neurodegenerative diseases that result in selective cell death photoreceptors. In the developed world, RP regarded as main cause blindness among working age population. The precise mechanisms eventually leading to remain unknown and date no adequate treatment for available. Poly ADP ribose polymerase (PARP) over activity involved photoreceptor degeneration pharmacological inhibition or genetic knock-down PARP1 protect photoreceptors mice...
Peripherin (peripherin/rds) is a membrane-associated protein that plays critical role in the morphogenesis of rod and cone photoreceptor outer segments. Mutations corresponding PRPH2 gene cause different types retinal dystrophies characterized by loss photoreceptors. Over activation poly-ADP-ribose polymerase (PARP) was previously shown to be involved animal models for hereditary dystrophies. This includes rd2 mouse, which suffers from human homologous mutation gene. In present study, we...
Abstract Retinitis pigmentosa (RP), an inherited blinding disease, is caused by a variety of different mutations that affect retinal photoreceptor function and survival. So far there neither effective treatment nor cure. We have previously shown poly(ADP-ribose)polymerase (PARP) acts as common critical denominator cell death in photoreceptors, qualifying it potential target for future therapeutic intervention. A significant fraction RP-causing the genes rod phosphodiesterase 6A (PDE6A)...
Hereditary retinal degeneration (RD) relates to a heterogeneous group of blinding human diseases in which the light sensitive neurons retina, photoreceptors, die. RD is currently untreatable and underlying cellular mechanisms remain poorly understood. However, activity enzyme poly-ADP-ribose polymerase-1 (PARP1) excessive generation (PAR) polymers photoreceptor nuclei have been shown be causally involved RD. The PARP1 large extent governed by its functional antagonist,...
The unconventional myosin VI, a member of the actin-based motor protein family myosins, is expressed in retina. Its deletion was previously shown to reduce amplitudes a- and b-waves electroretinogram. Analyzing wild-type VI-deficient Snell's Waltzer mice more detail, expression pattern VI retinal pigment epithelium, outer limiting membrane, plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves disturbed oscillatory potentials...
The expressions of ion channels by Müller glial cells (MGCs) may change in response to various retinal pathophysiological conditions. There remains a gap our understanding MGCs' responses photoreceptor degeneration towards finding therapies. study explores how an inhibition store-operated Ca2+ entry (SOCE) and its major component, Orai1 channel, MGCs protects photoreceptors from degeneration. revealed increased expression the 10 (rd10) mice. Enhanced oxidative stress markers was confirmed as...