- Retinal Development and Disorders
- Zebrafish Biomedical Research Applications
- Photoreceptor and optogenetics research
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Neuropharmacology Research
- Cell Image Analysis Techniques
- Advanced Biosensing Techniques and Applications
- Retinal Diseases and Treatments
- Neurobiology and Insect Physiology Research
- Connexins and lens biology
- Cardiomyopathy and Myosin Studies
- Glaucoma and retinal disorders
- Muscle Physiology and Disorders
- Bone fractures and treatments
- melanin and skin pigmentation
- Cancer Cells and Metastasis
- Animal testing and alternatives
- Neuroblastoma Research and Treatments
- Lymphatic System and Diseases
- Authorship Attribution and Profiling
- Erythrocyte Function and Pathophysiology
- Retinopathy of Prematurity Studies
- Ocular Oncology and Treatments
- Protease and Inhibitor Mechanisms
- Digital Holography and Microscopy
University of Basel
2012-2020
University of Zurich
2005-2014
Life Science Zurich
2014
ETH Zurich
2005-2010
École Polytechnique Fédérale de Lausanne
2005-2010
STZ eyetrial
1999-2005
TH Bingen University of Applied Sciences
2003
We examined optokinetic and optomotor responses of 450 zebrafish mutants, which were isolated previously based on defects in organ formation, tissue patterning, pigmentation, axon guidance, or other visible phenotypes. These strains carry single point mutations >400 essential loci. asked fraction the mutants develop blindness types impairments specific to visual system. Twelve failed respond either one both our assays. Subsequent histological electroretinographic analysis revealed unique...
Circulating tumor cells (CTCs) are shed from solid cancers in the form of single or clustered cells, and latter display an extraordinary ability to initiate metastasis. Yet, biological phenomena that trigger shedding CTC clusters a primary cancerous lesion poorly understood. Here, when dynamically labeling breast cancer along progression, we observe majority undergoing hypoxia, while CTCs largely normoxic. Strikingly, find vascular endothelial growth factor (VEGF) targeting leads shrinkage,...
Visual acuity, the ability of visual system to distinguish two separate objects at a given angular distance, is influenced by optical and neuronal properties system. Although many factors may contribute, ultimate limit photoreceptor spacing. In general, least one unstimulated flanked stimulated ones needed perceive as separate. This critical interval also referred Nyquist frequency according Shannon sampling theorem highest spatial where pattern can be faithfully transmitted. We measured...
The trafficking of intracellular vesicles is essential for a number cellular processes and defects in this process have been implicated wide range human diseases. We identify the zebrafish mutant lbk as novel model such disorders. displays hypopigmentation skin melanocytes retinal pigment epithelium (RPE), an absence iridophore reflections, internal organs (liver, intestine) well functional vision innate immune system (macrophages). Positional cloning, allele screen, rescue experiments...
An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore visual pigments (11-cis-retinal) is intrinsic vertebrate cone and rod vision. This process, called cycle, mostly characterized in rod-dominated retinas essentially depends on RPE65, an all-trans 11-cis-retinoid isomerase. Here we analysed role RPE65 zebrafish, a species with cone-dominated retina. We cloned zebrafish showed that its expression coincided photoreceptor development. Targeted gene knockdown resulted...
To characterize morphologic and physiological alterations in the retina of three laminin mutant zebrafish, bashful (bal, lama1), grumpy (gup, lamb1), sleepy (sly, lamc1), which were identified forward genetic screens found to be impaired visual functions.Mutant larvae observed for defects behavior by testing their optokinetic response (OKR). In addition, electroretinograms (ERG) measured retinal morphology was examined standard histology, immunocytochemistry, TUNEL assay, electron...
Abstract Retinomotor movements are morphological changes in the outer retina response to changing light conditions. They can be separated into two components: Migration of pigment granules within microvilli retinal epithelium (RPE) and positional photoreceptor cells. These optimize exposure cone rod photoreceptors light. The aim this study was analyze both time course retinomotor adult zebrafish maturation these processes developing fish. We show that used as a dark/light adaptation...
The singular structure of artemisinin, with its embedded 1,2,4-trioxane heterocycle, has inspired the discovery numerous semisynthetic artemisinin and structurally diverse synthetic peroxide antimalarials, including ozonides OZ277 (arterolane) OZ439 (artefenomel). Despite critical importance combination therapies (ACTs), precise mode action peroxidic antimalarials is not fully understood. However, it long been proposed that bond in other antimalarial peroxides undergoes reductive activation...
Abstract Confocal microscopy is used today on a daily basis in life science labs. This “routine” technique contributes to the progress of scientific projects across many fields by revealing structural details and molecular localization, but researchers need be aware that detection efficiency emission light path performance major influence confocal image quality. By design, large portion signal discarded imaging, leading decreased signal-to-noise ratio (SNR) which turn limits resolution. A...
Abstract Previous studies have analyzed photoreceptor development, some inner retina cell types, and specific neurotransmitters in the zebrafish retina. However, only minor attention has been paid to morphology of synaptic connection between photoreceptors second order neurons even though it represents transition from light sensitive receptor neuronal network visual system. Here, we describe appearance differentiation pre‐ postsynaptic elements at cone synapses developing together with...
purpose. To characterize retinal morphology and visual system function in the zebrafish mutant fade out (fad) to establish as a lower vertebrate model for Hermansky–Pudlak syndrome (HPS). methods. Retinal of fad larvae was examined between 3 9 days postfertilization (dpf) by standard histology, transmission electron microscopy, immunohistochemistry examination. Apoptotic cells were visualized TdT-mediated dUTP nick-end labeling (TUNEL) staining. Visual probed electroretinography behavioral...
Abstract The first synapse in the vertebrate visual system is photoreceptor between rod and cone photoreceptors second‐order bipolar cells. Although mutations nyctalopin gene ( NYX ) humans lead to congenital stationary night blindness (CSNB1), affecting synaptic transmission both types of ON‐bipolar cells, function cone‐dominant animal models has not been studied. Because larval zebrafish retina cone‐dominant, we isolated nyx ortholog raised a polyclonal antibody against protein. Nyctalopin...
ABSTRACT The accessory outer segment, a cytoplasmic structure running alongside the photoreceptor has been described in teleost fishes, excluding model organism zebrafish. So far, function of segment is unknown. Here, we describe ultrastructure zebrafish cone by electron microscopy. Starting at connecting cilium, runs parallel (COS). A thin plasma bridge connects with whose surface enlarged foldings and invaginations. Beside morphological descriptions, demonstrate that Usher protein myosin...
purpose. To characterize morphologic alterations in the retina of visual mutant zebrafish gantenbein (gnn) and to examine whether these correlate with those present human hereditary eye diseases. methods. The gnn was isolated by behavioral macroscopic screening. Retinas larvae were examined at different developmental stages from 2 9 days postfertilization (dpf) standard histologic staining techniques immunocytochemistry. Ultrastructural electron microscopy. genetic map position induced...
Funduscopy is one of the most commonly used diagnostic tools in ophthalmic practice, allowing for a ready assessment pathological changes retinal vasculature and outer retina. This non-invasive technique has so far been rarely animal model diseases, albeit its potential as screening assay genetic screens. The zebrafish (Danio rerio) well suited such screens ocular alterations. Therefore we developed funduscopy adult employed it tool to find alterations anterior segment fundus eye genetically...
Abstract The retinoic acid molecule, a vitamin A derivative, is of key importance for eye and photoreceptor development in vertebrates. Several studies have provided evidence that the ventral part retina particularly susceptible to impairment retinoid signalling during period its development. In zebrafish, targeted gene knockdown β,β‐carotene‐15,15′‐oxygenase (bcox), enzyme formation, provokes loss early results microphthalmia at larval stages. Using this model, we analysed consequences...
Reliable software is a prerequisite for successful operation of modern wide field fluorescence microscope. When used live cell imaging, acquisition speed particular interest. This both because biological processes can be highly-dynamic, and to avoid unnecessary photobleaching phototoxicity living samples. article shows that besides the hardware (microscope) components themselves, control an important influencing factor performance. We tested compared performance five different generic...