A5027917051- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Cancer, Hypoxia, and Metabolism
- Advanced biosensing and bioanalysis techniques
- interferon and immune responses
- Retinoids in leukemia and cellular processes
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Glaucoma and retinal disorders
- Circadian rhythm and melatonin
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Lupus Erythematosus Research
- High Altitude and Hypoxia
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- Cellular transport and secretion
- Heme Oxygenase-1 and Carbon Monoxide
- Erythropoietin and Anemia Treatment
- Virus-based gene therapy research
- Retinopathy of Prematurity Studies
- Connexins and lens biology
- Antioxidant Activity and Oxidative Stress
- Adipose Tissue and Metabolism
- Neuroscience of respiration and sleep
University of Zurich
2015-2024
University Hospital of Zurich
2002-2022
Cell Medica (Switzerland)
2011
Swiss Integrative Center for Human Health
2006-2009
Center for Pediatric Endocrinology Zurich
2009
Brooklyn College
1997
American College of Surgeons
1997
Age-related macular degeneration (AMD) is a progressive disease of the retinal pigment epithelium (RPE) and retina leading to loss central vision. Polymorphisms in genes involved lipid metabolism, including ATP-binding cassette transporter A1 ( ABCA1 ), have been associated with AMD risk. However, significance handling for pathogenesis remains elusive. Here, we study contribution efflux RPE by generating mouse model lacking its partner ABCG1 specifically this layer. Mutant mice show...
Survival and death of photoreceptors in degenerative diseases the retina is controlled by a multitude genes endogenous factors. Some may be involved process itself whereas others part an defense system. We show two models retinal degeneration that photoreceptor strongly induces expression leukemia inhibitory factor (LIF) subset Muller glia cells inner nuclear layer retina. LIF essential to induce extensive intraretinal signaling system which includes characterized upregulation Edn2, STAT3,...
Retinal degeneration is a major cause of severe visual impairment or blindness. Understanding the underlying molecular mechanisms prerequisite to develop therapeutic approaches for human patients. We show in three mouse models that induced and inherited retinal induces LIF CLC as members interleukin (IL)-6 family proteins, activates proteins Jak-STAT signaling pathway, up-regulates suppressors cytokine negative feedback loop. Inhibition Jak2 leads protection photoreceptors model but not...
Abstract In lower vertebrates, such as fish, Müller glia plays an essential role in the restoration of visual function after retinal degeneration by transdifferentiating into photoreceptors and other neurons. During this process, cells re‐enter cell cycle, proliferate, migrate from inner nuclear layer (INL) to photoreceptor where they express photoreceptor‐specific markers. This process transdifferentiation is absent mammals, loss leads permanent vision deficits. The mechanisms underlying...
The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited dystrophies age-related macular degeneration affect a substantial percentage of the world population. To identify isolate most competent cells for transplantation integration into retina, tracing during development would be an important added value. that aim, Chrnb4-EGFP mouse line was characterized throughout retinogenesis. It revealed sub-population early retinal progenitors...
The exact mechanisms and temporal sequence of neurodegeneration in multiple sclerosis are still unresolved. visual pathway including its unmyelinated retinal axons, can serve as a prototypic model experimental optic neuritis. We conducted longitudinal study combining imaging through optical coherence tomography (OCT) with immunohistochemical analyses nerve tissue at various time points autoimmune encephalomyelitis (EAE).Inner layer (IRL) thickness was measured 30 EAE 14 healthy control...
Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application recombinant human Epo (huEpo) protects the mouse retina against light-induced degeneration inhibiting photoreceptor cell apoptosis. Because apoptosis is also common path to loss in retinal dystrophies such as retinitis pigmentosa (RP), we tested whether high levels huEpo would reduce apoptotic death two models RP. We combined respective mutant lines with a transgenic line (tg6) that constitutively...
RPE65 is a retinal pigment epithelial protein essential for the regeneration of 11-cis-retinal, chromophore cone and rod visual pigments. Mutations in lead to spectrum dystrophies ranging from Leber's congenital amaurosis autosomal recessive retinitis pigmentosa. One most frequent missense mutations an amino acid substitution at position 91 (R91W). Affected patients have useful vision first decade life, but progressively lose sight during adolescence. We generated R91W knock-in mice...
Rod and cone visual pigments use 11-cis-retinal, a vitamin A derivative, as their chromophore. Light isomerizes 11-cis- into all-trans-retinal, triggering conformational transition of the opsin molecule that initiates phototransduction. After bleaching all-trans-retinal leaves opsin, light sensitivity must be restored by regeneration 11-cis-retinal. Under bright conditions retinal G protein-coupled receptor (RGR) was reported to support this acting photoisomerase in proposed photic cycle. We...
Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure the visible light, and although cellular within have been characterized extensively, role pigment epithelium (RPE) in this model less well understood. We demonstrate that exposition intense light causes immediate breakdown outer blood-retinal barrier (BRB). In a molecular level, we observed slackening adherens...
Abstract Little is known about the mechanisms underlying macular degenerations, mainly for scarcity of adequate experimental models to investigate cone cell death. Recently, we generated R91W;Nrl −/− double-mutant mice, which display a well-ordered all-cone retina with normal retinal vasculature and strong photopic function that generates useful vision. Here exposed wild-type ( wt ) mice toxic levels blue light analyzed their retinas at different time points post illumination (up 10 days)....
Mutations in OCRL encoding the inositol polyphosphate 5-phosphatase (Lowe oculocerebrorenal syndrome protein) disrupt phosphoinositide homeostasis along endolysosomal pathway causing dysfunction of cells lining kidney proximal tubule (PT). The can be isolated (Dent disease 2) or associated with congenital cataracts, central hypotonia and intellectual disability syndrome). mechanistic understanding Dent 2/Lowe remains scarce due to limitations animal models deficiency. Here, we investigate...
Abstract Background In inherited retinal disorders such as retinitis pigmentosa (RP), rod photoreceptor-specific mutations cause primary degeneration that is followed by secondary cone death and loss of high-acuity vision. Mechanistic studies are challenging because heterogeneity. Moreover, the detection early responses to especially difficult due paucity cones in retina. To resolve heterogeneity degenerating retina investigate events both types photoreceptors during degeneration, we...
Abstract Background Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting photoreceptor (PR) cells. Here, we addressed underlying pathological mechanisms PR degeneration by focusing on energy metabolism during chronic activation hypoxia-inducible factors (HIFs) rod PR. Methods We used two-photon laser scanning microscopy...
HIF1A is one of the major transcription factors that regulate tissue response to low oxygen tension. It controls expression a large number genes involved in cell survival, proliferation, angiogenesis, and other cellular processes. present at increased levels early postnatal retina. In this study its potential function during development mouse retina retinal vasculature was analyzed.A line generated with Cre-mediated Hif1a knockdown peripheral Retinal morphology were analyzed sections flat...
The peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) proteins are key regulators of cellular bioenergetics and accordingly expressed in tissues with a high energetic demand. For example, PGC-1α PGC-1β control organ function brown adipose tissue, heart, brain, liver skeletal muscle. Surprisingly, despite their prominent role the mitochondrial biogenesis oxidative metabolism, expression PGC-1 coactivators retina, an one highest energy demands per tissue weight, completely...
Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop disturb cell metabolism, function ultimately survival, potentially contributing pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels aged retina suggesting increased activity of transcription factors (HIFs)...
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 Background Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α retina strongly protects photoreceptors an animal model light-induced degeneration. To address molecular mechanisms protection, we analyzed transcriptome hypoxic using microarrays real-time PCR. Results exposure induced marked alteration with significantly...