A5060378968- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Museums and Cultural Heritage
- Photochromic and Fluorescence Chemistry
- Libraries and Information Services
- Connexins and lens biology
- Arts, Culture, and Music Studies
- Cellular transport and secretion
- Retinoids in leukemia and cellular processes
- Virus-based gene therapy research
- Retinal and Macular Surgery
- Endoplasmic Reticulum Stress and Disease
- bioluminescence and chemiluminescence research
- Nitric Oxide and Endothelin Effects
- CRISPR and Genetic Engineering
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Corneal Surgery and Treatments
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Glaucoma and retinal disorders
- Erythrocyte Function and Pathophysiology
- Retinopathy of Prematurity Studies
- Olfactory and Sensory Function Studies
University of California, San Francisco
2009-2019
Universitätsklinikum Aachen
2013-2019
RWTH Aachen University
2013-2016
University of North Texas
2012
University of North Texas Health Science Center
2012
University of Florida
2000-2012
Alfaisal University
2012
University of California, San Diego
2012
King Khalid University Hospital
2012
King Saud University
2012
Recent demonstrations of survival-promoting activity by neurotrophic agents in diverse neuronal systems have raised the possibility pharmacological therapy for inherited and degenerative disorders central nervous system. We shown previously that, retina, basic fibroblast growth factor delays photoreceptor degeneration Royal College Surgeons rats with retinal dystrophy that reduces or prevents rapid produced constant light rat. This light-damage model now provides an efficient way to assess...
Retinal pigment epithelial (RPE) cell dysfunction plays a central role in various retinal degenerative diseases, but knowledge is limited regarding the pathways responsible for adult RPE stress responses vivo. mitochondrial has been implicated pathogenesis of several forms degeneration. Here we have shown that postnatal ablation oxidative phosphorylation mice triggers gradual epithelium dedifferentiation, typified by reduction RPE-characteristic proteins and cellular hypertrophy. The...
The Royal College of Surgeons (RCS) rat is a widely studied animal model retinal degeneration in which the inability pigment epithelium (RPE) to phagocytize shed photoreceptor outer segments leads progressive loss rod and cone photoreceptors. We recently used positional cloning demonstrate that gene Mertk likely corresponds dystrophy ( rdy ) locus RCS rat. In present study, we sought determine whether transfer retina would result correction RPE phagocytosis defect preservation subretinal...
To determine whether mice that are homozygous for a targeted disruption of the Mer receptor tyrosine kinase gene (mer(kd)) manifest retinal dystrophy phenotype similar to RCS rats, which carry mutation in orthologous MERTK:Eyes mer(kd) and C57BL/6 wild-type (WT) were examined by light electron microscopy, whole-eye rhodopsin measurement, Ganzfeld electroretinography (ERG).The showed rapid, progressive degeneration photoreceptors (PRs). Features common rats included absence or near phagosomes...
The RCS rat is a widely studied model of recessively inherited retinal degeneration. genetic defect, known as <i>rdy</i> (retinal dystrophy), results in failure the pigment epithelium (RPE) to phagocytize shed photoreceptor outer segment membranes. We previously used positional cloning and<i>in vivo</i> complementation demonstrate that<i>Mertk</i> gene for <i>rdy</i>. have now primary RPE cell culture system that site action <i>Mertk</i> and obtain functional evidence key role Mertk...
Frogs maintained on a diurnal light-dark cycle (14 hours light and 10 darkness) shed their rod photoreceptor outer segment tips shortly after the onset of light. Shedding is synchronous occurs in about 25 percent photoreceptors each day. Prolonged exposure to total darkness decreases amount shedding, which results large burst shedding. Thus, frog retina, shedding shown be directly related stimulation.
Ribozyme-directed cleavage of mutant mRNAs appears to be a potentially effective therapeutic measure for dominantly inherited diseases. We previously demonstrated that two ribozymes targeted the P23H mutation in rhodopsin slow photoreceptor degeneration transgenic rats up 3 months age when injected before significant at postnatal day (P) 15. now have explored whether ribozyme rescue persists older ages, and are later after cell loss. Recombinant adeno-associated virus (rAAV) vectors...
Excessive lipid accumulation in Bruch's membrane (BrM) is a hallmark of ageing, the major risk factor for age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilise reverse cholesterol transport (RCT) activity to move into BrM, mediated through ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI).ABCA1 expression was assessed by transcription polymerase chain reaction (RT-PCR) western blotting human RPE cell extracts. Lipid assays were performed...
Purpose: To preserve photoreceptor cell structure and function in a rodent model of retinitis pigmentosa with P23H rhodopsin by selective inhibition the mutant allele using second generation antisense oligonucleotide (ASO). Methods: Wild-type mice rats were treated ASO intravitreal (IVT) injection mRNA protein expression measured. Transgenic expressing murine gene (P23H transgenic rat Line 1) administered either mouse-specific or control ASO. The contralateral eye was injected PBS used as...
CNTF is a neuroprotective agent for retinal degenerations that can cause reduced electroretinogram (ERG) amplitudes. The goal of the present study was to determine effects intraocular delivery on normal rat visual function.Full-field scotopic and photopic ERG amplitudes spatial frequency thresholds optokinetic response (OKR) adult Long-Evans rats were measured before after intravitreous injection or subretinal adenoassociated virus-vectored (AAV-CNTF) into one eye. Visual acuity also by...
Endoplasmic reticulum (ER) stress has been observed in animal models of retinitis pigmentosa expressing P23H rhodopsin. We compared levels tightly induced ER genes, Binding immunoglobulin protein (BiP) and CCAAT/enhancer-binding homologous (Chop), seven additional retinal degeneration arising from genetic or environmental causes.Retinas transgenic S334ter rhodopsin (lines 3, 4, 5) Royal College Surgeons (RCS RCS-p+) rats postnatal (P) days 10 to 120 were analyzed. In a constant light (CL)...
Inherited photoreceptor degenerations (IPDs) are the most genetically heterogeneous of Mendelian diseases. Many IPDs exhibit substantial phenotypic variability, but basis is usually unknown. Mutations in MERTK cause recessive IPD phenotypes associated with RP38 locus. We have identified a murine genetic modifier Mertk-associated degeneration, C57BL/6 (B6) allele which acts as suppressor. Photoreceptors degenerate rapidly Mertk-deficient animals homozygous for 129P2/Ola (129) allele, whereas...
The normal function of vertebrate photoreceptor cells depends on multiple interactions and transfer substances between the photoreceptors retinal pigment epithelium (RPE), but mechanisms these are poorly understood. Many thought to be mediated by interphotoreceptor matrix (IPM), a complex extracellular that surrounds lies them RPE. Histochemical, immunocytochemical, lectin probes for several IPM constituents revealed components in rat undergo major shift distribution or molecular...
Oxidative stress and photoreceptor apoptosis are prominent features of many forms retinal degeneration (RD) for which there currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein reduces oxidative upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis intravitreal injection STC-1 can rescue photoreceptors. first in rhodopsin...
Huntington disease (HD) is an inherited neurodegenerative that affects multiple brain regions. It caused by expanded polyglutamine tract in huntingtin (Htt). The development of therapies for HD and other diseases has been hampered factors, including the lack clear therapeutic targets, cost complexity testing lead compounds vivo. R6/2 mouse model widely used pre-clinical trials because its progressive robust neural dysfunction, which includes retinal degeneration. Profilin-1 a Htt binding...
The absence of Mertk in RCS rats results defective RPE phagocytosis, accumulation outer segment (OS) debris the subretinal space, and subsequent death photoreceptors. Previous research utilizing gene replacement therapy provided proof concept for treatment this form recessive retinitis pigmentosa (RP); however, beneficial effects on retinal function were transient. In present study, we evaluated whether delivery a MERTK transgene using tyrosine-mutant AAV8 capsid could lead to more robust...