A5091539242- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Retinoids in leukemia and cellular processes
- Aldose Reductase and Taurine
- Ocular Diseases and Behçet’s Syndrome
- Ocular Oncology and Treatments
- CRISPR and Genetic Engineering
- bioluminescence and chemiluminescence research
- Developmental Biology and Gene Regulation
- Connexins and lens biology
- Retinal and Optic Conditions
- Ubiquitin and proteasome pathways
- Photochromic and Fluorescence Chemistry
- Retinal Imaging and Analysis
- Prenatal Substance Exposure Effects
- Systemic Lupus Erythematosus Research
- Genomics and Chromatin Dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Zebrafish Biomedical Research Applications
- Inflammatory Bowel Disease
Washington University in St. Louis
2015-2025
Rocky Mountain MS Center
2009-2014
University of Colorado Denver
2010-2014
National Eye Institute
2011
National Institutes of Health
2011
Lions Eye Institute
2010
The antivascular endothelial growth factor agents ranibizumab and bevacizumab are used to treat ocular neovascular diseases. There have been recent reports of sustained elevation intraocular pressure after use either agent, which we hypothesize could be because high-molecular-weight aggregates.Enzyme-linked immunosorbent assay, size exclusion chromatography, polyacrylamide gel electrophoresis were analyze repackaged syringes obtained from three outside compounding pharmacies samples directly...
Abstract Genes encoding cell-surface proteins control nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding understanding of how disease-associated mutations cause pathology. Here we introduce a strategy to define complete portfolios full-length encoded by individual genes. Applying this approach neural molecules, identify thousands unannotated expressed retina brain. By mass...
Retinal ganglion cells (RGCs) relay visual information from the eye to brain. RGCs are first cell type generated during retinal neurogenesis. Loss of function transcription factor Atoh7, expressed in multipotent early neurogenic progenitors leads a selective and essentially complete loss RGCs. Therefore, Atoh7 is considered essential for conferring competence on generate Despite importance RGC specification, we find that inhibiting apoptosis Atoh7-deficient mice by Bax only modestly reduces...
Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse homeostasis, aging, diabetes, dry eye disease (DED), where tear deficiency predisposes cornea to recurrent In capture transcriptional states that accomplish continuous tissue turnover. We leverage our dataset...
Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration the neuroretina may occur prior to appearance microvascular changes; however, mechanisms underlying this neurodegeneration been elusive. Microglia are predominant resident immune cell in retina and adopt dynamic roles disease. Here, we show ablation retinal microglia ameliorates visual dysfunction type I diabetes mouse model. We also provide evidence enhanced...
HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint eye inflammation, respectively. Gastrointestinal inflammation has been suggested as a trigger axSpA. We recently identified bacterial peptide (YeiH) that can be presented by to expanded public T cell receptors (TCRs) in axSpA B27AAU. While YeiH is present enteric microbiota pathogens, additional evidence pathogenic cells...
Homeodomain transcription factors (HD TFs) are instrumental to vertebrate development. Mutations in HD TFs have been linked human diseases, but their pathogenic mechanisms remain elusive. Here, we use Cone-Rod Homeobox ( CRX ) as a model decipher the disease-causing of two mutations, p.E80A and p.K88N, that produce severe dominant retinopathies. Through integrated analysis molecular functional evidence vitro knock-in mouse models, uncover novel gain-of-function mechanisms: increases...
Age-related macular degeneration (AMD) is a leading cause of blindness featuring pathogenic neovascularization the choroidal vasculature (CNV). Although systemic immunity plays role in AMD, ocular signals that recruit and activate immune cells remain poorly defined. Using single-cell RNA sequencing, we prospectively profile peripheral blood mononuclear from 65 individuals including AMD controls, which integrate with existing choroid data. We generate network choroid-peripheral interactions...
Abstract Age‐related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of on homeostasis, we used short‐lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) hallmarks loss. Bulk single‐cell RNA‐sequencing (scRNAseq) three age groups (6‐, 12‐, 18‐week‐old) identified transcriptional fingerprints killifish retina, unveiling pathways also...
ABSTRACT Retinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines DNA (5mC) actively regulated for proper control of expression architecture. Numerous genes display active demethylation across development; a process that requires oxidation 5mC to 5-hydroxymethylcytosine (5hmC) controlled the ten-eleven translocation methylcytosine dioxygenase (TET) enzymes. Using an allelic series...
Retinitis pigmentosa (RP) is a genetically diverse blinding disorder lacking broadly effective therapies. We performed genome-wide in vivo CRISPR knockout screen mice carrying the P23H rhodopsin mutation (the most common cause of autosomal dominant RP United States) to systematically identify neuroprotective genes. discovered multiple knockouts that accelerated rod photoreceptor loss, validated top candidates, and showed overexpressing two genes-UFD1 UXT-preserved rods cones, maintained...
Mutations in the cone-rod-homeobox protein CRX are typically associated with dominant blinding retinopathies variable age of onset and severity. Five well-characterized mouse models carrying different Crx mutations show a wide range disease phenotypes. To determine if phenotype variability correlates distinct changes target gene expression, we perform RNA-seq analyses on three these compare results published data. Despite dramatic phenotypic differences between tested, graded expression...
Recent technological advances have delivered the genome-wide targets of many important transcription factors (TFs). However, increasing evidence suggests that not all target sites mediate regulatory function, raising questions how to determine which are active, what epigenetic consequences TF binding at these sites, and specificity is coded. To address questions, we focused on CRX, a disease-associated homeodomain required for photoreceptor gene expression development. Since CRX binds more...
The size of dendrite arbors shapes their function and differs vastly between neuron types. signals that control dendritic arbor remain obscure. Here, we find in the retina, starburst amacrine cells (SACs) rod bipolar (RBCs) express homophilic cell-surface protein AMIGO2. In Amigo2 knockout (KO) mice, SAC RBC dendrites expand while other retinal neurons stable. are divided into a central input region peripheral output provides asymmetric inhibition to direction-selective ganglion (DSGCs)....
Aldose reductase (AKR1B1) is an NADPH-dependent aldo-keto best known as the rate-limiting enzyme of polyol pathway. Accelerated glucose metabolism through this pathway has been implicated in diabetic cataract and retinopathy. Some human tissues contain AKR1B1 well AKR1B10, a closely related member gene superfamily. This opens possibility that AKR1B10 may also contribute to complications. The goal current study was characterize expression profiles eye. Using quantitative reverse...
Development of retinal structure and function is controlled by cell type-specific transcription factors widely expressed co-regulators. The latter includes the mixed-lineage leukemia (MLL) family histone methyltransferases that catalyze H3 lysine 4 di- tri-methylation associated with gene activation. One such member, MLL1, in central nervous system including retina. However, its role development unknown. To address this question, we knocked out Mll1 mouse progenitors, discovered MLL1 plays...
Genetic variations in ephrin type-A receptor 2 (EPHA2) have been associated with inherited and age-related forms of cataract humans. Here, we characterized the eye lens phenotype transcript profile germline Epha2 knock-in mutant mice homozygous for either a missense variant humans (Epha2-Q722) or novel insertion-deletion mutation (Epha2-indel722) that were both located within tyrosine-kinase domain EPHA2. Confocal imaging ex vivo lenses from Epha2-indel722 on fluorescent reporter background...
To identify molecular features that distinguish individuals with shared clinical of granulomatous uveitis.