A5012275431- Retinal Development and Disorders
- Developmental Biology and Gene Regulation
- Glaucoma and retinal disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Diseases and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- Epigenetics and DNA Methylation
- Zebrafish Biomedical Research Applications
- Wnt/β-catenin signaling in development and cancer
- Retinopathy of Prematurity Studies
- Immune cells in cancer
- Photoreceptor and optogenetics research
- Ubiquitin and proteasome pathways
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Retinoids in leukemia and cellular processes
- Genomics and Chromatin Dynamics
- Complement system in diseases
- interferon and immune responses
- MicroRNA in disease regulation
- Cellular transport and secretion
- Renal and related cancers
- Neurobiology and Insect Physiology Research
- Neurological Disease Mechanisms and Treatments
University of Utah
2016-2025
Janssen (Switzerland)
2025
Martin Luther University Halle-Wittenberg
2009
Institute of Neurobiology
2008
University of Cincinnati
2008
Howard Hughes Medical Institute
2001
University of Pennsylvania
2001
University of California, San Francisco
1991-1995
San Francisco Foundation
1991
Glaucoma is characterized by retinal ganglion cell (RGC) pathology and a progressive loss of vision. Previous studies suggest RGC death responsible for vision in glaucoma, yet evidence from other neurodegenerative diseases suggests axonal degeneration, the absence neuronal loss, can significantly affect function. To characterize degeneration DBA/2 mouse model we quantified RGCs mice various ages using neuronal-specific nuclear protein (NeuN) immunolabeling, retrograde labeling, optic nerve...
Abstract Changes in microglial cell activation and distribution are associated with neuronal decline the central nervous system (CNS), particularly under pathological conditions. Activated microglia converge on initial site of axonal degeneration human glaucoma, yet their part its pathophysiology remains unresolved. To begin with, it is unknown whether precedes or a late consequence retinal ganglion (RGC) neurodegeneration. Here we address this critical element DBA/2J (D2) mice, an...
purpose. In the context of retinal ganglion cell (RGC) axon degeneration in optic nerve that occurs glaucoma, microglia become activated, then phagocytic, and redistribute head. The authors investigated potential contribution activation to glaucoma progression DBA/2J chronic mouse model. methods. treated 6-week-old mice for 25 weeks with minocycline, a tetracycline derivative known reduce improve neuronal survival other models neurodegenerative disease. They quantified RGC numbers...
Little is known about molecular changes occurring within retinal ganglion cells (RGCs) before their death in glaucoma. Taking advantage of the fact that γ-synuclein (Sncg) mRNA expressed specifically and highly adult mouse RGCs, we show DBA/2J model glaucoma there not only a loss expressing this gene, but also downregulation gene expression Sncg many other genes large numbers RGCs. This RGCs occurs together with reductions FluoroGold (FG) retrograde transport. Surprisingly, are...
ABSTRACT We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 largely restricted the developing eye. Math5 retinal expression precedes differentiation of first neurons persists within progenitor cells until after birth. To position in hierarchy development, we compared Hes1 wild-type Pax6-deficient (Sey) embryos. downregulated Sey/+ eyes abolished Sey/Sey eye rudiments, whereas bHLH upregulated similar...
Nerve growth factor (NGF) promotes the survival and differentiation of specific populations neurons. The molecular mechanisms by which cells respond to NGF are poorly understood, but two clues have emerged recently. First, rapidly stimulates tyrosine phosphorylation several unidentified proteins in NGF-responsive pheochromocytoma cell line PC12 [Maher, P. (1988) Proc. Natl. Acad. Sci. USA 85, 6788-6791]. Second, protein-tyrosine kinase encoded protooncogene trk (p140trk), a member receptor...
The DBA/2J mouse is a model for secondary angle-closure glaucoma, due to iris atrophy and pigment dispersion, which ultimately lead increased intraocular pressure (IOP). study was undertaken correlate changes in retinal gene expression with IOP elevation by performing microarray analysis of RNA from mice at 3 months before disease onset 8 after elevation.IOP monitored monthly animals, animals normal (3 months) or elevated (8 were identified. prepared three individual retinas each age, the...
Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, mechanisms leading to onset progression remain unknown. Molecular analysis various glaucoma models has revealed involvement non-neuronal cell populations, including astrocytes, Mueller glia microglia, at early stages glaucoma. High-dose irradiation was reported have significant long-term protective...
Microglia serve key homeostatic roles, and respond to neuronal perturbation decline with a high spatiotemporal resolution. The course of all chronic CNS pathologies is thus paralleled by local microgliosis microglia activation, which begin at early stages the disease. However, possibility using live monitoring during disease progression predict severity neurodegeneration has not been explored. Because retina allows tracking fluorescent in their intact niche, here we investigated changes...
Dysregulation of the complement system is implicated in neurodegeneration, including human and animal glaucoma. Optic nerve retinal damage glaucoma preceded by local upregulation activation, but whether targeting this early innate immune response could have therapeutic benefit remains undefined. Because signals through three pathways that intersect at C3 here we targeted step to restore balance glaucomatous retina determine its contribution degeneration onset and/or progression. To achieve...
Microglia play important roles in shaping the developing CNS, and at early stages they have been proposed to regulate progenitor proliferation, differentiation, neuronal survival. However, these studies reveal contradictory outcomes, highlighting complexity of cell–cell interactions. Here, we investigate microglia function during embryonic mouse retina development, where only microglia, progenitors, neurons are present. In both sexes, determine that primarily interact with retinal find...
Microglia serve critical remodeling roles that shape the developing nervous system, responding to changing neural environment with phagocytosis or soluble factor secretion. Recent single-cell sequencing (scRNAseq) studies have revealed context-dependent diversity in microglial properties and gene expression, but cues promoting this are not well defined. Here, we ask how interactions apoptotic neurons state, including lysosomal lipid metabolism expression dependence on Colony-stimulating 1...
Progenitor cells in the central nervous system must leave cell cycle to become neurons and glia, but signals that coordinate this transition remain largely unknown. We previously found Wnt signaling, acting through Sox2, promotes neural competence Xenopus retina by activating proneural gene expression. now report Sox2 inhibit differentiation Notch activation. Independently of stimulates retinal progenitor proliferation this, when combined with block on differentiation, maintains fates....
Microglia have important remodeling functions in neurodevelopment, aging, and disease, with evidence for molecular diversity. However, the signaling pathways environmental cues that drive diverse states of microglia are incompletely understood. We profiled a discrete developing CNS region, murine retina. found distinct transcriptional signatures retinal across development peak postnatal density population resembles aging disease-associated (DAM) CD11c
Abstract Background Guselkumab (GUS), a dual-acting IL-23 inhibitor that potently neutralizes and binds to CD64 (a receptor on cells produce IL-23), is currently approved in the United States for treatment of ulcerative colitis (UC) worldwide plaque psoriasis psoriatic arthritis. While GUS has been shown be safe Crohn’s disease (CD) UC, safety results have only reported individual trials date. To characterize overall profile inflammatory bowel (IBD), we evaluated pooled data from Phase 2/3...
Abstract Activation of the bHLH factor Math5 ( Atoh7 ) is an initiating event for mammalian retinal neurogenesis, as it critically required ganglion cell formation. However, cis‐regulatory elements and trans‐acting factors that control expression are largely unknown. Using a combination transgenic mice bioinformatics, we identified phylogenetically conserved regulatory element to activate transcription during early neurogenesis. This drives in vivo, cross‐species assay. Previously, Pax6 was...
Transitions in competence underlie the ability of CNS progenitors to generate a diversity neurons and glia. Retinal progenitor cells mouse early-born cell types embryonically late-born largely postnatally. We find that transition from early late is regulated by Jarid2. Loss Jarid2 results extended production expression genes. can regulate histone modifications, we reduction repressive mark H3K27me3 on subset genes with loss Jarid2, most notably Foxp1. show Foxp1 regulates retinal types,...