A5013085396- Retinal Development and Disorders
- Glaucoma and retinal disorders
- Retinal Diseases and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Retinopathy of Prematurity Studies
- Nerve injury and regeneration
- Photoreceptor and optogenetics research
- Traumatic Brain Injury and Neurovascular Disturbances
- Physiological and biochemical adaptations
- Neurobiology and Insect Physiology Research
- Optical Coherence Tomography Applications
- Developmental Biology and Gene Regulation
- Animal Genetics and Reproduction
- Alzheimer's disease research and treatments
- Retinoids in leukemia and cellular processes
- Zebrafish Biomedical Research Applications
- Autophagy in Disease and Therapy
- Neuroscience and Neural Engineering
- Neurological Disorders and Treatments
- Traumatic Brain Injury Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- S100 Proteins and Annexins
University of California, Davis
2016-2024
Johns Hopkins University
2008-2018
Kennedy Krieger Institute
2008-2018
Johns Hopkins Medicine
2006-2016
H. L. Snyder Medical Foundation
2014
University of Baltimore
2014
University of Cincinnati
2008
Carnegie Institution for Science
1999-2005
Carnegie Observatories
1999-2005
Department of Embryology
1999-2005
It is generally accepted that healthy cells degrade their own mitochondria. Here, we report retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and these are internalized degraded by adjacent astrocytes. EM demonstrates through formation large protrusions originate from otherwise axons. A virally introduced tandem fluorophore protein reporter acidified reveals axonal originating associated with lysosomes within columns astrocytes in ONH. According to this...
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...
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...
Glaucoma, a major cause of blindness worldwide, is neurodegenerative optic neuropathy in which vision loss caused by retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for development neuroprotective drugs, we developed high-throughput RNA interference screen with primary RGCs used it to full mouse kinome. The identified dual leucine zipper kinase (DLK) as key target RGCs. In cultured RGCs, DLK signaling both necessary sufficient cell death....
Optic nerve head (ONH) astrocytes have been proposed to play both protective and deleterious roles in glaucoma. We now show that, within the postlaminar ONH myelination transition zone (MTZ), there are that normally express Mac-2 (also known as Lgals3 or galectin-3), a gene typically expressed only phagocytic cells. Surprisingly, even healthy mice, MTZ other constitutive internalize large axonal evulsions contain whole organelles. In mouse glaucoma models, further up-regulate expression....
Abstract Retinal ganglion cell (RGC) injury and death from glaucoma other forms of optic nerve disease is a major cause irreversible vision loss blindness. Human pluripotent stem (hPSC)-derived RGCs could provide source cells for the development novel therapeutic molecules as well potential cell-based therapies. In addition, such insights into human RGC development, gene regulation neuronal biology. Here, we report simple, adherent culture protocol differentiation hPSCs to using...
Abstract Glaucoma, a neurodegenerative disease affecting retinal ganglion cells (RGC), is leading cause of blindness. Since gliosis common in disorders, it important to describe the changes occurring various glial populations glaucoma animal models relation axon loss, as only that occur early are likely be useful therapeutic targets. Here, we glia within myelinated portion optic nerve (ON) both DBA/2J mice and rat ocular hypertension model. In models, found modest loss oligodendrocytes...
Under physiological conditions in vivo astrocytes internalize and degrade neuronal mitochondria a process called transmitophagy. Mitophagy is widely reported to be impaired neurodegeneration but it unknown whether how transmitophagy altered Alzheimer's disease (AD). Here we report that the internalization of significantly increased isolated from AD mouse brains. We also demonstrate degradation by mice at age 6 months onwards. Furthermore, for first time similar phenomenon between human...
One of the genes that is up-regulated by thyroid hormone (TH) during Xenopus laevis metamorphosis encodes a type III deiodinase (D3) inactivates TH. Transgenic X. tadpoles overexpressing GFP-D3 fusion protein were produced. These transgenic had high levels activity and resistant to exogenous TH added 1 week after fertilization. They developed normally throughout embryogenesis premetamorphic stages but became retarded in their development late prometamorphosis when endogenous reaches its...
Metamorphosis of anuran tadpoles is controlled by thyroid hormone (TH). Here we demonstrate that transgenic Xenopus laevis expressing a dominant negative form TH receptor-α are resistant to wide variety the metamorphic changes induced TH. This result confirms receptors mediate both early and late developmental programs metamorphosis as diverse growth in brain, limb buds, nose Meckel's cartilage, remodeling intestine, death resorption gills tail.
Previous analyses of the DBA/2J mouse glaucoma model show a sectorial degeneration pattern suggestive an optic nerve head insult. In addition, there are large numbers retinal ganglion cells (RGCs) that cannot be retrogradely labeled but maintain RGC gene expression, and many these have somatic phosphorylated neurofilament labeling. Here authors further elucidate features glaucomatous in rat ocular hypertension model.IOP was elevated Wistar rats by translimbal laser photocoagulation. Retina...
Exogenous treatment of zebrafish embryos with retinoic acid induces a duplication the retinas during development. These effects occur only when is applied within 2-hr period prior to and initial formation optic primordia, they are concentration-dependent. Light microscopic examination reveals that second retina derives from cells in ventral region developing eyecup normally become pigment epithelial cells. Two distinct ganglion cell fields usually observed eyes duplicated retinas. Bundles...
Significance Myelin segments facilitate fast conduction along axons, and thus the rapid transmission of information in nervous system. In absence pathology, myelin are generally regarded as highly stable structures with plasticity limited to growth-related increases thickness. We discovered that existing also capable shortening demonstrate involves a characteristic focal dystrophy develops at contact point phagocytic astrocyte. These astrocytes internalize large quantities from using known...
Significance Vertebrate retinal ganglion cells (RGCs) transmit all visual signals from the eye to brain, are pathogenic target in glaucoma, and require Atoh7 competence factor develop multipotent progenitors. transcription is controlled by dual cis regulatory elements, including a remote shadow enhancer (SE). In humans, loss of SE causes NCRNA disease, with congenital blindness due optic nerve aplasia. We generated mouse deletion model analyzed its effects on transcription, histology,...
Adult Xenopus laevis frogs made transgenic by restriction enzyme-mediated integration were bred to test the feasibility of establishing lines that express transgenes. All 19 animals raised sexual maturity generated progeny expressed transgene(s). The patterns and levels expression green fluorescent protein transgenes driven a viral promoter, rat four X. promoters all unaffected passage through germ line. These results demonstrate ease in .
Abstract Background Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia Down syndrome. Although several studies shown that potent effects on neural function, their role development is still poorly understood. In this study, we investigated link between abnormal cytokine levels using Xenopus laevis tadpole visual system, model frequently...
Thyroid hormone (TH) is required for limb development in Xenopus laevis . Specific cell types the growing were targeted expression of a dominant negative form TH receptor by sperm-mediated transgenesis. Limb muscle development, innervation from spinal cord, and cartilage growth can be inhibited without affecting patterning or differentiation other types. Remodeling skin occurs late metamorphosis after has formed. The coordination these independent programs affected part control that exerts...