A5026667958- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Retinopathy of Prematurity Studies
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Retinal and Optic Conditions
- Cellular transport and secretion
- Developmental Biology and Gene Regulation
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Peroxisome Proliferator-Activated Receptors
- Glaucoma and retinal disorders
- Ocular Disorders and Treatments
- interferon and immune responses
- Nuclear Receptors and Signaling
- Cholesterol and Lipid Metabolism
- Cancer, Hypoxia, and Metabolism
- Antioxidant Activity and Oxidative Stress
- Genetic Syndromes and Imprinting
- Herpesvirus Infections and Treatments
- Retinal Imaging and Analysis
Ottawa Hospital
2012-2023
Ottawa Hospital Research Institute
2011-2023
University of Ottawa
2013-2019
Friedrich Miescher Institute
2007-2014
Novartis (Switzerland)
2009
University of Alberta
2000-2003
In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to photoreceptors, important targets both basic preclinical research. particular, therapeutic strategy under investigation advanced forms blindness involves using optogenetic molecules render cells light-sensitive. Currently, delivery adequate levels gene expression is limiting step approach. synthetic...
Chromatin compaction mediates progenitor to post-mitotic cell transitions and modulates gene expression programs, yet the mechanisms are poorly defined. Snf2h Snf2l ATP-dependent chromatin remodelling proteins that assemble, reposition space nucleosomes, robustly expressed in brain. Here we show mice conditionally inactivated for neural progenitors have reduced levels of histone H1 H2A variants compromise fluidity transcriptional programs within developing cerebellum. Disorganized limits...
The gene elongation of very long chain fatty acids-4 (ELOVL4) has been shown to underlie phenotypically heterogeneous forms autosomal dominant macular degeneration. In this study, the extent evolutionary conservation and existence localization retinal expression was investigated across a wide variety species.Southern blot analysis genomic DNA bioinformatic using human ELOVL4 cDNA protein sequences, respectively, were performed identify species in which orthologues and/or homologues are...
Retinal neurons are highly vulnerable to a diverse array of neurotoxic stimuli that leads their degeneration, which is major contributor blindness. This review summarizes the role epigenetic factors in mediating neuronal homeostasis and survival protect against cell death neurodegenerative conditions. Studies human patients mouse models implicate numerous chromatin modifications neuroprotective processes including histone protein acetylation methylation, DNA ATP-dependent nucleosome...
Norrie disease (ND) is a congenital disorder characterized by retinal hypovascularization and cognitive delay. ND has been linked to mutations in 'Norrie Disease Protein' (Ndp), which encodes the secreted protein Norrin. Norrin functions as angiogenic factor, although its role neural development not assessed. Here, we show that Ndp expression initiated progenitors response Hedgehog (Hh) signaling, induces Gli2 binding promoter. Using combination of genetic epistasis acute RNAi-knockdown...
Purpose: Leber hereditary optic neuropathy (LHON) is a genetic form of vision loss that occurs primarily owing to mutations in the nicotinamide adenine dinucleotide dehydrogenase (ND) subunits make up complex I electron transport chain. LHON result apoptotic death retinal ganglion cells. We tested hypothesis gene therapy with X-linked inhibitor apoptosis (XIAP) would prevent cell and reduce disease progression vector-induced mouse model carries ND4 mutation. Methods: Adeno-associated virus...
ATRX is a chromatin remodeling protein that mutated in several intellectual disability disorders including alpha-thalassemia/mental retardation, X-linked (ATR-X) syndrome. We previously reported the prevalence of ophthalmological defects ATR-X syndrome patients, and accordingly we find morphological functional visual abnormalities mouse model harboring mutation occurring patients. The system observed these mice parallels Atrx-null retinal phenotype characterized by interneuron selective loss...
Background Morphological patterning of the cerebellum requires precise changes in Engrailed homeotic gene expression yet mechanisms controlling this process remain elusive. Here, we show that Iswi chromatin remodeling proteins, Smarca5 and Smarca1, are required for dynamic regulation Engrailed-1 (En1). Conditional Smarca5-null mice display abnormal cerebellar foliation, ataxia-like symptoms young mortality. Postnatal granule neuron progenitor expansion Purkinje cell (PC) development...
Background Atrx is a member of the SNF2 family chromatin remodeling proteins that functions by or repositioning nucleosomes at specific target genes using energy from ATP hydrolysis. Mutations in gene encoding cause human ATR-X syndrome, an X-linked disorder associated with severe mental retardation. We have shown targeted deletion this experimental mouse models results loss neuronal cell populations central nervous system (CNS). Compromised survival mutants may underlie intellectual...
Mutation of the α-thalassemia/mental retardation syndrome X-linked protein, ATRX, causes intellectual disability and is associated with pleiotropic defects including ophthalmological abnormalities. We have previously demonstrated that Atrx deficiency in mouse retina leads to selective loss inhibitory interneurons inner retinal dysfunction. Onset amacrine cell neurodegenerative phenotype Atrx-deficient retinas occurs postnatally after neuronal specification, coincides eye opening. Given this...