A5022174241- Iron Metabolism and Disorders
- Trace Elements in Health
- Retinal Diseases and Treatments
- Hemoglobinopathies and Related Disorders
- Barrier Structure and Function Studies
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Receptor Mechanisms and Signaling
- Retinal Imaging and Analysis
- Adipokines, Inflammation, and Metabolic Diseases
- Autoimmune Neurological Disorders and Treatments
- Nicotinic Acetylcholine Receptors Study
- Vascular Malformations Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Inflammasome and immune disorders
- Redox biology and oxidative stress
- Atherosclerosis and Cardiovascular Diseases
- Neurological diseases and metabolism
- Neurological and metabolic disorders
- Intracerebral and Subarachnoid Hemorrhage Research
- Infectious Encephalopathies and Encephalitis
- Calcium signaling and nucleotide metabolism
- Parkinson's Disease Mechanisms and Treatments
- Glaucoma and retinal disorders
- Cerebral Venous Sinus Thrombosis
Penn Presbyterian Medical Center
2017-2023
University of Pennsylvania
2014-2023
Children's Hospital of Philadelphia
2013-2014
Iron has been implicated in the pathogenesis of retinal degenerative diseases, including ocular siderosis. However, mechanisms iron-induced toxicity are incompletely understood. Previous work shows that intravitreal injection Fe2+ leads to photoreceptor (PR) oxidative stress, resulting PR death within 14 days, and cones more susceptible than rods damage. In order further investigate mechanism shed light on retinopathy other mouse models, Fe2+, Fe3+, or saline were injected into vitreous...
α-synuclein (α-syn) aggregation and accumulation drive neurodegeneration in Parkinson's disease (PD). The substantia nigra of patients with PD contains excess iron, yet the underlying mechanism accounting for this iron is unclear. Here, we show that misfolded α-syn activates microglia, which release interleukin 6 (IL-6). IL-6, via its trans-signaling pathway, induces changes neuronal transcriptome promote ferrous uptake decrease cellular export a pathway term sequestration response, or CISR....
Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, leading cause blindness older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models iron overload, as can catalyze reactive oxygen species formation RPE. Iron-loading cultured induced pluripotent stem cell-derived RPE increased lysosomal abundance, impaired proteolysis...
Anti-AMPAR encephalitis is a recently discovered disorder characterized by the presence of antibodies in serum or cerebrospinal fluid against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Here, we examine antigenic specificity anti-AMPAR antibodies, screen for new patients, and evaluate functional effects antibody treatment neurons.We developed fusion protein-based western blotting test antibodies. Antibody was also evaluated using immunocytochemistry HEK293 cells...
Age-related macular degeneration (AMD), the leading cause of irreversible blindness among Americans over 50, is characterized by dysfunction and death retinal pigment epithelial (RPE) cells. The RPE accumulates iron in AMD, overload triggers cell vitro vivo. However, mechanism accumulation AMD unknown. We show that high-fat-diet-induced obesity, a risk factor for drives systemic local inflammatory circuits upregulating interleukin-1β (IL-1β). IL-1β upregulates importers downregulates...
Purpose: Retinal iron accumulation is observed in a wide range of retinal degenerative diseases, including AMD. Previous work suggests that Müller glial cells may be important mediators transport, distribution, and regulation. A transgenic model cell loss recently demonstrated primary ablation leads to blood–retinal barrier leakage photoreceptor degeneration, it recapitulates clinical features macular telangiectasia type 2 (MacTel2), rare human disease loss. We used this mouse determine the...
Abstract Dysregulation of iron metabolism, and resultant cytotoxicity, has been implicated in the pathogenesis multiple sclerosis (MS) other neurodegenerative processes. Iron accumulation promotes cytotoxicity through various mechanisms including oxidative stress glutamate toxicity, occurs both MS patients experimental autoimmune encephalomyelitis (EAE) model MS. Divalent Metal Transporter1, a major importer cells, is stimulated by signaling Dexras1, small G protein member Ras family....
PURPOSE.Iron supplementation therapy is used for iron-deficiency anemia but has been associated with macular degeneration in a 43-year-old patient.Iron entry into the neurosensory retina (NSR) can be toxic.It important to determine conditions under which serum iron might cross blood retinal barrier (BRB) NSR.Herein, an established mouse model of systemic overload using high-dose intraperitoneal dextran (IP FeDex) was studied.In addition, because NSR expresses regulatory hormone hepcidin,...
OBJECTIVE: To understand the role of anti-NMDAR antibodies in pathogenesis autoimmune encephalitis and other neurological disorders. BACKGROUND: Anti-NMDAR encephalitis, a recently discovered syndrome associated with psychosis, altered consciousness, seizures, dyskinesias, autonomic dysfunction, is now known to be one most commonly identified causes encephalitis. IgG this may have increased affinity for open conformation n-methyl-D-aspartate receptor (NMDAR), transiently stabilize...