A5052282897- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Iron Metabolism and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Trace Elements in Health
- Hemoglobinopathies and Related Disorders
- Neurological Disorders and Treatments
- Cerebral Venous Sinus Thrombosis
- Adipokines, Inflammation, and Metabolic Diseases
- Retinal and Optic Conditions
- Vascular Malformations Diagnosis and Treatment
- Barrier Structure and Function Studies
- Calcium signaling and nucleotide metabolism
- Ophthalmology and Eye Disorders
- Retinal Development and Disorders
- Retinal Imaging and Analysis
- Neurological diseases and metabolism
- Immune cells in cancer
- Heme Oxygenase-1 and Carbon Monoxide
- Prenatal Screening and Diagnostics
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Autophagy in Disease and Therapy
- Angiogenesis and VEGF in Cancer
- Parvovirus B19 Infection Studies
Penn Presbyterian Medical Center
2015-2025
University of Pennsylvania
2015-2025
Northwestern University
2023-2024
Glaucoma is the leading cause of irreversible blindness and characterized by death retinal ganglion cells (RGCs). Recent studies have implicated pro-inflammatory microglia, macrophages, A1 astrocytes in pathogenesis neurodegenerative diseases. The role pro-inflammatory, neurotoxic glaucoma just beginning to be explored. Using a mouse model glaucoma, we demonstrate that ocular hypertension sufficient trigger production C1q, interleukin-1α (IL-1α), tumor necrosis factor α (TNF-α), three...
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...
Background/aims Glucagon-like peptide-1 receptor (GLP-1R) agonists regulate blood glucose and are commonly used to treat type 2 diabetes mellitus. Recent work showed that treatment with the GLP-1R agonist NLY01 decreased retinal neuroinflammation glial activation rescue ganglion cells in a mouse model of glaucoma. In this study, we an insurance claims database (Clinformatics Data Mart) examine whether exposure impacts glaucoma risk. Methods A retrospective cohort patients who initiated new...
Abstract Iron has been implicated in the pathogenesis of age‐related retinal diseases, including macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features model: geographic atrophy sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF photoreceptors, quantification bisretinoids,...
Glaucomatous neurodegeneration, a blinding disease affecting millions worldwide, has need for the exploration of new and effective therapies. Previously, glucagon-like peptide-1 receptor (GLP-1R) agonist NLY01 was shown to reduce microglia/macrophage activation, rescuing retinal ganglion cells after IOP elevation in an animal model glaucoma. GLP-1R use is also associated with reduced risk glaucoma patients diabetes. In this study, we demonstrate that several commercially available agonists,...
Because ferroportin (Fpn) is the only known mammalian cellular iron exporter, understanding its localization and regulation within retina would shed light on direction of retinal flux. The hormone hepcidin may regulate Fpn, as it triggers Fpn degradation in gut. Immunofluorescence was used to label retinas mice with 4 different genotypes (wild type; C326S, a hepcidin-resistant Fpn; knockout; ceruloplasmin/hephaestin double knockout). No significant difference levels observed these retinas....
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 Background Neovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1 −/− mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that may inhibit formation. NR4A1 is a transcription factor necessary for maturation of classical monocytes. While Nr4a1 are deficient monocytes, results confounded by macrophage hyper-activation. se2/se2 lack transcriptional...
The blood-retina barrier (BRB), which is disrupted in diabetic retinopathy (DR) and uveitis, an important anatomical characteristic of the retina, regulating nutrient, waste, water, protein, immune cell flux. BRB composed endothelial tight junctions, pericytes, astrocyte end feet, a collagen basement membrane, perivascular macrophages. Despite importance BRB, retinal macrophage function remains unknown. We found that macrophages resided on postcapillary venules superficial vascular plexus...
Thyroid eye disease (TED) is a complex autoimmune commonly associated with auto-immune thyroid disease. It characterized by progressive inflammation of the orbit and periocular tissues. TED number clinical presentations, rarely may be vision threatening. pathogenesis consists an reaction to TSHR IGF-1R on orbital fibroblasts resulting in inflammation, adipogenesis, fibrosis, edema. present active, inflammatory phase or later, quiescent phase. A grading systems exist evaluate severity...
SUMMARY Glaucoma is the leading cause of irreversible blindness worldwide and characterized by death retinal ganglion cells. Reduction intraocular pressure (IOP) only therapeutic mechanism available to slow disease progression. However, glaucoma can continue progress despite normalization IOP. New treatments are needed reduce vision loss improve outcomes for patients who have exhausted existing avenues. Recent studies implicated neuroinflammation in pathogenesis neurodegenerative diseases...
Abstract Importance Glucagon-like peptide-1 receptor (GLP-1R) agonists regulate blood glucose and are commonly used to treat Type II Diabetes Mellitus. Recent work has shown that treatment with the novel GLP-1R agonist, NLY01, decreased retinal neuroinflammation glial activation rescue ganglion cells in an animal model of glaucoma. Objective In this study, we insurance claims database examine whether agonist exposure impacts glaucoma risk. Design, Setting, Participants A retrospective cohort...