A5020986917- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Ocular Diseases and Behçet’s Syndrome
- Cancer, Stress, Anesthesia, and Immune Response
- Systemic Lupus Erythematosus Research
- Glaucoma and retinal disorders
- Immune Cell Function and Interaction
- Photoreceptor and optogenetics research
- T-cell and B-cell Immunology
- Psoriasis: Treatment and Pathogenesis
- Cytomegalovirus and herpesvirus research
- Lipid Membrane Structure and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Connexins and lens biology
- Pluripotent Stem Cells Research
- Immunotherapy and Immune Responses
- Otitis Media and Relapsing Polychondritis
- Hemoglobinopathies and Related Disorders
- RNA regulation and disease
- Dermatology and Skin Diseases
- Corneal Surgery and Treatments
- Cancer Immunotherapy and Biomarkers
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- bioluminescence and chemiluminescence research
- CRISPR and Genetic Engineering
National Eye Institute
2013-2024
National Institutes of Health
2014-2024
University of Alabama at Birmingham
2023
Abstract Th17 cells require IL-6 and TGFβ for lineage commitment IL-23 maintenance. Unexpectedly, naive IL-6−/− splenocytes stimulated with anti-CD3 produced normal amounts of IL-17 during the first 24 h culture. These rapid IL-6-independent producers were identified as predominantly DX5+ TCRβ+ NKT cells, a comparable response could be found using invariant NKT-specific ligand α-galactosylceramide. Human also IL-17. constitutively expressed IL-23R RORγt. Ligation either TCR or triggered...
Considerable progress has been made in testing stem cell-derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations induced pluripotent cells (iPSCs) underlie need robust manufacturing and functional validation clinical-grade iPSC-derived RPE before transplantation. Here, we developed mutation-free iPSCs from three AMD patients differentiated them into iPSC-RPE patches on biodegradable...
The development of neuroprotective strategies to attenuate retinal ganglion cell death could lead novel therapies for chronic optic neuropathies such as glaucoma. Intravitreal transplantation mesenchymal stem cells slows in models nerve injury, but the mechanism action remains unclear. Here we characterized effects and cell-derived factors organotypic explant culture an vivo model ocular hypertensive Co-culture rat human bone marrow-derived with explants increased survival, after 7 days ex...
Gene regulatory networks (GRNs) guiding differentiation of cell types and assemblies in the nervous system are poorly understood because inherent complexities interdependence signaling pathways. Here, we report transcriptome dynamics differentiating rod photoreceptors mammalian retina. Given that transcription factor NRL determines fate, performed expression profiling developing NRL-positive (rods) NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition...
Constitutive TGFβ signaling is important in maintaining retinal neurons and blood vessels a factor contributing to the risk for age-related macular degeneration (AMD), disease involving neurodegeneration microglial activation. How microglia influences pathological neuroinflammation unclear. We discovered that ablation of receptor, TGFBR2, adult mice induced abnormal numbers, distribution, morphology, activation status, promoted gene expression profile. TGFBR2-deficient secondary gliotic...
Abstract Immune privilege is used by the eye, brain, reproductive organs, and gut to preserve structural functional integrity in face of inflammation. The eye arguably most vulnerable and, therefore, also “privileged” tissues; paradoxically, it remains subject destructive autoimmunity. It has been proposed, although never proven vivo, that can induce T regulatory cells (Tregs) locally. Using Foxp3-GFP reporter mice expressing a retina-specific TCR, we now show uncommitted rapidly convert...
Experimental autoimmune uveitis (EAU) induced in mice by immunization with the retinal Ag interphotoreceptor retinoid-binding protein (IRBP) is a model of human uveitis. We examined whether T regulatory cells (Tregs) found uveitic eyes are IRBP specific, functionally suppressive, and play role natural resolution disease maintenance remission. Progressive increase Foxp3(+) Treg to effector cell (Teff) ratio correlated disease. At peak disease, up 20% Tregs (CD4(+)Foxp3(+)) 60% Teffs...
Lethal toxin (LeTx) plays a central role in anthrax pathogenesis, however cytotoxicity of LeTx has been difficult to demonstrate vitro. No cytolytic effect reported for human cells, contrast murine cell lines, indicating that lysis can not be considered as marker activity. We have recently shown macrophage‐like RAW 264.7 cells treated with or infected spores underwent changes typical apoptotic death. Here we from peripheral blood display proapoptotic behavior similar cells. TUNEL assay...
Stargardt retinopathy is an inherited form of macular degeneration caused by mutations in gene ABCA4 and characterized the accumulation lipid-rich deposits retinal pigment epithelium (RPE), RPE atrophy, photoreceptor cell death. Inadequate mechanistic insights into pathophysiological changes occurring have hindered disease treatments. Here, we show that knockout induced pluripotent stem cell-derived (STGD1-iRPE) from patients with differentiate normally but display intracellular lipid...
Abstract Poorly understood interactions with nonmalignant cells within the tumor microenvironment play an important role in cancer progression. Here, we explored between prostate and muscle that surround prostate. We found coculturing of skeletal or smooth expands subpopulations features characteristic stem-like cells, including anchorage-independent growth, elevated CD133 expression, drug resistance. These changes properties depend on: (i) cell–induced increases concentrations interleukins...
Abstract FOXE3 is a lens-specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of are indispensable for development, we examined transcriptome and proteome cells expressing truncated responsible Peters anomaly identified through linkage-coupled next-generation whole-exome sequencing. We found DNAJB1, an autophagy-associated protein, was only candidate exhibiting differential expression in both screens....
Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is restriction on cytotoxic immunity if not present in sufficient numbers tumor and draining lymph nodes take up relevant antigens. To address this bottleneck, we developed therapeutic based albumin fused FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that...
purpose. To investigate the role of HtrA2/Omi, a nuclear-encoded mitochondrial serine protease with proapoptosis function, under H2O2-induced oxidative stress in human RPE, Ccl2 − / Cx3cr1 double-knockout (DKO) mouse retina, and HtrA2/Omi-deficient mice. methods. Oxidative was induced ARPE-19 cells by 1 mM H2O2 for 2 hours. HtrA2/Omi caspase-3 expression evaluated using RQ-PCR, immunohistochemistry, or Western blot. Cell viability detected MTT assay. subcellular components activated were...
Appropriate regulation of IL-17 production in the host can mean difference between effective control pathogens and uncontrolled inflammation that causes tissue damage. Investigation conventional CD4+ T cells (Th17 cells) has yielded invaluable insights into function its regulation. More recently, we others reported from innate αβ+ cell populations, which was shown to occur primarily via IL-23R signaling through transcription factor STAT-3. In our current study, identify promyelocytic...
Pigment epithelium-derived factor (PEDF) is a cytoprotective protein for the retina. We hypothesize that this acts on neuronal survival and differentiation of photoreceptor cells in culture. The purpose present study was to evaluate neurotrophic effects PEDF its fragments an vitro model cultured primary retinal neurons die spontaneously absence trophic factors. used Wistar albino rats. Cell death assayed by immunofluorescence flow cytometry through TUNEL assay, propidium iodide, mitotracker,...
Here, we present evidence that caveolae-mediated endocytosis using LDLR is the pathway for SARS-CoV-2 virus internalization in ocular cell line ARPE-19. Firstly, found that, while Angiotensin-converting enzyme 2 (ACE2) expressed these cells, blocking ACE2 by antibody treatment did not prevent infection spike pseudovirions, nor blockade of extracellular vimentin and other cholesterol-rich lipid raft proteins. Next, implicated role cholesterol homeostasis showing incubating cells with...
The SARS-CoV-2 Spike glycoprotein (S protein) acquired a unique new 4 amino acid -PRRA- insertion sequence at residues (aa) 681-684 that forms furin cleavage site in S protein as well several glycosylation sites. We studied various statistical properties of the RNA level (CCUCGGCGGGCA). nucleotide composition and codon usage this are different from rest genome. One such features is two tandem CGG codons, although rarest This suggests could cause ribosome pausing result these rare codons. Due...
Here, we present a protocol for differentiating human-induced pluripotent stem cells into three distinct mesodermal cell types: vascular endothelial (ECs), pericytes, and fibroblasts. We describe steps using monolayer serum-free differentiation isolating ECs (CD31+) mesenchymal pre-pericytes (CD31-) from single set. then differentiate pericytes fibroblasts commercial fibroblast culture medium. The types differentiated in this are useful vasculogenesis, drug testing, tissue engineering...
Abstract Data from a small trial in patients with cancer suggest that isoquercetin (IQ) treatment lowered thrombosis biomarkers and prevented clinical thrombosis, but, to our knowledge, no studies of IQ have been conducted target thromboinflammation adults sickle cell disease (SCD). We randomized, double-blind, placebo-controlled steady-state SCD (hemoglobin SS [HbSS], HbSβ0thal, HbSβ+thal, or HbSC). The primary outcome was the change plasma soluble P-selectin (sP-selectin) after compared...
Th17 cells require IL‐6 and TGFβ for lineage commitment, IL‐23 maintenance. Unexpectedly, naive −/− splenocytes stimulated with anti‐CD3 produced normal amounts of IL‐17 during the first 24 h culture. These rapid IL‐6‐independent producers were identified as NKT by phenotype (TCRβ + /DX5 ) function (response to α–GalCer). Human also upon stimulation. constitutively expressed IL‐23R RORγt. Ligation either TCR or triggered production, both together had an additive effect suggesting independent...