A5018177416- Retinal Diseases and Treatments
- Cholesterol and Lipid Metabolism
- Sphingolipid Metabolism and Signaling
- Advanced Glycation End Products research
- Peroxisome Proliferator-Activated Receptors
- Dietary Effects on Health
- Circadian rhythm and melatonin
- Retinal Imaging and Analysis
- Systemic Lupus Erythematosus Research
- Retinal Development and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Pancreatic function and diabetes
- Adenosine and Purinergic Signaling
- Eicosanoids and Hypertension Pharmacology
- Retinopathy of Prematurity Studies
- Retinoids in leukemia and cellular processes
- Phagocytosis and Immune Regulation
- Glaucoma and retinal disorders
- Atherosclerosis and Cardiovascular Diseases
- Sirtuins and Resveratrol in Medicine
- Cancer, Lipids, and Metabolism
- Lipid Membrane Structure and Behavior
- Metabolomics and Mass Spectrometry Studies
- Angiogenesis and VEGF in Cancer
- Lipid metabolism and biosynthesis
Michigan State University
2016-2025
University of Oklahoma Health Sciences Center
2009-2024
Oklahoma City University
2024
University of Oklahoma
2024
Michigan United
2013-2021
Indiana University – Purdue University Indianapolis
2015
Indiana University Indianapolis
2015
Institute for Stem Cell Biology and Regenerative Medicine
2009
The Retina Center
2009
Robert Bosch (Australia)
2009
Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In
This study determined the effects of high glucose exposure and cytokine treatment on generation reactive oxygen species (ROS) activation inflammatory apoptotic pathways in human retinal endothelial cells (HRECs).Glucose consumption HRECs, pigment epithelial (HRPEs), Müller (HMCs) under elevated conditions was measured compared with treatment. Production ROS HRECs examined using 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA), spin-trap electron paramagnetic...
Fatty acid elongases and desaturases play an important role in hepatic whole body lipid composition. We examined the that key transcription factors played control of elongase desaturase expression. Studies with peroxisome proliferator-activated receptor α (PPARα)-deficient mice establish PPARα was required for WY14643-mediated induction fatty elongase-5 (Elovl-5), Elovl-6, all three [Δ5 (Δ5D), Δ6D, Δ9D]. Increased nuclear sterol-regulatory element binding protein-1 (SREBP-1) correlated...
Of the six fatty acid elongase (Elovl) subtypes expressed in mammals, adult rat liver expresses four subtypes: Elovl-5 > Elovl-1 = Elovl-2 Elovl-6. Overnight starvation and fish oil-enriched diets repressed hepatic activity livers of male rats. Diet-induced changes correlate with Elovl-6 mRNA abundance. Adult rats fed peroxisome proliferator-activated receptor alpha (PPARalpha) agonist WY14,643 have increased activity, Elovl-1, Elovl-5, Elovl-6, Delta5, Delta6, Delta9 desaturase abundance,...
The present epidemic of diabetes is resulting in a worldwide increase cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences the retina as being responsible for development this diabetic complication. However, contribution circulating cells maintenance, repair, dysfunction vasculature now becoming appreciated. Diabetic individuals have fewer endothelial progenitor (EPCs) their circulation these diminished migratory potential,...
Diabetic retinopathy (DR) is a microvascular complication of diabetes and the leading cause vision loss in working-age adults. Recent studies have implicated complement system as player development vascular damage progression DR. However, role activation DR are not well understood. Exosomes, small vesicles that secreted into extracellular environment, cargo proteins plasma, suggesting they can participate causing associated with We demonstrate IgG-laden exosomes plasma activate classical...
Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported ceramide generation critical for diabetic development. Here, in patients with proliferative retinopathy, identify vitreous imbalance pathologic long-chain C16-ceramides increasing and protective very C26-ceramides decreasing. generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize platforms, invented three-dimensional...
Docosahexaenoic acid (DHA(22:6n3)), the principal n3-polyunsaturated fatty (PUFA) in retina, has been shown to have a pronounced anti-inflammatory effect numerous vivo and vitro studies. Despite importance of vascular inflammation diabetic retinopathy, role DHA(22:6n3) cytokine-stimulated human retinal endothelial cells (hRVECs) not addressed.Cytokine-induced expression cell adhesion molecules (CAMs) was assessed by Western blot. The on cytokine-induced nuclear factor (NF)-kappaB signaling...
OBJECTIVE The results of the Diabetes Control and Complications Trial/Epidemiology Interventions cohort study revealed a strong association between dyslipidemia development diabetic retinopathy. However, there are no experimental data on retinal fatty acid metabolism in diabetes. This determined retinal-specific control animals. RESEARCH DESIGN AND METHODS Tissue gene protein expression profiles were by quantitative RT-PCR Western blot streptozotocin-induced rats at 3–6 weeks Fatty assessed...
The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate repair due to compromised bone marrow derived endothelial progenitor cells (EPCs). We propose that n-3 polyunsaturated fatty acid (PUFA) deficiency in diabetes results activation the central enzyme sphingolipid metabolism, sphingomyelinase (ASM) and ASM represents a molecular metabolic link connecting initial damage retina dysfunction EPCs.Type 2 rats on control...
Acid sphingomyelinase (ASM) is an important early responder in inflammatory cytokine signaling. The role of ASM retinal vascular inflammation and vessel loss associated with diabetic retinopathy not known represents the goal this study.Protein gene expression profiles were determined by quantitative RT-PCR Western blot. activity was using Amplex Red assay. Caveolar lipid composition analyzed nano-electrospray ionization tandem mass spectrometry. Streptozotocin-induced diabetes...
Lipid extraction using a monophasic chloroform/methanol/water mixture, coupled with functional group selective derivatization and direct infusion nano-ESI-high-resolution/accurate MS, is shown to facilitate the simultaneous analysis of both highly polar nonpolar lipids from single retina lipid extract, including low abundance ganglioside lipids, sphingolipids, abundant glycerophospholipids. Quantitative comparison showed that method yielded similar distributions those obtained established...
Activation of pro-inflammatory and pro-angiogenic pathways in the retina bone marrow contributes to pathogenesis diabetic retinopathy. We identified miR-15a as key regulator both through direct binding inhibition central enzyme sphingolipid metabolism, ASM, growth factor, VEGF-A. was downregulated cells. Over-expression downregulated, upregulated ASM VEGF-A expression retinal In addition effects, migration vascular repair function impaired inhibitor-treated circulating angiogenic cells...
Long-chain PUFAs (LC-PUFAs; C20–C22; e.g., DHA and arachidonic acid) are highly enriched in vertebrate retina, where they elongated to very-long-chain (VLC-PUFAs; C ≥28) by the elongation of fatty acids-4 (ELOVL4) enzyme. These acids play essential roles modulating neuronal function health. The relevance different lipid requirements rods cones disease processes, such as age-related macular degeneration, however, remains unclear. To better understand role LC-PUFAs VLC-PUFAs we investigated...
Docosahexaenoic acid (DHA(22:6,n3)) is the principal n3 polyunsaturated fatty (PUFA) in retina. The authors previously demonstrated that DHA(22:6,n3) inhibited cytokine-induced adhesion molecule expression primary human retinal vascular endothelial (hRVE) cells, target tissue affected by diabetic retinopathy. Despite importance of inflammation retinopathy, mechanisms underlying anti-inflammatory effects cells are not understood. In this study address hypothesis acts through modifying lipid...
Adipose tissue secretes factors linked to colon cancer risk including leptin. A hallmark of is sustained angiogenesis. While leptin promotes angiogenesis in adipose tissue, it unknown whether can induce epithelial cells produce that may drive angiogenesis, vascular development and therefore progression. The purpose this study was compare the effects leptin-stimulated differing adenomatous polyposis coli (Apc) genotype (gatekeeper tumor suppressor gene for cancer) on We employed novel colonic...
Rationale : Insulin-like growth factor binding protein (IGFBP)-3 modulates vascular development by regulating endothelial progenitor cell (EPC) behavior, specifically stimulating EPC migration. This study was undertaken to investigate the mechanism of IGFBP-3 effects on function and how mediates cytoprotection following injury. Objective To examine IGFBP-3–mediated repair Methods Results We used 2 complementary injury models: laser occlusion retinal vessels in adult green fluorescent (GFP)...
purpose. This study determined the role of proinflammatory cytokines known to be elevated in diabetic retina, namely IL-1β, TNFα, and IL-6, a high glucose–induced nuclear accumulation GAPDH retinal Müller cells, an event considered crucial for induction cell death. methods. With use transformed rat line (rMC-1) isolated human cells (HMCs), authors examined effect glucose (25 mM), mM) plus inhibitors caspase-1/IL-1β signaling pathway on accumulation, which was evaluated by immunofluorescence...
The authors have previously demonstrated that DHA inhibits cytokine-induced inflammation in human retinal endothelial cells (HRECs), the resident vasculature affected by diabetic retinopathy. However, anti-inflammatory mechanism of docosahexaenoic acid (DHA) is still not well understood. Sphingolipids represent a major component membrane microdomains, and ceramide-enriched microdomains appear to be prerequisite for inflammatory cytokine signaling. Acid sphingomyelinase (ASMase) neutral...
Purpose.: Chronic inflammation and dysregulation of circadian rhythmicity are involved in the pathogenesis diabetic retinopathy. MicroRNAs (miRNAs) can regulate clock machinery. We tested hypothesis that altered daily rhythm miR-146a expression diabetes contributes to retinal inflammation. Methods.: Nondiabetic STZ-induced rats kept 12/12 light/dark cycle were killed every 2 hours over a 72-hour period. Human endothelial cells (HRECs) synchronized with dexamethasone. Expression miR-146a,...
In this study, we assessed whether Per2 clock gene-mutant mice exhibit a vascular phenotype similar to diabetes. (B6.129-Per2(tm1Drw)/J) or wild-type control 4 and 12 months of age were used. To evaluate diabetes-like in mutant mice, retina was quantified for mRNA expression, degree diabetic retinopathy evaluated. Bone marrow neuropathy studied by staining femurs tyrosine hydroxylase (TH) neurofilament 200 (NF-200). The rate proliferation quantification bone progenitor cells (BMPCs)...