A5101970338- Retinal Diseases and Treatments
- Nitric Oxide and Endothelin Effects
- Renin-Angiotensin System Studies
- Dietary Effects on Health
- Neuroinflammation and Neurodegeneration Mechanisms
- Circadian rhythm and melatonin
- Retinopathy of Prematurity Studies
- Advanced Glycation End Products research
- Angiogenesis and VEGF in Cancer
- Diabetes and associated disorders
- Receptor Mechanisms and Signaling
- Growth Hormone and Insulin-like Growth Factors
- Diet and metabolism studies
- Heart Rate Variability and Autonomic Control
- Sphingolipid Metabolism and Signaling
- Pain Mechanisms and Treatments
- COVID-19 Clinical Research Studies
- Retinal Development and Disorders
- Antibiotics Pharmacokinetics and Efficacy
- Bacterial Identification and Susceptibility Testing
- Retinal Imaging and Analysis
- Ion Channels and Receptors
- Vagus Nerve Stimulation Research
- Eicosanoids and Hypertension Pharmacology
- Atherosclerosis and Cardiovascular Diseases
University of Alabama at Birmingham
2018-2025
University of Alabama
2018-2020
Indiana University – Purdue University Indianapolis
2014-2017
University of Florida
2005-2017
Indiana University School of Medicine
2014-2017
Indiana University Indianapolis
2017
Shanghai Jiao Tong University
2016
Ruijin Hospital
2016
Shanghai Institute of Hypertension
2016
Indiana University
2016
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...
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,...
Despite evidence that hyperactivity of the vasodeleterious axis (ACE/angiotensin II (Ang II)/AT1 receptor) renin-angiotensin system (RAS) is associated with pathogenesis diabetic retinopathy (DR) use inhibitors this has met limited success in control pathophysiology. We investigated hypothesis enhancing local activity recently established protective RAS, ACE2/Ang-(1-7), using adeno-associated virus (AAV)-mediated gene delivery ACE2 or Ang-(1-7) would confer protection against...
Diabetic cardiovascular complications are reaching epidemic proportions. Angiotensin-converting enzyme-2 (ACE2) is a negative regulator of the renin-angiotensin system. We hypothesize that loss ACE2 exacerbates induced by diabetes.To define role in diabetic complications.We used well-validated Akita mice, model human diabetes, and generated double-mutant mice using knockout (KO) (Akita/ACE2(-/y)). state was associated with increased whereas additional these leads to plasma tissue angiotensin...
p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied effect hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on retinal pigment epithelium (RPE) investigated its role regulation autophagy RPE survival against damage. Cultured human cell line ARPE-19 primary adult fetal cells were exposed to H2O2-induced...
Individuals with diabetes suffering from coronavirus disease 2019 (COVID-19) exhibit increased morbidity and mortality compared individuals without diabetes. In this Perspective, we critically evaluate argue that is due to a dysregulated renin-angiotensin system (RAS). Previously, have shown loss of angiotensin-I converting enzyme 2 (ACE2) promotes the ACE/angiotensin-II (Ang-II)/angiotensin type 1 receptor (AT1R) axis, deleterious arm RAS, unleashing its detrimental effects in As suggested...
The peptide hormone relaxin is a potent vasodilator with therapeutic potential in diseases complicated by vasoconstriction, including heart failure. However, the molecular mediators and magnitude of vasodilation may vary according to duration exposure artery type. objective these studies was determine mechanisms rapid (within minutes) relaxin-induced examine whether dilates arteries from different animal species vascular beds. Rat mouse small renal, rat mesenteric, human sc were isolated,...
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...
Highlights•At blood-neural barriers, only abluminal (tissue-side) VEGF-A induces permeability•Most VEGFR1 is localized on the luminal face of neural microvascular endothelium•Most VEGFR2 endothelium•Luminal stimulates Akt; permeability via p38SummaryThe vascular endothelium operates in a highly polarized environment, but to date there has been little exploration apicobasal polarization its signaling. We show that VEGF-A, histamine, IGFBP3, and LPA trigger unequal endothelial responses when...
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)...
By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow-neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced type 1 diabetes, suggesting a significant loss marrow innervation. This innervation associated with change hematopoiesis toward generation more monocytes and an altered diurnal release rodents patients diabetes. In hypothalamus granular insular cortex mice...
Diabetic retinopathy (DR) is a complication secondary to diabetes and the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, cure for DR has yet be realized. Several clinical trials have highlighted vital role dyslipidemia plays in progression DR. Additionally, it recently been shown that activation Liver X receptor (LXRα/LXRβ) prevents diabetic animal models. LXRs are nuclear receptors play key roles...
Angiotensin-converting enzyme 2 (ACE2) is the primary of vasoprotective axis renin angiotensin system (RAS). We tested hypothesis that loss ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2-/y were crossed with Akita mice, a model type 1 diabetes. When comparing -Akita mice to we observed reduction both short-term and long-term repopulating hematopoietic stem cells, shift hematopoiesis toward myelopoiesis, an impairment lineage- c-kit+ stem/progenitor cell...
Electroacupuncture (EA) performed in rats and humans using limb acupuncture sites, LI-4 LI-11, GV-14 GV-20 (humans) Bai-hui (rats) increased functional connectivity between the anterior hypothalamus amygdala mobilized mesenchymal stem cells (MSCs) into systemic circulation. In human subjects, source of MSC was found to be primarily adipose tissue, whereas rodents tissue sources were considered more heterogeneous. Pharmacological disinhibition rat enhanced sympathetic nervous system (SNS)...