A5020929451- Glaucoma and retinal disorders
- Connexins and lens biology
- Corneal surgery and disorders
- Antioxidant Activity and Oxidative Stress
- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Corneal Surgery and Treatments
- Retinoids in leukemia and cellular processes
- Cellular transport and secretion
- Advanced Glycation End Products research
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- High Altitude and Hypoxia
- Glycosylation and Glycoproteins Research
- Ocular Surface and Contact Lens
- Biomedical Research and Pathophysiology
- Biochemical effects in animals
- Food Chemistry and Fat Analysis
- Amino Acid Enzymes and Metabolism
- Retinopathy of Prematurity Studies
- Metabolism and Genetic Disorders
- Animal Genetics and Reproduction
- Microbial Metabolites in Food Biotechnology
- Free Radicals and Antioxidants
- Acute Kidney Injury Research
Indiana University Bloomington
2019-2024
Induk University
2023
Indiana University School of Medicine
2019
Indiana University
2019
University School
2019
University of Utah
2015-2017
Eye Institute of Utah
2016
University of Illinois Chicago
2009-2014
University of Illinois Urbana-Champaign
2010
Optineurin is a gene linked to amyotrophic lateral sclerosis, Paget disease of bone, and glaucoma, major blinding disease. Mutations such as E50K were identified in glaucoma patients. We investigated herein the involvement ubiquitin-proteasome pathway (UPP) autophagy, two routes for protein clearance, processing optineurin retinal ganglion cell model line RGC5 neuronal PC12 cells. It was found that endogenous level cells increased by treatment proteasomal inhibitor but not autophagic...
Significance Carotenoids are plant-derived pigment molecules that cannot be synthesized de novo by higher organisms. These physiologically relevant compounds function as potent antioxidants and light screening compounds, their supplementation has been shown to ameliorate the progression of such diseases age-related macular degeneration. Hundreds carotenoids present in plant world, but primate macula contains only three: lutein, zeaxanthin, meso -zeaxanthin. The presence -zeaxanthin foveal...
Background Glaucoma is a major blinding disease characterized by progressive loss of retinal ganglion cells (RGCs) and axons. Optineurin one the candidate genes identified so far. A mutation Glu50 to Lys (E50K) has been reported be associated with more severe disease. Optineurin, known interact Rab8, myosin VI transferrin receptor (TfR), was speculated have role in protein trafficking. Here we determined whether, how optineurin overexpression E50K affect internalization (Tf), widely used as...
SLC4A11 is a NH3 sensitive membrane transporter with H+ channel-like properties that facilitates Glutamine catabolism in Human and Mouse corneal endothelium (CE). Loss of activity induces oxidative stress cell death, resulting Congenital Hereditary Endothelial Dystrophy (CHED) edema vision loss. However, the mechanism by which prevents ROS production protects CE unknown. Here we demonstrate localized to inner mitochondrial transfected PS120 fibroblasts, where it acts as an NH3-sensitive...
Autophagy is a catabolic self-degradative pathway that promotes the degradation and recycling of intracellular material through lysosomal compartment. Although first believed to function in conditions nutritional stress, autophagy emerging as critical cellular pathway, involved variety physiological pathophysiological processes. dysregulation associated with an increasing number diseases, including ocular diseases. On one hand, mutations autophagy-related genes have been linked cataracts,...
Background Myocilin (MYOC) is a gene linked directly to juvenile- and adult-onset open angle glaucoma. Mutations including Pro370Leu (P370L) Gln368stop (Q368X) have been identified in patients. In the present study, we investigated processing of myocilin human trabecular meshwork (TM) cells as well inducible, stable RGC5 cell lines. Methodology/Principal Findings The turnover photoactivation experiments revealed that endogenous was short-lived protein. It found level TM increased by...
The Slc4a11 knock out (KO) mouse model recapitulates the human disease phenotype associated with congenital hereditary endothelial dystrophy (CHED). Increased mitochondrial reactive oxygen species (ROS) in KO is a major cause of edema and cell loss. Here, we asked if autophagy was activated by ROS mice.Immortalized lines corneal endothelia were used to measure lysosome protein expressions using Protein Simple Wes immunoassay. Autophagy functions examined wild type (WT) cells as well animals...
Purpose: Fuchs endothelial corneal dystrophy (FECD) is a progressive blinding disorder, characterized by increased excrescences (guttae), cell loss, and edema. These symptoms are hypothesized to be caused changes in the extracellular matrix (ECM) mitochondrial dysfunction endothelium. Despite this clinical biological relevance, comprehensive animal model that recapitulates all major disease characteristics currently unavailable. In study, we develop such improve our understanding of...
Fuchs Endothelial Corneal Dystrophy (FECD) is the irreversible degeneration of corneal endothelium. The only treatment transplantation. To develop therapies for FECD, identifying cellular causes onset and progression disease crucial. While cell culture studies associate elevated oxidative stress, endoplasmic reticulum endothelial-to-mesenchymal transition, apoptosis with behind remain elusive. Guttae or Descemets membrane deposits are earliest phenotype associated FECD composed unfolded...
Abstract Optineurin is a gene associated with normal tension glaucoma (NTG) and amyotrophic lateral sclerosis (ALS). Foci formation functional consequences including Golgi fragmentation, impairment of vesicle trafficking apoptosis were observed previously upon overexpression and/or mutation optineurin. In the current study, total 15 GFP tagged constructs that included NTG (E50K 2 bp-AG insertion), ALS (exon 5 deletion, R96L, Q398X, E478G) non-disease (L157A D474N) mutants series deletion...
meso-Zeaxanthin is a carotenoid that rarely encountered in nature outside of the vertebrate eye. It not constituent normal human diet, yet this comprises one-third primate macular pigment. In current study, we undertook systematic approach to biochemically characterize production meso-zeaxanthin eye.Fertilized White Leghorn chicken eggs were analyzed for presence carotenoids during development. Yolk, liver, brain, serum, retina, and RPE/choroid isolated, extracted. The samples on C-30 or...
Recent studies from Slc4a11 −/− mice have identified glutamine-induced mitochondrial dysfunction as a significant contributor toward oxidative stress, impaired lysosomal function, aberrant autophagy, and cell death in this Congenital Hereditary Endothelial Dystrophy (CHED) model. Because lysosomes are derived endoplasmic reticulum (ER)—Golgi, we asked whether ER function is affected by ROS KO corneal endothelial cells. In mouse tissue, observed the presence of dilated elevated expression...
Purpose: The conventional Slc4a11 knockout (KO) shows significant corneal edema at eye opening, a fact that complicates the study of initial events leading to edema. An inducible KO would provide opportunities examine early following loss activity. Methods: Flox (SF) mice were crossed with expressing estrogen receptor Cre Recombinase fusion protein and fed tamoxifen (Tm) for two weeks. Corneal thickness (CT) was measured by OCT. At eight weeks endpoint, oxidative damage, tight junction...
Congenital hereditary endothelial dystrophy (CHED) is a rare condition that manifests at an early age showing corneal edema, increased oxidative stress, mitochondrial dysfunction, and eventually apoptosis of the endothelium due to loss function membrane transport protein SLC4A11. This project tested whether replacing
OBJECTIVES/SPECIFIC AIMS: Purpose - The goal of this study is to understand how loss the membrane protein SLC4A11 alters endothelial cell metabolism thereby producing Corneal Endothelial Dystrophy. Studies from our lab indicated that glutamine-dependent mitochondrial dysfunction one outcomes SLC4a11 loss. In current study, we ask if autophagy and mitophagy pathways signaling regulate these processes are altered in KO cells. METHODS/STUDY POPULATION: Methods – Immortalized mouse WT lines were...