Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 8 of 8

Publication Record


The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.
Capozzi ME, Savage SR, McCollum GW, Hammer SS, Ramos CJ, Yang R, Bretz CA, Penn JS
(2020) Exp Eye Res 190: 107885
MeSH Terms: Adult, Animals, Cells, Cultured, Cytokines, Endothelial Cells, Ependymoglial Cells, Humans, Inflammation, Leukostasis, Male, Mice, Mice, Inbred C57BL, PPAR delta, PPAR-beta, Palmitic Acids, Real-Time Polymerase Chain Reaction, Retina, Retinitis, Sulfones, Thiophenes
Show Abstract · Added March 30, 2020
Diabetic retinopathy (DR) is triggered by retinal cell damage stimulated by the diabetic milieu, including increased levels of intraocular free fatty acids. Free fatty acids may serve as an initiator of inflammatory cytokine release from Müller cells, and the resulting cytokines are potent stimulators of retinal endothelial pathology, such as leukostasis, vascular permeability, and basement membrane thickening. Our previous studies have elucidated a role for peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in promoting several steps in the pathologic cascade in DR, including angiogenesis and expression of inflammatory mediators. Furthermore, PPARβ/δ is a known target of lipid signaling, suggesting a potential role for this transcription factor in fatty acid-induced retinal inflammation. Therefore, we hypothesized that PPARβ/δ stimulates both the induction of inflammatory mediators by Müller cells as well the paracrine induction of leukostasis in endothelial cells (EC) by Müller cell inflammatory products. To test this, we used the PPARβ/δ inhibitor, GSK0660, in primary human Müller cells (HMC), human retinal microvascular endothelial cells (HRMEC) and mouse retina. We found that palmitic acid (PA) activation of PPARβ/δ in HMC leads to the production of pro-angiogenic and/or inflammatory cytokines that may constitute DR-relevant upstream paracrine inflammatory signals to EC and other retinal cells. Downstream, EC transduce these signals and increase their synthesis and release of chemokines such as CCL8 and CXCL10 that regulate leukostasis and other cellular events related to vascular inflammation in DR. Our results indicate that PPARβ/δ inhibition mitigates these upstream (MC) as well as downstream (EC) inflammatory signaling events elicited by metabolic stimuli and inflammatory cytokines. Therefore, our data suggest that PPARβ/δ inhibition is a potential therapeutic strategy against early DR pathology.
Copyright © 2019 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Palmitic Acid Induces Müller Cell Inflammation that is Potentiated by Co-treatment with Glucose.
Capozzi ME, Giblin MJ, Penn JS
(2018) Sci Rep 8: 5459
MeSH Terms: Diabetic Retinopathy, Drug Interactions, Ependymoglial Cells, Gene Expression Regulation, Glucose, Humans, Inflammation, Palmitic Acid
Show Abstract · Added April 10, 2019
Chronic hyperglycemia is thought to be the major stimulator of retinal dysfunction in diabetic retinopathy (DR). Thus, many diabetes-related systemic factors have been overlooked as inducers of DR pathology. Cell culture models of retinal cell types are frequently used to mechanistically study DR, but appropriate stimulators of DR-like factors are difficult to identify. Furthermore, elevated glucose, a gold standard for cell culture treatments, yields little to no response from many primary human retinal cells. Thus, the goal of this project was to demonstrate the effectiveness of the free fatty acid, palmitic acid and compare its use alone and in combination with elevated glucose as a stimulus for human Müller cells, a retinal glial cell type that is activated early in DR pathogenesis and uniquely responsive to fatty acids. Using RNA sequencing, we identified a variety of DR-relevant pathways, including NFκB signaling and inflammation, intracellular lipid signaling, angiogenesis, and MAPK signaling, that were stimulated by palmitic acid, while elevated glucose alone did not significantly alter any diabetes-relevant pathways. Co-treatment of high glucose with palmitic acid potentiated the expression of several DR-relevant angiogenic and inflammatory targets, including PTGS2 (COX-2) and CXCL8 (IL-8).
0 Communities
1 Members
0 Resources
8 MeSH Terms
A specific phosphorylation regulates the protective role of αA-crystallin in diabetes.
Ruebsam A, Dulle JE, Myers AM, Sakrikar D, Green KM, Khan NW, Schey K, Fort PE
(2018) JCI Insight 3:
MeSH Terms: Aged, Animals, Cell Line, Crystallins, Diabetes Mellitus, Experimental, Diabetic Retinopathy, Electroretinography, Ependymoglial Cells, Female, Humans, Male, Mice, Mice, Knockout, Neurons, Phosphorylation, Rats, Rats, Sprague-Dawley, Recombinant Proteins, Retina, Streptozocin, Transfection, alpha-Crystallin A Chain, alpha-Crystallin B Chain
Show Abstract · Added April 3, 2018
Neurodegeneration is a central aspect of the early stages of diabetic retinopathy, the primary ocular complication associated with diabetes. While progress has been made to improve the vascular perturbations associated with diabetic retinopathy, there are still no treatment options to counteract the neuroretinal degeneration associated with diabetes. Our previous work suggested that the molecular chaperones α-crystallins could be involved in the pathophysiology of diabetic retinopathy; however, the role and regulation of α-crystallins remained unknown. In the present study, we demonstrated the neuroprotective role of αA-crystallin during diabetes and its regulation by its phosphorylation on residue 148. We further characterized the dual role of αA-crystallin in neurons and glia, its essential role for neuronal survival, and its direct dependence on phosphorylation on this residue. These findings support further evaluation of αA-crystallin as a treatment option to promote neuron survival in diabetic retinopathy and neurodegenerative diseases in general.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Müller glial microRNAs are required for the maintenance of glial homeostasis and retinal architecture.
Wohl SG, Jorstad NL, Levine EM, Reh TA
(2017) Nat Commun 8: 1603
MeSH Terms: 3T3 Cells, Animals, Cell Movement, Cells, Cultured, DEAD-box RNA Helicases, Ependymoglial Cells, Gene Expression Profiling, Homeostasis, Mice, Mice, Knockout, Mice, Transgenic, MicroRNAs, Microscopy, Confocal, Neuroglia, Retina, Ribonuclease III
Show Abstract · Added February 14, 2018
To better understand the roles of microRNAs in glial function, we used a conditional deletion of Dicer1 (Dicer-CKO) in retinal Müller glia (MG). Dicer1 deletion from the MG leads to an abnormal migration of the cells as early as 1 month after the deletion. By 6 months after Dicer1 deletion, the MG form large aggregations and severely disrupt normal retinal architecture and function. The most highly upregulated gene in the Dicer-CKO MG is the proteoglycan Brevican (Bcan) and overexpression of Bcan results in similar aggregations of the MG in wild-type retina. One potential microRNA that regulates Bcan is miR-9, and overexpression of miR-9 can partly rescue the effects of Dicer1 deletion on the MG phenotype. We also find that MG from retinitis pigmentosa patients display an increase in Brevican immunoreactivity at sites of MG aggregation, linking the retinal remodeling that occurs in chronic disease with microRNAs.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents.
Scarlett JM, Rojas JM, Matsen ME, Kaiyala KJ, Stefanovski D, Bergman RN, Nguyen HT, Dorfman MD, Lantier L, Wasserman DH, Mirzadeh Z, Unterman TG, Morton GJ, Schwartz MW
(2016) Nat Med 22: 800-6
MeSH Terms: Adipose Tissue, Animals, Blood Glucose, Blotting, Western, Body Composition, Brain, Carbon Radioisotopes, Deoxyglucose, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Diet, High-Fat, Disease Models, Animal, Ependymoglial Cells, Fibroblast Growth Factor 1, Forkhead Box Protein O1, Glucose Tolerance Test, Heart, Heat-Shock Proteins, Hyperglycemia, Hypothalamus, Injections, Intraventricular, Liver, Male, Mice, Mice, Knockout, Mice, Obese, Molecular Chaperones, Muscle, Skeletal, Myocardium, Neoplasm Proteins, Proto-Oncogene Proteins c-fos, Rats, Rats, Zucker, Real-Time Polymerase Chain Reaction, Receptor, Insulin, Remission Induction
Show Abstract · Added May 16, 2019
Type 2 diabetes (T2D) is among the most common and costly disorders worldwide. The goal of current medical management for T2D is to transiently ameliorate hyperglycemia through daily dosing of one or more antidiabetic drugs. Hypoglycemia and weight gain are common side effects of therapy, and sustained disease remission is not obtainable with nonsurgical approaches. On the basis of the potent glucose-lowering response elicited by activation of brain fibroblast growth factor (FGF) receptors, we explored the antidiabetic efficacy of centrally administered FGF1, which, unlike other FGF peptides, activates all FGF receptor subtypes. We report that a single intracerebroventricular injection of FGF1 at a dose one-tenth of that needed for antidiabetic efficacy following peripheral injection induces sustained diabetes remission in both mouse and rat models of T2D. This antidiabetic effect is not secondary to weight loss, does not increase the risk of hypoglycemia, and involves a novel and incompletely understood mechanism for increasing glucose clearance from the bloodstream. We conclude that the brain has an inherent potential to induce diabetes remission and that brain FGF receptors are potential pharmacological targets for achieving this goal.
0 Communities
1 Members
0 Resources
36 MeSH Terms
Mammalian retinal Müller cells have circadian clock function.
Xu L, Ruan G, Dai H, Liu AC, Penn J, McMahon DG
(2016) Mol Vis 22: 275-83
MeSH Terms: Animals, CLOCK Proteins, Cells, Cultured, Circadian Clocks, Circadian Rhythm, Ependymoglial Cells, Female, Fluorescent Antibody Technique, Indirect, Genetic Vectors, Humans, Lentivirus, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Small Interfering, Transfection
Show Abstract · Added March 18, 2020
PURPOSE - To test whether Müller glia of the mammalian retina have circadian rhythms.
METHODS - We used Müller glia cultures isolated from mouse lines or from humans and bioluminescent reporters of circadian clock genes to monitor molecular circadian rhythms. The clock gene dependence of the Müller cell rhythms was tested using clock gene knockout mouse lines or with siRNA for specific clock genes.
RESULTS - We demonstrated that retinal Müller glia express canonical circadian clock genes, are capable of sustained circadian oscillations in isolation from other cell types, and exhibit unique features of their molecular circadian clock compared to the retina as a whole. Mouse and human Müller cells demonstrated circadian clock function; however, they exhibited species-specific differences in the gene dependence of their clocks.
CONCLUSIONS - Müller cells are the first mammalian retinal cell type in which sustained circadian rhythms have been demonstrated in isolation from other retinal cells.
0 Communities
1 Members
0 Resources
MeSH Terms
Technical brief: Constant intense light exposure to lesion and initiate regeneration in normally pigmented zebrafish.
Rajaram K, Summerbell ER, Patton JG
(2014) Mol Vis 20: 1075-84
MeSH Terms: Albinism, Ocular, Animals, Animals, Genetically Modified, Apoptosis, Cell Dedifferentiation, Cell Proliferation, Disease Models, Animal, Ependymoglial Cells, Green Fluorescent Proteins, Light, Neural Stem Cells, Photoreceptor Cells, Vertebrate, Recombinant Proteins, Regeneration, Retina, Zebrafish
Show Abstract · Added January 20, 2015
Zebrafish are capable of robust and spontaneous regeneration of injured retina. Constant intense light exposure to adult albino zebrafish specifically causes apoptosis of rod and cone photoreceptor cells and is an excellent model to study the molecular mechanisms underlying photoreceptor regeneration. However, this paradigm has only been applied to lesion zebrafish of the nonpigmented albino genetic background, which precludes the use of numerous transgenic reporter lines that are widely used to study regeneration. Here, we explored the effectiveness of constant intense light exposure in causing photoreceptor apoptosis and stimulating regeneration in normally pigmented zebrafish retinas. We show that constant intense light exposure causes widespread photoreceptor damage in the dorsal-central retinas of pigmented zebrafish. Photoreceptor loss triggers dedifferentiation and proliferation of Müller glia as well as progenitor cell proliferation. We also demonstrate that the timeline of regeneration response is comparable between the albino and the pigmented retinas.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Mitigation of oxygen-induced retinopathy in α2β1 integrin-deficient mice.
Madamanchi A, Capozzi M, Geng L, Li Z, Friedman RD, Dickeson SK, Penn JS, Zutter MM
(2014) Invest Ophthalmol Vis Sci 55: 4338-47
MeSH Terms: Animals, Animals, Newborn, Cells, Cultured, Disease Models, Animal, Endothelium, Vascular, Ependymoglial Cells, Gene Expression Regulation, Integrin alpha2beta1, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Oxygen, Polymerase Chain Reaction, RNA, Retinopathy of Prematurity, Vascular Endothelial Growth Factor A
Show Abstract · Added February 19, 2015
PURPOSE - The α2β1 integrin plays an important but complex role in angiogenesis and vasculopathies. Published GWAS studies established a correlation between genetic polymorphisms of the α2β1 integrin gene and incidence of diabetic retinopathy. Recent studies indicated that α2-null mice demonstrate superior vascularization in both the wound and diabetic microenvironments. The goal of this study was to determine whether the vasculoprotective effects of α2-integrin deficiency extended to the retina, using the oxygen-induced retinopathy (OIR) model for retinopathy of prematurity (ROP).
METHODS - In the OIR model, wild-type (WT) and α2-null mice were exposed to 75% oxygen for 5 days (postnatal day [P] 7 to P12) and subsequently returned to room air for 6 days (P12-P18). Retinas were collected at postnatal day 7, day 13, and day 18 and examined via hematoxylin and eosin and Lectin staining. Retinas were analyzed for retinal vascular area, neovascularization, VEGF expression, and Müller cell activation. Primary Müller cell cultures from WT and α2-null mice were isolated and analyzed for hypoxia-induced VEGF-A expression.
RESULTS - In the retina, the α2β1 integrin was minimally expressed in endothelial cells and strongly expressed in activated Müller cells. Isolated α2-null primary Müller cells demonstrated decreased hypoxia-induced VEGF-A expression. In the OIR model, α2-null mice displayed reduced hyperoxia-induced vaso-attenuation, reduced pathological retinal neovascularization, and decreased VEGF expression as compared to WT counterparts.
CONCLUSIONS - Our data suggest that the α2β1 integrin contributes to the pathogenesis of retinopathy. We describe a newly identified role for α2β1 integrin in mediating hypoxia-induced Müller cell VEGF-A production.
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
1 Communities
1 Members
0 Resources
16 MeSH Terms