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Diabetic retinopathy macrophage

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https://www.readbyqxmd.com/read/29157600/receptor-structure-based-discovery-of-non-metabolite-agonists-for-the-succinate-receptor-gpr91
#1
Mette Trauelsen, Elisabeth Rexen Ulven, Siv A Hjorth, Matjaz Brvar, Claudia Monaco, Thomas M Frimurer, Thue W Schwartz
OBJECTIVE: Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. METHODS AND RESULTS: Here we first determined that the cis conformation of the succinate backbone is preferred and that certain backbone modifications are allowed for GPR91 activation. Through receptor modeling over the X-ray structure of the closely related P2Y1 receptor, we discovered that the binding pocket is partly occupied by a segment of an extracellular loop and that succinate therefore binds in a very different mode than generally believed...
December 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031855/furin-deficiency-in-myeloid-cellsleads-to-attenuated-revascularization-in-a-mouse-model-of-oxygen-induced-retinopathy
#2
Maria Vähätupa, Zuzet Martinez Cordova, Saara Aittomäki, Hannu Uusitalo, Tero A H Järvinen, Marko Pesu, Hannele Uusitalo-Järvinen
Diabetic retinopathy is a vision-threatening disease associated chronic retinal inflammation and hypoxia leading to abnormal angiogenesis. Furin, a member of the proprotein convertase family of proteins, has been implicated in the regulation of angiogenesis due to its essential role in the activation of several angiogenic growth factors, including vascular endothelial growth factor-C (VEGF-C), VEGF-D and transforming growth factor - β (TGF- β). In the present study, we evaluated expression of furin in the retina and its role in retinal angiogenesis...
October 12, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28980000/increased-indoleamine-2-3-dioxygenase-and-quinolinic-acid-expression-in-microglia-and-m%C3%A3-ller-cells-of-diabetic-human-and-rodent-retina
#3
Ping Hu, Nicholas H Hunt, Frank Arfuso, Lynn C Shaw, Mohammad Nasir Uddin, Meidong Zhu, Raj Devasahayam, Samuel J Adamson, Vicky L Benson, Tailoi Chan-Ling, Maria B Grant
Purpose: We investigated the relationship between inflammation, neuronal loss, and expression of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid (QUIN) in the retina of subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D) and in the retina of rats with T1D. Methods: Retinas from T1D (n = 7), T2D (n = 13), and 20 age-matched nondiabetic human donors and from T1D (n = 3) and control rats (n = 3) were examined using immunohistochemistry for IDO, QUIN, cluster of differentiation 39 (CD39), ionized calcium-binding adaptor molecule (Iba-1, for macrophages and microglia), Vimentin (VIM; for Müller cells), neuronal nuclei (NeuN; for neurons), and UEA1 lectin (for blood vessels)...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28965804/neutralization-of-placental-growth-factor-as-a-novel-treatment-option-in-diabetic-retinopathy
#4
Tine Van Bergen, Tjing-Tjing Hu, Isabelle Etienne, Geert E Reyns, Lieve Moons, Jean H M Feyen
The current standard of care in clinical practice for diabetic retinopathy (DR), anti-vascular endothelial growth factor (VEGF) therapy, has shown a significant improvement in visual acuity. However, treatment response can be variable and might be associated with potential side effects. This study was designed to investigate inhibition of placental growth factor (PlGF) as a possible alternative therapy for DR. The effect of the anti-PlGF antibody (PL5D11D4) was preclinically evaluated in various animal models by investigating different DR hallmarks, including inflammation, neurodegeneration, vascular leakage and fibrosis...
September 28, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28913545/periostin-in-vitreoretinal-diseases
#5
REVIEW
Shigeo Yoshida, Takahito Nakama, Keijiro Ishikawa, Shintaro Nakao, Koh-Hei Sonoda, Tatsuro Ishibashi
Proliferative vitreoretinal diseases such as diabetic retinopathy, proliferative vitreoretinopathy (PVR), and age-related macular degeneration are a leading cause of decreased vision and blindness in developed countries. In these diseases, retinal fibro(vascular) membrane (FVM) formation above and beneath the retina plays an important role. Gene expression profiling of human FVMs revealed significant upregulation of periostin. Subsequent analyses demonstrated increased periostin expression in the vitreous of patients with both proliferative diabetic retinopathy and PVR...
December 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28893413/fish-oil-emulsion-supplementation-might-improve-quality-of-life-of-diabetic-patients-due-to-its-antioxidant-and-anti-inflammatory-properties
#6
Lucia Laubertová, Katarína Koňariková, Helena Gbelcová, Zdeňka Ďuračková, Jana Muchová, Iveta Garaiova, Ingrid Žitňanová
Diabetes-related complications, including cardiovascular disease, retinopathy, nephropathy, and neuropathy, are a significant cause of increased morbidity and mortality among people with diabetes. Previous studies have confirmed that hyperglycemia has pro-oxidative and proinflammatory properties which cause diabetic complications. We hypothesized that supplementation of fish oil emulsion (FOE), rich in omega-3 polyunsaturated fatty acids, to diabetic patients might reduce hyperglycemia-induced pathological changes due to specific properties of FOE...
August 3, 2017: Nutrition Research
https://www.readbyqxmd.com/read/28819082/dysregulation-of-calpain-proteolytic-systems-underlies-degenerative-vascular-disorders
#7
Takuro Miyazaki, Akira Miyazaki
Chronic vascular diseases such as atherosclerosis, aneurysms, diabetic angiopathy/retinopathy as well as fibrotic and proliferative vascular diseases are generally complicated by the progression of degenerative insults, which are characterized by endothelial dysfunction, apoptotic/necrotic cell death in vascular/immune cells, remodeling of extracellular matrix or breakdown of elastic lamella. Increasing evidence suggests that dysfunctional calpain proteolytic systems and defective calpain protein metabolism in blood vessels contribute to degenerative disorders...
August 17, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28774737/the-mechanism-of-diabetic-retinopathy-pathogenesis-unifying-key-lipid-regulators-sirtuin-1-and-liver-x-receptor
#8
Sandra S Hammer, Eleni Beli, Nermin Kady, Qi Wang, Kiana Wood, Todd A Lydic, Goldis Malek, Daniel R Saban, Xiaoxin X Wang, Sugata Hazra, Moshe Levi, Julia V Busik, Maria B Grant
Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28419534/endocrine-imbalance-associated-with-proteome-changes-in-diabetes
#9
Ahmed Khairallah, Abo-Alela Farag, Dina Johar, Larry Bernstein
The dynamics of cellular metabolism involves rapid interactions between proteins and nucleic acids, proteins and proteins, and signaling. These involve the interactions with respect to the sulfur bond, noncovalent electrostatic interactions, protein structure stabilization and protein-ligand binding, weak electrostatic interactions in proteins, oxygen radicals that initiate a change in conformation and a chain of events. We review a development in molecular medicine that is a very promising work in progress...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28351645/targeting-of-12-15-lipoxygenase-in-retinal-endothelial-cells-but-not-in-monocytes-macrophages-attenuates-high-glucose-induced-retinal-leukostasis
#10
Ahmed S Ibrahim, Heba Saleh, Mohamed El-Shafey, Khaled A Hussein, Khaled El-Masry, Babak Baban, Nader Sheibani, Mong-Heng Wang, Amany Tawfik, Mohamed Al-Shabrawey
AIMS: Our previous studies have established a role for 12/15-lipoxygenase (LO) in mediating the inflammatory response in diabetic retinopathy (DR). However, the extent at which the local or systemic induction of 12/15-LO activity involved is unclear. Thus, the current study aimed to characterize the relative contribution of retinal endothelial versus monocytic/macrophagic 12/15-LO to inflammatory responses in DR. MATERIALS & METHODS: We first generated a clustered heat map for circulating bioactive lipid metabolites in the plasma of streptozotocin (STZ)-induced diabetic mice using liquid chromatography coupled with mass-spectrometry (LC-MS) to evaluate changes in circulating 12/15-LO activity...
June 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28346545/aqueous-cytokine-levels-are-associated-with-reduced-macular-thickness-after-intravitreal-ranibizumab-for-diabetic-macular-edema
#11
Tomoyasu Shiraya, Satoshi Kato, Fumiyuki Araki, Takashi Ueta, Tempei Miyaji, Takuhiro Yamaguchi
PURPOSE: It is controversial whether the administration of anti-vascular endothelial growth factor drugs for diabetic macular edema (DME) affects intraocular inflammatory cytokines. In this study, we measured cytokine concentration in aqueous humor before and after intravitreal injection of ranibizumab (IVR). The aim was to determine changes in cytokine concentration and their effects on DME reduction. METHODS: Twelve patients (13 eyes) with DME received two IVR (0...
2017: PloS One
https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#12
Shuntaro Ogura, Kaori Kurata, Yuki Hattori, Hiroshi Takase, Toshina Ishiguro-Oonuma, Yoonha Hwang, Soyeon Ahn, Inwon Park, Wataru Ikeda, Sentaro Kusuhara, Yoko Fukushima, Hiromi Nara, Hideto Sakai, Takashi Fujiwara, Jun Matsushita, Masatsugu Ema, Masanori Hirashima, Takashi Minami, Masabumi Shibuya, Nobuyuki Takakura, Pilhan Kim, Takaki Miyata, Yuichiro Ogura, Akiyoshi Uemura
In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28176950/circulating-monocytes-and-b-lymphocytes-in-neovascular-age-related-macular-degeneration
#13
Sven Magnus Hector, Torben Lykke Sørensen
BACKGROUND: Individuals with neovascular age-related macular degeneration (AMD) have altered number and distribution of retinal macrophages and show changes in circulating antibodies. We wanted to investigate the corresponding precursors, with subpopulations. We therefore measured monocyte and B-lymphocyte populations in individuals with neovascular AMD. DESIGN: This was an observational case-control study. PARTICIPANTS OR SAMPLES: A total of 31 individuals with neovascular AMD and 30 healthy age-matched controls were included...
2017: Clinical Ophthalmology
https://www.readbyqxmd.com/read/28170537/adenosine-deaminase-2-induced-hyperpermeability-in-human-retinal-vascular-endothelial-cells-is-suppressed-by-microrna-146b-3p
#14
Yara A Samra, Heba M Saleh, Khaled A Hussein, Nehal M Elsherbiny, Ahmed S Ibrahim, Khaled Elmasry, Sadanand Fulzele, Mamdouh M El-Shishtawy, Laila A Eissa, Mohamed Al-Shabrawey, Gregory I Liou
Purpose: We recently demonstrated that adenosine deaminase-2 (ADA2) contributes to diabetic retinopathy (DR) via up-regulating the production of inflammatory cytokines in macrophages. Also, microRNA (miR)-146b-3p has the ability to inhibit ADA2. The goal of this study was to investigate the potential role of ADA2 and therapeutic benefit of miR-146b-3p in retinal inflammation and endothelial barrier dysfunction during diabetes. Methods: Adenosine deaminase-2 activity was determined by colorimetric method in diabetic human vitreous...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28070752/absence-of-macrophage-migration-inhibitory-factor-reduces-proliferative-retinopathy-in-a-mouse-model
#15
Jing Wang, Jihong Lin, Ulrike Kaiser, Paulus Wohlfart, Hans-Peter Hammes
AIMS: Ischemia-induced neovascularization is the key feature of proliferative diabetic retinopathy. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory and proangiogenic cytokine, and its levels are elevated in the vitreous of patients with proliferative diabetic retinopathy. In this study, we aimed at investigating the relative potential of MIF in the ischemia-induced retinal neovascularization. METHODS: Both WT and MIF-knockout mice were subjected to the retinopathy of prematurity (ROP) model...
April 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/27570063/tissue-resident-macrophages-key-players-in-the-pathogenesis-of-type-2-diabetes-and-its-complications
#16
REVIEW
Reza Meshkani, Sanaz Vakili
There is increasing evidence showing that chronic inflammation is an important pathogenic mediator of the development of type 2 diabetes (T2D). It is now generally accepted that tissue-resident macrophages play a major role in regulation of tissue inflammation. T2D-associated inflammation is characterized by an increased abundance of macrophages in different tissues along with production of inflammatory cytokines. The complexity of macrophage phenotypes has been reported from different human tissues. Macrophages exhibit a phenotypic range that is intermediate between two extremes, M1 (pro-inflammatory) and M2 (anti-inflammatory)...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27564721/tgf%C3%AE-induces-bigh3-expression-and-human-retinal-pericyte-apoptosis-a-novel-pathway-of-diabetic-retinopathy
#17
B S Betts-Obregon, A A Mondragon, A S Mendiola, R G LeBaron, R Asmis, T Zou, F Gonzalez-Fernandez, A T Tsin
PurposeOne of the earliest hallmarks of diabetic retinopathy is the loss of retinal pericytes. However, the mechanisms that promote pericyte dropout are unknown. In the present study, we propose a novel pathway in which pericyte apoptosis is mediated by macrophages, TGFβ and pro-apoptotic BIGH3 (TGFβ-induced Gene Human Clone 3) protein.Patients and methodsTo elucidate this pathway, we assayed human retinal pericyte (HRP) apoptosis by TUNEL assay, BIGH3 mRNA expression by qPCR, and BIGH3 protein expression by western blot analysis...
December 2016: Eye
https://www.readbyqxmd.com/read/27474370/cd40-in-retinal-m%C3%A3-ller-cells-induces-p2x7-dependent-cytokine-expression-in-macrophages-microglia-in-diabetic-mice-and-development-of-early-experimental-diabetic-retinopathy
#18
Jose-Andres C Portillo, Yalitza Lopez Corcino, Yanling Miao, Jie Tang, Nader Sheibani, Timothy S Kern, George R Dubyak, Carlos S Subauste
Müller cells and macrophages/microglia are likely important for the development of diabetic retinopathy; however, the interplay between these cells in this disease is not well understood. An inflammatory process is linked to the onset of experimental diabetic retinopathy. CD40 deficiency impairs this process and prevents diabetic retinopathy. Using mice with CD40 expression restricted to Müller cells, we identified a mechanism by which Müller cells trigger proinflammatory cytokine expression in myeloid cells...
February 2017: Diabetes
https://www.readbyqxmd.com/read/27373871/diabetic-retinopathy-proteomic-approaches-to-help-the-differential-diagnosis-and-to-understand-the-underlying-molecular-mechanisms
#19
Éva Csősz, Eszter Deák, Gergő Kalló, Adrienne Csutak, József Tőzsér
Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness among patients with diabetes. The appearance and the severity of the symptoms correlate with the duration of diabetes and poor blood glucose level management. Diabetic retinopathy is also categorized as a chronic low-level inflammatory disease; the high blood glucose level promotes the accumulation of the advanced glycation end products and leads to the stimulation of monocytes and macrophages. Examination of protein level alterations in tears using state-of the art proteomics techniques have identified several proteins as possible biomarkers for the different stages of the diabetic retinopathy...
July 1, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27344677/cx3cr1-deficiency-accelerates-the-development-of-retinopathy-in-a-rodent-model-of-type-1-diabetes
#20
Eleni Beli, James M Dominguez, Ping Hu, Jeffrey S Thinschmidt, Sergio Caballero, Sergio Li Calzi, Defang Luo, Sumathi Shanmugam, Tatiana E Salazar, Yaqian Duan, Michael E Boulton, Susanna Mohr, Steven F Abcouwer, Daniel R Saban, Jeffrey K Harrison, Maria B Grant
In this study, the role of CX3CR1 in the progression of diabetic retinopathy (DR) was investigated. The retinas of wild-type (WT), CX3CR1 null (CX3CR1(gfp/gfp), KO), and heterozygous (CX3CR1(+/gfp), Het) mice were compared in the presence and absence of streptozotocin (STZ)-induced diabetes. CX3CR1 deficiency in STZ-KO increased vascular pathology at 4 months of diabetes, as a significant increase in acellular capillaries was observed only in the STZ-KO group. CX3CR1 deficiency and diabetes had similar effects on retinal neurodegeneration measured by an increase in DNA fragmentation...
November 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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