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Diabetic retinopathy macrophage

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https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#1
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
#2
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
#3
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
#4
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...
January 9, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/27570063/tissue-resident-macrophages-key-players-in-the-pathogenesis-of-type-2-diabetes-and-its-complications
#5
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
#6
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
#7
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
#8
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
#9
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"
https://www.readbyqxmd.com/read/27259471/roles-of-o-glcnac-in-chronic-diseases-of-aging
#10
REVIEW
Partha S Banerjee, Olof Lagerlöf, Gerald W Hart
O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity...
October 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/26948311/targeting-the-complement-system-for-the-management-of-retinal-inflammatory-and-degenerative-diseases
#11
REVIEW
Heping Xu, Mei Chen
The retina, an immune privileged tissue, has specialized immune defense mechanisms against noxious insults that may exist in diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), uveoretinitis and glaucoma. The defense system consists of retinal innate immune cells (including microglia, perivascular macrophages, and a small population of dendritic cells) and the complement system. Under normal aging conditions, retinal innate immune cells and the complement system undergo a low-grade activation (parainflammation) which is important for retinal homeostasis...
September 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26828415/composite-nanoformulation-therapeutics-for-long-term-ocular-delivery-of-macromolecules
#12
Vibhuti Agrahari, Vivek Agrahari, Wei-Ting Hung, Lane K Christenson, Ashim K Mitra
The purpose of this investigation is to design and synthesize novel pentablock (PB) copolymer (PB-1: PCL-PLA-PEG-PLA-PCL) based nanoformulations suspended in a thermosensitive gelling copolymer (PB-2: mPEG-PCL-PLA-PCL-PEGm) termed as composite nanoformulation. The composite nanoformulation was prepared to provide a sustained delivery of macromolecules over a longer duration with negligible burst release effect. The delivery system was designed to be utilized for the treatment of posterior segment ocular diseases such as age-related (wet) macular degeneration, diabetic retinopathy, and diabetic macular edema...
September 6, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/26603154/myeloid-derived-vascular-endothelial-growth-factor-and-hypoxia-inducible-factor-are-dispensable-for-ocular-neovascularization-brief-report
#13
Sidath E Liyanage, Alessandro Fantin, Pilar Villacampa, Clemens A Lange, Laura Denti, Enrico Cristante, Alexander J Smith, Robin R Ali, Ulrich F Luhmann, James W Bainbridge, Christiana Ruhrberg
OBJECTIVE: Ocular neovascularization (ONV) is a pathological feature of sight-threatening human diseases, such as diabetic retinopathy and age-related macular degeneration. Macrophage depletion in mouse models of ONV reduces the formation of pathological blood vessels, and myeloid cells are widely considered an important source of the vascular endothelial growth factor A (VEGF). However, the importance of VEGF or its upstream regulators hypoxia-inducible factor-1α (HIF1α) and hypoxia-inducible factor-2α (HIF2α) as myeloid-derived regulators of ONV remains to be determined...
January 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26352837/elevated-levels-of-cytokines-associated-with-th2-and-th17-cells-in-vitreous-fluid-of-proliferative-diabetic-retinopathy-patients
#14
Masaru Takeuchi, Tomohito Sato, Atsushi Tanaka, Tadashi Muraoka, Manzo Taguchi, Yutaka Sakurai, Yoko Karasawa, Masataka Ito
Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th) cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes) with PDR...
2015: PloS One
https://www.readbyqxmd.com/read/26312758/enriched-environment-protects-the-optic-nerve-from-early-diabetes-induced-damage-in-adult-rats
#15
Damián Dorfman, Marcos L Aranda, Ruth E Rosenstein
Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm) optic nerve (ON) could be the first structural change of the visual pathway in streptozotocin (STZ)-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE) or remained in a standard environment (SE) for 6 weeks...
2015: PloS One
https://www.readbyqxmd.com/read/26268591/proteome-analysis-of-retinal-glia-cells-related-inflammatory-cytokines-in-the-aqueous-humour-of-diabetic-patients
#16
Stela Vujosevic, Alessandra Micera, Silvia Bini, Marianna Berton, Graziana Esposito, Edoardo Midena
PURPOSE: Retinal glia cells (RGC) activation and release of inflammatory cytokines have been associated with development of diabetic retinopathy (DR). In this study, we evaluated by protein array the presence of aqueous humour (AH) cytokines secreted by RGC in patients with diabetes without DR and with mild DR. METHODS: This is a cross-sectional, case-control study. Thirty-five subjects (diabetics and controls) underwent full ophthalmic examination and AH samples collection before cataract surgery at the Department of Ophthalmology University of Padova...
February 2016: Acta Ophthalmologica
https://www.readbyqxmd.com/read/26222724/ft011-a-novel-cardiorenal-protective-drug-reduces-inflammation-gliosis-and-vascular-injury-in-rats-with-diabetic-retinopathy
#17
Devy Deliyanti, Yuan Zhang, Fay Khong, David R Berka, David I Stapleton, Darren J Kelly, Jennifer L Wilkinson-Berka
Diabetic retinopathy features inflammation as well as injury to glial cells and the microvasculature, which are influenced by hypertension and overactivity of the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic agent that has been reported to attenuate organ damage in diabetic rats with cardiomyopathy and nephropathy. However, the potential therapeutic utility of FT011 for diabetic retinopathy has not been evaluated. We hypothesized that FT011 would attenuate retinopathy in diabetic Ren-2 rats, which exhibit hypertension due to an overactive extra-renal renin-angiotensin system...
2015: PloS One
https://www.readbyqxmd.com/read/26219952/inhibition-of-nox1-4-with-gkt137831-a-potential-novel-treatment-to-attenuate-neuroglial-cell-inflammation-in-the-retina
#18
Devy Deliyanti, Jennifer L Wilkinson-Berka
BACKGROUND: Inflammation and the excess production of reactive oxygen species (ROS) contribute significantly to the pathogenesis of ischemic retinopathies such as diabetic retinopathy and retinopathy of prematurity. We hypothesized that GKT137831, a dual inhibitor of NADPH oxidases (NOX) 1 and NOX4, reduces inflammation in the ischemic retina by dampening the pro-inflammatory phenotype of retinal immune cells as well as macroglial Müller cells and neurons. METHODS: Ischemic retinopathy was induced in Sprague-Dawley rats by exposure to 80 % O2 cycled with 21 % O2 for 3 h per day from postnatal day (P) 0 to P11, followed by room air (P12 to P18)...
July 30, 2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/26193917/systemic-and-intravitreal-delivery-of-dendrimers-to-activated-microglia-macrophage-in-ischemia-reperfusion-mouse-retina
#19
Siva P Kambhampati, Alexander J M Clunies-Ross, Imran Bhutto, Manoj K Mishra, Malia Edwards, D Scott McLeod, Rangaramanujam M Kannan, Gerard Lutty
PURPOSE: Microglial activation and associated neuroinflammation play a key role in the pathogenesis of many diseases of the retina, including viral infection, diabetes, and retinal degeneration. Strategies to target activated microglia and macrophages and attenuate inflammation may be valuable in treating these diseases. We seek to develop dendrimer-based formulations that target retinal microglia and macrophages in a pathology-dependent manner, and deliver drugs, either intravenously or intravitreally...
July 2015: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/25914608/atf4-is-a-novel-regulator-of-mcp-1-in-microvascular-endothelial-cells
#20
Huibin Huang, Guangjun Jing, Joshua J Wang, Nader Sheibani, Sarah X Zhang
BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine that recruits monocyte/macrophage to the site of tissue injury and plays a critical role in microvascular complications of diabetes. However, the mechanisms underlying the regulation of MCP-1 are not fully understood. The present study aims to explore the role of activating transcription factor 4 (ATF4), an ER stress-inducible transcription factor, in regulation of MCP-1 expression and production in brain and retinal microvascular endothelial cells...
2015: Journal of Inflammation
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