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Diabetic retinopathy barrier

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https://www.readbyqxmd.com/read/28439518/diabetes-adult-neurogenesis-and-brain-remodeling-new-insights-from-rodent-and-zebrafish-models
#1
REVIEW
Anne-Claire Dorsemans, David Couret, Anaïs Hoarau, Olivier Meilhac, Christian Lefebvre d'Hellencourt, Nicolas Diotel
The prevalence of diabetes rapidly increased during the last decades in association with important changes in lifestyle. Diabetes and hyperglycemia are well-known for inducing deleterious effects on physiologic processes, increasing for instance cardiovascular diseases, nephropathy, retinopathy and foot ulceration. Interestingly, diabetes also impairs brain morphology and functions such as (1) decreased neurogenesis (proliferation, differentiation and cell survival), (2) decreased brain volumes, (3) increased blood-brain barrier leakage, (4) increased cognitive impairments, as well as (5) increased stroke incidence and worse neurologic outcomes following stroke...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28436035/nap-counteracts-hyperglycemia-hypoxia-induced-retinal-pigment-epithelial-barrier-breakdown-through-modulation-of-hifs-and-vegf-expression
#2
Agata Grazia D'Amico, Grazia Maugeri, Daniela Maria Rasà, Valentina La Cognata, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Diabetic macular edema (DME) is a common complication leading to a central vision loss in patients with diabetes. In this eye pathology, the hyperglycaemic/hypoxic microenvironment of pigmented epithelium is responsible for outer blood retinal barrier integrity changes. More recently, we have shown that a small peptide derived from the activity-dependent neuroprotective protein (ADNP), known as NAP, counteracts damages occurring during progression of diabetic retinopathy by modulating HIFs/VEGF pathway. Here, we have investigated for the first time the role of this peptide on outer blood retinal barrier (BRB) integrity exposed to hyperglycaemic/hypoxic insult mimicking a model in vitro of DME...
April 24, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28427064/emerging-issues-for-ultra-wide-field-angiography
#3
Alessandro Rabiolo, Luigi Antonio De Vitis, Riccardo Sacconi, Adriano Carnevali, Lea Querques, Francesco Bandello, Giuseppe Querques
Fluorescein angiography (FA) is a useful test in patients affected by diabetic retinopathy (DR) to evaluate the blood-retinal barrier integrity and the presence of non-perfused areas, vascular leakage, microvascular abnormalities, and neovascularization. The peripheral retina is involved in most DR lesions, and, thus, its proper visualization is crucial for the screening, diagnosis, monitoring, treatment, and prognosis of DR. To expand the field of view, wide-field and ultra-wide-field imaging have been developed, allowing images up to 200° of retinal surface in one single photo...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28427061/emerging-insights-into-pathogenesis
#4
Edoardo Midena, Elisabetta Pilotto
Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus (DM). Persistent hyperglycemia leads to the activation of multiple cellular pathways involved in the pathogenesis of DR, resulting in increased inflammation, oxidative stress, and vascular dysfunction. DR has been considered a "chronic, low-grade inflammatory disease of the retina". However, an increasing body of evidence suggests that inflammation and neurodegeneration both occur in human diabetes even before the development of clinical signs of DR...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28422378/cellular-retinoic-acid-bioavailability-in-various-pathologies-and-its-therapeutic-implication
#5
REVIEW
Makoto Osanai
Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling molecule in various cell types. We found that RA depletion caused by expression of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that the biological effect of RA on target cells is primarily determined by "cellular RA bioavailability", which is defined as the RA level in an individual cell, rather than by the serum concentration of RA...
April 19, 2017: Pathology International
https://www.readbyqxmd.com/read/28363730/what-factors-influence-uptake-of-retinal-screening-among-young-adults-with-type-2-diabetes-a-qualitative-study-informed-by-the-theoretical-domains-framework
#6
Amelia J Lake, Jessica L Browne, Gwyneth Rees, Jane Speight
AIMS: Young adults with type 2 diabetes (T2D, 18-39years) face increased risk of vision loss from diabetic retinopathy (DR). Retinal screening is essential to detect DR, yet screening rates for this group are low and little is known about the underlying factors influencing this important behavior. Using the theoretical domains framework (TDF) to guide data collection and analysis, we explored screening barriers and facilitator, contrasting them with a comparator group of older adults with T2D (40+ years)...
March 14, 2017: Journal of Diabetes and its Complications
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
#7
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...
March 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28347688/effects-of-diabetic-retinopathy-on-the-barrier-functions-of-the-retinal-pigment-epithelium
#8
Tina Xia, Lawrence J Rizzolo
Diabetic retinopathy is a debilitating microvascular complication of diabetes mellitus. A rich literature describes the breakdown of retinal endothelial cells and the inner blood-retinal barrier, but the effects of diabetes on the retinal pigment epithelium (RPE) has received much less attention. RPE lies between the choroid and neurosensory retina to form the outer blood-retinal barrier. RPE's specialized and dynamic barrier functions are crucial for maintaining retinal health. RPE barrier functions include a collection of interrelated structures and activities that regulate the transepithelial movement of solutes, including: diffusion through the paracellular spaces, facilitated diffusion through the cells, active transport, receptor-mediated and bulk phase transcytosis, and metabolic processing of solutes in transit...
March 29, 2017: Vision Research
https://www.readbyqxmd.com/read/28341661/vascular-endothelial-growth-factor-a165b-ameliorates-outer-retinal-barrier-and-vascular-dysfunction-in-the-diabetic-retina
#9
Nikita Ved, Richard P Hulse, Samuel M Bestall, Lucy F Donaldson, James W Bainbridge, David Bates
Diabetic retinopathy (DR) is one of the leading causes of blindness in the developed world. Characteristic features of DR are retinal neurodegeneration, pathological angiogenesis and breakdown of both the inner and outer retinal barriers of the retinal vasculature and RPE-choroid respectively. Vascular endothelial growth factor-A (VEGF), a key regulator of angiogenesis and permeability, is the target of most pharmacological interventions of DR. VEGF-A can be alternatively spliced at exon 8 to form 2 families of isoforms, pro- and anti-angiogenic...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28322323/anti-inflammatory-properties-of-shikonin-contribute-to-improved-early-stage-diabetic-retinopathy
#10
Po-Lin Liao, Cheng-Hui Lin, Ching-Hao Li, Chi-Hao Tsai, Jau-Der Ho, George C Y Chiou, Jaw-Jou Kang, Yu-Wen Cheng
Diabetic retinopathy (DR), a major microvascular complication of diabetes, leads to retinal vascular leakage, neuronal dysfunction, and apoptosis within the retina. In this study, we combined STZ with whole-body hypoxia (10% O2) for quicker induction of early-stage retinopathy in C57BL/6 mice. We also compared the effects of a high glucose condition combined with hypoxia (1% O2) to a low glucose condition by using retinal pigment epithelial (RPE) cells, which are a crucial component of the outer blood-retinal barrier and the damage is related to retinopathy...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322199/adrenomedullin-suppresses-vascular-endothelial-growth-factor-induced-vascular-hyperpermeability-and-inflammation-in-retinopathy
#11
Akira Imai, Yuichi Toriyama, Yasuhiro Iesato, Kazutaka Hirabayashi, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Hisaka Kawate, Megumu Tanaka, Tian Liu, Xian Xian, Liuyu Zhai, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Akihiro Yamauchi, Toshinori Murata, Takayuki Shindo
Diabetic macular edema (DME) is caused by blood-retinal barrier breakdown associated with retinal vascular hyperpermeability and inflammation, and it is the major cause of visual dysfunction in diabetic retinopathy. Adrenomedullin (ADM) is an endogenous peptide first identified as a strong vasodilator. ADM is expressed in the eyes and is up-regulated in various eye diseases, although the pathophysiological significance is largely unknown. We investigated the effect of ADM on DME. In Kimba mice, which overexpress human vascular endothelial growth factor in their retinas, the capillary dropout, vascular leakage, and vascular fragility characteristic of diabetic retinopathy were observed, and these changes were accompanied by retinal inflammation...
March 16, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28301218/retinal-pathology-is-associated-with-increased-blood-retina-barrier-permeability-in-a-diabetic-and-hypercholesterolaemic-pig-model-beneficial-effects-of-the-lppla2-inhibitor-darapladib
#12
Nimish K Acharya, Xin Qi, Eric L Goldwaser, George A Godsey, Hao Wu, Mary C Kosciuk, Theresa A Freeman, Colin H Macphee, Robert L Wilensky, Venkat Venkataraman, Robert G Nagele
Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#13
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/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/28162200/-the-protective-effect-of-human-umbilical-cord-mesenchymal-stem-cells-induced-neural-stem-cells-in-the-vitreous-on-the-blood-retinal-barrier-in-diabetic-rats
#15
M Dong, W Zhang, S Chen, J M Wang, H T Duan, J H Kong, Y X Wang, X Bi, J Song
Objective: To investigate the effect of intravitreal injection of neural stem cells (NSC) induced from human umbilical cord mesenchymal stem cells, and to provide a theoretical basis for the clinical treatment of blood-retinal barrier damage due to diabetic retinopathy (DR). Methods: Experimental study. Sixty male Sprague-Dawley rats were randomly divided into control group, DR group and NSC group. Diabetic rats were induced by injection of streptozotocin, and the control rats were injected with an equal volume of solvent...
January 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28152535/the-blood-retinal-barrier-in-the-management-of-retinal-disease-euretina-award-lecture
#16
José Cunha-Vaz
Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels...
2017: Ophthalmologica. Journal International D'ophtalmologie
https://www.readbyqxmd.com/read/28138697/niaspan-inhibits-diabetic-retinopathy%C3%A2-induced-vascular-inflammation-by-downregulating-the-tumor-necrosis-factor%C3%A2-%C3%AE-pathway
#17
Yang Wang, Xiangda Meng, Hua Yan
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early DR is characterized by vascular neuroinflammation, cell apoptosis and breakdown of the blood‑retinal barrier (BRB). However, optimal treatment options and associated mechanisms remain unclear. Niaspan, which is widely used in the prevention and treatment of hyperlipidemia‑associated diseases, has been reported to inhibit inflammation. However, the effects of Niaspan and the mechanisms underlying the anti‑inflammatory effects of Niaspan on DR have yet to be reported...
March 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28132907/gene-therapy-for-diabetic-retinopathy-are-we-ready-to-make-the-leap-from-bench-to-bedside
#18
REVIEW
Jiang-Hui Wang, Damien Ling, Leilei Tu, Peter van Wijngaarden, Gregory J Dusting, Guei-Sheung Liu
Diabetic retinopathy (DR), a chronic and progressive complication of diabetes mellitus, is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that further damages vision. A major contributor to the pathology is excess production of vascular endothelial growth factor (VEGF), a growth factor that induces formation of new blood vessels and increases permeability of existing vessels. Despite the recent availability of effective treatments for the disease, including laser photocoagulation and therapeutic VEGF antibodies, DR remains a significant cause of vision loss worldwide...
January 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28127564/ursodeoxycholic-acid-attenuates-endoplasmic-reticulum-stress-related-retinal-pericyte-loss-in-streptozotocin-induced-diabetic-mice
#19
Yoo-Ri Chung, Jeong A Choi, Jae-Young Koh, Young Hee Yoon
Loss of pericytes, an early hallmark of diabetic retinopathy (DR), results in breakdown of the blood-retinal barrier. Endoplasmic reticulum (ER) stress may be involved in this process. The purpose of this study was to examine the effects of ursodeoxycholic acid (UDCA), a known ameliorator of ER stress, on pericyte loss in DR of streptozotocin- (STZ-) induced diabetic mice. To assess the extent of DR, the integrity of retinal vessels and density of retinal capillaries in STZ-induced diabetic mice were evaluated...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28122462/current-treatment-strategies-and-nanocarrier-based-approaches-for-the-treatment-and-management-of-diabetic-retinopathy
#20
Kousalya Selvaraj, Kuppusamy Gowthamarajan, Veera Venkata Satyanarayana Reddy Karri, Uday K Barauah, Vanka Ravisankar, Gifty M Jojo
Diabetic retinopathy (DR) is a leading cause of blindness in all working age groups which contribute to patient's quality of life. Considering the anatomy and physiology of barriers in the eye, the treatment and management of pathologic ocular neovascularization in the posterior segment of the eye in DR is a challenging task. The current and emerging treatment strategies are discussed in this review for better understanding and treatment of the DR. Challenges in conventional therapy and recent developments in nanocarrier based approaches (polymeric, lipid nanoparticles, liposomes and dendrimers) and their advantages in targeting ocular tissues were also discussed in this review...
June 2017: Journal of Drug Targeting
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