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Diabetic retinopathy renin angiotensin

Tuhina Prasad, Lodi C W Roksnoer, Ping Zhu, Amrisha Verma, Yiming Li, Wendy W Batenburg, René de Vries, A H Jan Danser, Qiuhong Li
Purpose: Dysfunction of the renin-angiotensin system (RAS) contributes to pathogenesis of diabetic retinopathy (DR). Yet RAS blockers have only limited beneficial effects on progression of DR in clinical trials. The natriuretic peptide system offsets RAS, so that enhancing the activity of this system on top of RAS blockade might be beneficial. Neprilysin has an important role in the degradation of natriuretic peptides. Therefore, we hypothesize that dual angiotensin receptor-neprilysin inhibition (ARNI) may outperform angiotensin receptor blocker (ARB) in protection against DR...
December 1, 2016: Investigative Ophthalmology & Visual Science
Estrellita Uijl, Lodi C W Roksnoer, Ewout J Hoorn, A H Jan Danser
Coexistence of hypertension, diabetes mellitus and chronic kidney disease synergistically aggravates the risk of cardiovascular and renal morbidity and mortality. These high-risk, multi-morbid patient populations benefit less from currently available anti-hypertensive treatment. Simultaneous angiotensin II type 1 receptor blockade and neprilysin inhibition ('ARNI') with valsartan/sacubitril (LCZ696) might potentiate the beneficial effects of renin-angiotensin-aldosterone inhibition by reinforcing its endogenous counterbalance, the natriuretic peptide system...
December 2016: Current Hypertension Reports
Nadine Reichhart, Sergio Crespo-Garcia, Nadine Haase, Michaela Golic, Sergej Skosyrski, Anne Rübsam, Christina Herrspiegel, Norbert Kociok, Natalia Alenina, Michael Bader, Ralf Dechend, Olaf Strauss, Antonia M Joussen
AIMS/HYPOTHESIS: Although the renin-angiotensin system plays an important role in the progression of diabetic retinopathy, its influence therein has not been systematically evaluated. Here we test the suitability of a new translational model of diabetic retinopathy, the TetO rat, for addressing the role of angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy. METHODS: Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA) knockdown of the insulin receptor in rats, generating TetO rats...
January 2017: Diabetologia
Sónia Simão, Daniela F Santos, Gabriela A Silva
There is growing evidence on the role of ocular renin-angiotensin system (RAS) in the development of diabetic retinopathy (DR), particularly due to the trigger of oxidative stress and angiogenesis. Despite this there is no effective RAS-based therapy in DR capable of preventing retinal damage induced by RAS activation. We recently described that retinal pigment epithelium (RPE) cells express the main components of the RAS. We here propose to investigate the role of glucose upon the retinal RAS and whether aliskiren, a direct renin inhibitor, protects RPE cells from angiogenesis and oxidative stress...
October 1, 2016: Angiogenesis
Ben-Skowronek Iwona
Neurodegeneration is an initial process in the development of diabetic retinopathy (DR). High quantities of glutamate, oxidative stress, induction of the renin-angiotensin system (RAS) and elevated levels of RAGE are crucial elements in the retinal neurodegeneration caused by diabetes mellitus. At least, there is emerging proof to indicate that the equilibrium between the neurotoxic and neuroprotective components will affect the state of the retinal neurons. Somatostatin (SST), pigment epithelium-derived factor (PEDF), and erythropoietin (Epo) are endogenous neuroprotective peptides that are decreased in the eye of diabetic persons and play an essential role in retinal homeostasis...
2016: Current Neuropharmacology
G Currie, J Flynn, M Lindhardt, H Mischak, P Rossing, C Delles
OBJECTIVE: Microalbuminuria (MA) is a marker of diabetic nephropathy (DN) but also indicates subclinical inflammation and vascular disease, limiting its sensitivity and specificity for early prediction of DN in type 2 diabetes. A urinary proteomic classifier based on 273 peptides (CKD273) shows promise for early detection of DN; however, the influence of inflammation and subclinical vascular disease on CKD27 is unknown. DESIGN AND METHOD: To dissect the relationship between CKD273, vascular phenotypes and inflammation without the confounding influence of MA we studied 145 normoalbuminuric patients with Type 2 diabetes participating in the PRIORITY (Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetes with normoalbuminuria) trial...
September 2016: Journal of Hypertension
James M Dominguez, Ping Hu, Sergio Caballero, Leni Moldovan, Amrisha Verma, Gavin Y Oudit, Qiuhong Li, Maria B Grant
Angiotensin-converting enzyme (ACE)-2 is the primary enzyme of the vasoprotective axis of the renin angiotensin system that regulates the classic renin angiotensin system axis. We aimed to determine whether local retinal overexpression of adenoassociated virus (AAV)-ACE2 prevents or reverses diabetic retinopathy. Green fluorescent protein (GFP)-chimeric mice were generated to distinguish resident (retinal) from infiltrating bone marrow-derived inflammatory cells and were made diabetic using streptozotocin injections...
June 2016: American Journal of Pathology
Margarida Capitão, Raquel Soares
Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes and one of the most frequent causes of blindness in active age. Etiopathogenesis behind this important complication is related to several biochemical, hemodynamic and endocrine mechanisms with a preponderant initial role assumed by polyol pathways, increment of growth factors, accumulation of advanced glycation end products (AGE), activation of protein kinase C (PKC), activation of the renin-angiotensin-aldosterone system (RAAS), and leukostasis...
November 2016: Journal of Cellular Biochemistry
A O Luk, X Li, Y Zhang, X Guo, W Jia, W Li, J Weng, W Yang, W B Chan, R Ozaki, C C Tsang, M Mukhopadhyay, A K Ojha, E G Hong, K H Yoon, L Sobrepena, R M Toledo, M Duran, W Sheu, T Q Do, T K Nguyen, R C Ma, A P Kong, C C Chow, P C Tong, W Y So, J C Chan
AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled...
September 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Ivan Kos, Ingrid Prkačin
Diabetic nephropathy is the leading cause of end-stage chronic kidney disease in most developed countries. Hyperglycemia, hypertension and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Clinical picture includes a progressive increase in albuminuria, decline in glomerular filtration, hypertension, and a high risk of cardiovascular morbidity and mortality...
December 2014: Acta Medica Croatica: C̆asopis Hravatske Akademije Medicinskih Znanosti
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
Rafael Simó, Stefania Ballarini, José Cunha-Vaz, Linong Ji, Hermann Haller, Paul Zimmet, Tien Y Wong
The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising...
2015: Current Medicinal Chemistry
Uma Rai, Thilini R Thrimawithana, Celine Valery, Simon A Young
Somatostatin is an endogeneous cyclic tetradecapeptide hormone that exerts multiple biological activities via five ubiquitously distributed receptor subtypes. Classified as a broad inhibitory neuropeptide, somatostatin has anti-secretory, anti-proliferative and anti-angiogenic effects. The clinical use of native somatostatin is limited by a very short half-life (1 to 3min) and the broad spectrum of biological responses. Thus stable, receptor-selective agonists have been developed. The majority of these somatostatin therapeutic agonists bind strongly to two of the five receptor subtypes, although recently an agonist of wider affinity has been introduced...
August 2015: Pharmacology & Therapeutics
Justin C Sherwin, Jan Kokavec, Simon N Thornton
Variation in systemic hydration status, namely chronic systemic hypohydration or dehydration, can influence the development of several chronic non-ophthalmic diseases. Owing to the eye's high water content and unique system of fluid regulation, we hypothesized that hydration status may affect the eye in health and disease states. Therefore, we performed a systematic review of the current evidence implicating changes in hydration and their association with ocular physiology and morphological characteristics...
November 2015: Clinical & Experimental Ophthalmology
Mauro Rigato, Cristina Bittante, Mattia Albiero, Angelo Avogaro, Gian Paolo Fadini
CONTEXT: Diabetes reduces the levels of circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs), which promote vascular repair and are inversely correlated with cardiovascular risk. OBJECTIVE: The objective of the study was to test whether CPC/EPC levels predict onset/progression of microangiopathy in a cohort of type 2 diabetic (T2D) patients. DESIGN: This was a pseudoprospective study with a 3.9-year follow-up. SETTING: The study was conducted at a tertial referral diabetes outpatient clinic...
July 2015: Journal of Clinical Endocrinology and Metabolism
Rashidul Haque, Elizabeth H Hur, Annie N Farrell, P Michael Iuvone, Jennifer C Howell
PURPOSE: The (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), plays an important role in the physiologic and pathophysiological regulation of blood pressure and fluid/electrolyte homeostasis. The RAS including the PRR has been identified in retinal endothelial cells and other ocular tissues. In this study, the potential involvement of miRNAs in the posttranscriptional regulation of PRR was investigated in human retinal endothelial cells (hRECs) under high glucose (HG) conditions...
2015: Molecular Vision
Bin Wang, Fang Wang, Yue Zhang, Shi-Hua Zhao, Wen-Juan Zhao, Sheng-Li Yan, Yan-Gang Wang
BACKGROUND: Results of several studies have shown a possible beneficial effect of renin-angiotensin system (RAS) inhibitors on diabetic retinopathy, but the findings were contradictory. We did a systematic review and meta-analysis to assess the effect of RAS inhibitors on diabetic retinopathy. METHODS: We identified relevant publications in PubMed, Embase, Cochrane Library Central Register of Controlled Trials, and abstracts from main annual meetings. Only randomised controlled trials comparing angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) monotherapy with other antihypertensive drugs or placebo in type 1 or type 2 diabetes were eligible for inclusion in the analysis...
April 2015: Lancet Diabetes & Endocrinology
Thomas T van Sloten, Coen D A Stehouwer
No abstract text is available yet for this article.
April 2015: Lancet Diabetes & Endocrinology
Zohreh Rahimi, Mahmoudreza Moradi, Hamid Nasri
BACKGROUND: The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM) and its complications of retinopathy, neuropathy and cardiovascular disease (CVD). MATERIALS AND METHODS: The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM), T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014...
November 2014: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
Pugazhenthan Thangaraju, Amitava Chakrabarti, Dibyajyoti Banerjee, Debasish Hota, Tamilselvan, Alka Bhatia, Amod Gupta
BACKGROUND: Diabetes mellitus is a real pandemic of the modern world and the incidence of the disease is increasing at a tremendous rate with a number of complications involving major systems of the human body. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy and retinopathy. AIM: The study was designed to evaluate and compare effects of ramipril (angiotensin-converting enzyme inhibitor-ACEI) and telmisartan (angiotensin II receptor blocker - ARBs) combinations on the progression of retinopathy and nephropathy in the streptozotocin (STZ) induced diabetic model...
December 2014: North American Journal of Medical Sciences
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