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      Diabetic macular edema: new concepts in patho-physiology and treatment

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          Abstract

          Diabetic macular edema (DME), a serious eye complication caused primarily by hyperglycemia, is one of the major causes of blindness. DME, which is characterized by cystic retinal thickening or lipid deposition, is prone to relapse after successful treatment. DME is a complex pathological process caused by multiple factors, including breakdown of the inner and outer blood-retinal barriers, oxidative stress, and elevated levels of vascular endothelial growth factor which have been demonstrated in both preclinical and clinical studies. Starling’s law theory explains many of the features of DME. Early detection and treatment of DME can prevent vision loss. Current effective interventions for DME include treatment of systemic risk factors, such as elevated blood glucose, blood pressure and dyslipidemia. Ophthalmic treatments include laser photocoagulation, surgery and intraocular pharmacotherapy. New drugs, which are given by intraocular injection, have emerged in recent years to become first line treatment for DME that affects the central macula with loss of vision. Laser photocoagulation is still the gold standard of treatment for DME which does not involve the central macular. This review outlines these new treatments with particular emphasis on the optimal timing of how they are given.

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          The biology of vascular endothelial growth factor.

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            Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group.

            (1985)
            Data from the Early Treatment Diabetic Retinopathy Study (ETDRS) show that focal photocoagulation of "clinically significant" diabetic macular edema substantially reduces the risk of visual loss. Focal treatment also increases the chance of visual improvement, decreases the frequency of persistent macular edema, and causes only minor visual field losses. In this randomized clinical trial, which was supported by the National Eye Institute, 754 eyes that had macular edema and mild to moderate diabetic retinopathy were randomly assigned to focal argon laser photocoagulation, while 1,490 such eyes were randomly assigned to deferral of photocoagulation. The beneficial effects of treatment demonstrated in this trial suggest that all eyes with clinically significant diabetic macular edema should be considered for focal photocoagulation. Clinically significant macular edema is defined as retinal thickening that involves or threatens the center of the macula (even if visual acuity is not yet reduced) and is assessed by stereo contact lens biomicroscopy or stereo photography. Follow-up of all ETDRS patients continues without other modifications in the study protocol.
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              Complex phenotype of mice lacking occludin, a component of tight junction strands.

              Occludin is an integral membrane protein with four transmembrane domains that is exclusively localized at tight junction (TJ) strands. Here, we describe the generation and analysis of mice carrying a null mutation in the occludin gene. Occludin -/- mice were born with no gross phenotype in the expected Mendelian ratios, but they showed significant postnatal growth retardation. Occludin -/- males produced no litters with wild-type females, whereas occludin -/- females produced litters normally when mated with wild-type males but did not suckle them. In occludin -/- mice, TJs themselves did not appear to be affected morphologically, and the barrier function of intestinal epithelium was normal as far as examined electrophysiologically. However, histological abnormalities were found in several tissues, i.e., chronic inflammation and hyperplasia of the gastric epithelium, calcification in the brain, testicular atrophy, loss of cytoplasmic granules in striated duct cells of the salivary gland, and thinning of the compact bone. These phenotypes suggested that the functions of TJs as well as occludin are more complex than previously supposed.
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                Author and article information

                Contributors
                Journal
                Cell Biosci
                Cell Biosci
                Cell & Bioscience
                BioMed Central
                2045-3701
                2014
                14 May 2014
                : 4
                : 27
                Affiliations
                [1 ]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Lab, Beijing 100730 PR China
                [2 ]Macula Research Group, Save Sight Institute, The University of Sydney, Sydney, NSW, Australia
                [3 ]Discipline of Pathology, School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia
                Article
                2045-3701-4-27
                10.1186/2045-3701-4-27
                4046142
                24955234
                153573e5-f274-4114-a944-e5d9d113af54
                Copyright © 2014 Zhang et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 January 2014
                : 22 April 2014
                Categories
                Review

                Cell biology
                diabetic retinopathy,microvasculopathy,neuronal degenerative diseases,therapeutic strategy,apoptosis

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