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      Wound Healing Modulation in Glaucoma Filtration Surgery– Conventional Practices and New Perspectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II)

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          ABSTRACT

          Glaucoma filtration surgery is regularly performed for the treatment of glaucoma and trabeculectomy is often regarded as the ‘gold standard' glaucoma operation. The biggest risk of failure of the operation is bleb scarring. The advent of antifibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5FU) has vastly prolonged the longevity of the bleb, but concerns remain regarding the potential increase in postoperative complications. More selective therapeutic targets have therefore been explored. One of these is vascular endothelial growth factor (VEGF) inhibition. VEGF inhibition has a role not only in subconjunctival angiogenesis inhibition but also it has direct anti-fibrotic properties. Newer pharmacological compounds and materials have also been developed in recent years in attempt to modulate the wound healing in different ways after glaucoma surgery. These include physical barriers to scarring and vehicles for sustained release of pharmacological agents, and early promising results have been demonstrated. This two-part review will provide a discussion of the application of anti-fibrotic agents in glaucoma filtration surgery and evaluate the newer agents that have been developed.

          How to cite this article: Fan Gaskin JC, Nguyen DQ, Ang GS, O'Connor J, Crowston JG. Wound Healing Modulation in Glau coma Filtration Surgery–Conventional Practices and New Pers pectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II). J Curr Glaucoma Pract 2014;8(2):46-53.

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          Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1alpha, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.
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            The gap junction communication channel.

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              Connexins, connexons, and intercellular communication.

              Cells in tissues share ions, second messengers, and small metabolites through clusters of intercellular channels called gap junctions. This type of intercellular communication permits coordinated cellular activity. Intercellular channels are formed from two oligomeric integral membrane protein assemblies, called connexons, which span two adjacent cells' plasma membranes and join in a narrow, extracellular "gap." Connexons are formed from connexins, a highly related multigene family consisting of at least 13 members. Since the cloning of the first connexin in 1986, considerable progress has been made in our understanding of the complex molecular switches that control the formation and permeability of the intercellular channels. Analysis of the mechanisms of channel assembly has revealed the selectivity of inter-connexin interactions and uncovered novel characteristics of the channel permeability and gating behavior. Structure-function studies provide a molecular understanding of the significance of connexin diversity and demonstrate the unique regulation of connexins by tyrosine kinases and oncogenes.
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                Author and article information

                Contributors
                Journal
                J Curr Glaucoma Pract
                J Curr Glaucoma Pract
                JOCGP
                Journal of Current Glaucoma Practice
                Jaypee Brothers Medical Publishers
                0974-0333
                0975-1947
                May-Aug 2014
                12 June 2014
                : 8
                : 2
                : 46-53
                Affiliations
                Glaucoma Fellow, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Australia
                Consultant, Department of Ophthalmology, Mid Cheshire Hospitals, NHS Foundation Trust, Cheshire; Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire, UK
                Consultant, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Australia
                Consultant, Glaucoma Investigation and Research Unit, University Hospital Limerick, Ireland
                Professor, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Australia
                Author notes
                Jennifer C Fan Gaskin, Glaucoma Fellow, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Victoria, Australia Phone: 0061406494994, e-mail: drjfan@gmail.com
                Article
                10.5005/jp-journals-10008-1160
                4741169
                26997808
                968e4e1e-2b76-469a-9c60-7ed4a852c26b
                Copyright © 2014; Jaypee Brothers Medical Publishers (P) Ltd.

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

                History
                : 03 October 2013
                : 02 December 2013
                Categories
                Review Article

                glaucoma,wound healing modulation,filtration surgery.

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