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      Current and Future Techniques in Wound Healing Modulation after Glaucoma Filtering Surgeries

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          Abstract

          Filtering surgeries are frequently used for controlling intraocular pressure in glaucoma patients. The long-term success of operation is intimately influenced by the process of wound healing at the site of surgery. Indeed, if has not been anticipated and managed accordingly, filtering surgery in high-risk patients could end up in bleb failure. Several strategies have been developed so far to overcome excessive scarring after filtering surgery. The principal step involves meticulous tissue handling and modification of surgical technique, which can minimize the severity of wound healing response at the first place. However, this is usually insufficient, especially in those with high-risk criteria. Thus, several adjuvants have been tried to stifle the exuberant scarring after filtration surgery. Conventionally, corticosteroids and anti-fibrotic agents (including 5-fluorouracil and Mitomycin-C) have been used for over three decades with semi-acceptable outcomes. Blebs and bleb associated complications are catastrophic side effects of anti-fibrotic agents, which occasionally are encountered in a subset of patients. Therefore, research continues to find a safer, yet effective adjuvant for filtering surgery. Recent efforts have primarily focused on selective inhibition of growth factors that promote scarring during wound healing process. Currently, only anti-VEGF agents have gained widespread acceptance to be translated into routine clinical practice. Robust evidence for other agents is still lacking and future confirmative studies are warranted. In this review, we explain the importance of wound healing process during filtering surgery, and describe the conventional as well as potential future adjuvants for filtration surgeries.

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          The role of vascular endothelial growth factor in wound healing.

          A chronic wound is tissue with an impaired ability to heal. This is often a consequence of one of the following etiologies: diabetes, venous reflux, arterial insufficiency sickle cell disease, steroids, and/or pressure. Healing requires granulation tissue depending on epithelialization and angiogenesis. Currently no growth factor is available to treat patients with impaired healing that stimulates both epithelialization and angiogenesis. The objective is to review is the multiple mechanisms of vascular endothelial growth factor (VEGF) in wound healing. The authors reviewed the literature on the structure and function of VEGF, including its use for therapeutic angiogenesis. Particular attention is given to the specific role of VEGF in the angiogenesis cascade, its relationship to other growth factors and cells in a healing wound. VEGF is released by a variety of cells and stimulates multiple components of the angiogenic cascade. It is up-regulated during the early days of healing, when capillary growth is maximal. Studies have shown the efficacy of VEGF in peripheral and cardiac ischemic vascular disease with minimal adverse effects. Experimental data supports the hypothesis that VEGF stimulates epithelialization and collagen deposition in a wound. VEGF stimulates wound healing through angiogenesis, but likely promotes collagen deposition and epithelialization as well. Further study of the molecule by utilizing the protein itself, or novel forms of delivery such as gene therapy, will increase its therapeutic possibilities to accelerate closure of a chronic wound.
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            A three-dimensional view of the molecular machinery of RNA interference.

            In eukaryotes, small non-coding RNAs regulate gene expression, helping to control cellular metabolism, growth and differentiation, to maintain genome integrity, and to combat viruses and mobile genetic elements. These pathways involve two specialized ribonucleases that control the production and function of small regulatory RNAs. The enzyme Dicer cleaves double-stranded RNA precursors, generating short interfering RNAs and microRNAs in the cytoplasm. These small RNAs are transferred to Argonaute proteins, which guide the sequence-specific silencing of messenger RNAs that contain complementary sequences by either enzymatically cleaving the mRNA or repressing its translation. The molecular structures of Dicer and the Argonaute proteins, free and bound to small RNAs, have offered exciting insights into the molecular mechanisms that are central to RNA silencing pathways.
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              Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1.

              The therapeutic potential of placental growth factor (PlGF) and its receptor Flt1 in angiogenesis is poorly understood. Here, we report that PlGF stimulated angiogenesis and collateral growth in ischemic heart and limb with at least a comparable efficiency to vascular endothelial growth factor (VEGF). An antibody against Flt1 suppressed neovascularization in tumors and ischemic retina, and angiogenesis and inflammatory joint destruction in autoimmune arthritis. Anti-Flt1 also reduced atherosclerotic plaque growth and vulnerability, but the atheroprotective effect was not attributable to reduced plaque neovascularization. Inhibition of VEGF receptor Flk1 did not affect arthritis or atherosclerosis, indicating that inhibition of Flk1-driven angiogenesis alone was not sufficient to halt disease progression. The anti-inflammatory effects of anti-Flt1 were attributable to reduced mobilization of bone marrow-derived myeloid progenitors into the peripheral blood; impaired infiltration of Flt1-expressing leukocytes in inflamed tissues; and defective activation of myeloid cells. Thus, PlGF and Flt1 constitute potential candidates for therapeutic modulation of angiogenesis and inflammation.
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                Author and article information

                Journal
                Open Ophthalmol J
                Open Ophthalmol J
                TOOPHTJ
                The Open Ophthalmology Journal
                Bentham Open
                1874-3641
                29 February 2016
                2016
                : 10
                : 68-85
                Affiliations
                [1 ]Poostchi Eye Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
                [2 ]Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, USA
                Author notes
                [* ]Address correspondence to this author at the Poostchi Eye Research Center, Poostchi Clinic, Zand Street, Shiraz 7134997446, Iran; Tel: +98-71-32302830; Fax: +98-71-32355936; Email: masoumpour@ 123456yahoo.com
                Article
                TOOPHTJ-10-68
                10.2174/1874364101610010068
                4780518
                27014389
                78711978-bc11-4a89-b51c-22d4aaa43d63
                © Masoumpour et al.; Licensee Bentham Open.

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 26 July 2015
                : 18 August 2015
                : 18 August 2015
                Categories
                Article
                Suppl 1: M5

                Ophthalmology & Optometry
                anti-fibrotics,filtering surgery,glaucoma,trabeculectomy,wound healing
                Ophthalmology & Optometry
                anti-fibrotics, filtering surgery, glaucoma, trabeculectomy, wound healing

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