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      Neuroprotective agents in the management of glaucoma

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          Abstract

          Glaucoma is an optic neuropathy, specifically a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs) and their axons. The pathogenesis of RGC loss in glaucoma remains incompletely understood and a broad range of possible mechanisms have been implicated. Clinical evidence indicates that lowering intraocular pressure (IOP) does not prevent progression in all patients; therefore, risk factors other than those related to IOP are involved in the disease. The need for alternative, non-IOP-lowering treatments focused at preventing progression, that is, neuroprotectants, has become of interest to both the patient and the physician. Experimental evidence accumulated during the past two decades lend a great deal of support to molecules endowed with neuroprotective features. However, translation to the clinic of the latter drugs results unsuccessful mostly because of the lack of reliable in vivo measure of retinal damage, thus hampering the good therapeutic potential of neuroprotective agents given alone or as adjuvant therapy to IOP-lowering agents. Further research effort is needed to better understand the mechanisms involved in glaucoma and the means to translate into clinic neuroprotective drugs.

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          Most cited references67

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          Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex.

          The pathology of glaucoma has been extensively studied at the level of the retina and optic nerve head. Here the first clinicopathological case of human glaucoma is reported demonstrating degenerative changes in the brain involving the intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Pathological evidence of neural degeneration in this patient is correlated with clinical, optic nerve head, visual field, and neuroradiology findings. Neuropathology in the glaucoma brain is compared to age matched controls. In the presence of advanced human glaucoma with 50% visual field loss, neural damage is evident in multiple vision stations within the brain.
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            Phosphatidylcholine and the CDP-choline cycle.

            The CDP-choline pathway of phosphatidylcholine (PtdCho) biosynthesis was first described more than 50 years ago. Investigation of the CDP-choline pathway in yeast provides a basis for understanding the CDP-choline pathway in mammals. PtdCho is considered as an intermediate in a cycle of synthesis and degradation, and the activity of a CDP-choline cycle is linked to subcellular membrane lipid movement. The components of the mammalian CDP-choline pathway include choline transport, choline kinase, phosphocholine cytidylyltransferase, and choline phosphotransferase activities. The protein isoforms and biochemical mechanisms of regulation of the pathway enzymes are related to their cell- and tissue-specific functions. Regulated PtdCho turnover mediated by phospholipases or neuropathy target esterase participates in the mammalian CDP-choline cycle. Knockout mouse models define the biological functions of the CDP-choline cycle in mammalian cells and tissues. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. Copyright © 2012 Elsevier B.V. All rights reserved.
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              Coenzyme Q10 inhibits glutamate excitotoxicity and oxidative stress-mediated mitochondrial alteration in a mouse model of glaucoma.

              To test whether a diet supplemented with coenzyme Q10 (CoQ10) ameliorates glutamate excitotoxicity and oxidative stress-mediated retinal ganglion cell (RGC) degeneration by preventing mitochondrial alterations in the retina of glaucomatous DBA/2J mice.
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                Author and article information

                Contributors
                nucci@med.uniroma2.it
                Journal
                Eye (Lond)
                Eye (Lond)
                Eye
                Nature Publishing Group UK (London )
                0950-222X
                1476-5454
                23 February 2018
                23 February 2018
                May 2018
                : 32
                : 5
                : 938-945
                Affiliations
                [1 ]ISNI 0000 0001 2300 0941, GRID grid.6530.0, Ophthalmology Unit, Department of Experimental Medicine and Surgery, , University of Rome Tor Vergata, ; Rome, Italy
                [2 ]ISNI 0000 0004 1937 0319, GRID grid.7778.f, Department of Pharmacy, Health and Nutritional Sciences, , University of Calabria, ; Rende, Italy
                Author information
                http://orcid.org/0000-0002-3725-8211
                http://orcid.org/0000-0001-8540-6218
                Article
                50
                10.1038/s41433-018-0050-2
                5944652
                29472700
                7560186e-4d10-4745-ae15-0460c48e0416
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 November 2017
                : 22 January 2018
                : 25 January 2018
                Categories
                Review Article
                Custom metadata
                © The Royal College of Ophthalmologists 2018

                Vision sciences
                Vision sciences

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