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      Vitreous Antioxidants, Degeneration, and Vitreo-Retinopathy: Exploring the Links

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          Abstract

          The transparent vitreous body, which occupies about 80% of the eye’s volume, is laden with numerous enzymatic and non-enzymatic antioxidants that could protect the eye from oxidative stress and disease. Aging is associated with degeneration of vitreous structure as well as a reduction in its antioxidant capacity. A growing body of evidence suggests these age-related changes may be the precursor of numerous oxidative stress-induced vitreo-retinopathies, including vision degrading myodesopsia, the clinically significant entoptic phenomena that can result from advanced vitreous degeneration. Adequate intravitreal antioxidant levels may be protective against vitreous degeneration, possibly preventing and even improving vision degrading myodesopsia as well as mitigating various other vitreo-retinopathies. The present article is, therefore, a review of the different antioxidant molecules within vitreous and the inter-relationships between vitreous antioxidant capacity and degeneration.

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          Alpha-crystallin can function as a molecular chaperone.

          J. Horwitz (1992)
          The alpha-crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders and in cell lines under stress conditions. Here I show that alpha-crystallin can function as a molecular chaperone. Stoichiometric amounts of alpha A and alpha B suppress thermally induced aggregation of various enzymes. In particular, alpha-crystallin is very efficient in suppressing the thermally induced aggregation of beta- and gamma-crystallins, the two other major mammalian structural lens proteins. alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-crystallin, as judged by circular dichroism spectroscopy. My results thus indicate that alpha-crystallin refracts light and protects proteins from aggregation in the transparent eye lens and that in nonlens cells alpha-crystallin may have other functions in addition to its capacity to suppress aggregation of proteins.
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            Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective.

            D Venkat Ratnam, D D Ankola, V Bhardwaj … (2006)
            Antioxidants are emerging as prophylactic and therapeutic agents. These are the agents, which scavenge free radicals otherwise reactive oxygen species and prevent the damage caused by them. Free radicals have been associated with pathogenesis of various disorders like cancer, diabetes, cardiovascular diseases, autoimmune diseases, neurodegenerative disorders and are implicated in aging. Several antioxidants like SOD, CAT, epigallocatechin-3-O-gallate, lycopene, ellagic acid, coenzyme Q10, indole-3-carbinol, genistein, quercetin, vitamin C and vitamin E have been found to be pharmacologically active as prophylactic and therapeutic agents for above mentioned diseases. Antioxidants are part of diet but their bioavailability through dietary supplementation depends on several factors. This major drawback of dietary agents may be due to one or many of the several factors like poor solubility, inefficient permeability, instability due to storage of food, first pass effect and GI degradation. Conventional dosage forms may not result in efficient formulation owing to their poor biopharmaceutical properties. Principles of novel drug delivery systems need to be applied to significantly improve the performance of antioxidants. Novel drug delivery systems (NDDS) would also help in delivery of these antioxidants by oral route, as this route is of prime importance when antioxidants are intended for prophylactic purpose. Implication of NDDS for the delivery of antioxidants is largely governed by physicochemical characteristics, biopharmaceutical properties and pharmacokinetic parameters of the antioxidant to be formulated. Recently, chemical modifications, coupling agents, liposomes, microparticles, nanoparticles and gel-based systems have been explored for the delivery of these difficult to deliver molecules. Results from several studies conducted across the globe are positive and provided us with new anticipation for the improvement of human healthcare.
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              Structural macromolecules and supramolecular organisation of the vitreous gel.

              Paul Bishop (2000)
              The vitreous gel is a transparent extracellular matrix that fills the cavity behind the lens of the eye and is surrounded by and attached to the retina. This gel liquefies during ageing and in 25-30% of the oppulation the residual gel structure eventually collapses away from the posterior retina in a process called posterior retina in a process called posterior vitreous detachment. This process plays a pivotal role in a number of common blinding conditions including rhegmatogenous retinal detachment, proliferative diabetic retinopathy and macular hole formation. In order to understand the molecular events underlying vitreous liquefaction and posterior vitreous detachment and to develop new therapies it is important to understand the molecular basis of normal vitreous gel structure and how this is altered during ageing. It has previously been established that a dilute dispersion of thin (heterotypic) collagen fibrils is essential to the gel structure and that age-related vitreous liquefaction is intimately related to a process whereby these collagen fibrils aggregate. Collagen fibrils have a natural tendency to aggregate so a key question that has to be addressed is: what normally maintains the spacing of the collagen fibrils? In mammalian vitreous a network of hyaluronan normally fills the spaces between these collagen fibrils. This hyaluronan network can be removed without destroying the gel structure, so the hyaluronan is not essential for maintaining the spacing of the collagen fibrils although it probably does increase the mechanical resilience of the gel. The thin heterotypic collagen fibrils have a coating of non-covalently bound macromolecules which, along with the surface features of the collagen fibrils themselves, probably play a fundamental role in maintaining gel stability. They are likely to both maintain the short-range spacing of vitreous collagen fibrils and to link the fibrils together to form a contiguous network. A collagen fibril-associated macromolecule that may contribute to the maintenance of short-range spacing is opticin, a newly discovered extracellular matrix leucine-rich repeat protein. In addition, surface features of the collagen fibrils such as the chondroitin sulphate glycosaminoglycan chains of type IX collagen proteoglycan may also play an important role in maintaining fibril spacing. Furthering our knowledge of these and other components related to the surface of the heterotypic collagen fibrils will allow us to make important strides in understanding the macromolecular organisation of this unique and fascinating tissue. In addition, it will open up new therapeutic opportunities as it will allow the development of therapeutic reagents that can be used to modulate vitreous gel structure and thus treat a number of common, potentially blinding, ocular conditions.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Antioxidants (Basel)
                Journal ID (iso-abbrev): Antioxidants (Basel)
                Journal ID (publisher-id): antioxidants
                Title: Antioxidants
                Publisher: MDPI
                ISSN (Electronic): 2076-3921
                Publication date (Electronic): 20 December 2019
                Publication date Collection: January 2020
                Volume: 9
                Issue: 1
                Electronic Location Identifier: 7
                Affiliations
                [1 ]Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Co., X91 K236 Waterford, Ireland; eugene@ 123456ioes.ie
                [2 ]Institute of Eye Surgery, UPMC Whitfield, Buttlerstown, Co., X91 DH9W Waterford, Ireland
                [3 ]VMR Consulting Inc., Huntington Beach, CA 92647, USA; JSebag@ 123456vmrinstitute.com
                Author notes
                Author information
                https://orcid.org/0000-0001-7454-4447
                Article
                Publisher ID: antioxidants-09-00007
                DOI: 10.3390/antiox9010007
                PMC ID: 7022282
                PubMed ID: 31861871
                SO-VID: fb863b0e-9cad-4ddb-8cdc-252975daf573
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 26 November 2019
                Date accepted : 16 December 2019
                Categories
                Subject: Review

                Keywords: antioxidants,vitreous,oxidative stress,vitreous degeneration,floaters,vision degrading myodesopsia
                Data availability:
                Keywords: antioxidants, vitreous, oxidative stress, vitreous degeneration, floaters, vision degrading myodesopsia

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