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      Decreased Vitreal Hyaluronan Levels with Aging

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          Abstract

          Purpose: To investigate age-related changes in hyaluronan levels in human eyes before and after vitrectomy surgery, we measured the hyaluronan levels in the vitreous samples obtained during vitrectomy and postoperative fluid-air exchange. Methods: We obtained the vitreous during vitrectomy from 26 eyes of 26 patients with macular hole (MH) and 52 eyes of 52 patients with diabetic retinopathy (DR). After vitrectomy, we collected fluid samples during fluid-air exchange from 6 eyes with MH and 9 eyes with DR. The hyaluronan level was measured by the sandwich binding protein assay. Results: In the vitreous of the 54 eyes (26 eyes with MH and 28 eyes with DR and no vitreous hemorrhage), hyaluronan levels significantly decreased with patient age (r = –0.66, p < 0.00000005). Hyaluronan levels in postoperative vitreous fluid were significantly lower in 6 eyes with MH (p < 0.05) and 9 eyes with DR (p < 0.01) than those obtained during vitrectomy. Conclusions: There was a significant decrease in vitreous hyaluronan with aging. High-molecular-weight hyaluronan appears not to be formed in vitreous fluid after vitrectomy.

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          Most cited references 9

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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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            Evidence for structural changes in dermatan sulfate and hyaluronic acid with aging.

            Three dermatan sulfates (DS18, DS28, and DS35) were isolated from women's skin of ages 19 +/- 2.5, 35 +/- 3.5, 47 +/- 1.7, 60 +/- 0.8, and 75 +/- 5 years. They sequentially precipitated with 18, 28, and 35% ethanol. Their sulfate content was: 23.5, 25.3, and 29.0% (w/w) for DS18 at ages 19-35, 47, and 60 years, respectively; 29.0, 24.0, and 18.8% for DS28; and 18.0, 20.0, and 20.6% for DS35 at ages 19-47, 60, and 75 years, respectively. Both DS18 and DS28 decreased, respectively, from 0.030% (of wet-skin weight) to traces at age 75, and from 0.020 to 0.010% at 60 years. At age 75, DS28 apparently increased by 30%. The DS35 values (traces-0.006%) had no age-related trend. Hyaluronic acid (HA) precipitated with 45% ethanol, was 0.030% of skin-weight at ages 19-47, and decreased to 0.015 and 0.007% at 60 and 75 years, respectively. Its electrophoretic mobility was slower at age 47. In the oldest group, i.r. spectra of HA and DS35 displayed no bands at 1650-1600, 1380, and 1320 cm-1, and a new band at 1560 cm-1. Moreover, ninhydrin-positive material of HA and DS35 increased by 75 and 95%, respectively, and the reducing GlcNAc content of HA decreased. These data showed three chemically different dermatan sulfates (two of which were preponderant) and N-deacetylation of HA and DS35 of the oldest group. After age 47, total DS and HA considerably decreased, DS18 and DS35 were oversulfated, and DS28 became undersulfated with aging.
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              Posterior vitreous detachment

               L Larsson,  S Osterlin (1985)
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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                0030-3755
                1423-0267
                2009
                January 2009
                27 October 2008
                : 223
                : 1
                : 32-35
                Affiliations
                Departments of aOphthalmology and bLaboratory Medicine, Gunma University School of Medicine, Maebashi, Japan
                Article
                165682 Ophthalmologica 2009;223:32–35
                10.1159/000165682
                18953185
                © 2008 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, References: 20, Pages: 4
                Categories
                Original Paper

                Vision sciences, Ophthalmology & Optometry, Pathology

                Vitrectomy, Hyaluronan, Vitreous, aging

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