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      Ultrastructural Analysis of the Anterior Lens Epithelium in Cataracts Associated with Uveitis

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          Abstract

          Purpose: To investigate the transmission electron microscopic findings of lens epithelial cells (LECs) in patients with different subtypes of uveitis and to compare the findings with those in age-matched controls. Methods: In this prospective case-control study, the anterior lens capsules were taken from 47 eyes of 47 patients with uveitis of different subtypes (17 with Fuchs uveitis syndrome [FUS], 13 with ­Behçet’s uveitis, 10 with idiopathic uveitis, and 7 with herpetic keratouveitis) and from 15 eyes of 15 control patients. Results: In the FUS group, the LECs had homogeneous thickening and irregularity, with some small vacuoles and widespread, oval-shaped pigment clusters in some areas. In the Behçet uveitis group, there was evident thinning in the lens epithelium. The subepithelial tissue under the epithelium was thickened, and edematous areas were detected. In the idiopathic uveitis group, the LECs were thinner with small vacuoles, and the cubic structure of the LECs was transformed into a squamous one. Moreover, the LECs included some small vacuoles, similar to those in the FUS group. In the herpetic keratouveitis group, two prominent cell types were observed: (1) completely normal LECs and (2) degenerated-type LECs with pyknotic nuclei, condensation of chromatin, swelling in the cytoplasm, membrane ruptures, and intra­cytoplasmic inclusion bodies. In the control group, the LECs and all of their elements occurred in normal ultrastructural patterns, with the exception of a few small intraepithelial vacuoles, which were fewer in number and smaller than those in the FUS and idiopathic uveitis groups. Conclusion: The electron microscopic analysis of LECs of patients with different subtypes of uveitis revealed significant ultrastructural alterations, which may be related to the summation of oxidative stress and intraocular inflammation.

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          Most cited references43

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          Age-related nuclear cataract-oxidation is the key.

          Age is by far the biggest risk factor for cataract, and it is sometimes assumed that cataract is simply an amplification of this aging process. This appears not to be the case, since the lens changes associated with aging and cataract are distinct. Oxidation is the hallmark of age-related nuclear (ARN) cataract. Loss of protein sulfhydryl groups, and the oxidation of methionine residues, are progressive and increase as the cataract worsens until >90% of cysteine and half the methionine residues are oxidised in the most advanced form. By contrast, there may be no significant oxidation of proteins in the centre of the lens with advancing age, even past age 80. The key factor in preventing oxidation seems to be the concentration of nuclear glutathione (GSH). Provided that nuclear GSH levels can be maintained above 2 mm, it appears that significant protein oxidation and posttranslational modification by reactive small molecules, such as ascorbate or UV filter degradation products, is not observed. Adequate coupling of the metabolically-active cortex, the source of antioxidants such as GSH, to the quiescent nucleus, is crucial especially since it would appear that the cortex remains viable in old lenses, and even possibly in ARN cataract lenses. Therefore it is vital to understand the reason for the onset of the lens barrier. This barrier, which becomes apparent in middle age, acts to impede the flow of small molecules between the cortex and the nucleus. The barrier, rather than nuclear compaction (which is not observed in human lenses), may contribute to the lowered concentration of GSH in the lens nucleus after middle age. By extending the residence time within the lens centre, the barrier also facilitates the decomposition of intrinsically unstable metabolites and may exacerbate the formation of H(2)O(2) in the nucleus. This hypothesis, which is based on the generation of reactive oxygen species and reactive molecules within the nucleus itself, shifts the focus away from theories for cataract that postulated a primary role for oxidants generated outside of the lens. Unfortunately, due to marked variability in the lenses of different species, there appears at present to be no ideal animal model system for studying human ARN cataract.
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            Oxidative stress-induced cataract: mechanism of action.

            This review examines the hypothesis that oxidative stress is an initiating factor for the development of maturity onset cataract and describes the events leading to lens opacification. Data are reviewed that indicate that extensive oxidation of lens protein and lipid is associated with human cataract found in older individuals whereas little oxidation (and only in membrane components) is found in control subjects of similar age. A significant proportion of lenses and aqueous humor taken from cataract patients have elevated H2O2 levels. Because H2O2, at concentrations found in cataract, can cause lens opacification and produces a pattern of oxidation similar to that found in cataract, it is concluded that H2O2 is the major oxidant involved in cataract formation. This viewpoint is further supported by experiments showing that cataract formation in organ culture caused by photochemically generated superoxide radical, H2O2, and hydroxyl radical is completely prevented by the addition of a GSH peroxidase mimic. The damage caused by oxidative stress does not appear to be reversible and there is an inverse relationship between the stress period and the time required for loss of transparency and degeneration of biochemical parameters such as ATP, GPD, nonprotein thiol, and hydration. After exposure to oxidative stress, the redox set point of the single layer of the lens epithelial cells (but not the remainder of the lens) quickly changes, going from a strongly reducing to an oxidizing environment. Almost concurrent with this change is extensive damage to DNA and membrane pump systems, followed by loss of epithelial cell viability and death by necrotic and apoptotic mechanisms. The data suggest that the epithelial cell layer is the initial site of attack by oxidative stress and that involvement of the lens fibers follows, leading to cortical cataract.
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              The lens capsule.

              The lens capsule is a modified basement membrane that completely surrounds the ocular lens. It is known that this extracellular matrix is important for both the structure and biomechanics of the lens in addition to providing informational cues to maintain lens cell phenotype. This review covers the development and structure of the lens capsule, lens diseases associated with mutations in extracellular matrix genes and the role of the capsule in lens function including those proposed for visual accommodation, selective permeability to infectious agents, and cell signaling.
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2020
                March 2020
                13 December 2019
                : 63
                : 2
                : 213-221
                Affiliations
                [_a] aOphthalmology Department, Ercis State Hospital, Van, Turkey
                [_b] bOphthalmology Department, Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
                [_c] cDepartment of Anatomy, Hacettepe University, Ankara, Turkey
                Author notes
                *Kemal Tekin, MD, Ophthalmology Department, Ercis State Hospital, Kisla Street 7, Ercis, TR–65400 Van (Turkey), E-Mail kemal_htepe@hotmail.com
                Article
                504497 Ophthalmic Res 2020;63:213–221
                10.1159/000504497
                31838467
                2b414bcd-fd27-4bb5-98c6-8685d575725e
                © 2019 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.

                History
                : 21 August 2019
                : 31 October 2019
                Page count
                Figures: 5, Tables: 2, Pages: 9
                Categories
                Research Article

                Vision sciences,Ophthalmology & Optometry,Pathology
                Cataract,Electron microscopy,Lens epithelium,Ultrastructure,Uveitis

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