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      Rheological Properties and Age-Related Changes of the Human Vitreous Humor

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          Abstract

          The vitreous humor is a fragile, transparent hydrogel situated between the lens and the retina, occupying 80% of the eye's volume. Due to its viscoelastic behavior, the vitreous serves as a mechanical damper for the eye, absorbing impacts, and protecting the lens and retina. The vitreous liquefies with age, which compromises its function as a shock absorber and causes complications including retinal detachment, macular holes, and vitreous hemorrhage. Studies on the viscoelastic properties of the vitreous have been limited. Rheological testing of the vitreous has commonly been done on non-primate mammalian species. Human vitreous rheological properties have been previously reported; however, various measurement techniques were used, resulting in data that differed by orders of magnitude. Shear rheometry is commonly used to characterize soft tissues and hydrogels such as the vitreous humor. However, no human vitreous rheological data have been reported using this technique, preventing direct comparison to other published work. Additionally, no age-related changes in the mechanical properties of the human vitreous humor have been reported. Human vitreous samples ( n = 39, aged 62 ± 15 years) were tested using a shear rheometer. Small amplitude oscillatory shear and creep experiments were performed. The linear viscoelastic region of the human vitreous was found to be below 1% strain. The solid phase of the old human vitreous was found to be stiffer than the young human vitreous and the porcine vitreous. The stiffness of the human vitreous gel also appeared to be positively correlated with age. Vitreous dehydration due to a decrease in hyaluronic acid concentration with age was proposed to cause the stiffening of the solid phase of the vitreous gel. Vitreous liquefaction, therefore, might be characterized as a simultaneous increase in liquid volume and localized stiffening of the vitreous gel. The phase separation of the vitreous humor with age has been hypothesized as the cause of many vitreous-related complications. This study provides viscoelastic properties and age-related changes of the human vitreous humor, which will aid in the design of biomimetic vitreous substitutes, enhancement in analyzing intravitreal transport of therapeutics, and understanding the pathological conditions of the vitreous humor.

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          Most cited references27

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          Adult vitreous structure and postnatal changes.

          This review will focus on the molecular organisation of the adult vitreous and how it undergoes ageing changes throughout life that result in vitreous liquefaction and a predisposition towards posterior vitreous detachment and retinal break formation. At birth, the vitreous humour is in a gel state due to the presence of a network of fine collagen fibrils. With ageing, these collagen fibrils progressively aggregate due to a loss of type IX collagen from their surfaces. The aggregation of collagen fibrils may cause vitreous liquefaction which, when combined with an age-related weakening of postbasal vitreoretinal adhesion, predisposes to posterior vitreous detachment. Throughout postnatal life, the posterior border of the vitreous base migrates posteriorly from the ora serrata into the peripheral retina. This is due to new collagen synthesis by the peripheral retina. This new collagen intertwines with pre-existing cortical vitreous collagen to create new adhesions and thereby extends the vitreous base posteriorly. If irregularities in the posterior border of the vitreous base arise from this process, there is a predisposition towards retinal break formation during posterior vitreous detachment and subsequent rhegmatogenous retinal detachment.
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            Age-related liquefaction of the human vitreous body: LM and TEM evaluation of the role of proteoglycans and collagen.

            To evaluate morphologic aspects of age-related liquefaction of the human vitreous body by light and electron microscopy to provide a basis from which future studies directed at the pathogenesis of this phenomenon can be undertaken. The study focuses on changes in fibrillar collagen and proteoglycans (PGs). Morphologic aspects of intravitreal liquefied spaces and matrix areas surrounding them were examined in 13 adult human donor eyes (aged 21-80 years) by light (LM) and transmission electron microscopy (TEM). Collagen fibrils were visualized by using standard contrasting methods. PGs were specifically stained by cupromeronic blue (CB). Eyes from older donors contained larger spaces than eyes from younger ones. Transitions between matrix and spaces were abrupt or gradual. In transition areas of all specimens, a gradual decrease in the number of collagen fibers, and to a lesser extent of PGs was observed. In addition, a fragmentation of collagen fibers and an aggregation of PG-molecules around these fragments were found. Neither cells nor their fragments were observed in these areas. This is the first study to evaluate vitreous liquefaction at the light and electron microscopic level. A breakdown of collagen fibrils into smaller fragments seems to be crucial to the pathogenesis of age-related liquefaction of the human vitreous body. The mechanism inducing fragmentation of vitreous fibrils has yet to be elucidated. From the absence of cells and cellular remnants in all specimens, it is tentatively concluded that an extracellular process is involved.
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              Ageing of the vitreous.

              J. Sebag (1986)
              Changes that occur in the vitreous during ageing contribute to a variety of vitreo-retinal disorders. These age-related changes are rheologic, biochemical, and structural in nature. Our current knowledge of these ageing changes is reviewed. Hypotheses for the mechanisms of liquefaction (synchisis senilis) and posterior vitreous detachment are proposed.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                18 December 2018
                2018
                : 6
                : 199
                Affiliations
                [1] 1Department of Biomedical Engineering, The Ohio State University , Columbus, OH, United States
                [2] 2William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University , Columbus, OH, United States
                [3] 3Department of Ophthalmology and Visual Science, The Ohio State University , Columbus, OH, United States
                Author notes

                Edited by: Brittany Coats, University of Utah, United States

                Reviewed by: Alicia R. Jackson, University of Miami, United States; André P. G. Castro, Instituto Superior Técnico, Universidade de Lisboa, Portugal

                *Correspondence: Katelyn E. Swindle-Reilly reilly.198@ 123456osu.edu

                This article was submitted to Biomechanics, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2018.00199
                6305337
                30619846
                47112421-f8dd-4ed5-8dd1-d49000c1b792
                Copyright © 2018 Tram and Swindle-Reilly.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 October 2018
                : 04 December 2018
                Page count
                Figures: 7, Tables: 2, Equations: 1, References: 30, Pages: 12, Words: 7435
                Categories
                Bioengineering and Biotechnology
                Original Research

                rheometry,vitreous,aging,ocular biomechanics,liquefaction,eye,viscoelasticity,floaters

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