The vitreous body is a gel-like connective tissue two major macromolecular components, collagen and hyaluronic acid. The collagen molecule is responsible for the gel structure, and hyaluronic acid is believed to maintain the integrity of the structure. In aging or disease, hyaluronic acid is often degraded, and degradation is often caused by active radical or radical ion species generated enzymatically or non-enzymatically. In this process, gel structure of the vitreous is often lost, and changes in the structure (conformation) and interaction properties of hyaluronic acid are likely to occur. Our preliminary studies indicated that when hyaluronic acid is degraded, its conformation is defferent from normal (decreased molecular weight). In order to understand the role of hyaluronic acid in the vitreous and the structure-function relationship of the molecule, we plan to study in detail (1) the conformational aspects of hyaluronic acid of different molecular weights, (2) the mechanism by which hyaluronic acid is degraaded in the aged and diseased state, (3) the nature of changes of hyaluronic acid when it suffers degradation, (4) whether there is any change in the interaction properties between collagen and degraded hyaluronic acid, and (5) possible structural changes of hyaluronic acid in young, old, and diseased human vitreous, as available. To obtain low-molecular-weight hyaluronic acid (oligosaccharides), we will use hyaluronidase, and to study the mechanism of degradation we will use enzymatically and nonenzymatically generated radicals and radical ions. Spectroscopic techniques such as circular dichroism and fluorescence (using fluorescent probe) will be used to study the molecular properties of hyaluronic acid. Other techniques, such as viscosity, electron microscopy, and light scattering measurements will be used when applicable. The long-term objective of this proposal is to determine the biochemical and biophysical basis for the structural disorder of the vitreous in the aging process and in diseased states. Vitreous abnormalities are common phenomena in aging individuals and in eye diseases such as myopia, retinitis pigmentosa, and diabetic retinopathy. Liquefaction or shrinkage of the gel, membrane formation, and retinal detachment occur in many cases. This project is expected to yield information that will provide some insight into the cause of those abnormalities.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences A Study Section (VISA)
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Schepens Eye Research Institute
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Akiba, J; Kakehashi, A; Ueno, N et al. (1995) Serum-induced collagen gel contraction. Graefes Arch Clin Exp Ophthalmol 233:430-4
Akiba, J; Ueno, N; Chakrabarti, B (1994) Mechanisms of photo-induced vitreous liquefaction. Curr Eye Res 13:505-12
Kakehashi, A; Ueno, N; Chakrabarti, B (1994) Molecular mechanisms of photochemically induced posterior vitreous detachment. Ophthalmic Res 26:51-9
Hikichi, T; Ueno, N; Trempe, C L et al. (1994) Cross-linking of dermal collagen induced by singlet oxygen. Biochem Mol Biol Int 33:497-504
Kakehashi, A; Akiba, J; Ueno, N et al. (1993) Evidence for singlet oxygen-induced cross-links and aggregation of collagen. Biochem Biophys Res Commun 196:1440-6
Akiba, J; Ueno, N; Chakrabarti, B (1993) Age-related changes in the molecular properties of vitreous collagen. Curr Eye Res 12:951-4
Akiba, J; Ueno, N; Chakrabarti, B (1993) Molecular mechanisms of posterior vitreous detachment. Graefes Arch Clin Exp Ophthalmol 231:408-12
Ueno, N; Chakrabarti, B; Garg, H G (1992) Hyaluronic acid of human skin and post-burn scar: heterogeneity in primary structure and molecular weight. Biochem Int 26:787-96
Ueno, N; Chakrabarti, B (1989) Glycosaminoglycan conformations and changes on periodate oxidation. Biopolymers 28:1891-902
Ueno, N; Chakrabarti, B (1987) Changes in CD of hyaluronates and chondroitins upon periodate oxidation. Biopolymers 26:1413-20

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