Sodium hyaluronate (NaHA), a macromolecular component of the vitreous, plays an important role in stabilizing the gel vitreous structure. Changes in the chemical state or conformation of NaHA or its interaction with collagen could alter the gel state of the vitreous and result in liquefaction. Although vitreous liequefaction is part of the normal aging process, the loss of gel structure has been correlated with vitreous abnormalities. Liquefaction is related to posterior vitreous detachment which is a pathogenetic factor in various retinal disorders. Vitreous liquefaction is also a frequent finding in retinitis pigmentosa, high myopia, congenital retinoschisis, pars planitis, and Wagner's disease. The long-term objective of this proposal is to define the role of NaHA in the vitreous structure and the structure-function relationship of the molecular.
The specific aims of the proposal are: (1) Study of the macromolecular components of the vitreous including conformational studies of hyaluronate, the mechanism by which the molecule is degraded, and its interaction with collagen. Noncollagenous proteins will also be characterized, and their role in vitreous structure and function will be assessed. (2) With a newly developed technique, vitreous including human (normal, aged, and diseased) will be studied to define the role of hyaluronate, collagen, and noncollagenous proteins in the structural integrity of the tissue. (3) Liquefaction of bovine vitreous will be induced by photodynamic or enzymatic reaction and the protective role of vitreous ascorbic acid will be assessed. We will use fluorescent dye and periodate oxidation as probes to study conformational aspects of NaHA. To study the mechanism of NaHA degradation, we will use enzymatically, nonenzymatically, and photodynamically generated radical species to react with NaHA; we will then study the molecule structurally. Circular dichroism, fluorescence and high-performance liquid chromatography will be employed to study the molecular properties of NaHA.

National Institute of Health (NIH)
National Eye Institute (NEI)
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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
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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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