The long-term objectives are (a) to elucidate specific structural features of the individual crystallins in the lens and the interactions between them that give rise to a transparent structure in normal lenses, and (b) to understand the cause and mechanism by which lenses become opaque upon cataract formation. In this project period, studies will focus on defining the factors responsible for protein-protein aggregation, protein modifications, and increased stability in the supramolecular organization in normal lens, and the mechanism of destabilization of protein structure during cataractogenesis.
The specific aims are: (1) To determine the mechanism of protein-protein interaction leading to aggregation and insolubilization in normal aging and cataractogenesis. Studies include structure and stability of individual crystallins isolated from bovine and human lens. (2) To define the factors responsible for protein modification, such as pigmentation, insolubilization, and aggregation in human lens. Intact human lens, young, aged, and cataractous, will be investigated to understand the mechanism of protein modifications. In addition, lenses from India and the US will be studied, as described above, to distinguish the protein modifications under different environmental conditions (such as light), food habits, and malnutrition. (3) To investigate the structural changes of lens proteins due to glycation, carbamylation, and Ca2+ ion. In addition to appropriate chemical, biochemical, and spectroscopic techniques such as absorption, fluorescence, and circular dichroism (CD), the project will also use high-resolution nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and nuclear magnetic relaxation dispersion (NMRD) techniques to accomplish the aims.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY004161-09A1
Application #
3258680
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1982-12-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Schepens Eye Research Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02114
Liang, J J; Chakrabarti, B (1998) Intermolecular interaction of lens crystallins: from rotationally mobile to immobile states at high protein concentrations. Biochem Biophys Res Commun 246:441-5
Das, B K; Liang, J J; Chakrabarti, B (1997) Heat-induced conformational change and increased chaperone activity of lens alpha-crystallin. Curr Eye Res 16:303-9
Chakrabarti, B (1994) Differential domain folding/unfolding of gamma-crystallins: existence of two distinct groups. Indian J Biochem Biophys 31:344-50
Sen, A C; Walsh, M T; Chakrabarti, B (1992) An insight into domain structures and thermal stability of gamma-crystallins. J Biol Chem 267:11898-907
Araki, N; Ueno, N; Chakrabarti, B et al. (1992) Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging. J Biol Chem 267:10211-4
Sen, A C; Ueno, N; Chakrabarti, B (1992) Studies on human lens: I. Origin and development of fluorescent pigments. Photochem Photobiol 55:753-64
Bandyopadhyay, S; Chattopadhyay, D; Ghosh, S K et al. (1992) Studies on human lenses: II. Distribution and solubility of fluorescent pigments in cataractous and non-cataractous lenses of Indian origin. Photochem Photobiol 55:765-72
Koenig, S H; Brown 3rd, R D; Spiller, M et al. (1992) Intermolecular protein interactions in solutions of calf lens alpha-crystallin. Results from 1/T1 nuclear magnetic relaxation dispersion profiles. Biophys J 61:776-85
Ghosh, S K; Chattopadhyay, D; Sen, A C et al. (1991) Melittin-induced conformational changes in human lens protein. Curr Eye Res 10:1065-8
Walsh, M T; Sen, A C; Chakrabarti, B (1991) Micellar subunit assembly in a three-layer model of oligomeric alpha-crystallin. J Biol Chem 266:20079-84

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