The nature of protein-protein interactions of crystallins forms the basis for understanding the transparent and opaque properties of the normal and cataractous lens. Previous physical studies have suggested that weak, noncovalent interactions of these lens crystallins (i.e. alpha-gamma, alpha-beta, gamma-beta) may exist in the lens, where they are necessary for lens transparency. These interactions have hitherto not been well characterized, since they involve interactions that dissociate under normal analytical conditions. The central hypothesis of this proposal is that under true equilibrium conditions, noncovalent interactions of alpha-gamma, alpha-beta, and beta-gamma crystallins exist, and because of posttranslational modifications or genetic mutations, these interactions are perturbed during cataractogenesis of the lens, resulting in loss of lens transparency. We have developed the technique of microequilibrium dialysis to both detect and quantitate possible interactions.
The specific aim of this proposal will be to use this methodology to quantitate noncovalent interactions between different crystallins during cataractogenesis of the human lens. Using these novel methods, we will be able to ascertain the existence of these interactions and their possible alterations during lens opacification.
Opacification of the lens, known as cataract, is the leading cause of blindness in the world. Opacification is thought to be caused by abnormal interactions of proteins in the lens. The proposed research will characterize these interactions, and determine how they are altered during formation of cataracts.
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