Studies On Human Lens Protein

National Eye Institute

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Abstract

This laboratory uses a proteomics approach to study the proteins of the normal human lens and in cataracts of various etiologies. Lens dissections are done to obtain age-defined populations of fiber cells from lenses of all ages. Methodologies have been developed to yield high resolution separation of these proteins using two-dimensional polyacrylamide gel electrophoresis. Identification of the proteins and the characterization of their post-translational modifications are done by matrix assisted laser desorption ionization time of flight and electrospray mass spectrometry. The study has demonstrated extensive post-translational modifications of the crystallins that occur early in life and the development of a unique protein pattern of the lens nuclear fiber cells. Pathways for the processing of alpha crystallins are being studied. A focus is on the C-terminal cleavage of alpha crystallins and their biological significance. Results from this lab suggest that processing of alpha crystallins is altered in lens pathology. In certain cataracts high concentrations of C-terminally cleaved forms of alpha crystallins are present. The protein patterns of numerous cataracts have been determined. These data are now being analyzed with respect to the cataract etiology. A database of the proteins and their post-translational modifications throughout the human lens is being put together. Studies on the alpha crystallins are being done to understand the effects of the C-terminal cleavage on structure and function.