GENETICS AND BIOCHEMISTRY OF THE LENS IN CELL CULTURE

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For proper functioning of the lens, elasticity and clarity are of paramount importance. These characteristics are highly dependent on the integrity of the lens capsule basement membrane and the lens fiber cell crystallins and cell membranes. The system for their synthesis and maintenance is known to be delicate, however, and can often be disrupted in many diseases, generally leading to cataracts. We intend to continue our studies of the normal lens capsule basement membrane and the crystallins produced by the lens epithelium and fiber cells, and investigate how these proteins are affected by cataracts. We will establish cell lines from human normal and cataractous lens epithelium, as well as with appropriate mouse models in monolayer tissue culture. This will provide us with large quantities of biosynthetic products for direct biochemical and immunological study without the need for harsh extraction procedures. By use of somatic cell hybridization, we will investigate the genetic control of basement membrane and crystallin biosynthesis, and carry out gene mapping of the chromosomes responsible for the proteins and their processing enzymes. Furthermore, we will produce hybrids between normal x diseased, and diseased x diseased lens cells to investigate the mechanisms and controls that function in the biosynthesis of lens proteins. These data will help define the true nature of the molecules of the lens and further help to establish a biochemical basis for symptoms seen in the disease states. These studies will provide information about the biochemical and genetic regulation of lens proteins, specifically basement membrane and crystallins. The control of normal basement membrane and crystallin synthesis by cells is an important aspect of normal growth and development, and studies involved with understanding how such controls work, as well as the chromosomal localizations of the various lens proteins, will aid in our understanding of errors that occur in various lens proteins, will aid in our understanding of errors that occur in various hereditary and acquired disorders of the lens, such as cataract.