Like the beginning of the 20th century, the dawn of the 21st century is witnessing tremendous advances in developmental biology. Research on ocular lens development remains at the forefront of these advances, just as it was in 1900. The difference between then and now lies in the current synergism between developmental biology, genetics, and molecular biology that has led to the identification of the very molecules responsible for many of the inductive processes only descriptively defined earlier.

The period from the first descriptions of mice with transgenes targeted specifically to the lens until the present day, when lens-specific gene deletion has become almost routine, spans only about the past 20 years. It is in the context of this breathtaking influx of information that we thought it time to devote a text specifically and exclusively to lens development. Because of its simplicity and its predictable pattern of development and differentiation, the lens, arguably the sparkling jewel of anatomy, has attracted the attention of many developmental biologists. All stages of lens differentiation, from the proliferation of lens epithelial cells to the differentiation of mature, organelle-deficient fiber cells, are represented in the lens of any individual. Analogous to the rings of a tree, the components of the lens, from the newest cells born moments before tissue collection to the oldest cells originating during embryogenesis, offer a key to its life history.

Introduction

Since Kepler and Descartes first investigated the optics of the eye, the central role of the lens in light refraction has been appreciated. The lens must be extremely dense to refract light in the aqueous media in which it is suspended. The necessary density is achieved by the presence of the crystallins, proteins that accumulate to concentrations of 450 mg/ml or higher in the lens fiber cell cytoplasm (Fagerholm et al., 1981; Huizinga et al., 1989; Siezen et al., 1988). Since most proteins would aggregate and strongly scatter light long before accumulating to these high concentrations, the crystallins are believed to have a number of special properties that allow for the creation of the short range order necessary for lens transparency (Tardieu and Delaye, 1988). In the past 50 years, our understanding of the molecular nature of crystallins has increased exponentially, and now much is known about the structure, function and evolutionary origin of these proteins. Before the advent of molecular biology, proteins would be designated as crystallins if their concentration in the lens was sufficient to create a major peak on a size exclusion column, a band on a SDS-PAGE gel, or a spot on a two-dimensional protein gel. Practically, this working definition designated a protein as a crystallin if its concentration in the lens reached about 5% of the total water soluble protein (de Jong et al., 1994).

Introduction

The lens, like any other tissue, is dependent upon the cytoskeleton for its function. There are now a number of examples of mutated or overexpressed cytoskeletal proteins that have been shown to be the genetic basis of cataract, underlining the importance of the cytoskeleton to cell shape, intracellular organisation, and compartmentalisation in the lens. In other cell systems, the cytoskeleton enables the cell to maintain and diversify the internal complexities required for specialised cellular functions. In the lens, this requires specialised cell-cell interactions that allow adjacent plasma membranes to be closely apposed or interdigitated over most of their surface. Differentiation requires the programmed elongation of lens fiber cells and, by inference, the directed traffic of organelles, vesicles, and other cargoes in the highly elongated fiber cell. Finally, the lens is highly specialised in the maintenance and use of stable proteins, of which the cytoskeleton is but one example. Evolution has dictated the choice of the proteins and their structures to ensure that the lens efficiently refracts light onto the retina, and our task as cell biologists is to unravel this rich tapestry and to discover the contribution of the cytoskeleton to the function of this highly specialised tissue.

Major Components of the Lenticular Cytoskeleton

The lens, like all other tissues, possesses microtubules, microfilaments, and intermediate filaments, the three main cytoskeletal elements of most eukaryotic cells. These structural filaments in isolation are ineffective, as it is the linking, the attachment, and the transiently associating proteins that give the cytoskeleton functionality.