The vertebrate eye lens is a structure composed of epithelial cells and fiber cells arranged into a strikingly regular three-dimensional hexagonal packing geometry. At the equator of the lens, epithelial cells differentiate into lens fiber cells, which proceed to mature and elongate into transparent, organelle-free structures that permit the focusing of light. The spatial organization of lens fiber cells is one of the most precise examples of hexagonal packing in nature. The plasma membranes of lens fiber cells contain an elaborate spectrin-actin network homologous to that found in red blood cells. The key features of this network are spectrin strands that connect actin filaments, whose assembly and stability is, in turn, precisely regulated by tropomodulin (Tmod) at their pointed ends, by tropomyosin (TM) along their length, and by other proteins including adducin. This protein network attaches neighboring cells to each other via adhesion molecules, and long-range interactions in this protein network are proposed to impart lens fiber cells with regular packing geometry and mechanical properties. Our research has “focused” on investigating the hypothesis that Tmod and TM have both structural and functional roles in the membrane skeleton of lens fiber cells by regulating the assembly and stability of actin filaments. We are using transgenic mouse models to perturb the expression of lens membrane skeleton constituents and examine the consequences of these perturbations in lens morphogenesis and structure.

 

    Key questions are:

 

•  How does the absence of Tmod or TM affect actin filament assembly, lengths, or stability in the membrane skeleton of lens fiber cells?

 

•  What are the roles of actin, Tmod, and TM in membrane skeleton organization and functional properties of the lens fiber cell membrane?

 

•  How do actin filaments, Tmod, and TM facilitate the establishment and maintenance of lens fiber cell hexagonal packing as fiber cells differentiate, mature and age?

 

•  How do the mechanical properties of the lens fiber cell membrane skeleton permit accommodation and focusing?

 

•  What is the role of the membrane skeleton in lens fiber cell differentiation and lens morphogenesis during development ?

 

•  What roles do adhesion molecules and membrane channels and pumps play in establishing cell-cell contacts and facilitating fiber cell hexagonal packing?

 

•  How might defects in the membrane skeleton of lens fiber cells produce eye pathologies?