Abstract
Purpose: :
For normal function, the ocular lens must achieve and maintain optical clarity, as well as the exact geometry required to focus light, within narrow tolerances, on the retina. Additionally, in order to effect accommodation, the lens must be capable of shape change, followed by a return to its starting geometry. The molecular basis for the elastic properties that permit accommodation have not been identified. We hypothesized that the lens fiber cell-specific intermediate filament system (Beaded Filaments, or BFs) conferred in whole, or in part, to the elastic properties of the lens.
Methods: :
Targeted genomic deletion of genes for both beaded filament proteins were generated previously. Electrophysiologic measurements were made from both wild type and knockout mice to ensure that fiber cells from the knockout lenses were intact. The stiffness, resilience, and viscoelastic properties of lenses from wild type and knockout mice were measured in a custom compression device.
Results: :
Previous studies demonstrated that fiber cells from mice lacking in expression of either BF protein were capable of undergoing normal differentiation and assumption of the long range order that characterizes fiber cells from vertebrate lenses. However, over time, the differentiated phenotype of the fiber cell and the regularity of fiber cell packing was lost. Electrophysiologic measurements show that the fiber cells of the knockout animal do not differ from those of the wild type, eliminating cell death as a cause of these structural changes. Wild type lenses were significantly stiffer and less resilient than knockout lenses and exhibited higher rates of stress relaxation in older mice.
Conclusions: :
Our results indicate that BFs make a significant contribution to the material properties of the murine lens and suggest that BFs are likely to be even more important in humans and other species that rely more heavily on changes in lens shape during accommodation.
Keywords: cytoskeleton • accommodation • protein structure/function