The lens fiber cell-specific intermediate filament protein filensin is essential for beaded filament assembly. However, although beaded filaments are not needed for normal lens fetal development or fiber cell differentiation, they appear to be necessary for the long-term maintenance of optical clarity. The mechanism by which the absence of filensin and the beaded filament affects optical clarity has yet to be defined.

The 129/SvJ and 129/OLa strains of mice harbor a mutation that sharply reduces CP49 mRNA levels and essentially eliminates both CP49 and the beaded filament. These lenses exhibited a slow but progressive loss of optical clarity with age. Thus, the 129 strain of mouse behaves as a functional CP49 knockout. The loss of clarity in the lenses of these animals and the absence of beaded filaments (and any attendant interactions that may exist between beaded filaments and other lens proteins/structures) suggest that gene-targeting studies of lens proteins in which the 129 strain was used as a source of embryonic stem cells may need reevaluation.

The visual system of birds includes an efferent projection from a visual area, the isthmooptic nucleus in the midbrain, back to the retina. Using a combination of anterograde labeling of efferent fibers, reconstruction of dye-filled neurons, NADPH-diaphorase staining, and transmission electron microscopy we have examined the distribution of efferent fibers and their synaptic structures in the chicken retina. We show that efferent fibers terminate strictly within the ventral retina. In 2 completely mapped retinas, only 2 fibers from a total of 15,359 terminated in the dorsal retina. The major synapse made by each efferent fiber is with a single Efferent Target Amacrine Cell (TC). This synapse consists of 5-25 boutons of 2μm diameter, each with multiple active zones, pressed into the TC soma or synapsing with a basketwork of rudimentary TC dendrites in the inner nuclear layer (INL). This basketwork, which is sheathed by Muller cells processes, defines a private neuropil in the INL within which TCs were also seen to receive input from retinal neurons. In addition to the major synapse, efferent fibers typically produce several very thin processes that terminate nearby in single small boutons and for which the soma of a local amacrine cell is one of the likely postsynaptic partners. A minority of efferent fibers also give rise to a thicker process terminating in a strongly diaphorase positive ball about 5μm in diameter.

Fiber cells that arise later than 2 weeks of age undergo a structural differentiation program that is different from that of cells that arise earlier in development. This program includes the assembly of a series of regularly spaced, complex, lateral projections from the fiber cell that align themselves with similar structures in adjacent cells. Most if not all of the structural specialization occurs in cells that have lost their nuclei and organelles, suggesting that this component of fiber cell differentiation may not require ongoing transcription/translation.

The beaded filament is not required for the generation of the differentiated fiber cell phenotype but is required to maintain that differentiated state and the long range order that characterizes the lens at the tissue level.