Abstract
Purpose: :
Ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell packing and cell-cell adhesion. Approximately 87% of ephrin-A5 KO mice develop cataract. Here we investigated some early events of cataractogenesis and its light scattering elements associated with cataract formation in ephrin-A5 KO mice.
Methods: :
Lenses from ephrin-A5 wild-type and KO mice between 21-150 days old were studied with light microscopy, scanning EM, and freeze-fracture TEM.
Results: :
Lens opacities with various densities were first seen in ephrin-A5 KO mice at around 60 days old. The dense cataracts were located primarily in the nuclear region surrounded by transparent cortices from all eyes examined. Almost all nuclear cataracts protruded anteriorly toward the pupil. Thus some erupted tips of the cataracts made direct contact with the iris, as indicated by the presence of iris pigment and even small blood vasculatures. Also, as judged by the angle and direction, dislocation of nuclear cataracts to the outside of the lens surface occurred along the lens sutures. SEM showed that extensive undulating ridge surface patterns occupied the major portion of deep cortical and nuclear fibers in both transparent ephrin-A5 KO and WT mice. These normal ridge structures (~150 nm in diameter for each ridge) thus do not cause light scattering and opacity. In contrast, abundant membranous globules (~1000 nm in size) were consistently distributed only on the ridge surface in all ephrin-A5 KO cataracts examined. Many globules exhibited undulating ridge surface, suggesting these globules were derived from the underlying fiber cell membranes. More extensive distribution of smooth globules was also seen in the late stage of dense cataracts. Freeze-fracture TEM revealed that contiguous patches of square array particles (aquaporin junctions) were associated with these undulating ridge surfaces.
Conclusions: :
This study shows that accumulation of many large globules can cause light scattering and nuclear cataract in the ephrin-A5 KO mice. The results also suggest that cell-cell adhesion along the suture lines is more seriously affected by the loss of ephrin-A5, and as a result, the nuclear cataracts dislocate anteriorly or posteriorly toward the outside of the lens surface.
Keywords: cataract • cell membrane/membrane specializations • microscopy: electron microscopy