Abstract
Purpose::
To examine the cellular and molecular alterations that occur at basal ends of elongating lens fibers in a streptozotocin-induced diabetic rat model.
Methods::
Wistar rats (n=32) were given a single (tail vein) injection with streptozotocin, then lenses were enucleated at 1, 2, 3 and 4 weeks after injection and assessed under a dissecting microscope. Scanning electron microscopy (SEM) was utilized to assess changes to fiber end structure and migration patterns. F-actin was localized using phalloidin-FITC labeling and laser scanning confocal microscopy (LSCM).
Results::
Dissecting microscopic pictures of the posterior surface of the lens demonstrated rapid suture sub-branch formation beginning in the first week post-injection. Opacities were also apparent as early as the first week, but were not consistently present until 3-4 weeks after treatment. SEM demonstrated abnormal fiber end morphology, altered fiber end organization (manifested as swirling patterns) and, by 3-4 weeks after streptozotocin injection, regions of fiber breakdown. The well-characterized dilation of the extracellular space was also apparent. LSCM revealed that F-actin distribution in the basal membrane complex (BMC) was altered as compared to the predominantly peripheral pattern of labeling documented in normal lenses. Whereas some fiber ends displayed stress fiber-like organization of F-actin, others contained abundant phalloidin-labeled fragments, possibly as a result of cellular degeneration. Yet other fiber end profiles had a diffuse or cloud-like pattern of fluorescence.
Conclusions::
In the streptozotocin rat model, the morphology and arrangement of basal fiber ends is altered and the distribution of F-actin is dramatically rearranged. This data suggests that the migration patterns of elongating fibers are disrupted, leading initially to abnormal suture sub-branch formation and eventual PSC formation.
Keywords: cataract • diabetes • cytoskeleton