The internalization of posterior subcapsular cataracts (PSCs) in Royal College of Surgeons (RCS) rats. I. Morphological characterization

PURPOSE: To document lens ultrastructure during and after internalization o f posterior subcapsular cataracts (PSCs) in Royal College of Surgeons (RCS) rats, a model for human autosomal retinal degenerative disease. METHODS: RCS rat lenses at 2, 2.5, 3, 4, 6, 9, 12, and 15 months old were e nucleated and fixed. For light and transmission electron microscopy (TEM), lenses were embedded in epoxy and sectioned along the visual axis. For scan ning electron microscopy, lenses were dissected to expose the posterior fib ers in concentric growth shells down to the internalized PSC plaques. RESULTS: Overgrowth of the plaque began between 8 and 9 weeks postnatal and proceeded from the periphery to the posterior pole. This is in contrast to PSC formation which begins centrally and enlarges radially between 4-6 wee ks postnatal. Peripheral-to-central overgrowth resulted in the formation of a convexo-concave, disk-shaped suture plane oriented parallel to the capsu le. The initial fibers overlying the plaque were extremely flattened at the ir posterior ends. However, by 3 months postnatal, fiber ultrastructure was relatively normal and displayed only minor morphological irregularities. T hese temporal and structural changes were used to create 3-dimensional comp uter assisted-drawing (3D-CAD) reconstructions and animations. TEM examinat ion of plaques revealed scattered fiber defects such as membrane whorls, gl obular aggregates and intracellular voids in both the internalized plaques and the initial overgrowth. The internalized PSC plaques had comparable mor phology in all animals, regardless of age. Specifically, the posterior segm ents of fibers were enlarged and curved abnormally toward the capsule. CONCLUSIONS: PSC plaques are not internalized and broken down in the classi cal cell biological sense (i. e. via lysosomal degradation). Rather the pla ques retain their structure indefinitely as lens growth proceeds (albeit no t entirely normally). This demonstrates that the lens has a restricted abil ity to respond to growth defects and effect a limited recovery after PSC fo rmation.