Purpose: To document lens ultrastructure during and after internalization of 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 enucleated and fixed. For light and transmission electron microscopy (TEM), lenses were embedded in epoxy and sectioned along the visual axis. For scanning electron microscopy, lenses were dissected to expose the posterior fibers 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 weeks postnatal. Peripheral-to-central overgrowth resulted in the formation of a convexo-concave, disk-shaped suture plane oriented parallel to the capsule. The initial fibers overlying the plaque were extremely flattened at their posterior ends. However, by 3 months postnatal, fiber ultrastructure was relatively normal and displayed only minor morphological irregularities. These temporal and structural changes were used to create 3-dimensional computer assisted-drawing (3D-CAD) reconstructions and animations. TEM examination of plaques revealed scattered fiber defects such as membrane whorls, globular aggregates and intracellular voids in both the internalized plaques and the initial overgrowth. The internalized PSC plaques had comparable morphology in all animals, regardless of age. Specifically, the posterior segments of fibers were enlarged and curved abnormally toward the capsule.
Conclusions: PSC plaques are not internalized and broken down in the classical cell biological sense (i. e. via lysosomal degradation). Rather the plaques retain their structure indefinitely as lens growth proceeds (albeit not entirely normally). This demonstrates that the lens has a restricted ability to respond to growth defects and effect a limited recovery after PSC formation.