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K. J. Al-Ghoul, A. Joy, T. A. Mohammed; Structural and Cytoskeletal Alterations Precede Posterior Subcapsular Cataract Formation in Royal College of Surgeons Rats. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4385.
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© ARVO (1962-2015); The Authors (2016-present)
Preliminary investigations in our laboratory have shown altered morphology and arrangement of lens fiber ends in juvenile (4-6 weeks old) Royal College of Surgeons (RCS) rats during the formation of posterior subcapsular cataracts (PSCs). The changes included the rapid generation of multiple suture sub-branches and fiber end disorganization with an associated redistribution of F-actin in the basal membrane complex (BMC). The present study was undertaken to elucidate the earliest changes that initiate aberrant fiber end migration and to pinpoint their temporal sequence.
RCS rats (n=23) at ages 2, 2.5, 3, 3.5, 4, 5 and 6 weeks old were euthanized and lenses were enucleated. Fixed lenses from animals at 2-3.5 weeks old were processed either for scanning electron microscopy (SEM) to evaluate morphology, or immunofluorescent confocal microscopy (LSCM) to localize specific molecular components. Lenses from animals at 4-6 weeks old were analyzed by LSCM and correlated with previously published SEM data.
Two week old RCS rat lenses displayed the typical inverted Y suture pattern on their posterior aspects. However, by three weeks postnatal, most lenses exhibited at least one sub-branch. Although SEM revealed that most basal fiber ends had comparable size, shape and arrangement to those in age-matched Sprague-Dawley rats, scattered groups had altered morphological features. These included rounded or dome-shaped basal membranes and a lack of filopodial extensions. Two week old lenses showed a normal pattern of F-actin arrangement along the lateral membrane domains. Within the BMC, foci of F-actin were located at cell-cell vertices; the frequency of actin foci increased as a function of age. Cadherin distribution appeared normal at all ages. At lens sutures of two week old rats, opposing ends of fully elongated fibers abutted directly and lacked the complex cytoskeletal network seen in older RCS rats. In addition, fiber end dilations were observed at the sutures in all age groups. Small polar opacities developed between 4 and 5 weeks and progressed by six weeks to plaque-like PSCs comprised of enlarged fiber ends curved abnormally toward the capsule.
Defined structural and molecular variations were present at basal fiber ends as much as two weeks prior to cataractogenesis. The data suggests that the observed changes are associated with altered migration patterns and eventually culminate in cessation of fiber end migration.
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