Abstract
Abstract: :
Purpose:This study characterized spatial and temporal progression of murine cataracts resulting from expression of altered lenticular structural proteins: αA and αB crystallins, a chaperone protein and heat shock protein that have structural functions, CP49 and CP115, filamentous proteins, and SPARC that modulates lens capsule structure. Structural proteins are important for the development and maintenance of optical clarity. These mice are helpful models for the human aging cataract that progress slowly to mature opacity. Methods:Slit lamp microscopy was performed on the models at one month intervals. Slit lamp examinations (using a Nikon FS–2 slit lamp) are recorded via a digital video camera (Canon, Optura 20). The digital images are transferred to computer via fire wire into Adobe Premiere and processed using Adobe Photoshop. Densitometry analysis, using the NIH program, Image J, was used to quantitate the distribution of opacity in the lens. Results:The temporal progression of each model varied, as did the spatial distribution of opacity in the lens. The CP115 cataract appeared initially in the nucleus by the second month. The cataract progressed to form concentric cortical rings of opacity by the third month. By the eleventh month, the nuclear and ring opacities were most prominent. In the CP49 model, a nuclear opacity was seen by the second month and became more opaque with age. The cataract was manifest as concentric rings, similar to the distribution of opacity in the CP115 model. In the αA crystallin –/– mice, a nuclear cataract was obvious at one month of age. The progression of the cortical opacity proceeded from posterior to anterior. At four months, homogeneous opacity was observed throughout the nucleus and inner cortical layers, with a full stage cataract noted by month five. In αB crystallin knock–out models, a nuclear opacity developed by month two; by month five, cortical haziness was noticed. The αB crystallin models were similar to the control wildtype mice. SPARC null mice commonly developed anterior subcapsular opacity at approximately two months, when the posterior subcapsular cataract was initiated. By six months, the opacification grew to envelop a large portion of the lens. After 6 months, the lens capsule dissolved and the lens cell mass was extruded. Controls were clearer than the mutants, except for the αB crystallin model which appeared identical to its control. Conclusions: Slit lamp microscopy of structural protein mutants suggest that there are common features between opacification in mouse and human lens.
Keywords: cataract • protein structure/function