[Development of cataract in the ontogeny of senescence-accelerated oxys rats--the basic selection trait of this...

Previous research showed that clinical manifestations of cataract in OXYS rats closely match those of senile cataract in humans, which led to using this rat strain in studies on the pathogenesis of this disease and on efficacy of new therapeutic methods. The aim of the present work was to analyze morphological changes in the lens of OXYS rats at different stages of cataractogenesis by means of light microscopy and to assess mRNA levels of αA- and αB-crystallin genes in the lens. We studied the animals at age 20 days (no clinical signs of cataract), age 3 months (cataract prevalence is 100%), and at age 12 months (when in the majority of OXYS rats, aberrations in the lens correspond to pronounced stages of this disease). Age-matched Wistar rats served as controls. In the lens of 20-day-old OXYS rats, we detected minor aberrations in the packing of cortical fibers, signs of alterations in the activity of transport systems and/ or cell-to-cell contacts as well as a compensatory, by all appearances, increase in the density of the lens epithelium and upregulation of the αA- and αB-crystallin genes. At age 3 months, there were noticeable aberrations (and at 12 months, significantly enhanced aberrations) in the structure of the lens capsule and in organization of the cortical fibers of the lens, whereas a-crystallin expression dipped below than in the Wistar rats. Recently, we reported downregulation of a-crystallin gene expression in the retina of OXYS rats. Early cataract is the basic selection trait of this strain; continued selection for this trait led to the development of a constellation of signs of premature aging. These observations suggest that manifestations of cataract--early development of age-related diseases--may be linked to systemic changes in the expression and function of crystallins.