Cataracts are the major cause of blindness with an estimated 16 million people affected worldwide.1) The mechanism of cataract development is complicated and involves various factors including genetic factors, diabetes, smoking, nutrition, the cumulative effect of X-rays, ultraviolet irradiation, and alterations in both endocrine and enzymatic equilibria.2-7) Currently, radical oxygen species, especially those induced by UV rays in sunlight, are considered to be important in perturbing lens homeostasis. Following exposure to radical oxygen species, the calcium ion (Ca 2ϩ ) content in lens cells becomes elevated. 8,9) An elevated Ca 2ϩ content in the lens has been shown to activate calpain, a Ca 2ϩ -dependent protease. Furthermore, the degradation of lens proteins such as crystallin proteins results in an opaque lens. 8,9) Over the past several decades, there have been many studies exploring the mechanisms of cataract development.8) However, due to uncertainties regarding efficacy and safety, a potent anticataract drug for human cataracts has not yet been introduced.In studies to develop anti-cataract drugs, the selection of the experimental animal is very important. The UPL rat (UPLR), Shumiya cataract rat (SCR) and Ihara cataract rat (ICR/f; ICR) are hereditary cataractous strains, and it has been shown that these rats provide useful models in studies to develop anti-cataract drugs. Previous investigations have revealed that the proteolyses of some crystallins are significantly enhanced in UPLR, SCR and ICR lenses. [10][11][12][13][14] The Ca 2ϩ content in the cataractous lenses of UPLR, SCR and ICR are higher than in the lenses of Wistar rats, and autolytic products formed by calpain can also be detected in cataractous lenses.11,12,15,16) It is noteworthy that the cataracts formed in these rat models are not diabetic cataracts. Therefore, these rats have been used for studies to develop anti-cataract drugs. However, we recently reported that the increase in Ca 2ϩ content in the lenses of these rats is inhibited by an aminoguanidine, a selective inhibitor of inducible nitric oxide synthase (iNOS), and that the mechanism of Ca 2ϩ enhancement via iNOS among these rat models may differ. [17][18][19] Therefore, it is very important to clarify the mechanisms underlying the dysfunctions in Ca 2ϩ regulation in UPLR, SCR and ICR during cataract development.In the present study, we compare the mechanisms of the decrease in Ca 2ϩ outflow in the lenses of UPLR, SCR and ICR during cataract development.
MATERIALS AND METHODSAnimals Cataractous UPLR, SCR and ICR were used in this study. The UPLR and ICR were provided by Meijo University (Aichi, Japan), and SCR was a gift from the Tokyo Metropolitan Institute of Gerontology (Tokyo, Japan). They were housed under standard conditions (12 h/d fluorescent light (07:00-19:00), 25°C room temperature), and allowed free access to a commercial diet (CE-2, Clea Japan Inc., Tokyo, Japan) and water. All procedures were performed in accordance with the Association for Research in Vis...