Calb1在年龄相关性白内障发生过程中的作用机制研究

The increasing incidence of cataracts related with aging in our country. Surgical treatment mode has not satisfied the requirement of the flourish of cataract patients’ surgery. This serious problem become more prominent in areas which medical conditions are relatively backward. It is not completely clear of the pathogenesis of age-related cataract that still seriously limits the development of non-surgical treatment. Calbindin-D28K (Calb1) is the key Calcium buffer protein in vivo. Research show that the formation of cataracts was related to the calcium overload in lens. In the previous experiments we found Calb1 down-regulated expression in the lens with SD rats aged. But in sodium-selenite-induced cataract in SD rats Calb1 lever showed up-regulated expression with time. The results which what had been found above show that Calb1 is closely related to cataract formation. Yunnan province is located in the plateau with strong ultraviolet radiation. This is an important factor in the age-related cataract development. Our previous animal experiments is aimed at the formation and development of nuclear cataract in the sodium-selenite-induced cataract in SD rats and found the formation of cataract in animal model associated with Calb1 closely. And for the formation of cortical cataracts Calb1 expression changes need to be further in the process of experiment. So we proposed further explore Calb1 expression rule of change in cataract formation in vitro and vivo so that we can further clarify the mechanism on the formation of the age-related cataract.

我国与老龄化密切相关的白内障发生率与日俱增。以手术为主的治疗模式已经远远不能满足数量剧增的白内障患者的复明要求，特别是在医疗条件比较落后的地区问题更加突出。年龄相关性白内障目前发病机制的不完全明确依然严重限制着非手术治疗的发展。Calb1是体内Ca2+的关键缓冲蛋白，研究表明白内障的形成与晶状体内Ca2+超载相关；在前期的实验中我们发现Calb1随SD大鼠的老化表达呈现下降的趋势，而在SD大鼠硒性白内障模型中随时间的推移呈现表达升高的趋势，以上结果都表明Calb1与白内障的形成密切相关。云南地处高原紫外线辐射强，这是白内障发生的一个重要因素，我们前期动物实验主要针对核性白内障的形成与发展且与Calb1相关联，而对于皮质性白内障的形成过程中Calb1表达变化需进一步实验，因此我们拟通过体内、外实验进一步探索Calb1在白内障形成过程中的表达规律，从而进一步阐明其在白内障形成过程中的作用机制。

我国与老龄化密切相关的白内障发生率与日俱增。以手术为主的治疗模式已经远远不能满 足数量剧增的白内障患者的复明要求，特别是在医疗条件比较落后的地区问题更加突出。年龄相关性白内障目前发病机制的不完全明确依然严重限制着非手术治疗的发展。Calb1是体内Ca2+的关键缓冲蛋白，研究表明白内障的形成与晶状体内Ca2+超载相关;在前期的实验中我们发现Calb1随SD大鼠的老化表达呈现下降的趋势，而在SD大鼠硒性白内障模型中随时间的推移呈 现表达升高的趋势，以上结果都表明Calb1与白内障的形成密切相关。云南地处高原紫外线辐射强，这是白内障发生的一个重要因素，我们前期动物实验主要针对核性白内障的形成与发展且与Calb1相关联，而对于皮质性白内障的形成过程中Calb1表达变化需进一步实验，因此我们拟通过体内、外实验进一步探索Calb1在白内障形成过程中的表达规律，从而进一步阐明其在白内障形成过程中的作用机制。本实验发现中波紫外线（UVB）能够干扰人类晶状体上皮细胞内（HLEC）的Ca2+浓度，导致细胞内Ca2+超载，过表达Calb1的人类晶状体上皮细胞能明显抑制UVB引起的HLEC内Ca2+超载，并能显著地抑制UVB诱导的HLEC凋亡的发生。在体内实验中发现UVB在两周左右能诱发SD大鼠的晶状体皮质性白内障的发生，同时SD大鼠晶状体内Ca2+浓度明显增加，进一步说明UVB能导致晶状体内Ca2+浓度失衡，同时伴有晶状体内凋亡相关蛋白Bad和caspase-12表达明显升高，而Bcl-2显著下调。总之，我们推测UVB可能通过抑制晶状体上皮细胞Ca2+-ATP酶活性破坏晶状体上皮细胞内的Ca2+的稳态从而诱导晶状体上皮细胞凋亡的发生，与此同时Calb1通过缓冲晶状体细胞内Ca2+超载从而抑制细胞的凋亡从而抑制晶状体混浊的发生。