AGE RELATED CATARACT--ANTIBODY MEDIATED AUTOIMMUNE DISEA

白内障是世界上视力受损的主要原因，超过 60%的老年人口患有这种疾病。与年龄相关的 白内障一直被认为是衰老过程的结果，然而 年龄相关性白内障的病因仍然难以捉摸。其中之一 其原因可能与晶状体上皮细胞丢失有关。虽然镜头 上皮细胞在整个生命过程中保持增殖能力， 随着年龄的增长，上皮细胞密度会下降。 有趣的是，在涉及晶状体皮质的白内障中，显著的 据报道细胞密度较低。上皮细胞参与了 维持晶状体的生理功能，包括透明度。因此，镜头 动态平衡可能受到上皮细胞减少的干扰。 老式晶状体中的密度会导致白内障的形成。我们想要 找出导致晶状体上皮损伤的特定病因 细胞。有趣的是，超过40%的健康人类和超过80%的 的白内障患者表现出较高的抗体滴度 晶体蛋白表明产生了自身抗原。那些抗体 可能会破坏晶状体上皮细胞。 小鼠晶状体上皮细胞的特异性损伤(LECD) 与晶状体抗原有关，可能是由 针对晶体蛋白的抗体。自身抗体可能会通过 要么是内源性自身抗原，要么是存在于 有传染性的微生物。具有同源抗原的微生物感染 晶状体蛋白可以诱导较高水平的自身抗体 可能导致晶状体上皮细胞死亡和晶状体发育 混浊。因此，我们假设自身抗体可以对抗 晶体蛋白可诱导晶状体上皮细胞损伤，导致 导致白内障形成的上皮细胞死亡。为了测试 在这个假设中，我们提出了以下目标。1)检验假设 抗晶状体抗原的自身抗体可以在小鼠和在 培养晶状体上皮细胞；2)确定其基本机制 从而自身抗体损伤晶状体上皮细胞，无论是补体- 或者是细胞介导的，无论是针对细胞表面还是针对基底部 膜组分；3)确定是否渗漏国产晶状体 微生物抗原中的晶体蛋白或同源表位起作用 针对自身抗体；4)设计预防自身免疫的干预措施 实验动物的反应。这些研究可能会导致 预防人类老年性白内障的干预措施的发展。

Cataract is a major cause of visual impairment in the world and more than 60% of the elderly population suffers from this disorder. Age related cataracts have been thought to be a consequence of the aging process, yet the etiology of age related cataract continues to remain elusive. One of the causes may be due to loss of lens epithelial cells. Although lens epithelial cells remain capable of proliferation throughout life, with increasing age, epithelial cell density is known to decrease. Interestingly, in cataract involving the lens cortex, a significantly lower cell density was reported. Epithelial cells are involved in maintaining the physiology of the lens including transparency. Thus, lens homeostasis might be disturbed by a decrease in the epithelial cell density in older lenses resulting in cataract formation. We would like to find a specific etiology which causes damage to the lens epithelial cells. Interestingly, more than 40% of healthy humans and more than 80% of cataractous patients exhibit elevated antibody titers against crystallins suggesting that autoantigens are generated. Those antibodies might damage the lens epithelial cells. Specific lens epithelial cell damage (LECD) was observed in mice injected with lens antigens possibly by an autoimmune insult induced by the antibodies against crystallins. The autoantibodies might be raised by either endogenous autoantigens or cross-reacting antigens present in infectious microbes. Infection by microbes having homologous antigens to the lens proteins can induce the autoantibodies at higher levels which may result in death of the lens epithelial cells and development of lens opacification. Thus, we hypothesize that autoantibodies against crystallins can induce trauma to the lens epithelial cells, resulting in death of the epithelial cells which lead to cataract formation. To test this hypothesis we propose the following aims. 1) Test the hypothesis that autoantibodies against lens antigens can cause LECD in mice and in cultured lens epithelial cell; 2) To determine the basic mechanism whereby autoantibodies damage lens epithelial cell, whether complement- or cell-mediated, and whether directed against cell surface or basement membrane components; 3) To determine whether leaking indigenous lens crystallins or homologous epitopes in microbial antigens are responsible for autoantibodies; 4) Design interventions to prevent autoimmune response in laboratory animals. These studies could lead to the development of interventions to prevent age related cataract in human.