Sueno T, Inoue E, Singh D P, Awata T, Chylack L T, Shinohara T
Center for Ophthalmic Research, Brigham and Women's Hospital, Boston, MA 02115, USA.
Exp Eye Res. 1997 Mar;64(3):379-85. doi: 10.1006/exer.1996.0218.
Auto-antibodies (Abs) against lens antigens (Ags) are present in most patients with age-related cataract, and with complement they kill lens epithelial cells (LECs) in vitro. We studied, in an animal model, whether cytotoxic Abs against lens Ags can be suppressed by oral administration of the Ags. Mice were fed calf lens homogenate, 4 mg/mouse, every 4 days for 4-5 weeks, or bovine serum albumin (BSA) before and after immunisation with beta-crystallins emulsified in complete Freund's adjuvant (CFA). Sera from these animals were analysed for Abs to beta-crystallins by enzyme-linked immunosorbent assay (ELISA) and protein blot analysis. In addition, we studied the proliferative response of T-lymphocytes to beta-crystallins. The titer of anti-beta-crystallin Abs in the control animals fed BSA gradually increased to 1.5 x 10(-6) by the 5th week after the first injection. In contrast, the titer of anti-beta-crystallin Abs in animals fed calf lens homogenate was reduced to 30-70% of the control. Feeding lens homogenate prior to or concomitant with beta-crystallins immunization, was more effective than feeding after immunization (65% suppression vs. 30% suppression, respectively). Also the proliferative response of T-lymphocytes to beta-crystallins in mice fed homogenate was suppressed significantly. Thus, oral administration of lens homogenate is a specific and nontoxic method of suppressing anti-beta-crystallin Ab production in mice. We are exploring the therapeutic value of oral administration of lens proteins in age-related cataract.
大多数年龄相关性白内障患者体内存在针对晶状体抗原(Ag)的自身抗体(Ab),并且这些自身抗体与补体一起可在体外杀死晶状体上皮细胞(LEC)。我们在动物模型中研究了口服晶状体抗原是否能抑制针对晶状体抗原的细胞毒性自身抗体。给小鼠每4天喂食4mg/只的小牛晶状体匀浆,持续4 - 5周,或者在以完全弗氏佐剂(CFA)乳化的β-晶状体蛋白免疫前后喂食牛血清白蛋白(BSA)。通过酶联免疫吸附测定(ELISA)和蛋白质印迹分析来检测这些动物血清中针对β-晶状体蛋白的抗体。此外,我们研究了T淋巴细胞对β-晶状体蛋白的增殖反应。在首次注射后第5周,喂食BSA的对照动物中抗β-晶状体蛋白抗体的滴度逐渐增加至1.5×10⁻⁶。相比之下,喂食小牛晶状体匀浆的动物中抗β-晶状体蛋白抗体的滴度降至对照的30 - 70%。在β-晶状体蛋白免疫之前或同时喂食晶状体匀浆比免疫后喂食更有效(分别为65%抑制率对30%抑制率)。喂食匀浆的小鼠中T淋巴细胞对β-晶状体蛋白的增殖反应也被显著抑制。因此,口服晶状体匀浆是一种抑制小鼠体内抗β-晶状体蛋白抗体产生的特异性且无毒的方法。我们正在探索口服晶状体蛋白在年龄相关性白内障治疗中的价值。