Molecular mechanisms of cataract and glaucoma induced by mutations in the Na-HCO3 cotransporter

Na-HCO3协同转运蛋白突变诱发白内障和青光眼的分子机制

• 批准号: 13671826
• 负责人: TANAKA Yoshikazu
• 金额: $ 2.3万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671826/
• 关键词: NBC-1; band keratopathy; Cataract; Glaucoma

Proximal renal tubular acidosis (pRTA) associated with ocular abnormalities such as band keratopathy, cataracts, and glaucoma is caused by mutations in the Na-HCO3 cotransporter (NBC1). To clarify the mechanism by which NBC1 mutations lead to such ocular abnormalities, we performed immunohistochemical analysis of rat and human eyes. The results demonstrated both kidney-type (kNBC1) and a pancreatic type (pNBC1) transporter is present in the corneal endothelium, lens epithelium, and trabecular meshwork cells. We also detected the Na-HCO3 cotransport activity in human lens epithelial (HLE) cells, which was largely inhibited by specific ribozyme against NBC1. These results indicate that the normal transport activity of NBC1 is indispensable for the homeostasis in cornea and lens. NBC1 may also play an important role in regulation of aqueous humor outflow. In the subsequent studies we revealed the transport activity of Na-independent C1/HCO3 exchange activity in HLE cells, which seemed to be related to anion exchanger Aes.

与带状角膜病变、白内障和青光眼等眼部异常相关的近端肾小管酸中毒（pRTA）是由Na-HCO3共转运蛋白（NBC1）突变引起的。为了阐明NBC1突变导致这种眼部异常的机制，我们对大鼠和人眼进行了免疫组织化学分析。结果表明肾型（kNBC1）和胰腺型（pNBC1）转运蛋白均存在于角膜内皮、晶状体上皮和小梁网细胞中。我们还检测了Na-HCO3在人晶状体上皮细胞（HLE）中的共转运活性，该活性在很大程度上被NBC1特异性核酶抑制。这些结果表明，NBC1的正常转运活动对于角膜和晶状体的稳态是必不可少的。NBC1也可能在房水流出调控中发挥重要作用。在随后的研究中，我们揭示了HLE细胞中na无关的C1/HCO3交换活性的转运活性，这似乎与阴离子交换剂Aes有关。

项目成果

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