Regulation of pHi and Fluid Flux in Corneal Endothelium

描述(申请人提供)：SLC4A11是溶质连接转运蛋白家族的成员，突变导致人类先天性隐性遗传性内皮细胞营养不良(CHED2)和迟发性Fuchs内皮角膜营养不良(FECD)。非常有限的研究文献表明，该基因编码依赖于钠的碳酸氢盐转运体(BTR1)或硼酸盐转运体(NaBC1)。这表明SLC4A11编码的蛋白质是角膜内皮液体泵的一部分，或者是参与调节细胞内硼酸盐浓度的新的转运蛋白。我们的初步数据表明，硼酸盐可以是一种细胞抗氧化剂。在这个修订的应用中，我们提出了实验来确定NaBC1执行的运输类型，以及它的表达是否可以影响细胞内的硼酸盐浓度、细胞存活率和角膜内皮细胞中的活性氧水平。确定NaBc1的功能对于了解其在正常角膜内皮功能中的作用以及在这些角膜营养不良中所起的作用是重要的。 公共卫生相关性：角膜内皮营养不良，Fuchs和CHED2，导致角膜内皮细胞丢失，角膜水肿和视力低下。该项目研究了一种新描述的基因SLC4A11的作用，该基因具有与这些营养不良相关的突变。

DESCRIPTION (provided by applicant): Mutations in SLC4A11 a member of the family of solute linked transporters, cause CHED2 (recessive congenital hereditary endothelial dystrophy) and late onset Fuchs Endothelial corneal dystrophy (FECD) in humans. Very limited research literature suggests that this gene codes for a Na- dependent bicarbonate transporter (BTR1) or borate transporter (NaBC1). This suggests that SLC4A11 codes for a protein that is part of the corneal endothelial fluid pump or a new transporter involved in regulating intracellular borate concentrations. Our preliminary data suggests that borate can be a cellular anti- oxidant. In this revision application we propose experiments to determine the type of transport that NaBC1 performs and whether its expression can affect intracellular borate concentrations, cell survival, and reactive oxygen species levels in corneal endothelial cells. Determining the function of NaBC1 is important for understanding its role in normal corneal endothelial function and the role it has in these corneal dystrophies. PUBLIC HEALTH RELEVANCE: Corneal endothelial dystrophies, Fuchs and CHED2, result in loss of corneal endothelial cells, corneal edema and poor vision. This project examines the role of a newly described gene SLC4A11 that has mutations associated with these dystrophies.