Regulation of pHi and Fluid Flux in Corneal Endothelium

描述（由申请人提供）：SLC4A11突变是溶质连接转运蛋白家族的成员，在人类中导致CHED2（隐性先天性遗传性内皮营养不良）和晚发性富克斯内皮角膜营养不良（FECD）。非常有限的研究文献表明，该基因编码Na依赖性碳酸氢盐转运蛋白（BTR1）或硼酸盐转运蛋白（NaBC1）。这表明SLC4A11编码一种蛋白质，该蛋白质是角膜内皮液体泵的一部分，或参与调节细胞内硼酸盐浓度的新转运蛋白。我们的初步数据表明硼酸盐可能是一种细胞抗氧化剂。在这个修订申请中，我们提出了实验来确定NaBC1进行的运输类型，以及它的表达是否会影响角膜内皮细胞内硼酸盐浓度、细胞存活和活性氧水平。确定NaBC1的功能对于了解其在正常角膜内皮功能中的作用及其在角膜营养不良症中的作用非常重要。

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.