
<ArticleTitle>Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis.</ArticleTitle>
<AbstractText>Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the <prot>Na(+)-HCO(3)(-) cotransporter</prot> (<prot>NBC-1</prot>). However, the mechanism by which <prot>NBC-1</prot> inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (<prot>kNBC-1</prot>) and pancreatic type (<prot>pNBC-1</prot>) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both <prot>kNBC-1</prot> and <prot>pNBC-1</prot>. Although a Na(+)-HCO(3)-cotransport activity has not been detected in mammalian lens epithelia, cell pH (pH(i)) measurements revealed the presence of Cl(-)-independent, electrogenic Na(+)-HCO(3)-cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pH(i) recovery from acid load in the presence of HCO(3)(-)/CO(2) was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against <prot>NBC-1</prot>, consistent with a major role of <prot>NBC-1</prot> in overall HCO(3)-transport by the lens epithelium. These results indicate that the normal transport activity of <prot>NBC-1</prot> is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.</AbstractText>
