valinomycin and Glaucoma

Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na(+)-HCO(3)(-) cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) 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 kNBC-1 and pNBC-1. 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 NBC-1, consistent with a major role of NBC-1 in overall HCO(3)-transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.

Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Acidosis, Renal Tubular; Amiloride; Animals; Bicarbonates; Blotting, Western; Carrier Proteins; Cataract; Cells, Cultured; Chlorides; Cornea; Corneal Opacity; Epithelial Cells; Eye Proteins; Glaucoma; Humans; Ion Transport; Kidney Tubules, Proximal; Lens, Crystalline; Pancreas; Protein Isoforms; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Catalytic; RNA, Messenger; Sodium; Sodium-Bicarbonate Symporters; Valinomycin