Functional Roles of Electrogenic Sodium Bicarbonate Cotransporter NBCe1 in Ocular Tissues

Abstract

Electrogenic Na(+)-HCO(3) (-) cotransporter NBCe1 is expressed in several tissues such as kidney, eye, and brain, where it may mediate distinct biological processes. In particular, NBCe1 in renal proximal tubules is essential for the regulation of systemic acid/base balance. On the other hand, NBCe1 in eye may be indispensable for the maintenance of tissue homeostasis. Consistent with this view, homozygous mutations in NBCe1 cause severe proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataract. The widespread expression of NBCe1 in eye suggests that the inactivation of NBCe1 per se may be responsible for the occurrence of these ocular abnormalities. In this review, we discuss about physiological and pathological roles of NBCe1 in eye.

Keywords: NBCe1; band keratopathy; cataract.; glaucoma; proximal renal tubular acidosis.

Fig. (1)

Structures of NBCe1 variants and pRTA-related mutations. Different patterns in the squares indicate unique amino acids sequences. While NBCe1-A has a unique N-terminal, NBCe1-C has a unique C-terminal. Numbers in circles indicate pRTA-related NBCe1 mutations corresponding to Q29X (1), R298S (2), S427L (3), T485S (4), G486R (5), R510H (6), W516X (7), L522P (8), N721TxfsX29 (9), A799V (10), R881C (11), and S982NfsX4 (12). Q29X is an NBCe1-A specific mutation, leaving NBCe1-B and NBCe1-C intact. S982NfsX4 creates a flame-shift mutation in NBCe1-A and NBCe1-B, but may suppress the translation of NBCe1-C. The remaining mutations lie in the common region of NBCe1 variants.

Fig. (2)

Major sites of NBCe1 expression in eye.

Fig. (3)

Proposed mechanism of band keratopathy by NBCe1 mutations. Inactivation of NBCe1 may increase the concentration of bicarbonate in corneal stroma, which may facilitate the calcium deposition.