Functions of aquaporins in the eye

Abstract

The aquaporins (AQPs) are integral membrane proteins whose main function is to transport water across cell membranes in response to osmotic gradients. At the ocular surface, AQP1 is expressed in corneal endothelium, AQP3 and AQP5 in corneal epithelium, and AQP3 in conjunctival epithelium. AQPs are also expressed in lens fiber cells (AQP0), lens epithelium (AQP1), ciliary epithelium (AQP1, AQP4) and retinal Müller cells (AQP4). Mutations in AQP0 produce congenital cataracts in humans. Analysis of knockout mice lacking individual AQPs suggests their involvement in maintenance of corneal and lens transparency, corneal epithelial repair, intraocular pressure regulation, retinal signal transduction and retinal swelling following injury. The mouse phenotype findings implicate AQPs as potential drug targets for therapy of elevated intraocular pressure and ocular disorders involving the cornea, lens and retina. However, much research remains in defining cell-level mechanisms for the ocular AQP functions, in establishing the relevance to human eye disease of conclusions from knockout mice, and in developing AQPmodulating drugs.

In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors

“…elongation is triggered by the closure of the cGMP-gated (CNG) channels or attendant water transport via AQP4 channels in Müller cells, which swell in response to K + uptake (31). First, the rod OS swelling and backscattering increases are more than four orders of magnitude less sensitive to light than the closure of the CNG channels that underlies the rod's electrical response ( Fig.…”

Aquaporins at a glance

“…Mice lacking AQP5, which is expressed in salivary and airway submucosal glands, show defective secretion of saliva and airway mucus (Song and Verkman, 2001). AQPfacilitated fluid secretion has also been found in the ocular ciliary epithelium (Zhang et al, 2002;Verkman et al, 2008b), which produces aqueous fluid, and in the brain choroid plexus (Oshio et al, 2005), which produces cerebrospinal fluid (CSF). There is a caveat, however: AQPs appear to be required for active transepithelial fluid transport only when fluid transport rate, normalized to epithelial surface area, is very high, as it is in the proximal tubule and salivary gland.…”

Aquaporins: translating bench research to human disease

“…Another potential role for AQP protein-based diagnostics is in evaluating AQP expression in tissue specimens. Several studies have attempted to correlate AQP expression in tumor cells with tumor grade (reviewed by Verkman et al, 2008a), and AQP expression with human epilepsy (Lee et al, 2004), and ocular (reviewed by Verkman et al, 2008b) and skin (Olsson et al, 2006) diseases. Whether diagnostically useful or unique information can be obtained by such measurements remains to be seen.…”

“…Mutations in the major intrinsic protein (MIP) of the lens cause congenital cataracts (Berry et al, 2000). MIP (also called AQP0) is homologous to the AQPs, though its function in lens and the relationship between loss-of-function mutations and cataract formation are unclear (reviewed by Verkman et al, 2008b). Disease-causing mutations of other AQPs in humans have not been described.…”