The ins and outs of aqueous humour secretion.
The intraocular pressure (IOP) reflects a balance between inflow and outflow of aqueous humour. A major strategy in the medical treatment of glaucoma is to reduce inflow and thereby IOP. Understanding the mechanisms and regulation of inflow is thus of clear clinical relevance. Many mechanisms underlying inflow have been identified. The integration and regulation of these mechanisms is less clear. Aqueous humour is secreted across the ciliary epithelium by transferring solute, chiefly NaCl, from the stroma to the posterior chamber of the eye, with water passively following. The epithelium consists of two layers: the pigmented ciliary epithelial (PE) cells abutting the stroma, and the non-pigmented ciliary epithelial (NPE) cells facing the aqueous humour. Gap junctions link adjacent cells within and between these layers. Secretion proceeds in three steps: (1) uptake of NaCl from stroma to PE cells by electroneutral transporters, (2) passage of NaCl from PE to NPE cells through gap junctions, and (3) release of Na+ and Cl- through Na+,K+-activated ATPase and Cl- channels, respectively. Most of our understanding of inflow mechanisms has been obtained by studying in vitro preparations at subcellular, cellular and tissue levels. A particularly productive approach has been the electron probe X-ray microanalysis (EPMA) of the elemental composition of excised ciliary epithelium. This technique permits analysis of adjacent cells within different regions of the ciliary epithelium. EPMA of rabbit preparations has supported the idea that paired activity of Na+/H+ and Cl-/HCO3- antiports can be the dominant mechanism underlying the first step in secretion, stromal NaCl uptake by PE cells. EPMA also indicates that Cl- turnover is faster in the anterior than the posterior region of the epithelium. At the opposite epithelial surface, release of Na+ through Na+,K+-activated ATPase of NPE cells is also greater anteriorly than posteriorly. The accompanying release of Cl- through ion channels is enhanced by agonists of A3 adenosine receptors (ARs). The concepts that paired antiport activity is important in stromal NaCl uptake and that A3ARs modulate NaCl release into the aqueous humour were based on in vitro studies. The potential relevance of these conclusions to in vivo conditions has been tested by measurements of IOP in the living mouse. The results have confirmed the predictions that inhibitors of Na+/H+ antiports lower IOP, and that A3AR agonists and antagonists raise and lower IOP, respectively.
Civan
Mortimer M
MM
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. civan@mail.med.upenn.edu
Macknight
Anthony D C
AD
D000818:Animals; D017920:Antiporters / Q000502:physiology; D001082:Aqueous Humor / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology; D002924:Ciliary Body / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D012965:Sodium Chloride / Q000378:metabolism
D017920:Antiporters; D012965:Sodium Chloride