ATP Release Via Connexin Hemichannels Controls Intercellular Propagation of Ca Waves in Corneal Endothelial Cells - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 157

10.1 Introduction
This chapter discusses the mechanism and role of ATP-mediated intercellular
communication in coordinating the activity of endothelial cells of the cornea.
10.1.1 Corneal Endothelium
The corneal endothelium is a non-regenerative monolayer at the posterior surface
of the cornea. It separates the anterior chamber of the eye from the corneal stroma.
While the corneal endothelial monolayer has a barrier function similar to vascular
endothelium, and the cells express endothelial cell markers such as von Willebrand
factor (vWF) (see Table 10.1), most of the corneal endothelial cells are derived
from neural crest, instead of having a mesodermal origin [41]. However, it has been
demonstrated that neural stem cells can differentiate to the endothelial lineage [125].
As in vascular endothelium, corneal endothelial cells are interconnected by a
complex set of interendothelial junction proteins that comprise tight junctions,
adherens junctions and gap junctions. Whereas tight junctions and adherens junc-
tions form zipperlike pericellular structures along the cell border through their
homophilic adhesions of their transmembrane proteins, gap junctions form plaques
of transmembrane channels between adjacent cells.
The main physiological role of the corneal endothelium is to maintain the trans-
parency of the cornea by controlling stromal hydration. Decompensation of the
endothelium leads to stromal edema, and hence loss of visual acuity, and is a com-
mon indication for corneal transplantation. Unlike most tissues in the body, the
cornea is avascular; it contains no blood vessels to nourish it or to protect it against
infection. Instead, aqueous humor that circulates in the anterior chamber is largely
responsible for supplying nutrients to the cornea, while oxygen is supplied via the
tears as well as by the aqueous humor.
Because of its discontinuous focal tight junctions and the sinuous interdigita-
tion of lateral membranes of adjacent cells, the endothelium forms a leaky barrier,
which permits paracellular percolation of aqueous humor from the anterior cham-
ber into the cornea. The same discontinuous tight junctions and interdigitations of
the endothelium also function as a barrier by restraining excessive fluid leak into
the stroma. Furthermore, the fluid leak is counterbalanced by an active fluid trans-
port of the endothelial cells from the stroma into the anterior chamber of the eye.
Thereby, the endothelium carries out hydration control of the corneal stroma, which
is essential for maintaining corneal transparency (for review see [11]).
10.1.2 Intercellular Signaling Coordinates Function of the
Corneal Endothelium
In order to sustain these physiological functions in the absence of regeneration, the
corneal endothelium possesses a number of mechanisms to withstand extracellular