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VOL. 72 (3), 519-538, 2006 NEW PERSPECTIVES IN OCULAR PHARMACOLOGY...

mobilization (31, 32) the typical P2Y receptor second messenger
system, and MAPKinase cascade activation33 are involved. These
intracellular mechanisms which accelerate the rate of healing, seems
to be triggered by P2Y2 and P2Y4 membrane receptors (32). These
results match well with the effect of Ap4A, UTP and ATP we have
observed in our investigation, which indicates the activation of a
P2Y2 receptor.

Ap4A is effective inducing an increase in the rate of migration by
stimulating a P2Y2 receptor, while Ap3A and Ap5A do the opposite
by activating a P2Y6 receptor. This dual role of diadenosine
polyphosphates may have a physiological meaning in the intact
tissue. Corneal wound healing is a process that occurs in 3 main
steps as previously commented: lag phase, migration and mitosis
(33). It could be the case that in the intact corneal epithelium, P2Y2
receptors would be the relevant ones facilitating the migration rate
in intact corneas. It is necessary to take into consideration that in
primary corneal epithelial cells in culture, the lag phase is reduced.
This reduction is because the cells do not need to carry out some
pathophysiological processes that occur in the intact cornea after
injury. In the whole cornea, polymorphonuclear leukocytes remove
necrotic cells from the wound margin. Also, hemidesmosomal
attachments between the basament membrane and the basal cells
disappear (33). All these phenomena does not occur in our
preparation since it only contains a monolayer of epithelial cells.

On the other hand, P2Y6 would be critical stopping migration and
starting the third phase (mitosis). It is clear that we do not have any
evidence for the role of P2Y6 receptor to confirm this idea, but it
would not be strange to think about P2Y2 and P2Y6 as switchers that
control the transition from wound healing phase 2 to phase 3.

Nucleotides dinucleotides in the aqueous humour
and the control of intraocular pressure

Aqueous humour is a physiologically relevant fluid that permits
the nutrient supply to nonvascular structures such as the corneal
endothelial cells and the lens. This fluid contains measurable
amounts of both mono- and dinucleotides. The most relevant adenine

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