Page 92 - 72_03

JESÚS PINTOR AN. R. ACAD. NAC. FARM.

environmental medium. Foreign bodies, dirty or defective contact
lenses and also refractive surgery, produce injury on the corneal
epithelium, the most external part of the cornea.

The corneal wound healing process occurs in three main steps:
a lag phase in which after the injury happens cells surrounding
the affected area detach from Bowman’s membrane and those
cells which are affected by the injury are eliminated by
polymorphonuclear leukocytes. A second step in which the cells in
the periphery of the affected area move centripetally to cover the
free space, and finally, a proliferative step in which cells divide to
give the corneal epithelium its normal thickness.

Although all these stages are relevant, a critical step is the
migration phase since it avoids the invasion of bacteria to inner
parts of the eye, and other problems derived from an inadequate
corneal thickness.

In vivo experiments

We have investigated the possible effect of mono and
dinucleotides on the corneal wound healing process. The presence
of these substances in tears may suggest a role of them in the
healing process, therefore it was evaluated the possible role of
these compounds on corneal wound healing in vivo by means
of New Zealand white rabbits which were injured with n-heptanol.
In the absence of any added nucleotide (vehicle) the time of
re-epithelialisation of a 3 mm corneal wound is of 32.2 hours and
the rate of migration is 72.4 µm/hour. When the wounds are treated
with 100 µM UTP or Ap4A the rate of healing was accelerated to
121.6 µm/h and 93.7 µm/h respectively. None of the other mono or
dinucleotides did significantly modify the rate of healing (25).

The positive effect of these two compounds is mediated by P2Y
receptors and presumably P2Y2 since UTP and Ap4A are full agonists.
Also, the application of antagonists such as suramin, PPADS or
reactive blue 2, were able to reverse the effect produced by UTP and
Ap4A. Unfortunately due to the lack of more selective antagonists it
was not possible to fully confirm the P2Y receptor subtype (25).

526