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JESÚS PINTOR AN. R. ACAD. NAC. FARM.

mononucleotides found in the whole aqueous humour were AMP,
ADP, and ATP, which presented concentration values of 10.4 µM,
1.9 µM, and 1.0 µM, respectively (34). Investigations developed by
Mitchell et al. (18) describe the concentration of ATP in the ciliary
epithelium in particular in the immediate area where it is released.
The concentration values for ATP were between 4 and 8 µM. The
difference between both values may be as a consequence of either a
dilution effect or due to the activity of ecto-nucleotidases (35).
Diadenosine polyphosphates were also present in the aqueous
humour of the rabbit, at lower concentrations than ATP, their values
being 0.34 µM and 0.08 µM for Ap4A and Ap5A, respectively (34).

The presence of both mono and dinucleotides in the aqueous
humour is suggesting a physiological role of these substances in the
control of relevant processes such as intraocular pressure.

The control of intraocular pressure (IOP) is an important process
where nucleotides may participate as therapeutic agents. Glaucoma
is a pathology that, in many cases, is produced by an increase in the
IOP. Pathophysiology of elevated IOP is linked either with the
increased production of aqueous humour by ciliary body or an
increased outflow resistance. This raise in IOP is transmitted to the
retina, producing an occlusion of the posterior ciliary artery,
generating ischaemic optic atrophy and gradual retinal degeneration.
Moreover, the pressure can collapse optic nerve head structural
support and axons can be damaged by mechanical compression. The
final result of these complex negative actions is blindness (36).

IOP is a physiological process highly controlled by the nervous
system. The sympathetic and parasympathetic nervous systems
regulate both the production and drainage of aqueous humour. Part
of the pharmacological treatments for ocular hypertension lie in the
interference of either the synthesis of the aqueous humour
(controlled by the sympathetic system) or of its removal (regulated
by the parasympathetic). In this sense, many pharmacological
approaches have tried to reduce IOP by altering the functioning of
the innervation that controls the dynamics of aqueous humour. The
use of beta-blockers in order to reduce the production of aqueous
humour such as betaxolol or timolol is currently practised. Also, the
application of cholinergic agonists such as carbamylcholine has been

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