Therapeutic potential of nucleotides in the eye

Abstract

Adenine mononucleotides present the ability to produce changes in the intraocular pressure in New Zealand rabbits. Two main groups of compounds were found in terms of their behaviour-on the one hand, those that increased intraocular pressure, and on the other hand, those that reduced it. The hypotensive compounds showed a concentration-response behaviour, and were blocked by the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid. Moreover, the hypotensive compounds were unaffected by the pretreatment with sympathetic antagonists but were completely abolished by the parasympathetic antagonists. This fact suggests the possibility of these P2 receptors to be present at the cholinergic terminal that control intraocular pressure. Adenine mononucleotides also were assayed in their ability to increase tear secretion rate. This study showed that tear secretion is stimulated via P2Y 2 receptors. Drug Dev. Res. 52:190-195, 2001.

Presence of diadenosine polyphosphates in human tears

“…Diadenosine tetra-and diadenosine pentaphosphate were assayed at concentrations ranging from 10 -10 g/µl to 10 -4 g/µl. Values are the mean ±SEM of eight independent experiments UTP, diadenosine tetraphosphate (Ap 4 A) was the most effective at inducing an increase in tear secretion, as also observed elsewhere [15]. It was interesting to note that diadenosine triphosphate was ineffective at increasing tear secretion.…”

“…It was noteworthy to see that for all the tested dinucleotides only diadenosine tetraphosphate, Ap 4 A, presented interesting hypotensive properties [12]. Additionally, Ap 4 A, Ap 5 A and Ap 6 A can stimulate tear secretion after single-dose topical instillation in rabbits, as measured by the Schirmer test [15].…”

Pathophysiology and Therapeutic Potential of Purinergic Signaling

“…ATP, acting via both P2X and P2Y receptors, modulates retinal neurotransmission, affecting retinal blood flow and intraocular pressure. The ATP analog ␤,␥-methylene ATP is more effective in reducing intraocular pressure (40%) than muscarinic agonists such as pilocarpine (25%) and ␤-adrenoceptor blockers (30%), raising the potential for the use of purinergic agents in glaucoma (Pintor and Peral, 2001). Dinucleoside polyphosphates acting via P2Y 1 receptors on trabecular network cells increase aqueous humor outflow and may be another target for antiglaucomatous drugs (Soto et al, 2005).…”

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

“…Among these new potential substances to treat the elevation in IOP associated with glaucoma are nucleotides, emerging as interesting molecules since they are present in aqueous humour [4] and they can induce either an increase or a decrease in IOP, depending on the purinergic receptor that is stimulated [5]. Nucleotides have developed their importance in ocular physiology since they are involved in many crucial processes in most of the ocular structures [6].…”