Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap4A, in the aqueous humour

Castany, Marta; Jordi, I.; Català, Jaume; Gual, Arcadi; Morales, Miguel; Gasull, Xavier; Pintor, Jesús

doi:10.1016/j.exer.2010.12.004

Cited by 25 publications

(36 citation statements)

References 32 publications

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“…In the eye, this dinucleotide activates mainly P2Y 2 receptors [11] modifying several physiological factors such as intraocular pressure [12]. In this way, it has been possible to see that in normotensive New Zealand white rabbits, the topical application of Ap 4 A can produce a reduction in IOP [7].…”

Section: Introductionmentioning

confidence: 99%

“…One of these nucleotides is diadenosine tetraphosphate, Ap 4 A, which is present, both in animal and human aqueous humour [7][8][9]. Ap 4 A can activate P2X and P2Y purinergic receptors as well as its own dinucleotide receptor [10].…”

Section: Introductionmentioning

confidence: 99%

“…To complicate the complexity of dinucleotides in the regulation of aqueous humour dynamics even more, studies have shown that glaucomatous patients present increased levels of Ap 4 A in their aqueous humour [7], which were almost 15 times higher in glaucoma patients than in healthy individuals. This increase in the dinucleotide levels has also been described in the case of ATP [15].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

Fonseca

Martínez-Águila

Lara

et al. 2016

Purinergic Signalling

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Glaucoma is a neurodegenerative disease that produces blindness. The main factor associated with this disease is an abnormally elevated intraocular pressure (IOP). To date, some attempts have been made to demonstrate the role of nucleotides modulating IOP, but never in a model of glaucoma. The DBA/2J mouse is an animal that develops the pathology spontaneously, starting from the typical rise in IOP at 9 months of age. Using this animal model, together with a control mouse, C57BL/6J, it has been possible to monitor the elevation in IOP in the glaucomatous mice and to check the ability of the dinucleotide diadenosine tetraphosphate AKA Ap 4 A to reduce IOP. The topical application of Ap 4 A when IOP is maximal (9-12 months) reduced IOP 30.6 ± 6.6% in the DBA/2J and 17.9 ± 4.0% in the C57BL/ 6J mice. Concentration response curves in both animal strains produced similar pD2 values; these being 4.9 ± 0.5 and 5.1 ± 0.4 for the normotensive C57BL/6J and the glaucomatous DBA/2J respectively. Antagonist studies showed differences between the control and the glaucomatous animals. In particular, the main receptor reducing IOP in the control animal was the P2Y 1 receptor and in the glaucomatous model the P2Y 6 , although the participation of other P2 receptors cannot be ruled out. The long-term effect of Ap 4 A applied three times a week for 3 months showed a clear stop in the elevation of IOP in the glaucomatous model, thus indicating the possibility of using Ap 4 A as an effective compound for the treatment of glaucoma.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

Fonseca

Martínez-Águila

Lara

et al. 2016

Purinergic Signalling

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“…Aqueous humour, the secretion that nourishes the avascular structures of the eye such as cornea and lens, contains dinucleoside polyphosphates at low micromolar concentration (Castany et al, 2011;Pintor et al, 2003). Among the different dinucleotides, Pintor and colleagues have identified and quantified the presence of Ap 4 A (0.34 mM) and Ap 5 A (0.08 mM) in the aqueous humour of rabbits (Pintor et al, 2003).…”

Section: Presence In the Aqueous Humourmentioning

confidence: 99%

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Carracedo

Crooke

Guzmán-Aránguez

et al. 2016

Progress in Retinal and Eye Research

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a b s t r a c tDinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap 4 A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y 2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp 4 U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

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“…Furthermore, an increase in intraocular pressure releases ATP into the anterior chamber of the eye, and it was suggested that the elevated ATP may contribute to the extreme pain experienced by patients with both closed-and open-angle glaucoma [1,2]. Levels of ATP are decreased significantly in the lenses of the UPL rat, a cataract model, and it was suggested that the ATP decrease is associated with cataract development [3].…”

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confidence: 99%

Editorial

Burnstock

2011

Purinergic Signalling

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Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap4A, in the aqueous humour

Cited by 25 publications

References 32 publications

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

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