RT Journal Article
T1 Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma
A1 Fonseca, Begoña
A1 Martínez Águila, Alejandro
A1 Pérez de Lara, María Jesús
A1 Pintor, Jesús
AB 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 Ap4A to reduce IOP. The topical application of Ap4A 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 P2Y1 receptor and in the glaucomatous model the P2Y6, although the participation of other P2 receptors cannot be ruled out. The long-term effect of Ap4A 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 Ap4A as an effective compound for the treatment of glaucoma.
PB Springer
SN 1573-9538
YR 2016
FD 2016-11
LK https://hdl.handle.net/20.500.14352/17688
UL https://hdl.handle.net/20.500.14352/17688
LA eng
NO Received: 28 August 2016 /Accepted: 27 October 2016
NO Ministerio de Economía y Competitividad (MINECO)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 2 may 2024