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M. Castany, M. Morales, J. Catala, I. Jordi, J. Pintor, X. Gasull; Presence and Elevated Levels of Dinucleoside Polyphoshates in the Aqueous Humor of Glaucoma Patients. Invest. Ophthalmol. Vis. Sci. 2008;49(13):351.
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Previous studies have shown the presence of diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) as well as ATP in the aqueous humor (AH) of different species. When topically applied to the rabbit cornea, Ap4A decreased IOP while Ap5A increased it. Dinucleoside polyphospates activate different purinegic receptors (P2Y1, P2Y2 and P2Y4) present in trabecular meshwork cells and both, Ap3A and Ap4A, increase trabecular outflow facility in vitro perfused anteriors segments. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma.
AH was obtained at the time of cataract surgery from patients with (n=10) or without (n=6) chronic open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis using a 27-gauge needle on a tuberculin syringe. AH was immediately cooled at -80ºC and kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap4A and Ap5A.
Ap4A and Ap5A were detected in the AH of both experimental groups. No significant differences were found for Ap5A (control 29±3; glaucoma 39±3 nM). On the contrary, Ap4A levels were increased by 6-fold in the AH from glaucomatous eyes (control 42±29; glaucoma 297±32 nM).
Both, Ap4A and Ap5A were found for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap4A compared to controls. According to results in animal models, increased levels of Ap4A may be part of a homeostatic response in front of ocular hypertension to enhance outflow facility and decrease IOP. The physiopathological role of Ap4A and its use as a biomarker for glaucoma remains to be elucidated.
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