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

Previous studies have shown the presence of diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap4A decreased IOP while Ap5A increased it. 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 = 16) or without (n = 10) primary open-angle glaucoma. AH (0.1–0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap4A and Ap5A. Both, Ap4A and Ap5A were detected in the AH of both experimental groups. No significant differences were found for Ap5A. In contrast, Ap4A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5 ± 9.2 nM in normal individuals to 286.03 ± 30.9 nM in glaucomatous patients. In conclusion, both Ap4A and Ap5A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap4A compared to controls. The role of Ap4A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker.

Research highlights► Diadenosine polyphosphates are present in the human aqueous humour. ► This molecules can activate P2 receptors in the ciliary body and trabecular meshwork. ► Diadenosine polyphosphates are increased 15 times in primary open-angle glaucoma patients. ► Diadenosine tetraphosphate might be considered as a possible biomarker for glaucoma condition.