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Jesus J. Pintor, Alba Martin-Gil, Begoña Fonseca; Activation of TRPV4 Induces the Release of Diadenosine Tetraphosphate to the Aqueous Humour. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2052.
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To investigate if the activation of TRPV4 induces the release of nucleotides, mainly Ap4A, to the aqueous humour of New Zealand white rabbits.
In Vivo experiments were performed in New Zealand rabbits. Intraocular pressure was measured by means of a TonoVet rebound tonometer (Tiolat Oy, Helsinki) on normal and hypertensive eyes. Ocular hypertension was obtained by placing the animals in Trendelemburg position which produces venous stasis. Aqueous humor was removed in any given condition after anaesthesia and the aqueous was taken for HPLC analysis. In Vitro experiments were performed in immortalized NPE cells, kindly provided by Dr. Coca-Prados. Cells were incubated with a specific TRPV4 activators (4alpha-PDD and hypo-osmotic medium) and the TRPV4 blocker (ruthenium red). The supernatants were collected and analyzed with HPLC.
Ocular hypertension significantly increased Ap4A concentration in the rabbit aqueous humor (216,52% ± 9.44 vs. control, p<0.01) this effect being reversed by ruthenium red. In the case of the specific TRPV-4 activator, 4alpha-PDD (10 nM), this compound was able to raise Ap4A concentrations 138.31 %. In Vitro experiments showed that Ap4A levels increased 157,75 % after treatment with 4alpha-PDD and 665,97% for hypo-osmotic conditions, when compared to control. Ruthenium red reversed this effect when 4alpha-PDD was used, but was only able to partially reverse it in hypo-osmotic conditions.
These experiments demonstrated the involvement of TRPV4 in the release of Ap4A to the aqueous humor. This could explain the increased concentrations of Ap4A in glaucoma patients and support the idea of TRPV4 being an active target the control of intraocular pressure control.
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