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M. Perez de Lara, A. Crooke, C. Santano, J. Pintor; Silencing P2Y2 Receptors Reduce Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1480.
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© ARVO (1962-2015); The Authors (2016-present)
To silence the expression of P2Y2 receptors in New Zealand white rabbits and to check the effect this process produce on intraocular pressure (IOP).
The rabbit P2Y2 receptor was cloned and according to its sequence siRNA were designed to silence the expression of this protein. Male New Zealand rabbits were used for the experiment. The siRNAs were topically applied in one eye, the contralateral receiving the same volume of saline. Each of the treated eyes received an amount of 250 µg of the siRNA dissolved in 40 µL of 0.9 % NaCl. IOP was measured with a TONOVET tonometer, along ten days and, afterwards, animals were killed and both eyes were collected for immunohystochemical studies.
The application of the siRNA against the P2Y2 receptor produced a marked reduction of intraocular pressure which was measurable 24 hours after the application of the siRNA. The maximal reduction in IOP was 52 ± 3.2 % and this hipotensive effect remained for at least five days, after which the pressure values returned towards normal (initial) IOP values. The mean of reduction in IOP was roughly 40 % during the time the hypotensive effect was measurable. The immunohystochemical analysis by means of P2Y2 receptor antibodies demonstrated a reduction of 85 % in the labelling of the mentioned receptor in the cilliary processes, this result being consistent with the reduction in IOP observed.
The application of a siRNA that silence the P2Y2 receptor confirm the hypertensive role of this nucleotide in the control of IOP, that when silenced reduce concomitantly IOP to values which suggest its possible use for the treatment of ocular hypertension and glaucoma.
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