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J.J. Pintor, A. Mediero, A. Jimenez, A. Sesto, G. Gonzalez de Buitrago, A. Peral; SiRNA in the Treatment of Ocular Hypertension Targeting Alpha and Beta Adrenoceptors . Invest. Ophthalmol. Vis. Sci. 2006;47(13):403.
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© ARVO (1962-2015); The Authors (2016-present)
To study the effect of siRNA topical administration against α and ß adrenoceptors on intraocular pressure in New Zealand White rabbits to find a treatment for ocular hypertension and glaucoma.
We have designed siRNA for the following adrenergic receptor genes: ß1 (1 siRNA, 007), ß2 (2 siRNA, 012 and 011), α1A (1 siRNA, 097) and α1B (2 siRNA, 99 and 100). siRNAs were administered in saline solution (0.9% w/v) to a final volume of 40µl in one eye during four consecutive days and the opposite eye was taken as a control applying 40µl of sterile saline (0.9% w/v). With the ß2 (012), we did a re–application dose assay, in which we applied twice the protocol mentioned before with a resting day between them.
The 007 siRNA for ß1 (n=2) reduced IOP in 28.04 ± 2.98 % during 98 hours. ß2/012 siRNA (n=3) caused a decrease in IOP of 21.81 ± 1.55 % (being the control of IOP 100%), lasting 100 hours. ß2/012 gen re–application (n=1) caused a similar decrease in IOP (19.29 ± 0.89 %), lasting 223 hours. ß2/011 siRNA (n=2) did not have the same effect as ß2/012 gen. It produced a decrease in IOP of 14.90 ± 1.26 % during 22 hours. siRNA for α1A (097) (n=2) produced a decrease of 19.08 ± 2.04 % during 93 hours. Moreover, the two different siRNA for α1B (99 and 100) (n=2 each) produced a similar decrease in IOP (17.34 ± 2.26 % for 99 and 14.39 ± 1.49 % for siRNA 100), lasting from 74 hours (for 99) to 78 hours (for 100). As a control of IOP reduction we used Xalatan, which reduced IOP 23.40 ± 2.36 % during 5 to 6 hours.
The reduction of IOP with siRNA against α and ß adrenoceptors is comparable with those produced by commercial products. Moreover, siRNA have the advantage of presenting a long lasting effect compared to commercial pharmaceutical products.
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