Purchase this article with an account.
A. Peral, P. Loma, A. Mediero, A. Sesto, J. Pintor, A. I. Jimenez; Effect of Several siRNA in the Treatment of Ocular Hypertension and Glaucoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4808.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To study the effect of siRNA topical administration targeting Selectin E (ELAM), 11-beta-hydroxysteroid deydrogenase 2 (11-beta-HSD) and different components of renin/angiotensin pathway on intraocular pressure in New Zealand White rabbits to find a treatment for ocular hypertension and glaucoma.
We have designed siRNA using the predictive software SIRFINDER for the following genes: Angiotensin receptors (2 siRNA: ATR1/132 and ATR2/114), Renin (1 siRNA, 136), Cochlin (1 siRNA, 182), ELAM (1 siRNA, 036) and HSD (2 siRNA: 11HSD/01 and 11HSD/02). 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). IOP levels were measured from the beginning of the experiment several times a day along ten days. A control with commercial drugs and previously validated siRNAs, against carbonic anhydrases and beta adrenergic receptors, were used.
The two siRNAs for Angiotensin receptors (ATR1/132 and ATR2/114) (n=2 each) did not reduce IOP in a significant manner when compared with control. Renin/136 siRNA (n=2) caused a decrease in IOP of 17.12 ± 1.77 % (being the control of IOP 100%), lasting 57 hours. Cochlin/182 siRNA (n=4) produced a decrease in IOP (23.33 ± 1.51 %), lasting 78 hours. ELAM/036 siRNA (n=2) had a similar decrease in IOP as Renin/136 siRNA (18.69 ± 2.59%). Finally, the siRNAs for 11HSD (01 and 02) (n=4 each) also decreased IOP when compared with control (13.72 ± 1.43% and 17.50 ± 1.70% respectively). As a control of IOP reduction we used Xalatan, which reduced IOP 23.40 ± 2.36 % during 5 to 6 hours.
The siRNAs tested in this study showed two different behaviours: siRNAs targeting Angiotensin receptors did not cause any hypotensive effect, while the rest of siRNA tested (against Renin, Cochlin, ELAM and HSD) produced a reduction of IOP comparable with the one produced by commercial products (Xalatan). Moreover, siRNA have the advantage of presenting a long lasting effect compared to commercial pharmaceutical products.
This PDF is available to Subscribers Only