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M. Alarma-Estrany, T. Pelaez, A. Peral, A. Crooke, A. I. Guzman, J. Pintor; MT2 Melatonin Receptors Reduce IOP in Normotensive Rabbits. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4810.
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© ARVO (1962-2015); The Authors (2016-present)
To demonstrate that a MT2 melatonin receptor is involved in the reduction of IOP by means of the MT2 melatonin receptors agonist IIK7, and to determine the presence of MT2 receptors in the ciliary body in New Zealand white rabbits .
Melatonin and IIK7 were formulated in isotonic saline containing 1% DMSO and tested at a final concentration of 100µM . The compounds were applied unilaterally to the cornea at a fixed volume of 10 µL in New Zealand rabbits eyes. The contralateral eye received the same volume of saline + 1% DMSO (vehicle). Corneas were anaesthetized by applying 10 µl of 1:10 (v:v) of oxibuprocaine / tetracaine (4 mg and 1 mg respectively). IOP was measured by means of a TONOPEN® XL twice before the application of the solution and after that once every hour for at least 8 hours.Cryostat sections of ciliary body were utilized for immunohistochemical experiments. Sections were incubated with MT2 melatonin receptor antibody and subsequently incubated with a secondary IgG mouse labelled with TRITC, then, the tissues were observed under confocal microscopy.
While the hormone melatonin presented a sharp reduction in IOP of 20.2 ± 5.3 % compared to control (n=8), followed by a gradual return to control values 4 hours after the beginning of the experiment, 100 µM IIK7 reduced IOP 38.5 ± 3.2 % compared to control (n=8) and IOP remained low for almost 7 hours, returning to basal values after this period of time. Also, the non-selective melatonin antagonist luzindole partially returned the effect of IIK7 towards the control values (80.5 ±2.6 %, n=8) and the MT2 receptor antagonists 4-PPDOT and DH-97 returned the effect of IIK7 to control values (92.6 ± 6.3 % and 97.4 ± 3.3 % respectively, n=8). On the other hand, immunohistochemical studies showed the presence of MT2 melatonin receptors in the ciliary processes.
The results demonstrate that the main target of IIK7 in the control of IOP is the MT2 receptor which is founded in ciliary processes. Melatonin agonist as IIK7 may have clinical potential for treating elevated IOP.
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