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J. J. Pintor, P. Alarma-Estrany, A. Mediero, A. Crooke, A. Peral; Requirement of Intact Sympathetic Transmission for the Ocular Hypotensive Effect of Melatonin and IIK7. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2098.
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© ARVO (1962-2015); The Authors (2016-present)
The aim of this study is to confirm the relationship between the ocular hypotensive effects of melatonin an the MT2 agonist IIK7, and the sympathetic nervous system that control this process.
New Zealand white rabbits were used. Intraocular pressure (IOP) was measured by means of Tonopen®. Two IOP measurements were taken before any compound was instilled and after that once every hour for 8 hours after application of topical tetracaine. Chemical sympathectomy was performed injecting reserpine (2 mg/kg, intraperitoneally) once daily for 5 days (n=6). Control animals were injected with a similar volume of the vehicle. In another six animals, two injections of 0.2 ml of 10% 6-hydroxydopamine subconjunctival was performed. Contralateral eyes were injected with a similar volume of the vehicle. Cryostat sections of ciliary bodies were incubated with vesicular monoamine transporter (VMAT2) antibody (1:500) and then with a secondary guinea-pig IgG labelled with TRITC (1:250). After that, the tissues were observed under confocal microscopy.
When melatonin 100 µM (10 µl) was topically applied to the cornea the maximal reduction of IOP was 17.2 ± 2.0% (n=8). After melatonin application in reserpine or 6-hydroxydopamine treated animals, the values obtained were 4.7 ± 4.9 % and 5.2 ± 2.0 %, respectively. The instillation of IIK7 100 µM (10 µl) produced a reduction of 22.67 ± 4.00 %. When this analogue was topically applied after the treatment with reserpine or 6-hydroxydopamine, the reduction in IOP was 6.45 ± 2.49 % and 12.55 ± 2.00 %, respectively. The reduction it is also observed in the duration of the hypotensive effect. Immunohistochemical studies showed that non-treated animals had positive labelling for anti-VMAT2 along the ciliary processes. However, animals treated with reserpine or 6-hydroxydopamine were negative to VMAT2 antibody, indicating the success in the chemical sympathectomy.
The ocular hypotensive effects of melatonin and IIK7 are coupled to the sympathetic component controlling the synthesis and drainage of the aqueous humour.
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