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Hanan Awad Alkozi, Alejandro Martinez-Aguila, Begoña Fonseca, Almudena Crooke, Maria Jesus Perez de Lara, Jesus Pintor; Hypotensive effect of melatonin and its analogues in different animal models. Invest. Ophthalmol. Vis. Sci. 2014;55(13):566. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To demonstrate the potential use of melatonin and its analogues in decreasing IOP which is often elevated in glaucoma.
Different animals were used along this study: New Zealand white rabbits, normotensive and hypotensive by the Trendelenburg position (80 deg. head down). Mice, normotensive control model C57BL/6J and glaucomatous model DBA/2J. Hypertensive monkeys with laser induced unilateral glaucoma (data taken from a study done by Serle JB et al., 2004). Normotensive humans during cataract surgery (data taken from Ismail and Mowafi, 2009). Melatonin or analogues were topically applied except in the case of humans which was a single oral dose of 10 mg. All animals were kept with free access to food and water; they were submitted to controlled 12h/12h light/dark cycle. IOP measurements were taken by TonoPen (rabbits), TonoVet (rabbits) and Tonolab (mice). Single doses of the agonist at a concentration of 100 µM (10 µL), were topically applied unless other dose/volume is indicated. Contralateral eye received the same volume of vehicle.
Melatonin application reduced IOP in normotensive rabbits by 22.0% ± 1.6%, when compared to control animals, while melatonin analogue 5- metoxycarbonylamine N-acetyl tryptamine (5-MCA-NAT) had a reduction until 42.5% ± 1.6%. The effect of the latter lasted more than 8 hours, and also a long-term effect, till 3 days, was measured. In glaucomatous mice when applying melatonin it was also possible to detect a reduction of 33.4% ± 2.5% in IOP. This open the possibility to search for other glaucoma models such as the monkey laser induced glaucoma. In this sense, and as indicated by Serle et al., (2004), when 5-MCA-NAT is applied to hypertensive monkeys it resulted in a reduction of 19.2% ± 2.1% in IOP. Finally, when administering melatonin to normotensive humans there was also a reduction of 32.0% ± 3.2% over the patient’s initial IOP values (Ismail and Mowafi, 2009).
Melatonin and its analogues have already displayed an important pharmacological ability reducing intraocular pressure starting from simple experimental animals, moving towards glaucomatous models and finally tested in humans. This is clearly indicating that melatonin and analogues are new promising molecules for the treatment of elevated IOP often associated with glaucoma.
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