Background: Melatoninergic agents are known to reduce intraocular pressure (IOP). The
present study was performed to evaluate the effect of nanomicellar formulations of melatoninergic
agents on IOP in the rat. Methods: Tonometry was used to measure IOP in eyes instilled with
melatonin or agomelatine. Ocular hypertension was induced by the injection of methylcellulose in
the anterior chamber. Results: Melatonin formulated in nanomicelles had a longer lasting
hypotonizing effect on IOP with respect to melatonin in saline. Nanomicellar formulations of
melatonin and agomelatine, either alone or in combination, had lowering effects that did not
depend on their concentration or their combination, which, however, resulted in an increased
duration of the hypotonizing effect. The duration of the lowering effect was further increased by
the addition of lipoic acid. Conclusions: We demonstrated the effective hypotonizing activity of
melatonin and agomelatine in combination with lipoic acid. Although results in animals cannot be
directly translated to humans, the possibility of developing novel therapeutical approaches for
patients suffering from hypertensive glaucoma should be considered