Abstract
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.
Highlights
Physiological levels of intraocular pressure (IOP), ranging from 9 to 21 mmHg in humans, basically depend on the balance between the rate of aqueous humor production by the epithelium of the ciliary body and the rate of its main drainage through the trabecular meshwork and the canal of Schlemm into the vein circulation; when IOP is higher than normal, this is referred to as ocular hypertension [1].Glaucoma is a blinding disease representing the most common neurodegenerative pathology as it is expected to affect about 111 million people worldwide by 2040 [2]
We demonstrated the effective hypotonizing activity of melatonin and agomelatine in combination with lipoic acid
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
Summary
Physiological levels of intraocular pressure (IOP), ranging from 9 to 21 mmHg in humans, basically depend on the balance between the rate of aqueous humor production by the epithelium of the ciliary body and the rate of its main drainage through the trabecular meshwork and the canal of Schlemm into the vein circulation; when IOP is higher than normal, this is referred to as ocular hypertension [1].Glaucoma is a blinding disease representing the most common neurodegenerative pathology as it is expected to affect about 111 million people worldwide by 2040 [2]. The main approved treatments for glaucoma rely on the use of drugs that are able to reduce IOP, including prostaglandin analogs, β-adrenergic blockers, α-adrenergic agonists, carbonic anhydrase inhibitors, Rho kinase inhibitors, and cholinergic agonists, either as monotherapy or combination therapy [4]. These drugs reduce IOP by about 20% to 40%, which is usually efficacious in preventing (or at least delaying) pressure-induced. Neuroprotective molecules, eventually preventing retinal ganglion cell degeneration, have been reported to halt or delay glaucoma progression when used alone or in combination with IOP-lowering drugs [7]. 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, resulted in an increased duration of the hypotonizing effect
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