A Topical Formulation of Melatoninergic Compounds Exerts Strong Hypotensive and Neuroprotective Effects in a Rat Model of Hypertensive Glaucoma

International Journal of Molecular Sciences

Maurizio Cammalleri¹  Paola Bagnoli¹  Rosario Amato¹  Massimo Dal Monte¹  Roberta Corsaro²  Dario Rusciano²  Salvatore Pezzino² 

[1] Department of Biology, University of Pisa, via San Zeno, 31, 56127 Pisa, Italy;Sooft Research Center c/o, University of Catania, Via Santa Sofia, 89, 95123 Catania, Italy;

关键词: intraocular pressure;    timolol;    brimonidine;    melatonin/agomelatine;    electroretinography;    retinal ganglion cells;   

DOI  :  10.3390/ijms21239267

来源: DOAJ

【 摘 要 】

Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.

【 授权许可】

Unknown