Protection of trabecular meshwork cells by eyedrops containing high concentration of polyphenols

Abstract

Background: Glaucoma is caused by pro-apoptotic signals targeting retinal ganglion cells. In the high-pressure glaucoma, the source of these signals is the progressive degeneration of the trabecular meshwork. The first pathogenic event affecting this tissue is oxidative damage. Accordingly, the use of anti-oxidant to counteract glaucoma pathogenic cascade is a rationale strategy to be explored. In this paper we evaluate the ability of eyedrops containing high dose of polyphenols, hyaluronic acid and fatty acids to protect trabecular meshwork from oxidative stress.Methods: Human Trabecular meshwork endothelial cells were exposed in vitro to hydrogen peroxide either in presence or absence of eyedrops containing high dose of polyphenols. Ex-vivo experiments were performed in calf eye to evaluate the ability of eyedrops to cross cornea either alone or complexed with lipid nanoparticles.The tolerability of eyedrops was tested in vivo in rabbit eye.Results: Polyphenol enriched eyedrops were highly safe when used alone not altering viability, mitochondrial function and DNA integrity of trabecular meshwork cells. Eyedrops was effective in protecting trabecular meshwork cells from oxidative stress. These characteristics were not modified when eyedrops was carried by lipid nanoparticles.In calf eye polyphenolic eyedrops were able to cross cornea, an effect counteracted by the complexation with lipid nanoparticles.In vivo in rabbit eye, eyedrops were well tolerated and persisted for 20 min on outer corneal surface, a time is increased up to 16 h by complexation with nanoparticles.Conclusions: Polyphenolic eyedrops are safe and able to protect trabecular meshwork cells from oxidative stress.

Can Polyphenols in Eye Drops Be Useful for Trabecular Protection from Oxidative Damage?

“…3D-HTMCs, which, in addition to 500 µM H 2 O 2 , were treated with iTRAB ® showed both a significant decrease of ROS production ( Figure 1A) and an increase in the viability index ( Figure 1B) compared to the 3D-HTMCs exposed to only 500 µM H 2 O 2 [20,37,48]. These results highlight the anti-oxidant activity of iTRAB ® .…”

“…In fact, oxidative stress is responsible for the inflammatory condition which leads to TM damage and consequently to an outflow dysfunction [47]. In this regard, previous studies have evaluated the effect of several anti-oxidant compounds (i.e., polyphenols, carotenoids, resveratrol, vitamin E and N-acetylcysteine) in order to prevent or to counteract glaucoma [20,26,37,48,49]. In particular, the protective role of polyphenols towards the free radical attacks that affect TM has emerged, providing a greater chance of long-term visual function maintenance [1].…”

“…Therefore, in the ophthalmology field, for instance, the topical application of polyphenolsis strongly recommended in order to increase their therapeutic efficacy. Saccà et al (2019) have already demonstrated the effectiveness of the anti-oxidant iTRAB ® , that is the active principle of DRAIN drops ® , in two-dimensional TM cells subjected to chronic oxidative stress [37].…”

“…The effects of iTRAB ® , a concentrated mixture of polyphenols (≥2.5%) from Perilla frutescens [37] ( Figure S1), on the 3D-HTMCs were investigated after prolonged oxidative stress conditions.…”