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. Abbreviations: POAG: Primary Open Angle Glaucoma; TM: Trabecular Meshwork; NP: Lipid Nanoparticles; HDPE: High Dose Polyphenols Extract, SDPE: Standard Dose Polyphenols Extract.