Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

Abstract

Purpose A growing evidence in the scientific literature suggests that oxidative damage plays a pathogenic role in primary open-angle glaucoma. Therefore, it is of interest to test whether drugs effective against glaucoma display antioxidant activity. We test the hypothesis that the classic b-blocker therapy for glaucoma with timolol involves the activation of antioxidant protective mechanisms towards endothelial cells. Methods Oxidative stress was induced in cultured human endothelial cells by iron/ ascorbate with or without timolol pretreatment. Analysed parameters included cell viability (neutral red uptake and tetrazolium salt tests), lipid peroxidation (thiobarbituric reactive substances), and occurrence of molecular oxidative damage to DNA (8-hydroxy-2 0 -deoxyguanosine).Results Oxidative stress decreased 1.8-fold cell viability, increased 3.0-fold lipid peroxidation and 64-fold oxidative damage to DNA. In the presence of timolol, oxidative stress did not modify cell viability, whereas lipid peroxidation was increased 1.3-fold, and DNA oxidative damage 3.6-fold only.Conclusions The obtained results indicate that timolol exerts a direct antioxidant activity protecting human endothelial cells from oxidative stress. These cells employ mechanisms similar to those observed in the vascular endothelium. It is hypothesized that this antioxidant activity is involved in the therapeutic effect of this drug against glaucoma.

Sensitivity of Ocular Anterior Chamber Tissues to Oxidative Damage and Its Relevance to the Pathogenesis of Glaucoma

“…36 The TM is a complex cellular system that increases the contact surface between the endothelium and AH. 1 The TM is responsible for the AH outflow from the AC and Schlemm's canal. 33,35 The TM undergoes a progressive time-related decline in the number of cells until a dysfunction of the entire region occurs.…”

“…1 AH is secreted in the posterior chamber by the ciliary body and leaves the AC via two routes: the conventional (anterior) route is the through the TM, and the unconventional (posterior) route is through the uveoscleral pathway. 2 Uveoscleral outflow contributes to approximately 30% of the total amount of AH drainage.…”

Timolol Modulates Erythrocyte Nitric Oxide Bioavailability

“…However timolol preserves NO inside the erythrocyte will not favoured the formation of peroxinitrite in an oxygen reactive stress external environment. The antioxidant ability of timolol was evidenced in vitro in endothelial cells and neutrophils, as well in vivo in newborn rats under oxygen induced retinopathy [26][27][28].…”

Oxidative Stress Theory of Glaucoma

“…5 Other studies have also shown that timolol protects from free radical-induced apoptosis because of its antioxidant potential. 6 We may suggest that research studies in tear samples may help in deciding the oxidative potential of diverse topical glaucoma medications much more than the aqueous humor or vitreous body samples.…”