Deuterated polyunsaturated fatty acids provided protection against oxidative stress in ocular fibroblasts derived from glaucoma patients

Abstract

Glaucoma is a complex neurodegenerative disease of the optic nerve that leads to irreversible sight loss. Lowering intraocular pressure (IOP) medically or surgically represents the mainstay of treatment but despite adequate treatment optic nerve function can continue to deteriorate leading to blindness. There is significant clinical and experimental evidence that oxidative stress is involved in the pathogenesis of glaucoma. Decreasing the formation of lipid peroxidation products or scavenging them chemically could be beneficial in limiting the deleterious effects of oxidative stress in glaucoma. A solution to control the susceptibility of PUFAs to noxious lipid peroxidation reactions is by regioselective deuteration. Deuterium incorporated into PUFAs at bis-allylic positions (D-PUFAs) inhibits the rate-limiting step of lipid peroxidation. In this study, we have shown that Tenon's ocular fibroblasts from glaucoma patients have significantly increased basal oxidative stress compared to non-glaucomatous control patients. Furthermore, we have shown that deuterated polyunsaturated fatty acids (D-PUFAs) provide an enhanced rescue of menadione induced lipid peroxidation in both non-glaucomatous and glaucomatous Tenon's ocular fibroblasts using malondialdehyde (MDA) levels as a marker. Our study suggests that D-PUFAs may provide a potentially safe and effective method to reduce cytotoxic oxidative stress in glaucoma.

Keywords: Glaucoma; Lipid peroxidation; Malondialdehyde; Menadione; Oxidative stress; Polyunsaturated fatty acids; Primary open angle glaucoma; Tenon's ocular fibroblast.