Strategies to Reduce Oxidative Stress in Glaucoma Patients

Abstract

Background: Primary open-angle glaucoma (POAG) is a multifactorial pathology involving a variety of pathogenic mechanisms, including oxidative/nitrosative stress. This latter is the consequence of the imbalance between excessive formation and insufficient protection against reactive oxygen/nitrogen species.

Objective: Our main goal is to gather molecular information to better managing pathologic variants that may determine the individual susceptibility to oxidative/nitrosative stress (OS/NS) and POAG.

Method: An extensive search of the scientific literature was conducted using PUBMED, the Web of Science, the Cochrane Library, and other references on the topic of POAG and OS/NS from human and animal model studies published between 2010 and 2017. Finally, 152 works containing relevant information that may help understanding the role of antioxidants, essential fatty acids, natural compounds and other similar strategies for counteracting OS/NS in POAG were considered.

Results: A wide variety of studies have proven that antioxidants, among them vitamins B3, C and E, Coenzyme Q10 or melatonin, ω-3/ω-6 fatty acids and other natural compounds (such as coffee, green tea, bear bile, gingko biloba, coleus, tropical fruits, etc.,) may help regulating the intraocular pressure as well as protecting the retinal neurons against OS/NS in POAG.

Conclusion: Based on the impact of antioxidants and ω-3/ω-6 fatty acids at the molecular level in the glaucomatous anterior and posterior eye segments, further studies are needed by integrating all issues involved in glaucoma pathogenesis, endogenous and exogenous risk factors and their interactions that will allow us to reach newer effective biotherapies for preventing glaucomatous irreversible blindness.

Keywords: Glaucoma; antioxidants; essential fatty acids; natural compounds; nitrosative stress; oxidative stress..

Fig. (1)

Endogenous and exogenous sources capable to produce cellular response to reactive oxygen/nitrogen species (ROS/RNS). The level of reactive species is regulated by different antioxidant defense mechanisms. When there are low/normal levels of ROS/RNS the physiological functions are maintained. However when an excess of them exists, an oxidative stress occurs. (MDA: malondialdehyde; 4-HNE: 4 hydroxynonenal; SOD: superoxide dismutase; CAT: catalase; TAC: total antioxidant capacity; IL-6: interleuquin-6; TNFa: tumor necrosis factor alpha; NO: nitric oxide; ET-1: endothelin-1; GSH: glutathione; Gpx: glutathione peroxidase; Gtr: glutathione S-transferase; Hcys: homocysteine).

Fig. (2)

Flowchart showing the most relevant OMIC sciences.

Fig. (3)

Experimental glaucoma models. A) The most usual animal models utilized in glaucoma research have been set up in mice, rat and mini pig. B) Experimental rat model of chronic glaucoma by seriate intracameral injections of sodium hyaluronate in the left eye vs balanced salt solution injection in the sham operated right eye [92]. C) rat ocular tonometry. D) Whole mount retinal staining of the RGCs in the non glaucomatous rat eye, and E) showing the significant decrease in RGCs density in the induced glaucoma eye (left).