Role of Oxidative Stress in Ocular Diseases: A Balancing Act

Abstract

Redox homeostasis is a delicate balancing act of maintaining appropriate levels of antioxidant defense mechanisms and reactive oxidizing oxygen and nitrogen species. Any disruption of this balance leads to oxidative stress, which is a key pathogenic factor in several ocular diseases. In this review, we present the current evidence for oxidative stress and mitochondrial dysfunction in conditions affecting both the anterior segment (e.g., dry eye disease, keratoconus, cataract) and posterior segment (age-related macular degeneration, proliferative vitreoretinopathy, diabetic retinopathy, glaucoma) of the human eye. We posit that further development of therapeutic interventions to promote pro-regenerative responses and maintenance of the redox balance may delay or prevent the progression of these major ocular pathologies. Continued efforts in this field will not only yield a better understanding of the molecular mechanisms underlying the pathogenesis of ocular diseases but also enable the identification of novel druggable redox targets and antioxidant therapies.

Keywords: age-related macular degeneration; cataract; cornea; dry eye disease; epithelial–mesenchymal transition; glaucoma; keratoconus; mitochondrial dysfunction; proliferative vitreoretinopathy; reactive oxygen species; retina.

Figure 1

Redox homeostasis in the eye. A homeostatic balance of antioxidants and reactive oxygen species (ROS) is required for the healthy functioning of ocular tissues. An imbalance of antioxidants (AOX) and ROS through either the depletion of antioxidants or excessive ROS accumulation will result in oxidative stress and drive subsequent disease progression. Antioxidants are categorized as either enzymatic or non-enzymatic. ROS can be derived from either endogenous or exogenous sources. Examples of heavy metals include lead (Pb), arsenic (As), and mercury (Hg).

Figure 2

Factors driving oxidative damage during age-related macular degeneration (AMD) and the need for antioxidant defense systems to combat the pathophysiology of the disease.

Figure 3

Diabetes-induced hyperglycemia disrupts the redox balance, leading to oxidative stress in the retina. Under normal physiological conditions, there is a balance in the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and the antioxidant defense system. Diabetes-induced hyperglycemia promotes ROS/RNS generation while also suppressing the retinal antioxidant response, creating the imbalance known as oxidative stress. The AGE pathway, the polyol pathway, the hexosamine biosynthetic pathway (HBP), and the protein kinase C pathway are all sensitive to this disruption and play an important role in the downstream effects of hyperglycemia-induced retinal damage.