Oxidative stress in the light-exposed retina and its implication in age-related macular degeneration

Abstract

The retina continuously receives light to enable vision, and the related processes require a marked amount of energy. During active metabolism, reactive oxygen species (ROS) are generated in exchange. Although physiologically generated ROS may be removed by endogenous antioxidant systems, and the effects of oxidative stress may be recovered by repair systems to retain homeostasis and health, when ROS and oxidative stress exceed the capacity of the antioxidant and repair systems, the condition becomes pathological. Multiple mechanisms of oxidative stress and the effects of antioxidant and repair systems in the retina have long been analyzed using light-induced retinal degeneration models. Among the mechanisms, a positive feedback loop of oxidative stress and related inflammation may be involved in the pathogenesis of a blinding aging disease, age-related macular degeneration. Treatments for suppressing ROS and oxidative stress by administrating antioxidant products may support the tissue-protective function of antioxidant systems. Moreover, recent studies have proposed a new concept for maintaining homeostasis by supplying sufficient energy to activate the repair systems. The current review will help elucidate the influence of oxidative stress and guide future analyses to explore new therapeutic approaches for oxidative stress-mediated diseases.

Keywords: Age-related macular degeneration; Antioxidants; Inflammation; Oxidative stress; Retina; Tissue repair.

Fig. 1

Balance between oxidative stress and self-defense systems determines whether the cell/tissue/organ condition is pathological or healthy. Self-defense systems, such as antioxidant systems that remove ROS and alleviate oxidative stress, and repair systems that aid recovery from the resulting disorders, are present in vivo. If the accumulated ROS and oxidative stress exceed the capacity of the antioxidant and/or repair systems, cell/tissue/organ disorders and death ensue and may cause disease pathogenesis, although as long as the capacity of the antioxidant and repair systems is retained, the cells, tissues, and organs remain healthy. ROS, reactive oxygen species.

Fig. 2

Mechanisms of light-induced oxidative stress in cell death and tissue/organ disorders. Light-induced ROS modify DNA, proteins, and lipids to affect the DNA environment, including the DNA structures and epigenetics, signal transduction, protein folding, mitochondrial function, cell-surface condition, and the cytoskeleton to induce inflammation, disorganized autophagy, ER stress, energy crisis, and disruption of cell–cell interaction, which finally cause cell death and tissue/organ disorders. ROS, reactive oxygen species; ER; endoplasmic reticulum.

Fig. 3

The positive feedback loop of oxidative stress and inflammation causes age-related macular degeneration (AMD). Aging, continuous and/or excessive light exposure, smoking, metabolic syndrome, and single nucleotide polymorphisms cause and/or accelerate oxidative stress, which induces macrophage recruitment, cytokine expression, and inflammation and forms a positive feedback system and vicious cycle to finally cause AMD.

Fig. 4

Repair systems against oxidative stress require ATP. To repair ROS- and oxidative stress-induced damage, ATP and energy are required; promoting ATP production and/or suppressing ATP degradation may support supply sufficiency. However, when ATP is insufficient, the repair systems do not work properly. The decompensation finally induces cellular disorders and death. ROS, reactive oxygen species; ATP, adenosine triphosphate.

Fig. 5

Protective effects of lutein/zeaxanthin. Lutein and zeaxanthin are derived from food and delivered to the retina and block excessive light by absorbing blue light, which is of short wavelength and high energy, act as ROS scavengers and induce antioxidant enzymes to protect the retina from oxidative stress. ROS, reactive oxygen species. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)