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Introduction Glaucoma is an eye disease in which damage to the optic nerve leads to gradual vision loss. In glaucoma and other eye disorders, oxidative stress – the build-up of harmful reactive oxygen species (ROS) – has long been implicated in tissue injury (). Oxygen itself, however, plays a dual role in health. Our eyes need oxygen as a vital fuel: the retina has one of the highest oxygen demands in the body, for example, and oxygen is used constantly in nerve-cell metabolism. This is why supplemental oxygen (even in a hyperbaric oxygen therapy (HBOT) setting) can aid healing in some conditions. But paradoxically, too much oxygen can generate excess ROS and cause tissue damage. Under hyperoxic conditions (high oxygen levels), the body produces superoxide, hydrogen peroxide, and other radicals that trigger inflammation and cell injury (). In short, oxygen is life-giving at moderate levels but can be toxic at high doses () (). This “hyperoxia paradox” – oxygen as both medicine and poison – is central to understanding oxidative stress in glaucoma. Oxygen: Medicine and Menace in the Eye Oxygen is indispensable for normal eye function. Retinal cells (especially in the macula and photoreceptor layer) use oxygen to convert nutrients into energy. A steady oxygen supply from the choroid and retinal blood vessels keeps these neurons and support cells alive. In addition, oxygen delivered by blood to the trabecular meshwork (the filtering tissue that helps drain intraocular fluid) and the accommodating lens supports their metabolism. Clinically, supplemental oxygen is sometimes used to improve healing. For example, hyperbaric oxygen therapy (HBOT) – breathing 100% oxygen under pressure – is used for chronic wounds and radiation injury, and it can increase oxygen delivery to eye tissues. However, as medical sources warn, too much oxygen can be harmful (). Hyperoxia disturbs the body’s normal balance and produces a burst of ROS (). “Reactive oxygen species are known problematic by-products of hyperoxia,” notes the medical literature, which explains that excess ROS lead to a cycle of tissue injury, inflammation, and cell death (). In other words, what helps at low doses can hurt at high doses. Free radicals generated by hyperoxia will indiscriminately chemically modify nearby molecules (membranes, DNA, proteins), potentially crippling those cells. For instance, oxygen therapy that is prolonged or at very high pressure can cause oxygen toxicity, affecting sensitive organs. In the eye, this means that while a brief high-oxygen treatment might boost healing or blood flow, it could also spark damaging oxidative stress. Hormesis: Beneficial Stress? The concept of hormesis helps explain how a mild oxidative stress can sometimes be beneficial. Hormesis is a well-known two-phase response in biology: a low or moderate rise in a stressor tends to activate adaptive defenses, whereas very high levels overwhelm those defenses and become toxic (). Oxygen itself is a classic hormetic example: just above-normal oxygen helps cells function, but extreme hyperoxia injures them (). Some experts have even suggested that modest, intermittent bursts of oxygen could precondition tissues and strengthen antioxidant mechanisms. As one science new

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