Oxidative Stress & Antioxidants: Links to Eye Floaters and Disease

Reactive oxygen and nitrogen species are highly reactive compounds that originate both within the body (endogenously) and outside the body (exogenously).

• Endogenous sources: ROS/RNS are formed as a consequence of normal cellular processes and metabolism within the cells of our body.
• Exogenous: UV light, blue light, radiation, environmental pollutants, heavy metals, and many other factors can lead to ROS/RNS production too!

Because of their unstable molecular structures, these ROS/RNS species are highly reactive, meaning that they easily react with other molecules and modify them. If not tightly controlled, they can wreak havoc in cells. If levels of ROS/RNS get too high, various cellular structures can become damaged: proteins, lipids (like those which make up our cell membranes), and DNA are all at risk!

This is where antioxidants come in…

The term ‘antioxidants’ encompasses a spectrum of enzymes and molecules which work via enzymatic and non-enzymatic reactions to ‘mop up’ excess ROS/RNS and protect our cells from damage. These antioxidants can also come from both endogenous and exogenous sources:

• Endogenous: various enzymes and proteins are encoded by our own DNA and made by the body itself, they work to keep ROS/RNS levels at baseline (e.g. catalase, an enzyme that protects tissues against the toxic effects of peroxide by converting it into water and oxygen).
• Exogenous: the body also utilises many non-enzymatic, nutrient antioxidants that we cannot synthesise ourselves and so instead derive from our diet. These include compounds like vitamin C, vitamin B2, and trace metals such as zinc and selenium.

These antioxidants neutralise RNS/ROS by breaking them down or reacting with them before they can react with cells. Therefore, antioxidants limit potential cellular damage and keep ROS/RNS at low levels. 

Now you may be thinking: why low levels? Why not get rid of them altogether? Well, as we all know, biology is never that simple! Despite the damaging potential of RNS/ROS, they also serve crucial and irreplaceable roles in normal physiological processes which we absolutely need – like cell signalling and the immune response.

So we have established that we need both ROS/RNS molecules and antioxidants, and keeping this balance is crucial to maintaining healthy function of cells in our body…

What happens when this balance is disrupted and the levels of ROS/RNS get too high? This is when we run into the problem of oxidative stress: a ‘disturbance in the balance between the production of reactive oxygen / nitrogen species and antioxidant defences’. This has major implications for our health.

Before examining how oxidative stress can affect our health, we should take a look at its causes. Various aspects of the everyday, modern lifestyle can play important roles in its induction. These include:

• UV and Blue Light Exposure: Unprotected exposure to sunlight is a well-known cause of oxidative stress in the skin and eyes via photochemical reactions, while more recent studies have also noted the potential accumulative effect of repeated blue light exposure from digital devices.
   
• Unhealthy Diet: A diet high in ultra-processed foods, allergens and food additives has been associated with the development of changes within our cells that lead to oxidative stress. Ultra-processed food can contribute to oxidative stress in a variety of ways: chemical additives that can cause direct cellular damage, ingredients that can disrupt the gut microbiota and induce inflammation, advanced glycation end products that result from heating and processing, a high glycaemic index…  
   
• Smoking and Alcohol: These lifestyle habits are major causes of chronic oxidative stress and subsequent cell damage, and they are also shown to negatively impact psychological health.
   
• Lack of Exercise: Physical exercise can increase ROS production, but it also leads to increased production of antioxidants, which increases the body's resistance to oxidative stress. A sedentary lifestyle and physical inactivity appears to increase oxidative stress associated with aging.
   
• Exposure to Certain Chemicals: Various pesticides and insecticides seem to induce oxidative stress across many different cell types. Heavy metals, certain drugs, and environmental pollution appear to have similar detrimental effects too.
   
• Chronic Stress: Prolonged secretion of the stress hormone cortisol may play a critical role in the generation of ROS/RNS, the excess of which leads to oxidative stress.

Now we know what things may be causing oxidative stress, but how can this lead to disease?

As we established earlier, excess ROS/RNS molecules can damage proteins, lipids and DNA on a cellular level. This damage happens through various oxidative mechanisms:

• Proteins: Unwanted oxidation of proteins can cause structural damage, loss of enzyme activity and aggregation of proteins - all rendering them unable to fulfill their functions within the cell.
• Lipids: Lipid peroxidation occurs as a result of excess ROS/RNS, resulting in changes to cell membrane structure, affecting fluidity and membrane integrity. This is particularly damaging as it acts rapidly, damaging neighbouring molecules as a chain reaction.
• DNA: DNA bases can be oxidised, altering the ‘genetic code’ and ultimately affecting interpretation and transmission of genetic information in cells.

In summary, a lot of potential damage!

But what does this do to tissues, organs and systems as a whole? Well, oftentimes this damage can manifest as disease – as we see with the growing body of evidence implicating oxidative stress in the onset and progression of cancer, neurodegeneration, diabetes, rheumatoid arthritis, cardiovascular diseases and more.

Of course, the cells of our eyes are not immune to oxidative stress, so we also see numerous ocular diseases associated with oxidative stress. 

Various ocular conditions have been linked to the primary contributors of oxidative stress, like UV exposure, smoking, and diet. These diseases include glaucoma, cataracts, age-related macular degeneration, diabetic retinopathy and dry eye disease. The way in which oxidative stress causes damage and contributes to the development and/or progression of each of these conditions is dependent on the affected ocular tissue and the ROS/RNS at play. Let's consider a specific example with the disease keratoconus:

Keratoconus is a progressive corneal disease characterised by corneal thinning, ultimately resulting in decreased vision and eye discomfort. While disease onset is multifactorial, oxidative stress, with its causes, is a key risk factor.

• The cornea sits at the front of your eye and as a result absorbs approximately 80% of incident UV radiation (e.g. sunlight).
• Direct corneal exposure to UVA and UVB radiation can induce reactions in the cornea which produce ROS, which,  when in excess, result in the oxidation of DNA, lipids, proteins and enzymes. This damages these cellular components, leading to structural changes in the corneal layers, thinning of the cornea, and ultimately changes to its shape.
• Changes to the cornea can then result in decreased vision and increasing discomfort in sufferers of this disease.

Ageing is also a key risk factor for these diseases, which is heavily associated with weakened antioxidant defence systems and increased ROS/RNS production. 

We first want to reduce our eyes' exposure to exogenous sources of oxidative stress. 

Obviously, never stare at the sun. If possible, always try to wear sunglasses outdoors. UV can damage almost every part of the eye: on the cornea, it can lead to a painful condition called photokeratitis and also abnormal outgrowths; in the lens, it can lead to cataracts; on the retina, it can increase the risk of age-related macular degeneration. As tempting it is to top up your summer tan, sunbathing without sunglasses (even with your eyes closed) poses a serious risk to your eyes and also your skin (with UV exposure heavily linked to incidence of skin cancers).

As mentioned above, there’s some evidence to suggest blue light can also contribute to oxidative stress in the eye, and it is especially relevant if you spend a lot of time looking at screens. While the long-term effects of blue light exposure from digital devices are debated by scientists, it would be sensible to err on the side of caution and try to reduce your exposure. 

First and foremost, try to control and reduce your screen time. Most mobile devices have a ‘blue light filter’ or ‘night mode’. Wearing blue light glasses can be a great option too, especially if they improve your visual comfort. Limiting blue light a couple of hours before bed can also help with falling asleep and overall sleep quality!

To learn more about the science of blue light and how you can protect your eyes from it, check out our article: ‘Is Blue Light Actually Bad for Your Eyes?: A Comprehensive Guide’. 

UV and blue light are two major exogenous sources of oxidative stress. It is important to protect your eyes from them. Meanwhile, you should also try to optimise your eyes' internal antioxidant stores:

As we previously discussed, an unhealthy diet, such as one comprising lots of ultra-processed foods, can increase oxidative stress. Furthermore, diet-related conditions such as diabetes can contribute to oxidative stress and inflammation and cause eye diseases. It is therefore important to avoid ultra-processed foods and also those with a high glycaemic index, which negatively affect blood sugar levels. 

The Mediterranean diet can reduce oxidative stress in the body as a whole. It is also rich in nutrients and antioxidants that have been proven beneficial for eye health. 

Some nutrients are especially important to eye health: vitamin C, vitamin A, vitamin E, omega-3s, lutein and zeaxanthin… Make sure that you obtain enough of them from your diet. 

If you find it difficult to access a variety of nutrients from high-quality food sources, one option could be to take a nutritional supplement to ensure you’re getting your daily recommended vitamins, minerals, and other antioxidant compounds. Another reason is that the bioavailability of nutrients varies according to the source. For example, even though dark green leafy vegetables are rich in carotenoids, their bioavailability is low. Therefore, you might need to have a large amount of a certain food to meet the recommended daily intake of a certain nutrient.

While antioxidant supplementation remains a topic of debate, some studies have shown promising results of nutritional supplements' potential for alleviating eye disease symptoms or slowing eye disease progression. For example:

• The Age-Related Eye Disease Study (AREDS) and AREDS2 (sponsored by the National Eye Institute) concluded that an oral supplement containing vitamin C, vitamin E, zinc, copper, lutein, and zeaxanthin can reduce the risk of progression of intermediate Age-Related Macular Degeneration (AMD) to advanced AMD.

It should be noted that supplements are not meant to treat diseases and some supplements can interact with medications. It is advisable to consult your GP or eye doctor if you have pre-existing medical conditions or are taking medications. Finally, always check the nutritional information table and the list of ingredients to make sure that the formulation is safe, effective, and backed by recommended guidelines and peer-reviewed studies. 

Bonus tip: Regular moderate exercise, avoiding smoking, and reducing daily stress are 3 more great ways to reduce oxidative stress and improve overall health!

We have considered how oxidative stress arises and how it links to disease both in the body as a whole and the eyes in particular, and then we covered some key, actionable tips you can start using straight away to help reduce oxidative stress in yourself. We hope this has answered your questions about oxidative stress and antioxidants and given you some insight into how the science behind it all works!

This article is contributed by our research writer, Ruby Mullens. She holds a Master's in Biochemistry from the University of Oxford.