Are you worried about the effect of ageing on your appearance and visual acuity? Collagen, one of the most abundant proteins in the body, is linked to both of these age-associated degenerative processes. We've taken a look at the latest research on the links between ageing collagen and eye disease, and evaluated whether there are any steps you can take to prevent your collagen deteriorating, backed by science.
Table of Contents
Introduction
Ageing is an inevitable part of life that nevertheless causes anxiety in much of the population. One survey found that 53% of people feared losing their eyesight as they age. Similarly, another study found that 42% of women aged 25-44 regularly worry about the visible signs of ageing.
One uniting component of these two fears is the ageing of collagen, one of the most important proteins in the body. Its breadth of purpose and importance in skin, joints, and our eyes have led to collagen being the key target for many anti-ageing treatments.
In this article we’ll explain what collagen is and how its deterioration during ageing may contribute to several age-related eye conditions. We’ll also evaluate the different methods of treatment and prevention of ageing to help you protect your eyes and whole-body collagen health.
What is collagen?
Collagen refers to a large family of similar fibrous proteins. ‘Fibrous’ means these are proteins with a repeating unit that extends like a chain into a long fibre. Keratin, the protein which forms hair and nails, is another example of a fibrous protein.
Unlike keratin, collagen is flexible and elastic, whilst still remaining strong. Because of this, collagen is found all over the body, including in joints, tendons, blood vessels, skin, and eyes. In general, collagen is secreted outside of cells and has a role in holding your body’s cells together in a less rigid way than other kinds of structural tissues such as bones.
There are over 28 types of collagen, all of which have a similar repeating motif that creates this elasticity. Different arrangements of collagen fibres have different properties, meaning collagen can take on several physiological functions. The properties of collagen in connective tissue can be modified in this way, as well as with the addition of other fibrous proteins such as elastin (which increases elasticity) or keratin (which is more rigid).
For example, type I and II collagens bundle together in long filaments, producing thick fibrils that are resistant to pressure. In general, thicker fibrils are stiffer and stronger, but less elastic.
Type I collagen is by far the most abundant in the body, being present in bones, tendons, blood vessels, skin, and the cornea of the eye. The arrangement of type I collagen fibrils is an important part of their function. Tendons need to resist stretch from muscles to ensure muscle contraction efficiently results in body movement, and so type I collagen fibrils in tendons are aligned in parallel.
Skin acts as a barrier against the outside world, so stretch and elasticity are more important to prevent the skin from tearing. In skin, type I collagen forms a matrix with type III collagen which does not bundle together so is more elastic. Fibrils have a more random alignment to allow stretch and stability in all directions.
The vitreous, a gel-like substance that fills the eye, has a similar collagen matrix to that found in skin, except instead type II collagen fibrils are arranged more orderly so that the vitreous can be transparent. Type IX collagen fibrils, which don’t form bundles, connect type II fibrils and keep them separated. Like with many other collagen-containing tissues, fibrous carbohydrates such as hyaluronan also play a key role in supporting structure and ensuring the thicker collagen I or II bundles are arranged correctly.
Collagen clearly plays a huge role in many organs in the body. However, the delicate balance of different types of collagen and how they are arranged means that several different conditions can arise as damage accumulates over time. Next we’ll take a look at how damage causes these conditions.
How Collagen May Deteriorate as we Age
Collagen aggregation with age:
Most of what we know about age-related damage to collagen comes from studies on ageing skin. Although skin has some unique properties that might limit the breadth of insight provided by these studies, they still give us useful details on collagen in the entire body.
As we age, collagen-dependent tissues become less elastic and more fragile. This means joints get stiffer, skin starts to sag and is more wrinkly, and blood vessels are weaker. Ageing of connective tissues can lead to diseases such as atherosclerosis (build-up of plaque in blood vessels), osteoporosis (bone weakness), osteoarthritis (joint deterioration), coronary heart disease, and many more.
At the microscopic level, collagen fibrils in older individuals clump together (aggregate) in larger bundles which are more rigid. Whilst these thicker fibrils offer higher tensile strength, their lack of flexibility makes them more brittle, causing weakness which can develop into the previously mentioned diseases.
What causes collagen aggregation?
Highly reactive chemicals called reactive oxygen species (ROS) are produced as a normal part of energy metabolism, and can also be caused by external factors such as exposure to UV radiation and certain pollutants.
ROS are usually kept under control by antioxidants, which react with ROS to produce more stable waste products. However, if ROS levels get too high to be controlled, they can react with and damage important cellular components such as DNA, proteins and cell membranes, ultimately leading to cell death. This is called oxidative stress.
Glycation is a related process where free sugar molecules react with proteins in a similarly damaging way, and oxidative stress and glycation compound in a process called glycoxidation, exacerbating damage. When ROS react with biological molecules, they make them more reactive and therefore susceptible to glycation by free sugar molecules. Glycation of biological molecules also increases their susceptibility to oxidative stress, and may cause the release of metal ions which can facilitate further ROS production. To learn more about ROS and oxidative stress, check out our article on the topic.
In connective tissues, the extracellular matrix (the collagen network outside of cells) can generate ROS when exposed to UV, as the intense energy is absorbed by proteins in the matrix. Free sugars such as glucose are present in the extracellular matrix as they are present in tissue fluid (or for the eye, in the aqueous humour), which is produced by higher-pressure, oxygenated blood, and provides nutrients and oxygen to tissues.
High concentrations of ROS and free sugar molecules lead to reactions with collagen that cause crosslinking with neighbouring fibrils. This means fibrils get permanently fixed to each other in larger bundles. Since antioxidant levels decrease with age, tissues become less capable of dealing with ROS. Increased glycation is also associated with ageing and causes collagen aggregation. Therefore, ageing leads to increased collagen aggregation as there is increased oxidative damage to collagen fibrils.
ROS can damage collagen by more indirect means, too. When connective tissues are oxidatively stressed, multiple signalling pathways are activated that cause the secretion of protein-digesting enzymes called metalloproteinases which target and destroy collagen.
Fibroblasts, the cells responsible for producing collagen in skin and tendons, can die as a result of oxidative stress, preventing the repair of damaged collagen.
Some tissues, such as the vitreous of the eyes, have only a small number of fibroblasts and are not thought to regenerate damaged collagen, meaning oxidative damage is permanent.
Other Causes of Collagen Damage
UV radiation and some pollutants such as ozone and particulates (microscopic solid material) can also cause oxidative damage to collagen. UV radiation contains a lot of energy which can ionise chemicals in cells, making them more reactive.
UV is also thought to be the main cause of oxidative stress in the eye, the high-energy radiation leading to the breakdown of molecules to produce ROS. Oxidative stress in cells causes the secretion of signals which induce inflammation. Inflammation resulting from UV exposure and tissue damage (as seen when you get sunburnt) can also attract white blood cells which release collagen- and elastin-digesting enzymes, further degrading collagen.
Pollutants also contribute to collagen oxidation by reacting with chemicals to produce ROS. The skin and eyes are more susceptible to these exogenous sources of ROS since they are exposed on the exterior of our bodies.
Oxidative stress caused by UV and pollutants is not that extreme in the short term but irreversible damage accumulates over time. The below image exemplifies the effect of UV on skin and collagen, showing a truck driver who had just one side of their face exposed to the sun over their career. UV exposure has caused collaged aggregation and fibroblast damage which increases wrinkles and cannot be reversed. This accumulation over a lifetime, on top of a decrease in antioxidants as you age, is part of age’s association with oxidative damage to connective tissues.
How Does Damaged Collagen Affect Your Eye Health
The cornea and trabecular meshwork:
The surface of the eye is constantly exposed to UV and pollutants. The cornea is a protective sheet of tissue which lies over the lens and contains type I and III collagen. If this collagen network becomes weakened, the cornea can stretch and bulge in a condition called keratoconus, which distorts vision.
There is conflicting evidence as to whether this results from oxidative damage to the collagen in the cornea since the disease is usually only seen in younger people (who have accumulated less oxidative damage), and some treatments actually utilise oxidation of collagen to cause aggregation, making fibrils thicker and stronger, stabilising the cornea.
Even though it’s unclear whether oxidative damage leads to keratoconus, other diseases such as dry eye disease and pterygium can result from UV and pollutant-induced oxidative damage to the cornea, so protecting your eyes with UV-blocking sunglasses is recommended.
Oxidative stress is known to cause more serious damage to other collagen-reliant structures in the eye. The trabecular meshwork is also located in the front portion of the eye and serves as a drainage route for aqueous humour, a liquid which is secreted into the eye to provide nutrients to structures such as the lens and iris.
When the trabecular meshwork accumulates oxidative damage, aqueous drainage is slowed, causing a build up of pressure which can damage the optic nerve. This causes glaucoma, a degradation of the optic nerve that can result in permanent blindness.
Cells in the trabecular meshwork are tightly regulated to control collagen and other fibrous protein content to alter the rate of aqueous flow out of the eye. Oxidative damage appears to increase the secretion of collagens, especially type I and IV. Glycoxidation also leads to thicker collagen fibrils, which makes the meshwork even thicker and less porous, blocking aqueous outflow and increasing pressure in the eye.
In 2020, it was estimated around 76 million people in the world suffered from glaucoma, almost 1% of the world’s population at the time.
The vitreous and floaters:
The vitreous, a transparent matrix of collagen and hyaluronan that fills the eye, can also be damaged by oxidative stress. Most fibrils in the vitreous are type II filaments which are connected to each other by collagen type IX. Type IX collagen keeps the type II fibrils associated whilst maintaining distance from each other, providing space for compression of the eye. Whilst the fibrous carbohydrate hyaluronan is not essential for the structure of the vitreous, another carbohydrate called chondroitin sulphate is required for type IX collagen to bind type II collagen.
In the vitreous, photosensitising molecules such as riboflavins absorb UV, facilitating ROS generation. When ROS react with collagen in the vitreous, collagen dissociates from hyaluronan and crosslinks with itself, clumping together into large fibril bundles.
When these are dense enough and pass our line of vision, they can be seen as floaters, dark squiggles and lines that move with your vision. Whilst they are technically harmless, they can be irritating to deal with, and for some people, they have a major impact on their mental health, with one study on over 300 individuals showing participants would prefer to sacrifice 1.1 years every decade than live with floaters.
The vitreous has a very small fibroblast count, so it is not considered to synthesise new collagen. Whilst there is some evidence that collagen in the vitreous is synthesised after birth, this is not thought to be substantial enough to repair and replace damaged collagen. Therefore, oxidative damage to the vitreous is considered to be irreversible.
Oxidative stress is correlated with the degeneration of the vitreous. As collagen type II fibrils pack more closely together, the overall volume of the vitreous decreases. At the same time, connective proteins which connect the back of the vitreous to the retina (the part of your eye that detects light and sends that information to your brain) also deteriorate, eventually leading to detachment of the vitreous from the retina. This is a slow process that can take months to years but can feel sudden when separation is complete since it exposes a dense collagen network at the back of the vitreous which appears like a large cobweb-shaped floater.
Floaters and vitreoretinal detachment are not considered serious eye conditions. However, studies have shown floaters significantly decrease contrast sensitivity, making it difficult to make out details in the dark, as well as quality of life.
Furthermore, although vitreoretinal detachment is more commonly seen in older patients, it is becoming more common in young people. These are widespread conditions, and by 80-90 years old, on average 50% of the vitreous is liquefied, and 25% of people will experience vitreoretinal detachment.
How to Protect and Improve Collagen Health
Collagen damage can lead to a range of conditions affecting your general health as well as directly impacting vision. There are ostensibly two approaches to dealing with collagen damage: one is taking measures to protect yourself from oxidative stress, and the other is trying to repair collagen that is already damaged. Plenty of commercial options are available, but are any of them effective?
Oxidative stress resulting from high levels of ROS produced by the body can be combated by increasing levels of antioxidants.
Many antioxidants such as lutein, zeaxanthin and beta-carotene can be readily accessed through a balanced diet - for a list of several antioxidants and the foods they can be found in, check out our article on natural cures for floaters.
Several studies have found antioxidants lower oxidative stress biomarker levels. Furthermore, studies on collagen-related eye conditions have shown promising results for antioxidants as preventatives.
One study compiling several pre-clinical and clinical trials found that, in animal models, antioxidants such as vitamin C and zinc have consistently lowered the risk of developing glaucoma.
However, the results in human trials are more unclear, with one study in the Netherlands performed on over 4,000 participants across 11.3 years on average which provided an antioxidant mixture of 500mg vitamin C, 200IU vitamin E, 15mg beta-carotene, 2mg copper, and 80mg zinc, and found no effect on the development of glaucoma. However, the same study showed that antioxidants could significantly reduce the risk of other oxidative damage-induced eye conditions such as age-related macular degeneration, demonstrating their potential to prevent oxidative damage to collagen in our eyes.
An early study sought to address collagen damage that leads to floaters and was carried out on 61 patients, half of whom were provided with an antioxidant formula containing 125mg lysine, 40mg vitamin C, 5mg zinc, and extracts from Seville oranges and grapes, which are high in antioxidants. Due to the large amounts of UV the eye is exposed to, the vitreous has a high antioxidant capacity, and these supplement components are among some of the antioxidants naturally present in the vitreous whose concentration gradually decreases as we age.
The study produced promising results, with 77% of those taking the supplement reporting fewer floaters, compared to just 23% on the placebo. However, the study had a comparatively small sample size, and it remains to be seen how antioxidants can reverse supposedly irreversible damage to the vitreous. Nevertheless, this is a positive early study that warrants further exploration.
UV and high-energy visible blue light have been directly correlated with various skin and eye conditions (including cataracts, age-related macular degeneration and different cancers) which are also correlated with oxidative stress. Therefore, sunglasses and sun cream are commonly recommended.
One study tested the UV and blue light-blocking ability of several brands of sunglasses and found no correlation between the actual protection provided and the price of each pair, nor with the protection claimed to be provided by advertisements.
That’s not particularly useful for a consumer, but the study did find tinted polycarbonate sunglasses offered the most protection, blocking 100% UV radiation and up to 99.8% of high-energy blue light. Suncream has been shown in several clinical trials to reduce the risk of UV-correlated skin cancers, and studies have also demonstrated its ability to prevent oxidative stress, meaning it’ll protect collagen from oxidative damage too.
Antioxidants, whether through diet or supplementation, and preventative measures such as sunglasses and sun cream, all offer protection against oxidative damage to collagen. However, can damaged collagen be regenerated? Scientists have tested oral supplements containing collagen, with a review compiling these results, finding collagen supplementation significantly improved skin elasticity and hydration, suggesting old, damaged collagen had been replaced. Supplements contained 2.5-10g of collagen per day, and each study lasted between 8-24 weeks.
A more recent review evaluating 19 studies, covering a total of 1,125 patients, found hydrolysed collagen (short fragments of collagen which are more easily absorbed in the gut) significantly improved skin hydration and elasticity, and reduced wrinkles. Hydrolysed collagen peptides are still too large to be absorbed in the intestine, so are likely broken down further to fragments just two or three amino acids long before absorption. There’s no guarantee with any collagen supplement that the peptides absorbed would be used to produce collagen, as amino acids may be repurposed to synthesise any protein the body needs.
However, these supplements provide some resources which are more specific to collagen, such as prolylhydroxyproline and hydroxyprolylglycine. Lysine, which cannot be made by our bodies so must be obtained from diet, is also present at high concentration in collagen. Beyond its use in synthesising collagen, lysine is an antioxidant which also binds to free sugar molecules, limiting glycation, and so could protect collagen from glycoxidation. In this way, collagen supplements may provide some benefit over more general protein supplements.
Vitamin C has often been explored as a supplement to support collagen. Vitamin C combines with enzymes called hydroxylases to synthesise collagen, and free vitamin C when not associated with hydroxylases is a powerful antioxidant.
Some preclinical trials on both animals and humans have been promising, with a systematic review of 10 trials finding the studies proved vitamin C supplementation significantly increased type I collagen production. Another study on 300 participants combined the approaches we’ve seen, providing a collagen supplement which also contained several antioxidants and other vitamins/minerals, and found that, after 12 weeks of daily consumption, those taking the supplement had significantly reduced signs of ageing and increased type I, III and IV collagen production. These results are promising.
However, despite the inclusion of known antioxidants such as lysine and vitamin C, there is no evidence towards these supplements providing any protection against oxidative stress-related disease. Furthermore, tissues such as the vitreous are highly unlikely to benefit from these supplements, since they rely on collagen-synthesising cells to utilise their ingredients.
Conclusion
Collagen plays an important role in all sorts of connective tissues, and oxidative stress in these tissues accumulates as we age due to an age-associated decrease in antioxidant levels and a lifetime of exposure to UV and blue light.
Oxidative damage to collagen is responsible for several symptoms we associate with age, such as stiff joints, fragile and wrinkly skin, weak bones, and increased floaters in vision. Especially when it comes to eyesight, protecting collagen from oxidative damage is necessary to reduce the risk of developing conditions such as glaucoma, pterygium, vitreoretinal detachment and floaters, which are all relatively common, especially in the elderly.
Whilst clinical trials are still only in early stages, there’s good grounds to believe blocking UV with sunglasses and sun cream can reduce oxidative damage to tissues and collagen, with UV exposure being associated with several skin and eye cancers and degenerative diseases.
Similarly, antioxidant consumption in diet and via supplements has been shown to lower the levels of ROS. All of these approaches will help protect the collagen that supports skin, bones, and in the eyes, the cornea, trabecular meshwork, vitreous, and more.
Trials on collagen supplements have shown potential in healing damage and increasing collagen production. Whilst these have mainly been tested in the context of reversing the ageing of the skin, their success suggests it’s worth studying their effect on other diseases associated with collagen damage. Structures such as the vitreous are nevertheless unlikely to see much benefit since collagen-synthesising cells are not present regardless of supplementation.
Scepticism towards collagen supplements is still recommended since we've yet to see large-scale, double-blind clinical trials. Nevertheless, increasing collagen consumption through meat and fish, as well as antioxidant consumption through maintaining a balanced diet, will always be a positive for your health, and protect against more than just collagen-related diseases.
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