From ... in Biology — Dec 2, 2024

Reducing Oxidative Stress in the Lens Protects Against Cataracts

Cataracts are a condition that makes the lens of the eye cloudy, causing blurred vision, much like looking through a foggy window or a smudged camera lens.

This occurs due to protein buildup in the eye's lens. Without treatment, cataracts gradually worsen, leading to more vision loss and, eventually, blindness.

Cataracts usually develop with age, and they're very common among older adults. Statistics show that more than half of Americans aged 80 or older either have a cataract or have undergone cataract surgery. Besides aging, other risk factors include heavy alcohol use, smoking, diabetes, exposure to harmful substances, certain medications and eye injuries. Currently, about 24.4 million Americans over age 40 are affected by cataracts, and this number is expected to double to about 50 million by 2050. In response to this growing challenge, researchers at the University of Auckland, New Zealand, explored new strategies for cataract treatment by minimizing oxidative stress in the eye's lens, offering hope to people diagnosed with this condition.

Published in October 2024 in the journal Antioxidants, the featured review focused on increasing levels of the antioxidant glutathione (GSH) within the lens, as it plays an essential role in neutralizing oxidative damage. The researchers emphasized that while glutathione is naturally present in high concentrations in young people with healthy lenses, aging and certain conditions like diabetes lead to a decline in glutathione levels. This depletion leaves the lens vulnerable to oxidative stress, ultimately resulting in the formation of cataracts. The challenge, however, is how to effectively deliver glutathione to different regions of the lens, particularly the nucleus, which is the most affected by age. The authors evaluated several methods for enhancing glutathione levels in the lens. One key approach is activating the Nrf2 pathway, which has been shown to protect the lens from oxidative damage by promoting the production of antioxidant enzymes. According to the researchers: "Nrf2 has been linked to many processes, including regulation of cellular stress responses, drug metabolism and defense against carcinogenesis and

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infiammatory insults. Importantly, Nrf2 functions as a major regulator of cellular resistance to oxidants, controlling 20 antioxidant genes, some of which involve the regulation of GSH homeostasis through synthesis and regeneration of GSH." Nrf2 operates as a transcription factor, meaning it moves into the cell's nucleus to activate the expression of genes responsible for producing antioxidants. Under normal conditions, Nrf2 is bound to a protein called Keap1 in the cytoplasm, which keeps it inactive. However, when oxidative stress occurs, specific molecules modify Keap1, releasing Nrf2 and allowing it to enter the nucleus. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) on DNA. This binding activates several genes that enhance the cell's antioxidant capacity, including those involved in synthesizing and regenerating GSH. Increased GSH helps neutralize reactive oxygen species (ROS) in the lens, preventing oxidative damage to lens proteins. By promoting this cascade of antioxidant gene expression, Nrf2 strengthens the eye's natural defenses against oxidative stress. The authors noted that this mechanism is particularly beneficial for targeting the cortex of the lens, where diabetic cataracts typically begin, as well as age-related damage.

Alongside strategies that enhance antioxidant pathways like Nrf2, the researchers also examined cysteine and its analogs as a way to boost glutathione levels in the lens. Cysteine is the key amino acid needed for glutathione synthesis and is known for its strong antioxidant effects. It's primarily produced through the transsulfuration pathway, where the enzyme cystathionine-beta-synthase (CBS) converts homocysteine into cystathionine, which then becomes cysteine. Direct cysteine uptake pathways also contribute to glutathione synthesis. Studies on human and porcine lenses exposed to hydrogen peroxide show that oxidative stress increases CBS levels. This response appears to boost cysteine production, providing more GSH to help protect the lens's cells from oxidative damage.

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The researchers analyzed two cysteine analogs — N-acetylcysteine (NAC) and N- acetylcysteine amide (NACA), which both delay cataract formation, according to animal studies. In particular, NAC delayed cataract formation in diabetic rats and reduced dense nuclear opacities in selenite-induced cataracts. However, the researchers noted that it has relatively low bioavailability and hydrophilicity. NACA, on the other hand, is a more lipophilic derivative of NAC. It has increased membrane permeability, making it effective at lower concentrations. Studies have demonstrated NACA's ability to inhibit selenite-induced cataracts and protect against oxidative stress by enhancing GSH levels and inhibiting the formation of malondialdehyde, a marker of oxidative stress. Additionally, diNACA, a precursor to NACA, has emerged as a unique option for cataract prevention. Unlike NAC and NACA, which primarily work by increasing GSH, diNACA appears to protect lens proteins through mixed disulfide formation, providing an alternative pathway to counteract oxidative damage.

The authors also examined the effects of enhancing the lens's microcirculation system as a way to reduce oxidative stress and delay age-related nuclear cataracts. Unlike other tissues, the lens lacks a direct blood supply and instead relies on an internal microcirculation system to move essential nutrients and antioxidants to its core region. This system uses ion-driven fiow to circulate water and ions throughout the lens. The researchers observed that the microcirculation system could rapidly deliver nutrients like glucose and glutathione to the deeper layers of the lens, reaching the nucleus more eficiently. One approach for upregulating this microcirculation system is by adjusting the pressure inside the lens. This is done using two specialized channels, TRPV1 and TRPV4, which naturally adjust the movement of water molecules in response to changes in pressure or fiuid balance

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within the lens. Activating these channels keeps pressure optimal, helping more nutrients reach the lens's core, where they protect against cataract-causing damage. The authors added: "[T]he upregulation of the microcirculation system could be coupled with the delivery of cysteine permeable analogs … This would ensure that these analogs are delivered to the lens nucleus, where they could cross the lipid bilayer and so bypass the need for a membrane transporter and alleviate oxidative stress in the region of the lens most impacted by age-related nuclear cataract." However, while these advancements offer noninvasive ways to slow cataract progression, cataract surgery remains a common solution when vision loss becomes severe. If you're considering surgery, it is essential to weigh the risks involved in this procedure.

Cataract surgery involves removing the clouded lens and replacing it with an artificial one. It's one of the most common surgical procedures, but it is not without risk. Dry eyes occur in 42% of patients who underwent cataract surgery, while up to 21% experience droopy eyelids. Additional side effects include fioaters, retinal detachment, eye infections, glaucoma, further vision loss and even secondary cataracts. I encourage considering one or more natural remedies before resorting to surgery. While scientific evidence on their effectiveness is limited — largely due to a lack of funding for research into nonprofitable natural compounds — that doesn't mean they're ineffective. Foods, nutrients and supplements can't be patented, making them far less lucrative than medications, but they also carry minimal risk. Adding more nutrients to your diet won't harm you; at worst, you may not see an immediately noticeable effect. Keep in mind that natural approaches take weeks or months to show results, so patience and consistency are key to benefiting from them.

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Given their minimal risk, I believe natural remedies are a safer first step worth trying before surgery.

Certain nutrients play a particularly important role in maintaining eye health, reducing the risk of age-related issues and supporting clear vision. Here are three powerhouse nutrients that have been shown to promote eye health: 1. Lutein — Often called the "eye vitamin," this carotenoid is naturally found in high concentrations in the retina and macula, where it helps filter out damaging blue light, which contributes to digital eye strain and oxidative stress over time. Lutein also acts as a protective antioxidant, reducing the risk of age-related macular degeneration (AMD) and cataracts. Your body can't produce lutein on its own, so you need to get it from food or supplements. Dark, leafy greens like spinach, kale and Swiss chard are excellent sources, as are colorful fruits. Egg yolks are also a good source, with the added benefit of helping lutein absorption thanks to their fat content. Lutein also works better when combined with its sister compound, zeaxanthin, which is why you'll often find them paired in supplements. 2. Vitamin C — While most people associate vitamin C with immune health, it's also an ally for visual health. This powerful antioxidant vitamin plays a role in building and maintaining collagen, the protein that gives structure to your eyes, particularly in the cornea and sclera (the white part of your eye). The lens of your eye contains a higher concentration of vitamin C than almost any other body tissue — about 20 times higher than in the blood. This isn't by accident; your eyes need this vital nutrient to protect against UV damage and inhibit oxidative stress that leads to cataracts. Citrus fruits are obvious sources, but bell peppers, strawberries and broccoli are good sources. Regular intake of vitamin C has been linked to slower cataract

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progression and better overall eye health. 3. Astaxanthin — Another potent antioxidant, astaxanthin is found to have protective benefits against various eye conditions, including cataracts, age-related macular degeneration (AMD), cystoid macular edema, diabetic retinopathy, glaucoma and infiammatory eye conditions like retinitis, iritis, keratitis, and scleritis. Astaxanthin has also been shown to ameliorate light-induced damage, as well as damage to the photoreceptor cell, ganglion cell and neurons of the inner retinal layers. It also supports both visual acuity and maintains healthy eye pressure and energy levels. If you're considering supplementation, I recommend starting with 4 milligrams (mg) per day and working your way up to about 8 mg per day — or more if you're also suffering from chronic infiammation. Taking your astaxanthin supplement with a small amount of healthy fat, such as grass fed butter, coconut oil or low-PUFA eggs, will optimize its absorption.

Along with increasing your intake of the nutrients mentioned above, there are natural, common-sense lifestyle strategies I recommend adopting to protect your healthy vision, such as: Avoid blue light — Blue light, such as that from electronic screens, reduces melatonin in your lens, which causes cataracts. Avoiding blue light becomes even more important if you do opt for cataract surgery, as your natural lens has some built-in protection against blue light whereas the artificial lens does not. UV-blocking artificial lenses are available through special order, but it's not standard. So, if you do get cataract surgery, wear blue-blocking glasses when looking at screens and when in artificial lighting indoors.

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Quit smoking — Smoking significantly increases free radical production throughout your body, putting your health — and especially your vision — at risk. For lifelong healthy vision, it's essential to avoid the damage that smoking causes to your eyes. Care for your cardiovascular system by getting regular exercise — High blood pressure damages the tiny blood vessels in your retina, restricting healthy blood fiow. Maintaining a regular exercise routine is effective for lowering blood pressure and also plays a key role in balancing insulin and leptin levels, both of which are essential for eye health. Maintain healthy blood sugar levels — Chronically elevated blood sugar damages your eyes and obstructs blood fiow to your retina. One of the best ways to maintain healthy blood sugar is by eliminating ultraprocessed foods from your diet, as they're typically loaded with harmful fats and processed sugar. Avoid seed oils and processed foods — Your eyes are highly susceptible to and damaged by polyunsaturated fats (PUFAs) such as linoleic acid (LA), so avoid cooking with seed oils (aka vegetable oils) and stay clear of processed foods, fast food meals and most restaurant food. Avoid aspartame — Vision problems are one of the many acute symptoms of aspartame poisoning. This substance is commonly found in "sugar-free" or "diet" products, such as diet sodas, low-calorie yogurts, sugar-free gum and other processed snacks and drinks. Always check ingredient labels for aspartame or related brand names like NutraSweet or Equal to steer clear of this artificial sweetener. Opting for natural sweeteners like honey or maple syrup instead supports your health without the risks associated with aspartame.

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