Study on Lutein for Eye Health

Lutein, a nutrient pigment widely present in the retina, is a recognized safe substance that protects the eyes by absorbing blue light, neutralizing harmful free radicals, and inhibiting inflammatory responses in the eye. It has a protective and alleviating effect on eye diseases such as myopia, diabetic retinopathy, and cataracts [2]. This article provides a brief review of the eye protection mechanism of lutein and its role in the prevention and treatment of myopia.

1 Overview of lutein

1.1 Properties and sources of lutein

Lutein is an oxygenated carotenoid, the structure of which is shown in Figure 1. The conjugated double bond structure present in the carbon chain of the lutein molecule gives it strong absorption capacity for blue light at 400–500 nm, which makes it appear yellow, and it is easily oxidized. At the same time, the molecule contains a violone ring dihydroxy structure, which allows it to better perform the biological functions of absorbing blue light and anti-oxidation in the body [3].

Lutein cannot be synthesized in the human body on its own and can only be supplemented by eating outside food. Dark green leafy vegetables and orange foods are usually rich in lutein [4]. See Table 1. Because lutein is fat-soluble, its bioavailability is higher in foods with a high fat content and relatively low in fruits. Therefore, egg yolk is considered a better source of lutein. In addition, some flowers and algae also contain a lot of lutein, such as marigolds and chlorella [5].

1.2 Biological safety of lutein

In recent years, there have been more and more reports on the benefits of lutein for visual health, and dietary supplements rich in lutein have become increasingly popular, which has aroused public concern about its biosafety. A 2013 study on age-related eye diseases [6] found that after more than 4,000 patients with age-related macular degeneration had been supplemented with 10 mg/d lutein for 5 years, apart from some patients experiencing slight yellowing of the skin, there were no adverse health effects. In a study by Parekh et al. [7] on the effect of lutein on visual and cognitive function improvement in adolescent children, it was found that a combined supplement of 10 mg/d lutein and 2 mg zeaxanthin given to 60 children for 180 consecutive days did not cause significant toxic reactions. Another study on the effect of lutein on macular pigment optical density (MPOD) showed that after 120 days of taking 30 mg/d lutein, no side effects were found [8]. To date, no studies have shown that lutein supplementation can lead to poisoning. The current recommended dosage of lutein is 10 mg per day, which is relatively safe.

2 Lutein's eye protection mechanism

The macula, the central part of the retina, is the area of the eye with the sharpest vision. It is responsible for color recognition, motion detection and visual contrast sensitivity. Lutein, which is abundant in the macula, is essential for protecting and improving visual function. It maintains visual health mainly through three mechanisms: acting as a blue light filter, acting as an antioxidant and acting as an anti-inflammatory agent.

2.1 Blue light filter

In modern society, the human eye is constantly exposed to high-energy blue light emitted from electronic devices such as mobile phones, computers, and LED lights. If the intensity and duration of the light exceeds the retina's tolerance, it can lead to photodamage. Ham et al. [9] found that high-energy blue light induced photodamage 100 times stronger than low-energy infrared light when investigating the effect of laser wavelength on rhesus monkey retinal damage. Ju Yahang et al. [10] found that cell proliferation was significantly inhibited when retinal pigment epithelium (RPE) cells were irradiated with blue light of different wavelengths, and that the degree of cell damage increased with the shortening of the wavelength. Lutein is mainly distributed in the Henle fiber layer of the retina, and light must pass through lutein before reaching the photoreceptor. It has been reported [11] that lutein can absorb up to 90% of incident blue light, thereby effectively protecting the eye fundus from light damage.

2.2 Antioxidants

The retina is one of the most metabolically active and oxygen-consuming tissues in the body, and is also rich in unsaturated fatty acids. As the eyes are constantly exposed to light, the retina is prone to oxidative stress and the production of endogenous reactive oxygen species (ROS) [12]. These ROS are highly reactive because they contain unpaired electrons and can cause oxidative reactions with mitochondria, lipids, proteins, nucleic acids, etc. in the macula, causing irreversible damage to the retina [13]. With age, the RPE layer of the retina also continues to accumulate lipofuscin, making the eye more sensitive to oxidative stress and further increasing oxidative damage to the retina [14].

However, the presence of the lutein antioxidant in the macula can inhibit free radical production, quench excess ROS, and reduce lipofuscin deposition, thereby protecting the retina from oxidative damage. Toragall et al. [15] prepared a lutein-loaded chitosan-sodium alginate nanocarrier, which was shown to effectively prevent H2O2-induced oxidative stress in ARPE-19 cells. Madhavan et al. [16] found that lutein supplementation in mice significantly increased the levels of antioxidant enzymes and macular pigments in the body. Lutein also inhibits the increase in ROS levels in ARPE-19 cells mediated by high glucose [17]. In addition, Sundelin et al. [18] found that lutein treatment of rabbit and bovine RPE cells significantly reduced the production of lipofuscin. When lutein is used in combination with other antioxidants, it can better reduce the accumulation of lipofuscin and help protect photoreceptors [19].

2.3 Anti-inflammatory agent

ROS is not only a key molecule in the harmful effects of oxidative stress, but also directly or indirectly activates a variety of pro-inflammatory transcription factors, such as nuclear factor κB, hypoxia-inducible factor 1 α, and signal transducer and activator of transcription (STAT3), thereby triggering inflammatory responses and the development of inflammatory diseases [20]. Previous studies have shown that lutein can reduce the inflammatory response in the retina by blocking the expression of inflammatory mediators.

Wang et al. [21] used an ultrasonic homogenization method to prepare a lutein nanoemulsion and found that it had potential anti-inflammatory activity, significantly inhibiting the levels of various inflammatory factors such as interleukin (IL)-6 and IL-10 and monocyte chemoattractant protein-1 in RAW264.7 cells. Chen et al. [22] found that after treating human corneal epithelial cells with lutein/polyvinyl alcohol eye drops, the expression levels of inflammatory factors such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were significantly reduced, and the inflammatory response of the retina was effectively reduced. Ahn et al. [23] believe that lutein may regulate the activation of the ROS-mediated STAT3 inflammatory signaling pathway and the expression levels of various inflammatory mediators [IL-1β, IL-6, monocyte ehe- moattractant protein-1 (MCP-1), TNF-α] by reducing ROS levels, thereby achieving an anti-inflammatory mechanism. See Figure 2.

3 Research progress on lutein in the prevention and treatment of myopia

To date, there have been no large-scale clinical trials that have shown a direct relationship between lutein intake and the incidence of myopia. However, this does not mean that lutein has no effect on myopia. In 2017, a cross-sectional study of 4,166 people aged 65 and over was initially aimed at investigating the effects of ultraviolet radiation and serum vitamin D on myopia, but the results unexpectedly found that Among the 20% of subjects with higher lutein concentrations in plasma, myopia was reduced by about 40%, indicating that high plasma lutein concentrations help prevent myopia [24].

Lutein powder is the main component of macular pigment. Supplementation with lutein can increase MPOD levels and prevent macular pigment loss in myopic people, thereby avoiding serious eye diseases [25]. Hyaluronic acid has the effect of retaining water, moisturizing, repairing and protecting myopia. Some studies have shown that lutein can control the development of myopia by acting on the retinoic acid receptor to induce the production of hyaluronic acid [26]. In addition, a study of 471 mother-child pairs in Singapore found that when the lutein concentration in the mother during pregnancy was high, the probability of the offspring developing myopia was reduced, suggesting that adequate lutein intake during pregnancy may be beneficial to the visual health of the offspring [27].

Currently, eye drops such as tropicamide and atropine are commonly used in clinics to improve myopia. Zhang Jiwei [28] treated myopia patients with a combination of tropicamide eye drops and lutein soft capsules for 3 months and found that the total clinical effective rate of the combination treatment was as high as 96.7%, which was much higher than that of tropicamide eye drops alone. Omega-3 fatty acids play a key role in promoting the development of retinal tissue. Oral omega-3 can significantly improve the unaided visual acuity, refraction and mean visual field defects of adolescents. When combined with lutein for the treatment of myopia, the efficacy is significantly better than that of omega-3 alone [29]. This shows that the combination of related drugs and lutein can significantly improve the therapeutic effect of myopia.

4 Outlook

In summary, lutein has broad application prospects in myopia prevention based on its eye protection efficacy and safety. However, there are still deficiencies in current clinical studies, such as small sample sizes and short intervention periods (less than 1 year) in most studies. It is hoped that future clinical studies will be able to thoroughly explore the role of lutein in myopia prevention.

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