The global prevalence of visual impairment is steadily increasing, largely driven by aging populations. It is estimated that by 2050, the number of people living with blindness will rise to 61m, and people with moderate or severe visual impairment could increase to over 834m.
Oxidative stress, chronic inflammation, and neurodegenerative processes underlie the pathogenesis of many eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts, contributing to progressive vision loss and functional impairment.
Carotenoids such as lutein, zeaxanthin, and meso-zeaxanthin, are potent antioxidants and anti-inflammatory mediators in the retina. Although the benefits of increasing macular pigment levels through carotenoid supplementation have been demonstrated, the full neuroprotective potential of these compounds has not yet been fully explored.
To review current data regarding the mechanisms of action of carotenoids and their potential clinical significance in the prevention and treatment of diseases of the retina, optic nerve, lens and eye surface, researchers in Poland analyzed studies published within the last 10 to 15 years and up to January 2026.
According to the findings published on Nutrients, lutein exhibits a particularly high capacity for blue light absorption, protecting against cellular damage in the retina as filtering short-wavelength radiation reduces the formation of light-induced reactive oxygen species (ROS).
Experimental studies have demonstrated that even at low concentrations—insufficient to produce an optical filtering effect—lutein protects the retina through direct scavenging of free radicals.
“These findings suggest that macular carotenoids act both at the preventive stage by absorbing radiation that initiates oxidative stress, and at the secondary stage, by neutralizing already formed free radicals,” the researchers wrote.
“Furthermore, their influence on the modulation of inflammatory pathways, mitochondrial function, and stability of the blood-retinal barrier underscores their importance in maintaining ocular tissue homeostasis.”
Bioavailability of carotenoids
The bioavailability of carotenoids is subject to the presence of fats in the diet, the dietary source, and intestinal transport mechanisms involving specific proteins such as Scavenger Receptor Class B Type I (SR-BI) and Niemann-Pick C1-Like 1 (NPC1L1).
These factors determine their serum concentration and the efficiency of distribution to ocular tissues, which directly influences their biological activity.
Available clinical and epidemiological data suggest that an adequate intake of carotenoids, particularly lutein and zeaxanthin, may help reduce the risk of developing and slow the progression of retinal diseases, including AMD.
However, their effects depend on many factors, such as interactions with other dietary components, genetic factors, and disease stage.
Supporting neuronal survival
Apart from their antioxidant and anti-inflammatory properties, macular carotenoids exhibit a range of biological functions essential for maintaining the structural and functional integrity of the retina and the visual system.
Studies in cellular and animal models suggest that they may participate in intercellular communication by influencing gap junction function, which plays a key role in maintaining cellular homeostasis.
Preclinical studies have shown that lutein exerts neuroprotective effects by reducing oxidative stress, inhibiting extracellular-signal-regulated kinase (ERK) pathway activation, and protecting synaptic proteins such as synaptophysin.
Additionally, some animal studies found that lutein prevents the decline of brain-derived neurotrophic factor (BDNF), while others indicated that lutein protects retinal ganglion cells and inner retinal layers from degeneration induced by pathological processes. This is particularly important as retinal neurons lack regenerative capacity, and their loss is irreversible.
Macular carotenoids also demonstrate a characteristic distribution within retinal structures—beyond the fovea, high concentrations are observed in the inner plexiform layer.
Notably, lutein is the predominant carotenoid in the visual cortex of the brain, and its concentration strongly correlates with retinal levels. This suggests a functional relationship between carotenoid status in the eye and the central nervous system.
“The presence of lutein and zeaxanthin in both the retina and the brain indicates their potential role in protecting neuronal structures rich in polyunsaturated fatty acids and in optimizing visual signal transmission.”
Human clinical studies have discovered that supplementation with lutein and zeaxanthin increases macular pigment optical density (MPOD), which is associated with improvements in visual function parameters such as visual acuity and contrast sensitivity.
Nevertheless, the magnitude of these effects remains moderate, and depends on dose, duration of supplementation, and individual variability.
Translational barriers and future perspectives
Despite increasing evidence for the beneficial benefits of carotenoids on eye health, there remains a need for clinical trials to definitively establish their therapeutic efficacy, optimal doses, and long-term safety.
Most of the postulated molecular processes, such as regulation of Nrf2 (Nuclear factor erythroid 2-related factor 2), NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (Mitogen-Activated Protein Kinase) proteins and mitochondrial signaling pathways, have been demonstrated mainly in in vitro studies and experimental animal models so far.
On the other hand, clinical trials have focused mostly on functional outcomes such as MPOD alterations, visual acuity and contrast sensitivity rather than elucidating these intracellular processes in human retinal tissue.
“Future studies should include large-scale randomized controlled trials with molecular biomarkers and clinical endpoints to better understand the connection between carotenoid-induced molecular changes and visual outcomes.
“Moreover, future research should explore tailored supplementation regimens according to individual genetic and metabolic factors, and assess their long-term clinical effectiveness. Addressing these obstacles will be crucial to the translation of promising experimental findings into evidence-based practice in ophthalmology,” the researchers concluded.
Source: Nutrients. doi: 10.3390/nu18152467. “Bioactive Properties of Carotenoids in Ocular Diseases: Antioxidant, Anti-Inflammatory, and Neuroprotective Effects”. Authors: Justyna Łapińska, et al.
