Schepens/Harvard study provides direct proof of dietary nutrient’s essential role in protecting the retina from the damaging effects of light
Research performed at Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School has established that the dietary zeaxanthin (zee-uh-zan’-thin) plays an essential role in protecting the retina of the eye from the damaging effects of light.
From the many carotenoids in the diet, the human retina selectively accumulates only two: zeaxanthin and lutein. Their concentration is so high in the macula, (the retinal region responsible for fine visual activities) that the carotenoids are visible as a dark yellow spot called the macular pigment. Because these carotenoids absorb blue light, and because they are powerful antioxidants, scientists have hypothesized that they protect the retina. Working with quail as an animal model, the Schepens project provided the first direct experimental evidence that carotenoids do protect the retina.
Clinical Relevance of the New Findings
Macular pigment has been implicated as a risk factor in age-related macular degeneration (AMD), the most prevalent cause of vision loss in the elderly. Vision loss in AMD is due to the irreversible death of photoreceptors and/or the invasion of leaky, unwanted blood vessels into the retina. At advanced stages of this progressive disease, everyday activities such as reading, driving, or even seeing the face of a loved one become impossible.
It is estimated that more than 17 million Americans may have symptoms of AMD and that 2 million having functional blindness; 500,000 new cases are diagnosed each year. Some clinical studies have found evidence that people with higher dietary or serum levels of zeaxanthin and lutein had reduced risk for advanced stages of age-related macular degeneration, but others have found no association.
Significantly lower macular pigment levels have been found in people with factors known to increase risk for AMD (e.g. smoking), in eyes with AMD, and in eyes at high risk for AMD. Epidemiologic studies have shown that people with higher dietary or plasma lutein/zeaxanthin have reduced risk for advanced stages of AMD. It is not yet clear whether the reduced risk for AMD is due to lutein/zeaxanthin or due to some other nutrient in the plants containing carotenoids. The Schepens work has clearly shown that the carotenoids protect the retina from light damage in animals. Some studies, but not all, have identified light damage as a risk factor in AMD.
The Research and Findings
To test this hypothesized protection, the team selected Japanese quail, because the retina resembles the human macula in having more cone photoreceptors than rods, and in highly selective accumulation of zeaxanthin and lutein from their diet. Rodents were not studied because their retinas have very few cones and do not accumulate carotenoids. The studies examined the effect of manipulating dietary carotenoids on light damage to retinas. C. Kathleen Dorey, principal investigator formerly with Schepens and now with R&D Consulting, and her colleagues raised quail on diets that were normal, carotenoid-deficient, or carotenoid-deficient supplemented with high doses of zeaxanthin.
In the short-term study, reported in the November 2002 issue of Investigative Ophthalmology and Visual Science (IOVS), the team divided the carotenoid-deficient quail into two groups, and for one week preceding light damage, they fed one group zeaxanthin-supplemented diet. The study established that photoprotection was strongly correlated with the concentration of zeaxanthin in the retinas of the quail. Retinas with low concentrations of zeaxanthin had suffered severe light damage, as evidenced by a very high number of apoptotic photoreceptor cells, while the group with high zeaxanthin concentrations had minimal damage. Apoptosis is programmed cell death, the final common pathway for photoreceptor death in retinal degeneration.
In the long-term study1, reported in the November 2002 issue of Experimental Eye Research, groups of quail were raised for six months on carotenoid-deficient, normal or zeaxanthin-supplemented diets before exposure to brighter light. The results showed extensive damage to the retina in the carotenoid-deficient animals, as evidenced by large numbers of both dying photoreceptors and gaps or “ghosts” marking sites where photoreceptors had died. The group of quail with normal dietary levels of zeaxanthin showed significantly less retinal damage than did the zeaxanthin-deprived group, while the quail group receiving high levels of zeaxanthin had few ghosts in their retinas.
These experiments by Dr. Dorey’s team showed protection of both rod and cone photoreceptors. The research further demonstrated that retinas were protected by both zeaxanthin and another antioxidant, vitamin E. Damage in these experiments was clearly reduced by zeaxanthin and tocopherol, but not lutein. Further experiments would be needed to determine whether elevated lutein would offer protection.
These results are reminiscent of the early 20th century discovery of the role of vitamins. In those experiments, extensive efforts were made to show that dietary deficiency of a compound caused health problems that were reversed by adding the substance back to the animal’s diet.
The results of the Schepens studies come on the heels of the Age Related Eye Disease Study (AREDS), sponsored by the National Eye Institute of the National Institutes of Health, which concluded that daily consumption of a formula containing high doses of dietary antioxidants are effective in slowing the progression of AMD in patients with advanced stages of the disease. It is noteworthy that zeaxanthin and lutein, two antioxidants selectively concentrated by the macula, were not commercially available when the AREDS began and were, therefore, not able to be included in that study.
The Implications for Macular Degeneration
Commenting on the implications of the Schepens studies, Dr. Dorey said: “AMD is a multi-factorial disease clearly influenced by both genetic (family history) and environmental factors (diet, and possibly light history). The retina is constantly exposed to oxidative injury, a leading candidate for initiating or accelerating retinal degeneration. Zeaxanthin is well suited to its role in maintaining retinal health, and may be an important strategy to prevent or intervene in macular degeneration. It accumulates in the macula where it absorbs harmful blue wavelength light, and it accumulates in the RPE and the most vulnerable portions of the photoreceptors where its potent anti-oxidant capacity can prevent oxidative damage, a problem that increases with aging.
“Our studies showed that light damage was strongly influenced by the amount of zeaxanthin in the retina, and that significantly greater retinal protection was provided at dietary levels higher than those normally occurring in the diet. Zeaxanthin has been extensively studied for safety and has been reviewed as a dietary ingredient by the FDA. We hope this work further stimulates interest in clinical trials, and believe that zeaxanthin has a potential to eventually complement other strategies to improve the treatment of this vision-robbing disease.”
The research team included:
- Lauren R. Thomson, M.D. Yoko Toyoda, M.D. Z-Y Wong, M.D., Francois C. Delori, Ph.D., and C. Kathleen Dorey, Ph.D. (now with R&D Consulting) at Schepens Eye Research Institute.
- Kevin M. Garnett, BS, MBA at Applied Food Biotechnology, Inc. (O’Fallon, Mo.)
- Kimberly M. Cheng, Ph.D. and Cathleen R. Nichols at Department of Animal Sciences, University of British Columbia (Vancouver)
- Neal E. Craft, Craft Technologies, Inc. (Wilson, N.C.)
References
- Toyoda Y, Thomson LR, Langner A, Craft NE, Garnett KM, Nichols CR, Cheng KM, Dorey CK. Effect of dietary zeaxanthin on tissue distribution of zeaxanthin and lutein in quail. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1210-21. PMID: 11923268. ↩︎