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The first experiments in animals were completed in 1980 when a group depleted a primate's (macaque monkey) diet of xanthophylls for three years. Upon examination of the excised retinas, many AMD-like pathologies were seen including lipofuscin accumulation, abnormal cones and RPE abnormalities.
The Japanese quail were studied in the latter part of that decade by Fite et. al. and was picked up in the mid-1990s by Dr. K. Dorey and colleagues at Schepens/Harvard Medical School. The quail contain a cone-rich retina, forms drusen, and show other symptoms similar to those of AMD in humans. In addition, they accumulate the macular pigments selectively from their diet. The Schepens' team carried out extensive light damage and aging studies by manipulating the diet of the birds such that their retina contained little, normal, or high levels of zeaxanthin. These series of studies for the first time directly demonstrated experimentally that retinal zeaxanthin dramatically, and in a dose related manner, protects rods and cones from light damage. In addition to these conclusions, the Schepen's team also demonstrated that beta-carotene did not show positive effects in this animal model of light damage.
- The protection was mediated by reduced apoptosis of both types of photoreceptors and slowed both the rate and total amount of cell death.
- Showed positive or protective effects in the aged quail like basal membrane thickening
- Prevented the migration of destructive glial cells into the retina
- Demonstrated that adipose and liver tissue compete with retina for serum xanthophylls and that the "retinal capture" efficiency for zeaxanthin over lutein is about 4:1
- The quail lens xanthophylls content can be increased by up to five fold by dietary manipulation.
In 2002, a number of the researchers involved with first primate studies repeated the light damage experiments using a blue laser in monkeys. This group supplemented directly with lutein or zeaxanthin for six months. The researchers concluded that zeaxanthin was more photoprotective than lutein by gross size and number of lesions and that the greater spread of lesions in the lutein-fed monkeys suggested a free-radical mechanism. While primate research is probably the most appropriate animal model for studying xanthophylls and eye health, it is very expensive and time consuming. We can expect more results to come in from experiments with Japanese quail.
Small clinical intervention trials have been initiated with lutein supplements. In 2002, Richer, et al. described the results of a prospective, 12-month, placebo controlled, double-blind, crossover trial with lutein supplementation in 90 male veterans with atrophic AMD. With lutein supplements of 10 mg/day there were significant concurrent improvements in visual function including glare recovery, contrast sensitivity, and distant/near visual acuity. Video documentation of patients' symptoms pre and post treatment were consistent with objective data. The addition of other antioxidants provided an added improvement with contrast sensitivity. This study confirmed again that AMD is a nutrition-responsive group of multi-component pathologies.
In 2001, an Italian group presented the effects of a lutein/zeaxanthin supplement at 18 months in a three-year, single-blind, placebo-controlled, randomized, parallel group study of 50 early stage AMD patients. At 18 months, the study was showing marginal but measurable improvement in visual acuity and drusen progression.
Most recently, in 2002, a Spanish group investigated lutein in 17 cataract patients in a double-blind supplementation trial with lutein ¡¾ alpha tocopherol. These 15 mg doses three times per week for two years showed significant improvements in visual acuity and glare sensitivity in people with age-related cataracts.
These small intervention trials are showing promising results in an early stage of the disease with visual functions important to the patient and their view of symptoms. The reports are consistent with individual reports and accounts from patients. The definitive result for the FDA is likely to be statistical relevance in a functional end-point (visual acuity, three lines of improvement). The ophthalmology community will wait for definitive improvements in visual acuity coupled with significant improvements in fundus photograph grading and other acceptable gross pathology improvements including area of atrophy and lack of neo-vascularization. |