FROM:
Alternative Medicine Review 1999 (Oct); 4 (5): 342–359 ~ FULL TEXT
Kathleen A. Head, ND
Introduction
During the past few decades numerous studies have been published on
the efficacy of nutritional and botanical medicines in the prevention and
treatment of ocular diseases, including macular degeneration, diabetic
retinopathy, retinitis pigmentosa, cataracts, glaucoma, and others. Part
One of this review will explore the research on diseases of the retina,
including macular degeneration, retinopathy, and retinitis pigmentosa.
Part Two (to be published in a future issue) will include a review of the
literature on cataracts, glaucoma, and other non-retinal disorders.
Macular Degeneration
Age-related macular degeneration (AMD) is the leading cause of visual
impairment and blindness in older Americans. Laser photocoagulation therapy
is effective in only a small percent of late-stage cases--those with neovascularization
and exudates. Therefore, prevention is of prime importance in reducing
the health impact on this growing elderly population.
Pathophysiology
Macular degeneration is characterized by atrophy of the macular disk.
Tissues most effected are the photoreceptors and the retinal pigmented
epithelium (RPE) (see Figure 1). The photoreceptors
most sensitive to damage are the rods and the blue-light sensitive cones.
Two types of AMD have been identified: an atrophic form, which involves
pigmentary changes in the macula without hemorrhage or scar formation,
and disciform macular degeneration, characterized by an exudative mound
and sub- and intraretinal hemorrhage. [1]
In both types the retinal pigment cells degenerate, with a resulting loss
of rods and cones. Risk factors include family history of macular disease,
cigarette smoking, [2] light exposure, [3]
light iris pigmentation, [4] chemical exposure,
history of cardiovascular disease, decreased hand grip strength, and hyperopia. [5]
Antioxidants and AMD
While the etiology of macular degeneration is not fully understood,
evidence from animal studies points to the role of free radical damage
from light exposure as a potential contributing factor. The photoreceptors
of the eye are high in polyunsaturated fatty acids (PUFAs), particularly
docosahexaenoic acid (DHA), especially in their outer-segment membranes.
DHA is readily oxidized in the oxygen-rich environment of the retina. [6]
Several of the known risk factors for AMD, including cigarette smoking
and light exposure, appear to be at least partially related to oxidative
stress.
Animal studies have demonstrated exposure to UV light, ionizing radiation,
or visible light can lead to free radical formation and subsequent lipid
peroxidation of the photoreceptor membranes. The resulting retinal damage
is similar to that noted in humans with macular degeneration. [7]
Antioxidants including vitamins C and E, and the carotenoids lutein and
zeaxanthin, are found in high concentrations in the retina. Vitamin C is
found in aqueous portions of cells throughout the retina, vitamin E in
the photoreceptor outer segment membranes, and the carotenoids throughout
the retina, but especially concentrated in the macula. [7]
Antioxidants enjoy a symbiotic, mutual recycling relationship in the
retina (see Figure 2). Vitamin E, the
major lipid-soluble antioxidant in the retina, scavenges peroxyl radicals,
yielding phenoxyl radicals which are then reduced by ascorbate, recycling
vitamin E in the retina. Glutathione appears to be unsuccessful at recycling
vitamin E in the absence of ascorbate. Dihydrolipoic acid enhances ascorbate's
protective effect by regenerating it from dehydroascorbate. [8]
Although cigarette smoking has been linked to a higher-than-normal risk
of developing AMD, a Finnish study, which examined the effect of vitamin
E (50 mg/day), beta carotene (20 mg/day), or the combination in male smokers
found no decreased incidence in AMD after 5-8 years. [9]
Epidemiological data suggests the importance of antioxidants in the
prevention of macular degeneration. Individuals with low plasma concentrations
of carotenoids and antioxidant vitamins were found to have an increased
risk for AMD. [10] A study of 976 subjects
found a high antioxidant index achieved by vitamins C and E and beta carotene
was protective for AMD. While this study found high serum levels of these
substances to offer protection, supplementation of vitamins did not seem
to provide protection. [11]
Vitamin E
The study cited above on 976 subjects also found high serum levels of
vitamin E (as a-tocopherol) alone was protective for AMD. [11]
The Physician's Health Study evaluated 21,120 individuals over a period
of 12.5 years, none of whom had a diagnosis of AMD at the beginning of
the study. Supplementation with vitamin E resulted in a 13-percent reduced
risk of AMD (which was statistically insignificant). [12]
Users of a multivitamin demonstrated a statistically insignificant 10-percent
reduced risk.
Rat retinal studies have found low levels of vitamin A coupled with
low levels of vitamin E appear to contribute to retinal damage similar
to that seen in macular degeneration. Depressed levels of vitamin A in
the presence of a vitamin E-free diet led to a five-fold increase in lipofuscin
granule deposits in the pigment epithelial cells, marked disruption of
photoreceptor outer segment membranes, and significant loss of photoreceptor
cells (rods and cones equally). When vitamin A levels were higher, the
same retinal damage without the loss of photoreceptor cells was in evidence.
The conclusion which can be drawn from this study is that vitamin A status
plays a significant role in the extent of retinal damage caused by a vitamin
E deficiency. [13] Retinal degeneration, with lesions such as photoreceoptor
outer segment degeneration similar to that seen in human macular degeneration,
has been reported in dogs with low serum vitamin E levels who were fed
homemade diets deficient in vitamin E. [14]
Vitamin C
Ascorbic acid given to rats prior to exposure to intense light was found
to protect against degeneration of retinal pigment and photoreceptors.
Light contributed to a five-to-six-fold increase in phagosome density,
a measure of light damage. Animals who received prior treatment with ascorbate
did not demonstrate an increase in phagosome density. [15]
Therefore, vitamin C appears to protect against some of the damaging effects
of light exposure. However, the catch-22 is that vitamin C levels have
been found to decrease in retinas exposed to light. [16]
Another animal study found vitamin C slowed the light-induced loss of photoreceptor
cells. [17]
Vitamin C appears to protect the eye from light damage via its antioxidant
effects. Rats exposed to bright light experienced deterioration of the
rod outer segments (an effect similar to that which occurs in human AMD).
Supplementation with ascorbate prevented loss of rhodopsin and preserved
DHA, preventing its oxidation. [18] In this
study, the protective effect of vitamin C occurred only if given prior
to light exposure.
Dietary Effects on AMD
The Beaver Dam Eye Study evaluated, via a food frequency questionnaire,
the diets of 2,003 individuals age 43-84. The study found significant inverse
associations between dietary intakes of carotenoids and vitamin E and the
development of macular lesions large drusen (subretinal pigment epithelial
deposits) and other pigmentary abnormalities consistent with future
development of macular degeneration. [19]
Other studies have also found intake of dietary carotenoids to be protective
for AMD. Goldberg and associates at the University of Illinois, in analyzing
the data from the first National Health and Nutrition Examination Survey
(NHANES-1), found a negative correlation between intake of fruits and vegetables
high in beta carotene and the development of AMD. [20]
Seddon et al found a higher intake of spinach or collard greens was associated
with a substantially lower risk for AMD. [21]
Green leafy vegetables, as well as many other fruits and vegetables, are
high in the carotenoid lutein which, as previously mentioned, is found
in high concentrations in the retina, especially in the region of the macula.
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