THE
STANDARD
(none)
Volume 2, No. 1
Free Radicals, Antioxidants and Eye Diseases
Thomas G. Guilliams Ph.D.
Our ability to see is made possible in part by the fact that our eyes allow light to
pass
through with relative ease. This makes the eye the most susceptible organ to oxidative damage
caused by light, toxins (smoke), atmospheric oxygen, and abrasion. In the United States, age-
related
macular degeneration is the leading cause of blindness for persons over 60 years of age.
Cataracts
are still the leading cause of visual impairments in the U.S., resulting in the highest portion
of
the Medicare budget, consuming $3.2 billion annually. Both of these diseases have been shown to
be
a direct result of accumulated oxidative damage. Unfortunately, except for the replacement of
opaque
lenses, there is no treatment for either of these conditions. We hope to show here that through
diet
and the generous use of certain antioxidants you can help your patients greatly reduce and
possibly
reverse the oxidative damage that leads to Age-related Macular degeneration
(ARMD) and cataracts.
The macula is the central portion of the retina responsible for acute and detailed vision. In
the central portion of
the macula, called the fovea centralis, the innermost layers of the retina are displaced to one
side allowing light to
pass unimpeded to this portion of the retina. This allows for increased visual acuity, but also
increases the
possibility of light induced damage to this area of the retina. Macular degeneration is
characterized by a gradual loss
in central acuity and the presence of drusen
(bumps) in the macula. This is commonly called the "dry" form, and constitutes about 90% of the
cases of macular
degeneration. The other 10%, called "wet" form, is characterized by rapid loss of central
acuity, neovascularization,
and vessel leakage. "Wet" ARMD is treatable with laser therapy, while "dry" ARMD is considered
untreatable.
As ultraviolet and blue light pass through the retina to the photoreceptors (rods and cones)
and the pigmented
epithelial (PE) cells, reactive oxygen species are generated. The conversion of this light
energy into a nerve impulse
by the photoreceptors generates more free radicals. Typically, these free radicals are reactive
oxygen species such as
hydrogen peroxide, superoxide and hydroxyl radicals. These reactive molecules are quick to grab
electrons from
surrounding molecules to add to their unpaired electrons. This is fine when the surrounding
molecules are one of the
many antioxidants in the eye, which are able to quench free radicals without themselves
becoming free radicals. If
instead the electron is taken from one of the lipids in the photoreceptor membranes (stacks of
memranous discs that are
rich in polyunsaturated fatty acids), lipid peroxidation cascades through the photoreceptor
outer segments. These may
be subsequently quenched by vitamin E or other lipid soluble antioxidants, or they will
continue to damage the
integrity and fluidity of these membranes.
When photoreceptor membranes become damaged, the outer portion is sloughed off into the PE
cells, and new discs are
regenerated. PE cells are equipped to phagocytize, digest and recycle these compounds under
normal conditions.
However, when these molecules have been modified by oxidation of their unsaturated bonds, they
are not easily digested
by the lysosomal enzymes. The result is a build-up of undigested molecules in the PE cells
called lipofuscin granules.
When a sufficient amount of lipofuscin has accumulated, the PE cells deposit these granules
resulting in a bump between
the pigmented epithelial cells and choriod. This bump is called drusen
(German: "bumps"). This physical and metabolic separation of the PE cells and the
photoreceptors from their blood
supply in the choroid results in damage to the photoreceptors and eventually macular
degeneration (See Figure 1).
A case-control study was performed to determine the risk factors associated with ARMD. They
found these risk factors,
reported with their odd
ratio: arterial hypertension (OR=1.28), coronary disease (OR=1.31), hyperopia (OR=1.33), and
lens opacities or previous
cataract surgery
(OR=1.55) (3). Those individuals who are aphakic (have had their lens
removed) were 4.6 times more likely to have ARMD (4).
A cataract is a lens that limits the transmission of light to the retina because it has become
opaque. The incidence of
cataracts in persons 65-75 years range from 21% in white men to nearly 40% in black women (2). Overall, this effects
nearly 10 million Americans, resulting in 600,000 lens replacement surgeries per year in the
United States. A number of
factors contribute to the development of cataracts, these include congenital defects, trauma,
age, and metabolic or
toxic agents. By far the two most common factors would be age (often called senile cataracts)
and disorders of
carbohydrate metabolism (especially diabetes).
Proteins in the lens are unusually long lived and are thus subject to extensive and accumulated
oxidative damage. The
damaged proteins accumulate, aggregate, and precipitate; causing the lens to loose its
transparency. Of critical
importance is the decrease in the Na+/K+ ATPase, resulting in the inability to maintain steady
concentrations of Na+,
K+, and Ca++ within the lens. The decreased activity of this enzyme is thought to be associated
with oxidative damage
to the sulfhydryl portions of the molecule, usually protected by the interaction of several
antioxidants, especially
glutathione (GSH), ascorbate, superoxide dismutase (SOD), and catalase. Like the processes
leading to ARMD, senile
cataracts are the result of years of damage and accumulated oxidation. Several reviews are
available that discuss the
relationship between cataracts and oxidative damage
(5,6,7,8).
The deficiency of proper glucose metabolism in the diabetic patient leads to two ocular
conditions: diabetic
retinopathies, and diabetic cataracts. Diabetes is the leading cause of acquired blindness in
the U.S., retinopathies
account for most of these. Diabetic retinopathies are associated with microaneurisms behind the
retina causing edema
and are prone to leakage (called background or non-proliferative type) or by new blood vessel
formation
(neovascularization) on the surface of the retina (called proliferative type). Laser
photocoagulation is often used to
destroy and delay neovascularization, which, if untreated, can result in the loss of vision for
nearly 10% of IDDM
patients.
Diabetic cataracts, and to some extent retinopathies, seem to have a direct relationship with
the enzyme aldose
reductase (9). Hyperglycemia stimulates the conversion of glucose to sorbitol
in the lens via aldose reductase.
Sorbitol cannot be transported through the lens membrane and is therefore accumulated in the
lens tissue. This
creates a hypertonic condition, causing water to flow into the lens tissue to maintain osmotic
equilibrium. Membrane
permeability is thus altered, resulting in the loss of several important molecules including
glutathione, magnesium,
and potassium. The use of aldose reductase inhibitors to reduce the sorbitol concentration
within the eye has shown
positive results for diabetic cataracts (10) as well as retinopathies (11).
Click on image
|
Fig 1 Free Radicals, Antioxidants, and Macular Degeneration
|
|
Antioxidants-The key to prevention: As we have outlined already, the cumulative
effects of oxidative damage are the primary cause of macular degeneration
and cataract formation. It would seem quite logical then, that antioxidants would play a direct
role in preventing and
possibly reversing the formation of these conditions. This hypothesis has been confirmed by
several recent scientific
studies and is now becoming more widely understood and accepted by those who have patients with
an increased risk for
such conditions (1,12).
Ascorbate accumulates in ocular tissues several times higher than in plasma, and furthermore is
at a higher
concentrations than other water soluble antioxidants in the ocular tissue. Ascorbate levels, as
we shall see, are
critical to the overall antioxidant protection of the eye. It has been shown that, in cells
isolated from the retinal
pigmented epithelium, the amount of radiation delivered by a visible laser was directly
proportional to the amount of
ascorbic acid oxidized to dehydro-L-ascorbic acid (DHA) (13). This implies
that ascorbate is one of the first
antioxidants used to quench light-induced free radicals. This would be expected since ascorbic
acid is very effective
at quenching hydrogen peroxide radicals, one of the major secondary free radicals formed during
the quenching of
superoxide by SOD (superoxide is formed directly from light energy). Ascorbate is also able to
protect alpha tocopherol
(Vitamin E) from oxidation within the rod outer segments (14), a function
that is enhanced by both glutathione and
lipoic acid. The interrelationship between ascorbic acid and glutathione is an interesting and
important one in the
regeneration of ocular antioxidants and retarding disease potential (15).
While one would expect that the levels of vitamin C would be quite adequate in the diet of most
Americans, this would
be a false assumption. In 1998, researchers at Arizona State University found that 30% of the
494 middle class
individuals studied were vitamin C depleted upon examination of routine blood test (16). In fact, vitamin C deficiency
has been listed among causative factors for aging macular degeneration (17).
Diabetics and smokers (two groups with
increased risk of oxidative ocular diseases) have been shown to have reduced levels of vitamin
C. Typical supplemental
levels of vitamin C range from 500 mg per day all the way to bowel tolerance (5-10g per day for
some). One to two grams
per day of vitamin C (as ascorbic
acid)
should provide more than adequate levels of this water-soluble antioxidant in the ocular
tissues. Patients should keep
in mind the addition of various flavonoids with vitamin C supplementation, as these are
integral to the function of
vitamin C (see flavonoid section).
The antioxidant role of vitamin E is straightforward. As the body's major lipid-soluble
membrane-bound free radical
quenching molecule, vitamin E is vital to the prevention of lipid peroxidation. The average
level of vitamin E (alpha
tocopherol) was lower in individuals with macular degeneration than in age and risk matched
controls
(18). In placebo-controlled studies, oral vitamin E was able to increase the
glutathione levels
in the aqueous humor and lenses of
humans, rabbits and rats (19). Supplemention of 400IU vitamin E (as natural
D-alpha tocopherol)
is commonly recommended
to all individuals to help with the 'normal' oxidative load. An additional 400IU (total of
800IU) per day would be suggested for those individuals who are currently fighting or are at
high risk for cardiac
condition, cancers, and oxidative eye diseases.
The role of glutathione in the antioxidant protection of the eye cannot be overestimated. A
tripeptide made from
glycine, cysteine, and glutamic acid, glutathione is the most prevalent cellular thiol and
accounts for more than 90%
of the sulfur in many cells. Ocular concentrations of glutathione are very high when compared
with most other tissues
and decreased levels of glutathione are associated with both age related macular degeneration
and cataract, and in
diabetic patients with similar conditions.
Glutathione is critical in maintaining the reduced state of sulhydryl-containing proteins in
the lens. As mentioned
earlier, the accumulation of sorbitol in the lens will allow glutathione to "leak out" of lens
tissues, making them
more susceptible to oxidative damage. In a recent study, older patients with diabetes had a
significantly reduced level
of total glutathione (GSHt), while all older patients without diabetes had a lower level of the
reduced form of
glutathione (GSH) (20). This would suggest that increasing the levels of
GSH is important in all elderly patients,
while in the case of diabetics an increase in GSHt is also important. Glutathione deficiency
(serum and aqueous humor)
was also noted in individuals with glaucoma, although the administration of lipoic acid was
able to increase
glutathione levels in these patients (21).
Unfortunately, serum levels of glutathione are affected little by oral administration of
glutathione
(22). The oral
administration of N-acetyl cysteine, on the other hand, has been shown to significantly
increase levels of glutathione
in serum, intracellularly (23,24), as well as in cultured
lens cells
(25). Lipoic Acid (21), vitamin E (19), and
ascorbic acid
(15)
levels all have positive effects on the GSHt and/or GSH, confirming the integral link
glutathione plays in the
antioxidant cascade that prevents ocular damage.
Formerly known as thioctic acid, alpha-lipoic acid is considered one of the most versatile
antioxidants. Having a lipid-soluble portion, a water-soluble portion and two thiol groups
allows
lipoic acid to recharge vitamin E, ascorbic acid
(14) and glutathione (21). In experimentally
induced cataract formation in rats, glutathione, ascorbate, and vitamin E were depleted to 45,
62,
and 23% of controls respectively; but were maintained at 84-97% of control levels when lipoic
acid
was administered to the animals (26).
Lipoic acid has also been shown to inhibit the activity of
aldose reductase in hyperglycaemic conditions
(27), indicating another way it may prevent cataract
formation. Administration of lipoic acid improved visual function of glaucoma patients in as
little
as 2 months at 150 mg per day (28).
The therapeutic use of lipoic acid is growing for many
different conditions, age-related and oxidative eye diseases are clearly conditions where
lipoic
acid would be indicated.
Extracts of Ginkgo Biloba L. (GBE), standardized to 24% ginkgo flavonoglycosides and 6% terpene
lactones, have been
used for many years to increase blood flow to the brain, as well as other conditions, with
excellent results. While
its use in retinal protection is less popular in comparison, the biochemistry and clinical data
make GBE one of the
best choices for such an application. In 1986 research was conducted that showed that the eye
tissue was among only a
few tissues that had a high affinity to labeled GBE
(29). In the same year, a second group performed a small (10
patient) clinical trial using GBE on patients with ARMD. Even with a small sample size, they
were able to realize a
significant difference in visual acuity and visual field between
those patients on GBE and those on placebo (30).
Ginkgo extracts were shown to protect retinas from the damage induced by xenobiotics such as
chloroquine
(31),
proteolytic enzymes (32), induced retinal detachment
(33), direct addition of oxidizing agents (34), enhanced
illumination of the retina (35),
ischemic/reperfusion studies in diabetic rat retinas (36), as well as
induced
diabetic retinopathy (37). Since this covers virtually every route of
oxidative and
metabolic damage the retina is
likely to face, GBE is absolutely essential to the therapy of any
individual with ongoing or potential retinal damage.
|
Cartenoids and Related Compounds
|
|---|
There are nearly 600 naturally occurring carotenoids, 10 of which are frequently found in human
serum, and two of
which are found in high concentrations in the macula lutea: lutein and zeaxanthin (38). It is believed that they serve
two primary roles; to absorb excess photon energy, and to quench free-radicals before they
damage the lipid membranes.
Studies have shown that increased dietary intake of carotenoids, especially lutein and
zeaxanthin, increase macular
pigment (39) and lower the risk of age-related macular degeneration (40). Dark green leafy vegetables like spinach and
collard greens are excellent dietary sources for these molecules. Furthermore, supplemental
lutein (30 mg/day for 140
days) was able to reduce the amount of blue light transmitted to the photoreceptors and the
pigmented epithelial
cells, the ARMD sensitive tissues, by 30 to 40% (41). Lycopene, another
carotenoid that is quite abundant in tomatoes,
is the most abundant carotenoid in the serum. Low serum levels of lycopene have been shown to
increase the risk of
ARMD (18). We are just beginning to see the many uses of this particular pigment/antioxidant
and more research will
continue to come forth on its use in ARMD, as well as in other conditions.
The antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase, and catalase are
vital to the quenching of
free radicals in the lens and retina. Each of these enzymes requires divalent cations
(coenzymes)
in order to function. SOD requires zinc, copper, and manganese; catalase requires zinc and
copper, and glutathione
peroxidase requires selenium. Studies on monkeys with oxidative stressed retinas shows a 60%
reduction in the activity
of catalase and glutathione peroxidase as well as a 4-fold reduction in zinc concentration
compared with normal
controls (42).
Studies done more than 10 years ago showed that oral zinc therapy was able to significantly
reduce visual loss, when
compared to placebo (43). The apparent benefit of supplemental zinc has a mechanism in addition
to acting as a
coenzyme to both SOD and catalase. The set of RPE lysosomal enzymes responsible for digesting
the sloughed-off portion
of the photoreceptors, in particular alpha-mannosidase, beta-galactosidase, N-acetyl-beta
glucosaminidase, and N-
acetyl beta galactosaminidase, have significantly reduced activity upon aging
(44). This will
increase the likelihood
of lipofuscin build-up and eventually drusen and ARMD. Alpha-mannosidase, a critical enzyme for
the degradation of rod
outer segments, derived from older individuals can be stimulated 2-fold by the addition of zinc
(45). These data would
suggest that while copper, selenium, and manganese are important to maintain proper antioxidant
protection; zinc has
both a history and biochemistry that suggest it should be used therapeutically for ARMD and
cataracts.
Flavonoids are the class of compounds first discovered by Szent-Gyorgyi in the mid 1930's and
designated by him as
"vitamin P". These compounds, and the larger designation polyphenols, are responsible for most
of the pigments of
fruits and berries. These compounds also have many important health benefits when taken orally,
among them,
antioxidant and aldose reductase inhibition. For more than 20 years, the aldose reductase
inhibition of flavonoids
like quercetin, quercetrin, and myricitrin has been studied
(46), and used effectively to slow
the progression of
cataracts (47,48).
Quercetin, and its glycosides quercetrin and guaijaverin, have been shown to
inhibit human lens
aldose reductase in vitro (49). Furthermore, the well-known interaction between flavonoids and
vitamin C (remember
ascorbate's pivotal role in ocular antioxidation) make flavonoids a certain addition to any
natural therapeutic
approach for macular degeneration and cataracts.
Any discussion of plant compounds used for the eye is incomplete without the mention of
anthocyanosides, especially
those derived from bilberry (Vaccinium myrtillus L.). Originally used to improve night vision,
extracts of bilberry
are being used in France and Germany for vascular conditions, retinopathies, and night vision.
As would be expected of
anthocyanosides, research has shown them to have a positive influence on the permeability and
tendency to hemorrhage
of retinal vessels, especially in patients with diabetic retinopathy
(50).
Taurine is an amino acid, synthesized by the body from methionine and cysteine. It has for
years been used as a
supplemental ingredient for health concerns, primarily cardiovascular, where its interaction
with calcium-dependent
pathways help it relax the heart muscle during diastole. Retinal concentrations of taurine are
quite high and it is
required for the proper development of the retinal tissues in both man and animals. Taurine has
been shown to directly
stimulate the proliferation of human retinal pigmented epithelial cells (RPE)
(51), protect
rod outer segments from
damage due to light exposure, regulate calcium influx, and regulate signal transduction in the
retina (52). Taurine
was among vitamin E, C, and lipoic acid in its ability to protect lens tissue from protein
leakage (cataract
model) during exposure to gamma irradiation (53). The use of taurine for macular degeneration
and cataract protection
is a welcome addition to the natural products already discussed because its mechanism is quite
different from the
antioxidants, enzymes, flavonoids or metals.
|
Conclusion: Diet vs Supplementation
|
|---|
The question always arrives. How then shall we supply these natural
substances: by the diet alone, or through supplementation? The answer is
essentially: both; but of course is not that simple. Even a diet very rich in a variety of
fresh fruits and vegetables
would fall short of the recommended intakes that would be suggested for individuals suffering
from or at risk for
oxidative eye diseases. However, the facts show that only 9% of Americans daily consume the two
fruits and three
vegetables recommended by the NCI
(54). The elderly, the population most effected by these
conditions, are very
reluctant to change dietary habits and are more likely to benefit from supplementation of the
ingredients listed
above. These recommendations are coming from even the most reluctant and hesitant sources (55).
In fact, a study of
17,000 male physicians over 5 years showed that those physicians who took a multivitamin (not
specifically designed
for the
eye) were 27% less likely to develop cataracts (56). Studies are continuing with many of the
ingredients listed here
in long-term, double-blinded, placebo controlled clinical trials.
Practitioners should try to get patients to consume as many green leafy vegetables as possible,
things such as spinach
and collard greens. They should increase the intake of fruits and yellow vegetables. The more
natural pigments, the
better. Avoid rancid and trans-fatty acids, these will always lead to increased lipid
peroxidation, decrease
antioxidant concentrations, and tax an already loaded lipid enzymatic machinery. Older patients
should supplement
their diet with a broad multivitamin and mineral product that gives them adequate levels of all
the B vitamins,
magnesium, and the trace minerals. Patients with active oxidative damage should take immediate
measures to increase
the intake of as many of the ingredients listed in this article as possible, as well as reduce
exposure to direct
sunlight with the use of sunglasses that block UV-light. It should be noted that there is no
other treatment
available, and these processes can be slowed, stopped and possibly reversed with diet and
supplemental ingredients.
Again, we see that within the natural world there are a number of compounds that have profound
effects on conditions
that are listed as essentially incurable. And once again the established medical paradigm
reveals their view of these
conditions and their treatment is still rather short-sighted.
- van der Hagen AM, Yolton DP, Kaminski MS, et al.
Free radicals and antioxidant supplementation: a review of their roles in age related macular
degeneration.
J Am Optom Assoc 1993; 64:871-78
[PubMed]
- Klein BE and Klein R.
Cataracts and macular degeneration in older Americans.
Arch Ophthalmol 1982; 100(4):571-3
[PubMed]
- Chaine G, Hullo A, Sahel J, et al.
Case-control study of the risk factors for age related macular degeneration.
France-DMLA Study Group.
Br J Ophthalmol 1998; 82(9):996-1002
[PubMed]
- Liu IY, White L, LaCroix AZ.
The association of age-related macular degeneration and lens opacities
in the aged.
Am J Public Health 1989; 79(6):765-9
[PubMed]
- Kaluzny JJ and Kaluzny J.
Contemporary views on the pathogenesis and possible prophylaxis of age related cataracts.
[article in polish].
Pol Merkuriusz Lek 1997; 2(7):76-8
[PubMed]
- Varma SD, Devamanoharan PS, Morris SM.
Prevention of cataracts by nutritional and metabolic antioxidants.
Crit Rev Food Sci Nutr 1995; 35(1-2):111-29
[PubMed]
- Taylor A.
Cataract: relationship between nutrition and oxidation.
J Am Coll Nutr 1993; 12(2):138-46
[PubMed]
- Varma SD, Chand D, Sharma YR.
Oxidative stress on lens and cataract formation: role of light and oxygen.
Curr Eye Res 1984; 3(1):35-57
[PubMed]
- Lightman S.
Does aldose reductase have a role in the development of the ocular complications of diabetes?
Eye 1993; 7(Pt2):238-41
[PubMed]
- Crabbe MJ.
Aldose reductase inhibitors and cataract.
Int Ophthalmol 1991; 15(1):25-36
[PubMed]
- Hotta N, Koh N, Sakakibara F, et al.
An aldose reductase inhibitor, TAT, prevents electroretinographic abnormalities and ADP-induced
hyperaggregability in streptozotocin-induced diabetic rats.
Eur J Clin Invest 1995; 25(12):948-54
[PubMed]
- Rose RC, Richer SP, Bode AM.
Ocular oxidants and antioxidant protection.
Proc Soc Exp Biol Med 1998; 217(4):397-407
[PubMed]
- Glickman RD, Lam KW.
Oxidation of ascorbic acid as an indicator of photooxidative stress in the eye.
Photochem Photobiol 1992; 55(2):191-6
[PubMed]
- Stoyanavsky DA, Goldman R, Darrow RM, et al.
Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with
exogenous dihydrolipoic acid.
Curr Eye Res 1995; 14(3):181-9
[PubMed]
- Winkler BS, Orselli SM, Rex TS.
The redox couple between glutathione and ascorbic acid: a chemical and physiological
perspective.
Free Radic Biol Med 1994; 17(4):333-349
[PubMed]
- Johnston CS, Thompson LL.
Vitamin C status of an outpatient population.
J Am Coll Nutr 1998; 17(4):366-70
[PubMed]
- Tso MO.
Pathogenic factors of aging macular degeneration.
Ophthalmology 1985; 92(5):628-35
[PubMed]
- Mares-Perlman JA, Brady WE, Klein R, et al.
Serum antioxidants and age-related macular degeneration in a population-based
case-control study.
Arch Ophthalmol 1995; 113(12):1518-23
[PubMed]
- Costagliola C, Iuliano G, Menzione M, et al.
Effect of vitamin E on glutathione content in red blood cells, aqueous humor and lens of humans and other
species.
Exp Eye Res 1986; 43(6): 905-14
[PubMed]
- Samiec PS, Drews-Botsch C, Flagg EW, et al.
Glutathione in human plasma: decline in association with aging, age-related macular
degeneration and diabetes.
Free Radic Biol Med 1998; 24(5):699-704
[PubMed]
- Bunin AIa, Filina AA, Erichev VP.
A glutathione deficiency in open-angle glaucoma and the approaches
to its correction. [Article in Russian]
Vestn Oftalmol 1992; 108(4-6):13-5
[PubMed]
- Witschi A, Reddy S, Stofer B, Lauterburg BH.
The systemic availability of oral glutathione.
Eur J Clin Pharmacol 1992; 43(6):667-9
[PubMed]
- De Quay B, Malinverni R, Lauterburg BH.
Glutathione depletion in HIV-infected patients: role of cysteine deficiency and
effect of oral N-acetylcysteine.
AIDS 1992; 6(8):815-9
[PubMed]
- Pendyala L, Creaven PJ.
Pharmacokinetic and pharmacodynamic studies of N-acetlycysteine, a potential
chemopreventative agent during phase I trial.
Cancer Epidemiol Biomarkers Prev 1995;4(3):245-51
[PubMed]
- Holleschau AM, Rathbun WB, Nagasawa HT.
An HPLC radiotracer method for assessing he ability of L-cysteine prodrugs to
maintain glutathione levels in the cultured rat lens.
Curr Eye Res 1996;15(5):501-10
[PubMed]
- Maitra I, Serbinova E, Tritschler HJ, Packer L.
Stereospecific effects of R-lipoic acid on buthione sulfoximine-induced
cataract formation in newborn rats.
Biochem Biophys Res Commun 1996; 221(2):422-9
[PubMed]
- Ou P, Nourooz-Zadeh J, Tritschler HJ, Wolff S.
Activation of aldose reductase in rat lens and metal-ion chelation by aldose
reductase inhibitors and lipoic acid.
Free Radic Res 1996; 25(4):337-46
[PubMed]
- Filina AA, Davydova NG, Endrikhovski SN, Shamshinova AM.
Lipoic acid as a means of metabolic therapy of open-angle glaucoma. [Article in Russian].
Vestn Oftalmol 1995; 111(4):6-8
[PubMed]
- Moreau JP, Eck CR, McCabe J, Skinner S.
Absorption, distribution and elimination of a labelled extract of Ginkgo biloba
leaves in the rat. [Article in French].
Presse Med 1986; 15(31):1458-61
[PubMed]
- Lebuisson DA, Leroy L, Rigal G.
Treatment of senile macular degeneration with Ginkgo biloba extract.
A preliminary double-blind drug vs. placebo study. [Article in French]
Presse Med 1986 15(31):1556-8
[PubMed]
- Droy-Lefaix MT, Vennat JC, Besse G, Doly M.
Effects of Ginkgo biloba extract (EGb 761) on chloroquine induced retinal alterations.
Lens Eye Toxic Res 1992;9(3-4):521-8
[PubMed]
- Pritz-Hohmeier S, Chao TI, Krenzlin J, Reichenbach A.
Effects of in vivo application of the ginkgo biloba extract EGb 761 (Rokan) on
the susceptibility of mammalian retinal cells to proteolytic enzymes.
Ophthalmic Res 1994;26(2):80-6
[PubMed]
- Baudouin C, Ettaiche M, Imbert F, et al.
Inhibition of preretinal proliferation by free radical scavengers
in an experimental model of tractional retinal detachment.
Exp Eye Res 1994; 59(6):697-706
[PubMed]
- Droy-Lefaix MT, Cluzel J, Menerath JM, et al.
Antioxidant effect of a Ginkgo biloba extract (Egb 761) on the retina.
Int J Tissue React 1995;17(3):93-100
[PubMed]
- Grosche J, Hartig W, Reichenbach A.
Expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS),
and Bcl-2 protooncogene protein by Muller (glial) cells in retinal light damage of rats.
Neurosci Lett 1995;185(2):119-22
[PubMed]
- Szabo ME, Droy-Lefaix MT, Doly M.
Direct measurement of free radicals in ischemic/reperfused diabetic
rat retina.
Clin Neurosci 1997; 4(5):240-5
[PubMed]
- Doly M, Droy-Lefaix MT, Braquet P.
Oxidative stress in diabetic retina.
EXS 1992; 62:299-307
[PubMed]
- Schalch W.
Carotenoids in the retina- a review of their positive role in preventing or
limiting damage caused by light and oxygen.
EXS 1992; 62:280-98
[PubMed]
- Hammond BR Jr, Curran-Celentano J, Judd S, et al.
Sex differences in macular pigment optical density: relation to plasma carotenoid
concentrations and dietary patterns.
Vision Res 1996:36(13):2001-12
[PubMed]
- Seddon JM, Ajani UA, Sperduto RD, et al.
Dietary carotenoids, vitamin A, C and E and advanced age-related macular degeneration.
Eye Disease Case-Control Study Group.
JAMA 1994;272(18):1413-20
[PubMed]
- Landrum JT, Bone RA, Joa H, et al.
A one year study of the macular pigment: the effect of 140 days of a lutein supplement.
Exp Eye Res 1997; 65(1):57-62
[PubMed]
- Nicolas MG, Fujiki K, Murayama K, et al.
Studies on the mechanism of early onset macular degeneration in cynomolgus
monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress.
Exp Eye Res 1996; 62(4):399-408
[PubMed]
- Newsome DA, Swartz M, Leone NC, et al.
Oral Zinc in macular degeneration.
Arch Ophthalmol 1988; 106(2):192-8
[PubMed]
- Cingle KA, Kalski RS, Bruner WE, et al.
Age-related changes of glycosidases in human retinal pigment epithelium.
Curr Eye Res 1996;15(4):433-8
[PubMed]
- Wyszynski RE, Bruner WE, Cano DB, et al.
A donor-age-dependent change in the activity of alpha-mannosidase in human cultured RPE cells.
Invest Ophthalmol Vis Sci 1989; 30(11):2341-7
[PubMed]
- Varma SD, Mikuni I, Kinoshita JH.
Flavonoids as inhibitors of lens aldose reductase.
Science 1975; 188:1215-6
[PubMed]
- Varma SD, Mizuno A, Kinoshita JH.
Diabetic cataracts and flavonoids.
Science 1977; 195:205-6
[PubMed]
- Varma SD, El-Aguizy HK, Richards RD.
Refractive change in alloxan diabetic rabbits. Control by flavonoids I.
Acta Ophthalmol (Copenh) 1980; 58(5):748-59
[PubMed]
- Chaudhry PS, Cabrera J, Juliani HR, Varma SD.
Inhibition of human lens aldose reductase by flavonoids, sulindac and
indomethacin.
Biochem Pharmacol 1983; 32(13):1995-8
[PubMed]
- Scharrer A, Ober M.
Anthocyaosides in the treatment of retinopathies. [Article in German].
Klin Monatsbl Augenheilkd 1981; 178(5):386-9
[PubMed]
- Gabrielian K, Wang HM, Ogden TE, Ryan SJ.
In vitro stimulation of retinal pigment epithelium proliferation by taurine.
Curr Eye Res 1992; 11(6):481-7
[PubMed]
- Lombardini JB.
Taurine: retinal function.
Brain Res Rev 1991; 16(2):151-69
[PubMed]
- Bantseev V, Bhardway R, Rathbun W, et al.
Antioxidants and cataract: (cataract induction in space environment and application to
terrestrial aging cataract).
Biochem Mol Biol Int 1997; 42(6):1189-97
[PubMed]
- Anderson RE, Kretzer FL, Rapp LM.
Free radicals and ocular disease.
Adv Exp Med Biol 1994; 366:73-86
[PubMed]
- Brown NA, Bron AJ, Harding JJ, Dewar HM.
Nutrition supplements and the eye.
Eye 1998; 12(1):127-33
[PubMed]
- Seddon JM, Christen WG, Manson JE, et al.
The use of vitamin supplements and the risk of cataract among US male physicians.
Am J Public Health 1994; 84(5):788-92
[PubMed]
Get Adobe Reader
Top
Macular Degeneration
Cataracts
Antioxidants: