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Fish oil and
Omega-3
fatty acids in ophthalmological research
Retinal pigment
epithelial acid
lipase activity and lipoprotein receptors: effects of dietary omega-3
fatty
acids
PURPOSE: To show that fish oil-derived omega-3 polyunsaturated fatty
acids, delivered to the retinal pigment epithelium (RPE) by circulating
low-density lipoproteins (LDL), enhance already considerable RPE
lysosomal acid lipase activity, providing for more efficient hydrolysis
of intralysosomal RPE lpids, an effect that may help prevent
development of age-related macular degeneration (ARMD). METHODS:
Colorimetric biochemical and histochemical techniques were used to
demonstrate RPE acid lipase in situ, in vitro, and after challenge with
phagocytic stimuli. Receptor-mediated RPE uptake of fluorescently
labeled native, aceto-acetylated, and oxidized LDL was studied in vitro
and in vivo. LDL effects on RPE lysosomal enzymes were assessed.
Lysosomal enzyme activity was compared in RPE cells from monkeys fed
diets rich in fish oil to those from control animals and in cultured
RPE cells exposed to sera from these monkeys. RESULTS: RPE acid lipase
activity was substantial and comparable to that of mononuclear
phagocytes. Acid lipase activity increased significantly following
phagocytic challenge with photoreceptor outer segment (POS) membranes.
Receptor-mediated RPE uptake of labeled lipoproteins was determined in
vitro. Distinctive uptake of labeled lipoproteins occurred in RPE cells
and mononuclear phagocytes in vivo. Native LDL enhanced RPE lysosomal
enzyme activity. RPE lysosomal enzymes increased significantly in RPE
cells from monkeys fed
fish oil-rich diets and in cultured RPE cells exposed to their sera.
CONCLUSIONS: RPE cells contain substantial acid lipase for efficient
metabolism of lipids imbided by POS phagocytosis and LDL uptake. Diets
rich in fish oil-derived omega-3 fatty acids, by enhancing acid lipase,
may reduce RPE lipofuscin accumulation, RPE oxidative damage, and the
development of ARMD.
Elner VM.; Retinal pigment epithelial acid lipase activity and
lipoprotein receptors: effects of dietary omega-3 fatty acids.
Department of Ophthalmology, University of
Michigan,
Ann Arbor, USA. Trans Am Ophthalmol Soc 2002;100:301-38
Dietary fat and fish
intake
and age-related maculopathy
OBJECTIVE: To assess whether dietary intake of fat or fish is
associated with age-related maculopathy (ARM) prevalence. DESIGN:
Cross-sectional, urban population-based study. PARTICIPANTS: People (N
= 3654) aged 49 years or older. MAIN OUTCOME MEASURES: Subjects with
ARM were identified from masked grading of retinal photographs. A
145-itemself-administered, semiquantitative food frequency
questionnaire was completed adequately by 88.8% of participants and was
used to assess intakes of dietary fat and fish. RESULTS: A higher
frequency of fish consumption was associated with decreased odds of
late ARM (odds ratio for frequency of consumption more than once per
week compared with less than once per month, 0.5). Subjects with higher
energy-adjusted intakes of cholesterol were significantly more likely
to have late ARM, with an increased risk for late ARM for the highest
compared with the lowest quintile of intake (odds ratio, 2.7).
CONCLUSION: The amount and type of dietary fat intake may be associated
with ARM.
Smith W, Mitchell P, Leeder SR.; Dietary fat and fish intake
and
age-related maculopathy; National Centre for Epidemiology and
Population
Health, Australian National University, Australian Capital Territory;
Arch
Ophthalmol 2000 Mar;118(3):401-4
The metabolism of omega-3
polyunsaturated
fatty acids in the eye
Study of the metabolism, physiological importance, biological effects,
and
pathological role of omega-3-polyunsaturated fatty acids, particularly
DHA,
remains a relatively unexplored field. The notion that DHA in membranes
such
as those of photoreceptors has no function but to contribute to
membrane fluidity is probably an oversimplification. More specific
roles are envisaged in the structure and function of retinal and
synaptic membranes. One such function may be to provide EPA by
retroconversion which, in turn, will be oxygenated to biologically
active metabolites that may affect other eicosanoids or directly elicit
or induce other functions. A better understanding of the already
described alterations in membrane properties of outer segments in
inherited retinal degeneration may also lead to further elucidation of
the fundamental mechanisms involved in senile macular degeneration and
other retinal diseases. The fact that aging enhances the oxidative
stress on cells and that the visual cells are enriched in DHA may
result in functional impairments; DHA peroxidation may deplete crucial
phospholipids from their sites in specific membrane domains. Also, DHA
peroxidation generates toxic products that can damage the shedding of
photoreceptor discs or their phagocytosis by the retinal pigment
epithelium. Docosanoids, oxygenated derivatives of DHA that resemble
eicosanoids, may well prove to be unique mediators of physiological
processes in the central nervous system, including the retina, and may
play a role
in some ocular pathologies. More thorough knowledge of these compounds
can
be expected to lead to important new insights into ocular physiology
and
pathophysiology, just as research on the eicosanoid system, the primary
subject
of this volume, has achieved. However, it is of even more immediate
importance
that we bear in mind the potential contribution of docosanoids to
retinal
physiology and pathology and to other ocular processes when considering
treatment
modalities or when interpreting the results of research studies that
involve
manipulation of the cyclooxygenase and lipoxygenase pathways. The
effects
currently assigned to eicosanoids by virtue of their inhibition of the
cyclooxygenase
or lipoxygenase systems may, in part, be consequences of concomitant
alterations
in the production of docosanoids, especially in the eye, where the
retina
is an especially rich source of DHA, the endogenous precursor of this
recently
discovered family of metabolites.
Bazan NG.; The metabolism of omega-3 polyunsaturated fatty
acids
in the eye: the possible role of docosahexaenoic acid and docosanoids
in
retinal physiology and ocular pathology; Louisiana State University
Medical
Center School of Medicine, LSU Eye Center, New Orleans 70112.; Prog
Clin
Biol Res 1989;312:95-112
Iris color, skin sun sensitivity, and
age-related
maculopathy
Blue iris color was associated with an increased risk of both late AMD
and early ARM in this population. Abnormal skin sensitivity to sunlight
was
also associated with an increased risk of late AMD.
Iris color, skin sun sensitivity, and age-related maculopathy.
The Blue Mountains Eye Study; Mitchell P, Smith W, Wang JJ.; Department
of Ophthalmology, University of Sydney, Westmead Hospital, Australia;
Ophthalmology
1998 Aug;105(8):1359-63
Blue Mountains Eye Study
"CONCLUSIONS: Our cohort study of an older population could not find
evidence
of protection associated with usual dietary antioxidant or zinc intakes
(including
use of supplements) on the 5-year incidence of early ARM." Dietary
antioxidant
intake and incidence of early age-related maculopathy: the Blue
Mountains
Eye Study; Flood V, Smith W, Wang JJ, Manzi F, Webb K, Mitchell P;
Department
of Public Health and Community Medicine, Westmead Hospital, University
of
Sydney, Sydney, Australia.
"CONCLUSION: These findings provide no evidence of a protective
association between serum alpha tocopherol or beta carotene and
age-related maculopathy. " Serum beta carotene, alpha tocopherol, and
age-related maculopathy: the Blue Mountains Eye Study; Smith W,
Mitchell P, Rochester C. National Centre
for Epidemiology and Population Health, Australian National University,
Australia.Am J Ophthalmol. 1997 Dec;124(6):838-40.
Dietary fat and risk for advanced age-related macular degeneration
OBJECTIVE: To evaluate the relationship between intake of total and
specific types of fat and risk for advanced age-related macular
degeneration (AMD), the leading cause of irreversible blindness in
adults.
DESIGN: A multicenter eye disease case-control study.
SETTING: Five US clinical ophthalmology centers.
PATIENTS: Case subjects included 349 individuals (age range, 55-80
years) with the advanced, neovascular stage of AMD diagnosed within 1
year of their enrollment into the study who resided near a
participating clinical center. Control subjects included 504
individuals without AMD but with other ocular diseases. Controls were
from the same geographic areas as cases and were frequency-matched to
cases by age and sex.
MAIN OUTCOME MEASURES: Relative risk for AMD according to level of fat
intake, controlling for cigarette smoking and other risk factors.
RESULTS: Higher vegetable fat consumption was associated with an
elevated risk for AMD. After adjusting for age, sex, education,
cigarette smoking, and other risk factors, the odds ratio (OR) was 2.22
(95% confidence interval [CI], 1.32-3.74) for persons in the highest vs
those in the lowest quintiles of intake (P for trend,.007). The risk
for AMD was also significantly elevated for the highest vs lowest
quintiles of intake of monounsaturated (OR, 1.71) and polyunsaturated
(OR, 1.86) fats (Ps for trend,.03 and.03, respectively). Higher
consumption of linoleic acid was also associated with a higher risk for
AMD (P for trend,.02). Higher intake of omega-3 fatty acids was
associated with a lower risk for AMD among individuals consuming diets
low in linoleic acid, an omega-6 fatty acid (P for trend,.05; P for
continuous variable,.03). Similarly, higher frequency of fish intake
tended to reduce risk for AMD when the diet was low in linoleic acid (P
for trend,.05). Conversely, neither omega-3 fatty acids nor fish intake
were related to risk for AMD among people with high levels of linoleic
acid intake. CONCLUSION: Higher intake of specific types of fat -
including vegetable, monounsaturated, and polyunsaturated fats and
linoleic acid - rather than total fat intake may be associated with a
greater risk for advanced AMD. Diets high in omega-3 fatty acids and
fish were inversely associated with risk for AMD when intake of
linoleic acid was low.
Seddon JM, Rosner B, Sperduto RD, Yannuzzi L, Haller JA, Blair
NP, Willett W.; Dietary fat and risk for advanced age-related macular
degeneration.;
Epidemiology Unit, Department of Ophthalmology,
Massachusetts
Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. ;
Arch Ophthalmol 2001 Aug;119(8):1191-9
See also:
The lutein-free diet, a
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"For carnivorous and omnivorous species the main sources of vitamin A
are the retinyl esters from prey tissues. For herbivorous species the
main source is carotenoids. Many carnivores, including several species
of canines, bears and mustelides, do not absorb dietary carotenoids as
such or only at
levels below the limits of detection" Slifka et al. 1999
