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

(Macular Degeneration Publications)

"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

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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