Age-related macular degeneration: prevention and treatment. A review

Age-related macular degeneration (AMD) is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA), particularly, docosahexaenoic acid (DHA), are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE) is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase) and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids). Specific antioxidant food supplement containing ascorbic acid (500 mg), vitamin E (400 IU) and beta carotene (15 mg) coupled with zinc (80 mg of zinc oxide) and copper (2 mg of copper oxide) results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It requires for nerve impulse generation.

1. Bressler N. M., Silva J. C., Bressler S. B. et al. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. Retina 2005; 25:130‑42.

2. Hyun H. J., Sohn J. H., Ha D. W. et al. Depletion of intracellular zinc and cooper with TPEN results in apoptosis of cultured human retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2001; 42 (2): 460‑465.

3. Klein R., Klein B. E., Jensen S. C. et al. Medication use and the 5‑year incidence of early age-related maculopathy: the Beaver Dam Eye Study. Arch. Ophthalmol. 2001;119 (9): 1354‑9.

4. Kiselyova TN, Polunin GS, Budzinskaya MV, Lagutina YM, Vorobyova MV. [Modern approaches to treatment and prevention of macular degeneration] Russk.med. zhurn. [Russian Medical Journal] 2007; 2: 78‑79. (in Russia).

5. Kim S. R., Nakanishi K., Itagaki Y. et al. Photooxidation of A2‑PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin. Exp. Eye Res. 2006; 82 (5): 828‑39.

6. Gass J. D. Choroidal neovascular membranes their visualization and treatment //Trans.Am.Acad. Ophthal. Otolaryng. 1973; 77: 310‑320.

7. Evans Jr. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration// Cochrane Database Syst. Rev. 2006;19 (2): 54.

8. Smirnoff N. Ascorbic acid: metabolism and functions of a multi-facetted molecule//Current Opinion in Plant Biology 2000; 3: 229‑235.

9. Vinderling J. R., Dielemans I., Bots M. L. Age-related macular degeneration is associated with atheroclerosis. The Rotterdam Study Am. J. Opid. 1995;142 (4): 404‑409.

10. Lyle B. J., Mares-Perlman J. A., Klein B. E. et al. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am. J. Epidemiol. 1999;149 (39): 801‑809.

11. Claver C. AMD Genetics. Effects of AMD-causing genes worst in smokers and those with poor diets. Eurotimes 2012;17 (3): 28.

12. Ostrovskiy MA. [Clinical physiology of vision]. Klinicheskaya fiziologiya zreniya. М.,2002. 39 с. — Moscow, 2002. — 39 pp. (in Russia).

13. The Age- Related Eye Disease Study Research Group. A randomized, placebocontrolled, clinical trial of high-dose supplementation with vitamins C and E, beta-carotene, and zinc for age-related macular degeneration and vision loss.

14. AREDS Report No.8. Arch. Ophthalmol. 2001;119: 1417‑1436.

15. Beatty S., Koh H-H. Henson D., Bouston M. et al. Role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 2000;45:115‑134.

16. Gottsch J. D, Bynoe L. A., Harlan J. B. et al. Light-induced deposits in Bruch’s membrane of protoporphyric mice. Arch. Ophthalmol. 1993;111:126‑129.

17. Norkus E. P., Norkus K. L., Dharmarajan T. S. et al. Serum lutein response is greater from free lutein than from esterified lutein during 4 weeks of supplementation in healthy adults. Am Coll Nutr. 2010;29:575‑85.

18. Lamb L. E., Simon J. D. A2E: a component of ocular lipofuscin. Photochem. Photobiol.

19. ; 79 (2): 127‑36.

20. Blokhina O., Virolainen E., Fagerstedt K. V. Antioxidants, Oxidative Damage and Oxygen Deprivation Stress: a Review. Annals of Botany 2003; 91: 179‑194.

21. Moeller S. M., Parekh N., Tinker L. et al. Associations between intermediate age — related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age — related Eye Disease Study (CAREDS): ancillary study of the Women’s

22. Health Initiative.Arch Ophthalmol. 2006; 124: 1151‑1162.

23. Bone R. A., Landrum J. T., Mayne S. T. et al. Macular pigment in donor eyes with and without AMD: a case-control study.Invest. Ophthalmol. Vis. Sci. 2001; 42: 235‑240.

24. Delcourt C, Carriere I, Delage M, et al, POLA Study Group. Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age — related maculopathy and cataract: the POLA Study. Invest Ophthalmol Vis Sci. 2006; 47:

25. ‑2335.

26. Seddon J. M., Ajani U. A., Sperduto R. D. Dietary carotenoids, vitamin A, C and E and advanced age-related macular degeneration: Eye Disease case-Control Study Group. JAVA 1994; 272: 1413‑1420.

27. Richer S., Stiles W., Statkute L. et al. Double-masked, placebo-controlled, randomized atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 2004;75 (4): 216‑30.

28. Tan J. S., Wang J. J., Flood V., et al. Dietary antioxidants and the long — term incidence of age — related macular degeneration: the Blue Mountains Eye Study. Ophthalmology. 2008; 115: 334‑341.

29. Zeimer M., Hense H. W., Heimes B. et al. The macular pigment: short– and intermediate — term changes of macular pigment optical density following supplementation with lutein and zeaxanthin and co — antioxidants. The LUNA Study / Ophthalmologe 2009;106:29‑36.

30. SanGiovanni J. P., Agron E., Clemons T. E. et al. Omega-3 long-chain polyunsaturated fatty acid intake inversely associated with 12‑year progression to advanced age-related macular degeneration.Arch Ophthalmol. 2009;127 (1): 110‑112.

31. SanGiovanni J. P., Chew E. Y., Agron E. et al. The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23. Arch Ophthalmol. 2008;126 (9):1274‑1279.