Abstract
Background
Age-related macular degeneration (AMD) is associated with lower melanin pigmentation and is more prevalent among the elderly Caucasian population than among Africans. A correlation between light iris colour, fundus pigmentation and the incidence of AMD is reported. Moreover, melanin represents the main storage of zinc in the eye. Zinc enhances antioxidant capacity through its function as a cofactor of important enzymes or by influencing gene expression of regulatory elements in the eye. In this study, we investigated the uptake and storage of zinc in the human choroid/retinal pigment epithelium (RPE) complexes in dependence on the fundus pigmentation as judged by the iris colour.
Material and methods
Choroid/RPE complexes of blue and brown human eyes were used. Tissues without any substitution served as controls. Specimens from choroid/RPE complexes were incubated with 100 μM zinc chloride for 24 h. After incubation, pieces of the complexes were stored to investigate the uptake of zinc. The rest of the tissues were kept for 3 and 7 days in culture medium (DMEM) for storage examination. The concentration of zinc was measured by inductively coupled plasma mass spectrometry.
Results
After 24 h of zinc treatment the concentration of zinc in the choroid/RPE complexes of blue eyes was not significantly increased. The concentration of zinc in highly pigmented tissues (brown eyes) was increased by the factor 5.1 after 24 h and remained at high levels after 3 days (factor 4.4) and 7 days (factor 2.8).
Conclusions
Zinc uptake in the choroid/RPE complex correlates to the iris colour. Alterations of the degree of iris pigmentation result in differences of zinc uptake and storage in the choroids. A potential protective role of zinc may be more prominent in dark- than in light-coloured eyes.
Similar content being viewed by others
References
Andrzejczyk J, Buszman E (1992) Interaction of Fe3+, Cu2+ and Zn2+ with melanin and melanoproteins from bovine eyes. Acta Biochim Pol 39:85–88
Bales CW, Steinman LC, Freeland-Graves JH, Stone JM, Young RK (1986) The effect of age on plasma zinc uptake and taste acuity. Am J Clin Nutr 44:664–669
Borovansky J, Horcicko J, Duchon J (1976) The hair melanosome: another tissue reservoir of zinc. Physiol Bohemoslov 25:87–91
Borovansky J, Riley PA (1983) The effect of divalent cations on Cloudman melanoma cells. Eur J Cancer Clin Oncol 19:91–99
Borovansky J, Riley PA (1989) Cytotoxicity of zinc in vitro. Chem Biol Interactions 69:279–291
Borovansky J, Vedralova E, Hach P (1991) An estimate of melanosome concentration in pigment tissues. Pigment Cell Res 4:222–224
Bray TM, Bettger WJ (1990) The physiological role of zinc as an antioxidant. Free Radic Biol Med 8:281–291
Brewer GJ, Hill GM, Prasad AS, Cossack ZT (1983) Biological roles of ionic zinc. Prog Clin Biol Res 129:35–51
Chaine G, Hullo A, Sahel J, Soubrane G, Espinasse-Berrod MA, Schutz D, Bourguignon C, Harpey C, Brault Y, Coste M, Moccatt, D, Bourgeois H (1998) Case-control study of the risk factors for age related macular degeneration. Br J Ophthalmol 82:996–1002
Chew EY, Davis MD, Seddon JM, Clemons TE, Hubbard LD (2002) The effect of anti-oxidant and zinc supplements on change in drusen size/area in the Age-Related Eye Disease Study (AREDS). Invest Ophthalmol Vis Sci: ARVO, abstract
Clemons TE, Kurinij N, Sperduto RD, AREDS Research Group (2004) Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13. Arch Ophthalmol.122:716–726
Eye Disease Case-Control Study Group (1992) Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 110:1701–1708
Feeney L (1978) Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies. Investig Ophthalmol Vis Sci 17:583–600
Frank RN, Puklin JE, Stock C, Canter LA (2000) Race, iris colour, and age-related macular degeneration. Trans Am Ophthalmol Soc 98:109–117
Friedman DS, O’Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J Eye Diseases Prevalence Research Group (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572
Galin MA, Nano HD, Hall T (1962) Ocular zinc concentration. Invest Ophthalmol 1:142–148
Gregor Z, Joffe L (1978) Senile macular changes in the black Africans. Br J Ophthalmol 62:547–550
Hollyfield JG, Shadrach KG, West K, Sun J, Nakata K, Crabb JW (2004) Comparison of Bruch’s membrane/choroid complex during aging in Caucasian and African American eyes: identification of differences that may underlie the susceptibility to AMD. ARVO (abstract)
Jourdan E, Emonet-Piccardi N, Didier C, Beani JC, Favier A, Richard MJ (2002) Effects of cadmium and zinc on solar-simulated light-irradiated cells: potential role of zinc-metallothionein in zinc-induced genoprotection. Arch Biochem Biophys 405:170–177
Kadonaga JT, Carner KR, Masiarz FR, Tjian R (1987) Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell 51:1079–1090
Karcioglu ZA (1982) Zinc in the eye. Surv Ophthalmol 27:114–122
Klein R, Klein BE, Jensen SC, Mares-Perlman JA, Cruickshanks KJ, Palta M (1999) Age-related maculopathy in a multiracial United States population: the National Health and Nutrition Examination Survey III. Ophthalmology 106:1056–1065
Kokkinou D, Kasper HU, Bartz-Schmidt KU, Schraermeyer U (2004) The pigmentation of human iris influences the uptake and storing of zinc. Pigment Cell Res 17:515–558
Kulick MK, Hoffman CJ (1995) Nutrition supplement usage recommendation by eye specialists for macular degeneration of the eye: a state-wide survey of Michigan. Top Clin Nutr 10:67–77
Larsson BS (1993) Interaction between chemicals and melanin. Pigment Cell Res 6:127–133
Leure-duPree AE, Bridges CD (1982) Changes in retinal morphology and vitamin A metabolism as a consequence of decreased zinc availability. Retina 2:294–302
Mares-Perlman JA, Klein R, Klein BE, Greger JL, Brady WE, Palta M, Ritter LL (1996) Association of zinc and antioxidant nutrients with age-related maculopathy. Arch Ophthalmol 114:991–997
McGinness J, Proctor P (1973) The importance of the fact that melanin is black. J Theor Biol 39:677–678
Melnyk LJ, Morgan JN, Fernando R, Pellizzari ED, Akinbo O (2003) Determination of metals in composite diet samples by inductively coupled plasma-mass spectrometry. J AOAC Int 8:439–447
Mitchell P, Smith W, Wang JJ (1998) Iris colour, skin sun sensitivity, and age-related maculopathy. The Blue Mountains Eye Study. Ophthalmology 105:1359–1363
Newsome DA, Swartz M, Leone NC, Elston RC, Miller ED (1988) Oral zinc in macular degeneration. Arch Ophthalmol 106:192–198
Newsome DA, Oliver PD, Dupree DM, Miceli MV, Diamond JG (1992) Zinc uptake by primate retinal pigment epithelium and choroids. Curr Eye Res 11:213–217
Newsome DA, Tate DJ Jr, Alcock NW, Oliver PD (1994) Zinc content of human retinal pigment epithelium (RPE) declines with age. Investig Ophthalmol Vis Sci 35(Suppl):1768
Newsome DA, Miceli MV, Tate DJ Jr, Alcock NW, Oliver PD (1995) Zinc content of human retinal pigment epithelium decreases with age and macular degeneration, but superoxide dismutase activity increases. J Trace Elem Exp Med 8:193–199
Nicolas CM, Robman LD, Tikellis G, Dimitrov PN, Dowrick A, Guymer RH, McCarty CA (2003) Iris colour, ethnic origin and progression of age-related macular degeneration. Clin Experiment Ophthalmol 31:465–469
Panessa BJ, Zadunaisky JA (1981) Pigment granules: a calcium reservoir in the vertebrate eye. Exp Eye Res 32:593–604.
Potts AM, Au PC (1976) The affinity of melanin for inorganic ions. Exp Eye Res 22:487–491
Prasad AS (1991) Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Nutr 53:403–412.
Prevent Blindness America, Vision problems in US, May 2004
Rimbach G, Markant A, Pallauf J, Kramer K (1996) Zinc—update of an essential trace element. Z Ernahrungswiss 35:123–142
Sackett CS, Schenning S (2002) The age-related eye disease study: the results of the clinical trial. Insight 27:5–7
Samuelson DA, Smith P, Ulshafer RJ, Hendricks DG, Whitley RD, Hendricks H, Leone NC (1993) X-ray microanalysis of ocular melanin in pigs maintained on normal and low zinc diets. Exp Eye Res 56:63–70
Sarks SH, Arnold JJ, Killingsworth MC, Sarks JP (1999) Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study. Br J Ophthalmol 83:358–368
Sarks JP, Sarks SH, Killingsworth MC (1994) Evolution of soft drusen in age-related macular degeneration. Eye 8:269–283
Sarna T (1992) Properties and function of the ocular melanin—a photobiophysical view. J Photochem Photobiol B 12:215–258
Schilsky ML, Blank RR, Czaja MJ, Zern MA, Scheinberg IH, Stockert RJ, Sternlieb I (1989) Hepatocellular copper toxicity and its attenuation by zinc. J Clin Invest 84:1562–1568
Smith W, Mitchell P, Webb K, Leeder SR (1999) Dietary antioxidants and age-related maculopathy. The Blue Mountains eye study. Ophthalmology 106:761–767
Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, Hofman A, Jensen S, Wang JJ, de Jong PT (2001) Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology 108:697–704
Song YM, Chen MD (2003) Zinc supplementation attenuates thioacetamide-induced liver injury and hyperglycemia in mice. Biol Trace Elem Res 92:173–180
Stur M, Tittl M, Reitner A, Meisinger V (1996) Oral zinc and the second eye in age-related macular degeneration. Investig Ophthalmol Vis Sci 37:1225–1235
Tate DJ, Miceli MV, Newsome DA, Alcock NW, Oliver PD (1995) Influence of zinc on selected cellular functions of cultured human retinal pigment epithelium. Curr Eye Res 14:897–903
Tate DJ Jr, Miceli MV, Newsome DA (1997) Zinc induces catalase expression in cultured fetal human retinal pigment epithelial cells. Curr Eye Res 16:1017–1023
Teillet L, Tacnet F, Ripoche P, Corman B (1995) Effect of aging on zinc and histidine transport across rat intestinal brush-border membranes. Mech Ageing Dev 79:151–167
Turnlund JR, Keyes WR (2002) Isotope ratios of trace elements in samples from human nutrition studies determined by TIMS and ICP-MS: precision and accuracy compared. Food Nutr Bull 23(3 Suppl):129–132
Vajdic CM, Kricker A, Giblin M, McKenzie J, Aitken J, Giles GG, Armstrong BK (2001) Eye colour and cutaneous nevi predict risk of ocular melanoma in Australia. Int J Cancer 92:906–912
Vallee B, Auld D (1990) Zinc coordination, function and structure of zinc enzymes and other proteins. Am Chem Soc 29:5647–5659
Weiter JJ, Delori FC, Wing GL, Fitch KA (1985) Relationship of senile macular degeneration to ocular pigmentation. Am J Ophthalmol 99:185–187
Weiter JJ, Delori FC, Wing GL, Fitch KA (1986) Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. Investig Ophthalmol Vis Sci 27:145–152
Acknowledgements
The authors would like to thank Ms Susanna Jayasinghe for excellent technical assistance and Ms Judith Birch for helpful corrections.This work was supported by a grant from the Ilse Palm Stiftung, Koeln Fortune Programm (DFG Schr 436/11-1, DFG Schr 436/12-1).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kokkinou, D., Kasper, H.U., Schwarz, T. et al. Zinc uptake and storage: the role of fundus pigmentation. Graefe's Arch Clin Exp Ophthalmo 243, 1050–1055 (2005). https://doi.org/10.1007/s00417-005-1197-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-005-1197-7