Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지

Effects of Hyperhomocysteinemia on the Immunohistochemical Reactivity for Vimentin in the Retinal Glial Cell

면역조직화학적 방법을 이용한 흰쥐의 호모시스테인 수준과 망막 손상의 관련성 연구

  • Lee Insun (Department of Food and Nutritional Sciences, Asia Food and Nutrition Research Center, Ewha Womans University) ;
  • Lee Hwayoung (Department of Anatomy, Ewha Medical Research Center) ;
  • Chang Namsoo (Department of Food and Nutritional Sciences, Asia Food and Nutrition Research Center, Ewha Womans University)
  • 이인선 (이화여자대학교 생활환경대학 식품영양학과, 아시아식품영양연구소) ;
  • 이화영 (이화여자대학교 의과대학 해부학교실) ;
  • 장남수 (이화여자대학교 생활환경대학 식품영양학과, 아시아식품영양연구소)
  • Published : 2005.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

It has been suggested that the elevated plasma homocysteine may lead to retinal dysfunction. We investigated the effects of plasma levels of homocysteine and folate on the retinal glial cells' injuries. Male Sprague-Dawley rats were raised either on a control diet or on an experimental diet containing 3.0 g/kg homocystine without folic acid for 10 weeks. Plasma homocysteine concentrations were measured by a HPLC-fluorescence detection method. Plasma folate and vitamin B/sub 12/ levels were analyzed by a radioimmunoassay. The response of Muller cells which are the principal glial cells of the retina was immunohistochemically examined using an antibody for vimentin, a cytoskeletal protein belonging to the family of intermediate filament. At 2 weeks, the homocystine diet induced a twofold increase in plasma homocysteine, and a concomitant increase in the expression of vimentin in the Muller cells' processes spanning from the inner to outer membranes of the retina indicating arterial degeneration. At 10 weeks, the homocystine diet induced a fourfold increase in plasma homocystine, but vimentin immunoreactivity in the retinas was similar in both groups. In conclusion, increased plasma homocysteine levels have influence on morphological and functional changes of Muller cells in the retina. (Korean J Nutrition 38(2): 96～103, 2005)

Keywords

References

  1. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 274: 1049-1057, 1995 https://doi.org/10.1001/jama.274.13.1049
  2. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA. Hyperhomocysteinemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 95: 1119-1121, 1997
  3. Duan J, Murohara T, Ikeda H, Sasaki KI, Shintani S, Akita T, Shimada T, lmaizumi T. Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia. Arterioscler Thromh Vase Biol 20: 2579-2585, 2000
  4. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I. Hyperhomocysteinemia, an independent risk factor for vascular disease. N Engl J Med 324: 1149-1155, 1991 https://doi.org/10.1056/NEJM199104253241701
  5. Perna AF, lngrosso D, De Santo NG. Homocysteine and oxidative stress. Amino Acids 25: 409-417, 2003 https://doi.org/10.1007/s00726-003-0026-8
  6. Becker A, Kostense PJ, Bos G, Heine RJ, Dekker JM, Nijpels G, Bouter LM, Stehouwer CDA. Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes. J Internal Medicine 253: 293-300, 2003 https://doi.org/10.1046/j.1365-2796.2003.01113.x
  7. Buysschaert M, Wallemacq PE, Dramais AS, Hermans MP. Hyperhomocysteinemia in Type 2 diabetes. Diabetes Care 23: 1816-1822, 2000 https://doi.org/10.2337/diacare.23.12.1816
  8. Stamler JS, Osborne JA, Jaraki O, Rabbani LE, Mullins M, Singel D, Loscalzo J. Adverse vascular effects of homocystine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 91: 308-318, 1993 https://doi.org/10.1172/JCI116187
  9. Upchurch GR, Welch GN, Ramdev N, Fabian A, Keaney JF, Loscalzo J. The effect of homocysteine on endothelial cell nitric oxide production. FASEB J 9: A876, 1995
  10. Blom HJ. Consequences of homocysteine export and oxidation in the vascular system. Semin Thromb Hemost 26 (3) : 227-232, 2000 https://doi.org/10.1055/s-2000-8467
  11. Manson JB. Biomarkers of nutrient exposure and status in one-carbon methyl metabolism. J Nutr 133: 941S-947S, 2003
  12. Pak KJ, Chan SL, Mattson MP. Homocysteine and folate deficiency sensitize oligodenderocytes to the cell death-promoting effects of a presenilin-1 mutation and amyloid beta-peptide. Neuromolecular Med 3 (2): 119-128, 2003 https://doi.org/10.1385/NMM:3:2:119
  13. Koo BS. Circulatory disturbances and vascular disorders of the retina. J Korean Ophthalmol Soc 11: 55-62, 1970
  14. Grozdanic SD, Sakaguchi DS, Kwon YH, Kardon RH, Sonea IM. Functional characterization of retina and optic nerve after acute ocular ischemia in rats. Invest Ophthalmol Vis Sci 44: 2597-2605, 2003 https://doi.org/10.1167/iovs.02-0600
  15. Newman E, Reichenbach A. The Muller cell, a functional element of the retina. Trends Neurosci 19: 307-312, 1996 https://doi.org/10.1016/0166-2236(96)10040-0
  16. Lewis GP, Fisher SK. Up-regulation of glial fibrillary acidic protein in response to retinal injury: its potential role in glial remodeling and a comparison to vimentin expression. Int Rev Cytol 230: 263-290, 2003 https://doi.org/10.1016/S0074-7696(03)30005-1
  17. Brown BA, Marx JL, Ward TP, Hollifield RD, Dick JS, Brozetti JJ, Howard RS, Thach AB. Homocysteine: A risk factor for retinal venous occlusive disease. Ophthalmology 109: 287-290, 2002 https://doi.org/10.1016/S0161-6420(01)00923-X
  18. Looker HC, Fagot-Campagna A, Gunter EW, Pfeiffer CM, Venkat Narayan KM, Knowler WC, Hanson RL. Homocysteine as a risk factor for nephropathy and retinopathy in Type 2 diabetes. Diabetologia 46: 766-772, 2003 https://doi.org/10.1007/s00125-003-1104-x
  19. Axer-Siegel R, Bourla D, Ehrlich R, Dotan G, Benjamini Y, Gavendo S, Weinberger D, Sela BA. Association of neovascular agerelated macular degeneration and hyperhomocysteinemia. Am J Ophthalmol 137 (1): 84-89, 2004 https://doi.org/10.1016/S0002-9394(03)00864-X
  20. Perry DJ. Hyperhomocysteinaemia. Baillieres Clin Heamatol 12: 451-477, 1999
  21. Kim YI. Folate, colorectal carcionogenesis, and DNA methylation: lessons from animal studies. Environ Mol Mutagen 44: 10-25, 2004 https://doi.org/10.1002/em.20025
  22. Bailey LB, Gregory JF. Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 129 (5) : 919-922, 1999
  23. Iskandar BJ, Nelson A, Resnick D, Pate Skene JH, Gao P, Johnson C, Cook TD, Hariharan N. Folic aicd supplementation enhances repair of the adult central nervous system. Ann Neurol 56: 221-227, 2004 https://doi.org/10.1002/ana.20174
  24. Reeves PG. Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr 127 (5 Suppl). 838S-841S, 1997
  25. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422: 43-52, 1987 https://doi.org/10.1016/0378-4347(87)80438-3
  26. Feeney L, Berman ER. Oxygen toxicity: membrane damage by free radicals. Invest Ophthalmol 15: 789-792, 1976
  27. Lewis GP, Fisher SK Muller cell outgrowth after retinal detachment: association with cone photoreceptors. Invest Ophthalmol Vis Sci 41: 1542-1545, 2000
  28. Hollyfield JG, Frederick JM, Tabor GA, Ulshafer RS. Metabolic studies on retinal tissue from a donor with a dominantly inherited chorioretinal degeneration resembling sectoral retinitis pigmentosa. Ophthlmology 91 (2): 191-196, 1984
  29. Eagle RC. Mechanisms of maculopathy. Ophthalmology 91 (6) : 613-625, 1984
  30. Rogers S, Witz G, Anwar M, Hiatt M, Hegyi T. Antioxidant capacity and oxygen radical disease in the preterm newborn. Arch Pediatr Adolesc Med 154: 544-548, 2000
  31. Hayden MR, Tyagi SC. Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: The pleiotropic effects of folate supplementation. J Nutr 3 (1) : 4, 2004
  32. Selhub J. Homocysteine metabolism. Annu Rev Nutr 19: 217-246, 1999 https://doi.org/10.1146/annurev.nutr.19.1.217
  33. Sawle P, Foresti R, Green CJ, Motterlini R. Homocysteine attenuates endothelial haem oxygenase-1 induction by nitric oxide (NO) and hypoxia. FEBS Letters 508: 403-406, 2001 https://doi.org/10.1016/S0014-5793(01)03117-9
  34. Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW. Vascular permeability in experimental diabetes is associated with reduced endothelial occluding content: vascular endothelial growth factor decreases occlusion in retinal endothelial cells. Penn State Retina Reasearch Group. Diabetes 47: 1953-1959, 1998 https://doi.org/10.2337/diabetes.47.12.1953
  35. Cameron NE, Eaton SE, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 44: 1973-1988, 2001 https://doi.org/10.1007/s001250100001
  36. Ugarte M, Osborne NN. The localization of endogenous zinc and the in vitro effect of exogenous zinc on the GABA immunoreactivity and formation of reactive oxygen species in the retina. Gen Pharmacol 30(3): 297-303, 1998 https://doi.org/10.1016/S0306-3623(97)00358-3
  37. Lewis GP, Erickson PA, Guerin CJ, Anderson DH, Fisher SK. Changes in the expression of specific Muller cell proteins during long-term retinal detachment. Exp Eye Res 49: 93-111, 1989 https://doi.org/10.1016/0014-4835(89)90079-1
  38. Vine AK. Hyperhomocysteinemia: a new risk factor for central retinal vein occlusion. Trans Am Ophthalmol Soc 98: 493-503, 2000
  39. Pianka P, Almog Y, Man O, Goldstein M, Sela BA, Loewenstein A. Hyperhomocysti- nemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology 107 (8): 1588-1592, 2000 https://doi.org/10.1016/S0161-6420(00)00181-0
  40. Winkler BS, Arnold MJ, Brassell MA, Puro DG. Energy metabolism in human retinal Muller cells. Invest Ophthalmol Vis Sci 41: 3183-3190, 2000
  41. Mizuno K, Sato K. Reassessment of histochemistry of retinal glycogen. Exp Eye Res 21: 489-497, 1975 https://doi.org/10.1016/0014-4835(75)90130-X
  42. Kumagai A, Glasgow BJ, Pardridge WM. GLUT-1 glucose transporter expression in the diabetic and nondiabetic human eye. Invest Ophthalmol Vis Sci 35: 2887-2894, 1994
  43. Chan WY, Cheng RSY, Yew DT. Postnatal changes of vascular endothelial growth factor (VEGF) expression in the retinae of normal and hypertensive rats. Life Science 66: 1615-1625, 2000 https://doi.org/10.1016/S0024-3205(00)00481-1