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Homocysteine and nitric oxide levels in plasma of patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open-angle glaucoma

  • Clinical Investigation
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Abstract

Purpose

To evaluate plasma total homocysteine (tHcy) and nitric oxide (NO) marker levels in patients with pseudoexfoliation syndrome (PXS), pseudoexfoliation glaucoma (PXG), primary open-angle glaucoma (POAG), and normal controls.

Methods

This cross-sectional, prospective study involved 19 patients with POAG, 18 with PXS, 22 with PXG, and 20 control subjects. Fasting tHcy levels of all study participants were determined using a fluorescence polarization immunoassay method. Quantitation of total nitrate was based on the Griess reaction, in which a chromophore with a strong absorbance at 545 nm is formed by reaction of nitrite with a mixture of naphthylethylenediamine and sulphanilamide.

Results

The mean plasma homocysteine level was statistically significantly elevated in the PXS (p=0.033) and the PXG (p=0.023) groups but not in the POAG group (p=0.996) when compared with the control group. Multiple logistic regression analyses comparing the various patient groups with the single control group indicated that elevation in plasma homocysteine concentration was a significant risk factor for PXS (odds ratio per 1 μmol/l increase in homocysteine concentration=2.05, 95% CI=1.19–3.52) and PXG (odds ratio per 1 μmol/l increase in homocysteine concentration=1.36, 95% CI=1.00–1.85) but was not a significant risk factor for POAG (odds ratio per 1 μmol/l increase in homocysteine concentration=0.99, 95% CI=0.78–1.26). NO markers levels were found to be slightly higher in PXS and PXG patients than control and POAG patients but the differences were not statistically significant (p=0.151). Multiple logistic regression analyses comparing the various patient groups with the single control group indicated that elevation in NO marker concentration was not a significant risk factor for PXS (odds ratio per 1 μmol/l increase in NO concentration=1.00, 95% CI=0.99–1.01), PXG (odds ratio per 1 μmol/l increase in NO concentration=1.00, 95% CI=0.99–1.00) and POAG (odds ratio per 1 μmol/l increase in NO concentration=0.99, 95% CI=0.99–1.00). No statistically significant correlations were observed between plasma tHcy and NO markers in study groups (p>0.05).

Conclusion

Elevated levels of homocysteine in pseudoexfoliation patients with and without glaucoma may partly explain the increased risk of vascular disease among patients with pseudoexfoliation. No significant difference was found in plasma NO markers among the POAG, PXS, PXG, and the control subjects.

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References

  1. Bagi Z, Ungvari Z, Koller A (2002) Xanthine oxidase-derived reactive oxygen species convert flow-induced arteriolar dilatation to constriction in hyperhomocysteinemia. Arterioscler Thromb Vasc Biol 22:28–33

    Article  Google Scholar 

  2. Becquet F, Courtois Y, Goureau O (1997) Nitric oxide in the eye: multifaceted roles and diverse outcomes. Surv Ophthalmol 42:71–82

    Google Scholar 

  3. Bellamy MF, Mc Dowell IF (1997) Putative mechanisms for vascular damage by homocysteine. J Inherit Metab Dis 20:307–315

    Article  Google Scholar 

  4. Bleich S, Jünemann A, Von Ahsen N, Lausen B, Ritter K, Beck G, Naumann GOH, Kornhuber J (2002) Homocysteine and risk of open-angle. J Neural Transm 109:1499–1504

    Article  Google Scholar 

  5. Bleich S, Roedl J, Von Ahsen N, Schlötzer-Schrehardt U, Reulbach U, Beck G, Kruse EF, Naumann GOH, Kornhuber J, Jünemann AGN (2004) Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Am J Ophthalmol 138:162–164

    Article  Google Scholar 

  6. Bories PN, Bories C (1995) Nitrate determination in biological fluids by an enzymatic one-step assay with nitrate reductase. Clin Chem 41:904–907

    Google Scholar 

  7. Chang CJ, Chiang CH, Chow JC, Lu DW (2000) Aqueous humor nitric oxide levels differ in patients with different types of glaucoma. J Ocular Pharmacol Ther 16(5):399–406

    Google Scholar 

  8. Charpiot P, Bescond A, Augier T, Chareyre M, Fraterno M, Rolland PH, Garçon D (1998) Hyperhomocysteinemia induces elastolysis in minipigs arteries: structural consequences, arterial site specificity and effect of captopril-hydrochlorothiazide. Matrix Biol 17:559–574

    Article  Google Scholar 

  9. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991) Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 324:1149–1155

    Google Scholar 

  10. Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 36:1440–1443

    Google Scholar 

  11. Cursiefen C, Hündel A, Schonherr U, Naumann GOH (1997) Pseudoexfoliation syndrome in patients with branch and central retinal vein thrombosis. Klin Monatsbl Augenheilkd 211:17–21

    Google Scholar 

  12. Deussen A, Sonntag M, Vogel R (1993) l-Arginine-derived nitric oxide: a major determinant of uveal blood flow. Investig Ophthalmol Vis Sci 34:129–134

    Google Scholar 

  13. Galassi F, Renieri G, Sodi A, Ucci F, Vannozzi L, Masini E (2004) Nitric oxide proxies and ocular perfusion pressure in primary open-angle glaucoma. Br J Ophthalmol 88:757–760

    Article  Google Scholar 

  14. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G (1997) Plasma homocysteine as a risk factor for vascular disease: the European concerted action project. JAMA 277:1775–1781

    Article  CAS  PubMed  Google Scholar 

  15. Harju M, Vesti E (2001) Blood flow of the optic nerve head and peripapillary retina in exfoliation syndrome with unilateral glaucoma or ocular hypertension. Graefe Arch Clin Exp Ophthalmol 239:271–277

    Google Scholar 

  16. Hill CH, Lateef AM, Engels K, Samsell L, Baylis C (1997) Basal and stimulated nitric oxide in control of kidney function in the aging rat. Am J Physiol 272:R1747–R1753

    Google Scholar 

  17. Leblhuber F, Walli J, Artner-Dworzak E, Vrecko K, Widner B, Reibnegger G, Fuchs D (2000) Hyperhomocysteinemia in dementia. J Neural Transm 107:1469–1474

    Article  Google Scholar 

  18. Leibovitch I, Kurtz S, Shemesh G, Goldstein M, Sela B, Lazar M, Loewenstein A (2003) Hyperhomocysteinemia in pseudoexfoliation glaucoma. J Glaucoma 12:36–39

    Article  Google Scholar 

  19. Lincoln J, Hoyle CHV, Burnstock G (1997) Nitric oxide in health and disease. Cambridge University Press, Cambridge

    Google Scholar 

  20. Linner E, Popovic V, Gottfries CG, Jonsson M, Sjogren M, Wallin A (2001) The exfoliation syndrome in cognitive impairment of cerebrovascular or Alzheimer’s type. Acta Ophthalmol Scand 79:283–285

    Google Scholar 

  21. Lobo A, Naso A, Arheart K, Kruger WD, Abou-Ghazala T, Alsous F, Nahlawi M, Gupta A, Moustapha A, van Lente F, Jacobsen DW, Robinson K (1999) Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. Am J Cardiol 83:821–825

    Article  Google Scholar 

  22. Luksch A, Polak K, Beier C, Polska E, Wolzt M, Dorner GT, Eichler HG, Schmetterer L (2000) Effects of systemic NO synthase inhibition on choroidal and optic nerve head blood flow in healthy subjects. Investig Ophthalmol Vis Sci 41:3080–3084

    Google Scholar 

  23. Luscher TF (1990) Imbalance of endothelium derived relaxing and contracting factors. Am J Hypertens 3:317–330

    Google Scholar 

  24. Mann RM, Riva CE, Stone RA, Barnes GE, Cranstoun SD (1995) Nitric oxide choroidal blood flow regulation. Investig Ophthalmol Vis Sci 36:925–930

    Google Scholar 

  25. Mccully KS (1996) Atherogenesis and the chemical pathology of homocysteine. Review. Eur J Lab Med 4:121–128

    Google Scholar 

  26. Mercie P, Garnier O, Lascoste L, Renard M, Closse C, Durrieu F, Marit G, Boisseau RM, Belloc F (2000) Homocysteine-thiolactone induces caspase-independent vascular endothelial cell death with apoptotic features. Apoptosis 5:403–411

    Article  Google Scholar 

  27. Mitchell P, Wang JJ, Smith W (1997) Association of pseudoexfoliation syndrome with increased vascular risk. Am J Ophthalmol 124:685–687

    Google Scholar 

  28. Moore P, El-sherbeny A, Roon P, Schoenlein PV, Ganapathy V, Smith SB (2001) Apoptotic cell death in the mouse retinal ganglion cell layer is induced in vivo by the excitatory amino acid homocysteine. Exp Eye Res 73:45–57

    Article  CAS  PubMed  Google Scholar 

  29. Mujumdar VS, Aru GM, Tyagi SC (2001) Induction of oxidative stress by homocysteine impairs endothelial function. J Cell Biochem 82:491–500

    Article  Google Scholar 

  30. Nathanson JA, McKee M (1995) Identification of an extensive system of nitric oxide producing cells in the ciliary muscle and outflow pathway of the human eye. Investig Ophthalmol Vis Sci 36:1765–1773

    Google Scholar 

  31. Naumann GOH, Schlotzer-Schrehardt U, Küchle M (1998) Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations. Ophthalmology 105:951–968

    Google Scholar 

  32. Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG (1995) Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 346:1395–1398

    Article  Google Scholar 

  33. Pianka P, Almog Y, Man O, Goldstein M, Sela BA, Loewenstein A (2000) Hyperhomocysteinemia in patients with nonarteritic anterior ischemical optic neuropathy, central retinal artery occlusion and central retinal vein occlusion. Ophthalmology 107:1588–1592

    Article  Google Scholar 

  34. Puustjärvi T, Blomster H, Kontkanen M, Punnonen K, Teräsvirta M (2004) Plasma and aqueous humour levels of homocysteine in exfoliation syndrome. Graefe Arch Clin Exp Ophthalmol 24 Mar 30 [Epub ahead of print]

  35. Ritch R, Schlötzer-Schrehardt U (2001)Exfoliation syndrome. Surv Ophthalmol 45:265–315

    Google Scholar 

  36. Schlötzer-Schrehardt U, Küchle M, Naumann GOH (1991) Electron-microscopic identification of pseudoexfoliation material in extrabulbar tissue. Arch Ophthalmol 109:565–570

    Google Scholar 

  37. Schlötzer-Schrehardt U, Koca MH, Naumann GOH, Volkholz H (1992) Pseudoexfoliation syndrome: ocular manifestation of a systemic disorder ? Arch Ophthalmol 110:1752–1756

    Google Scholar 

  38. Schmidt HHHW, Lohmann SM, Walter U (1993) The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Biochim Biophys Acta 1178:153–175

    Article  CAS  PubMed  Google Scholar 

  39. Schumacher S, Schlötzer-Schrehardt U, Martus P, Lang W, Nauman GOH (2001) Pseudoexfoliation syndrome and aneurysms of the abdominal aorta. Lancet 357:359–360

    Article  Google Scholar 

  40. Sood HS, Cox MJ, Tyagi SC (2002) Generation of nitrotyrosine precedes activation of metalloproteinase in myocardium of hyperhomocysteinemic rats. Antioxid Redox Signal 4(5):799–804

    Article  Google Scholar 

  41. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH (1992) A prospective study of plasma homocysteine and risk of myocardial infarction in US physicians. JAMA 268:877–881

    Article  Google Scholar 

  42. Streeteen BW, Li Z-Y, Wallace RN, Eagle RC, Keshgegian AA (1992) Pseudoexfoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome. Arch Ophthalmol 110:1757–1762

    Google Scholar 

  43. Sugiyama T, Oku H, Ikari S, Ikeda T (2000) Effect of nitric oxide synthase inhibitor on optic nerve head circulation in conscious rabbits. Investig Ophthalmol Vis Sci 41:1149–1152

    Google Scholar 

  44. Tsai DC, Hsu WM, Chou CK, Chen SJ, Peng CH, Chi CW, Ho LL, Liu JH, Chiou SH (2002) Significant variation of the elevated nitric oxide levels in aqueous humor from patients with different types of glaucoma. Ophthalmologica 216(5):346–350

    Article  Google Scholar 

  45. Tyagi SC (1998) Homocysteine redox receptor and regulation of extracellular matrix components in vascular cells. Am J Physiol 274:396–405

    Google Scholar 

  46. Van Oort FV, Melse-Boonstra A, Brouwer IA, Clarke R, West CE, Katan MB, Verhoef P (2003) Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. Am J Clin Nutr 77(5):1318–1323

    Google Scholar 

  47. Vessani RM, Ritch R, Liebmann JM, Jofe M (2003) Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol 136:41–46

    Article  Google Scholar 

  48. Wang G, Medeiros FA, Barshop BA, Weinreb RN (2004) Total plasma homocysteine and primary open-angle glaucoma. Am J Ophthalmol 137:401–406

    Article  Google Scholar 

  49. Warsi AA, Davies B, Morris-Stiff G, Hullin D, Lewis MH (2004) Abdominal aortic aneurysm and its correlation to plasma homocysteine, and vitamins. Eur J Vasc Endovasc Surg 27:75–79

    Article  Google Scholar 

  50. Yüksel N, Karabaş L, Arslan A, Demirci A, Çağlar Y (2001) Ocular hemodynamics in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Ophthalmology 108:1043–1049

    Article  Google Scholar 

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Acknowledgements

This study was supported by grants from the Medical Research Council of Kocaeli University (2003/51).

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Correspondence to Özgül Altintaş.

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Altintaş, Ö., Maral, H., Yüksel, N. et al. Homocysteine and nitric oxide levels in plasma of patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open-angle glaucoma. Graefe's Arch Clin Exp Ophthalmol 243, 677–683 (2005). https://doi.org/10.1007/s00417-004-1097-2

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  • DOI: https://doi.org/10.1007/s00417-004-1097-2

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