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Klin Monbl Augenheilkd 2018; 235(02): 163-174
DOI: 10.1055/s-0044-101621
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Stellenwert vom Homocystein beim Glaukom

Significance of Homocysteine in Glaucoma
Anselm Jünemann
1   Universitätsaugenklinik, Universitätsmedizin Rostock, Rostock
,
Robert Rejdak
2   Tadeusz Krwawicz Chair of Ophthalmology, Medical University, Chmielna, Poland
,
Bettina Hohberger
3   Universitätsklinikum Erlangen, Augenklinik, Erlangen
› Author Affiliations
Further Information

Publication History

eingereicht 22 January 2018

akzeptiert 23 January 2018

Publication Date:
15 February 2018 (online)

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Zusammenfassung

In der multifaktoriellen Pathogenese der glaukomatösen Optikusatrophie spielen endotheliale Dysfunktion und vaskuläre Dysregulation eine Rolle. Eine Hyperhomocysteinämie als Risikofaktor für die endotheliale Dysfunktion ist sowohl mit dem primären Offenwinkelglaukom als auch mit dem sekundären Offenwinkelglaukom bei Pseudoexfoliationssyndrom assoziiert. In dieser Übersichtsarbeit wird die aktuelle Datenlage zur Assoziation zwischen Homocysteinmetabolismus und Glaukomerkrankung dargelegt sowie eine mögliche Rolle der Hyperhomocysteinämie in der Pathogenese und Progression der Glaukomerkrankung erläutert. Die Bedeutung von Homocystein für die Regulationsstörung der extrazellulären Matrix, der Vasotoxizität, der Neurodegeneration sowie der Epigenetik wird dargelegt. Die Prävention und Therapie der Glaukomerkrankung durch Beeinflussung des Homocysteinspiegels wird diskutiert.

Abstract

Endothelial dysfunction and vascular dysregulation play a role in the multifactorial pathogenesis of glaucomatous optic nerve atrophy. Hyperhomocysteinemia is a risk factor for endothelial dysfunction and is associated with primary open-angle glaucoma as well as secondary open-angle glaucoma in the pseudoexfoliation syndrome. This paper reviews the literature on the association between homocysteine metabolism and glaucomatous disease and explains the possible role of hyperhomocysteinemia in the pathogenesis and progression of glaucoma. We discuss the role of exogenous modifiable risk factors for the prevention and therapy of glaucoma, as well as modification of these factors by changes in life style, such as weight reduction, changes in nutrition and physical activity. The roles of homocysteine in regulating the extracellular matrix, vasotoxicity, neurodegeneration, and epigenetics are explained. Prevention and therapy of glaucoma by regulation of homocysteine levels are discussed.

Schlüsselwörter

Homocystein - Hyperhomocysteinämie - Offenwinkelglaukom - Vitamine - endotheliale Dysfunktion

Key words

homocysteine - hyperhomocysteinemia - open-angle glaucoma - vitamins - endothelial dysfunction
 

  • Literatur

  • 1 Jünemann A. Medicinal glaucoma therapy. What can we learn from large randomized clinical trials?. Ophthalmologe 2013; 110: 1134-1148
    CrossrefPubMedGoogle Scholar
  • 2 Jünemann A, Huchzermeyer C, Rejdak R. et al. Dyslipidämien und Glaukome. Klin Monatsbl Augenheilkd 2014; 231: 1203-1214
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Škovierová H, Vidomanová E, Mahmood S. et al. The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci 2016; 17: 1733-1751
    CrossrefPubMedGoogle Scholar
  • 4 Seshadri S, Beiser A, Selhub J. et al. Plasma homocysteine as a risk factor for dementia and Alzheimerʼs disease. N Engl J Med 2002; 346: 476-483
    CrossrefPubMedGoogle Scholar
  • 5 Joosten E, Lesaffre E, Riezler R. Are different reference intervals for methylmalonic acid and total homocysteine necessary in elderly people?. Eur J Haematol 1996; 57: 222-226
    PubMedGoogle Scholar
  • 6 Rasmussen K, Moller J, Lyngbak M. et al. Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation. Clin Chem 1996; 42: 630-636
    PubMedGoogle Scholar
  • 7 Ubbink JB, Becker PJ, Vermaak WJ. et al. Results of B-vitamin supplementation study used in a prediction model to define a reference range for plasma homocysteine. Clin Chem 1995; 41: 1033-1037
    PubMedGoogle Scholar
  • 8 Nygard O, Nordrehaug JE, Refsum H. et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337: 230-236
    CrossrefPubMedGoogle Scholar
  • 9 Vessani RM, Ritch R, Liebmann JM. et al. Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol 2003; 136: 41-46
    CrossrefPubMedGoogle Scholar
  • 10 Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999; 354: 407-413
    CrossrefPubMedGoogle Scholar
  • 11 Andreotti F, Burzotta F, Manzoli A. et al. Homocysteine and risk of cardiovascular disease. J Thromb Thrombolysis 2000; 9: 13-21
    PubMedGoogle Scholar
  • 12 Meleady R, Graham I. Plasma homocysteine as a cardiovascular risk factor: causal, consequential, or of no consequence?. Nutr Rev 1999; 57: 299-305
    PubMedGoogle Scholar
  • 13 Schnyder G, Roffi M, Pin R. et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2000; 345: 1593-1600
    PubMedGoogle Scholar
  • 14 Janssen MC, den Heijer M, Cruysberg JR. et al. Retinal vein occlusion: a form of venous thrombosis or a complication of atherosclerosis? A meta-analysis of thrombophilic factors. Thromb Haemost 2005; 93: 1021-1026
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Ueland PM, Nygård O, Vollset SE. et al. The Hordaland homocysteine studies. Lipids 2001; 36 (Suppl.) S33-S39
    CrossrefPubMedGoogle Scholar
  • 16 Bleich S, Jünemann A, von Ahsen N. et al. Homocysteine and risk of open-angle glaucoma. J Neural Transm (Vienna) 2002; 109: 1499-1504
    CrossrefPubMedGoogle Scholar
  • 17 Roedl JB, Bleich S, Reulbach U. et al. Homocysteine levels in aqueous humor and plasma of patients with primary open-angle glaucoma. J Neural Transm (Vienna) 2007; 114: 445-450
    CrossrefPubMedGoogle Scholar
  • 18 Roedl JB, Bleich S, Schlotzer-Schrehardt U. et al. Increased homocysteine levels in tear fluid of patients with primary open-angle glaucoma. Ophthalmic Res 2008; 40: 249-256
    CrossrefPubMedGoogle Scholar
  • 19 Clement CI, Goldberg I. Methylenetetrahydrofolate reductase 677 C–T and homocysteine levels in Turkish patients with pseudoexfoliation. Clin Exp Ophthalmol 2006; 34: 500-504
    PubMedGoogle Scholar
  • 20 Micheal S, Qamar R, Akhtar F. et al. MTHFR gene C677T and A1298C polymorphisms and homocysteine levels in primary open angle and primary closed angle glaucoma. Mol Vis 2009; 15: 2268-2278
    PubMedGoogle Scholar
  • 21 Leibovitch I, Kurtz S, Shemesh G. et al. Hyperhomocystinemia in pseudoexfoliation glaucoma. J Glaucoma 2003; 12: 36-39
    CrossrefPubMedGoogle Scholar
  • 22 Bleich S, Roedl J, Von Ahsen N. et al. Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Am J Ophthalmol 2004; 138: 162-164
    CrossrefPubMedGoogle Scholar
  • 23 Altintas O, Maral H, Yuksel N. et al. Homocysteine and nitric oxide levels in plasma of patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol 2005; 243: 677-683
    CrossrefPubMedGoogle Scholar
  • 24 Saricaoglu MS, Karakurt A, Sengun A. et al. Plasma homocysteine levels and vitamin B status in patients with pseudoexfoliation syndrome. Saudi Med J 2006; 27: 833-837
    PubMedGoogle Scholar
  • 25 Cumurcu T, Sahin S, Aydin E. Serum homocysteine, vitamin B12 and folic acid levels in different types of glaucoma. BMC Ophthalmol 2006; 6: 6
    CrossrefPubMedGoogle Scholar
  • 26 Roedl JB, Bleich S, Reulbach U. et al. Homocysteine in tear fluid of patients with pseudoexfoliation glaucoma. J Glaucoma 2007; 16: 234-239
    CrossrefPubMedGoogle Scholar
  • 27 Roedl JB, Bleich S, Reulbach U. et al. Vitamin deficiency and hyperhomocysteinemia in pseudoexfoliation glaucoma. J Neural Transm (Vienna) 2007; 114: 571-575
    CrossrefPubMedGoogle Scholar
  • 28 Turgut B, Kaya M, Arslan S. Levels of circulating homocysteine, vitamin B6, vitamin B12, and folate in different types of open-angle glaucoma. Clin Interv Aging 2010; 5: 133-139
    PubMedGoogle Scholar
  • 29 Tranchina L, Centofanti M, Oddone F. et al. Levels of plasma homocysteine in pseudoexfoliation glaucoma. Graefes Arch Clin Exp Ophthalmol 2011; 249: 443-448
    CrossrefPubMedGoogle Scholar
  • 30 Türkcü FM, Köz OG, Yarangümeli A. et al. Plasma homocysteine, folic acid, and vitamin B12 levels in patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and normotensive glaucoma. Medicina (Kaunas) 2013; 49: 214-218
    PubMedGoogle Scholar
  • 31 Wang G, Medeiros FA, Barshop BA. et al. Total plasma homocysteine and primary open-angle glaucoma. Am J Ophthalmol 2004; 137: 401-406
    CrossrefPubMedGoogle Scholar
  • 32 Turaçli ME, Tekeli O, Özdemir F. et al. Methylenetetrahydrofolate reductase 677 C–T and homocysteine levels in Turkish patients with pseudoexfoliation. Clin Exp Ophthalmol 2005; 33: 505-508
    CrossrefPubMedGoogle Scholar
  • 33 Zacharaki F, Hadjigeorgiou GM, Koliakos GG. et al. Plasma homocysteine and genetic variants of homocysteine metabolism enzymes in patients from central Greece with primary open-angle glaucoma and pseudoexfoliation glaucoma. Clin Ophthalmol 2014; 8: 1819-1825
    PubMedGoogle Scholar
  • 34 Xu F, Zhao X, Zeng SM. et al. Homocysteine, B vitamins, methylenetetrahydrofolate reductase gene, and risk of primary open-angle glaucoma. A meta-analysis. Ophthalmology 2012; 119: 2493-2499
    CrossrefPubMedGoogle Scholar
  • 35 Xu F, Zhang L, Li M. Plasma homocysteine, serum folic acid, serum vitamin B12, serum vitamin B6, MTHFR and risk of pseudoexfoliation glaucoma: a meta-analysis. Graefes Arch Clin Exp Ophthalmol 2012; 250: 1067-1074
    CrossrefPubMedGoogle Scholar
  • 36 Rössler CW, Baleanu D, Reulbach U. et al. Plasma homocysteine levels in patients with normal tension glaucoma. J Glaucoma 2010; 19: 576-580
    CrossrefPubMedGoogle Scholar
  • 37 Li J, Xu F, Zeng R. et al. Plasma homocysteine, serum folic acid, serum vitamin B12, serum vitamin B6, MTHFR, and risk of normal-tension glaucoma. J Glaucoma 2016; 25: e94
    CrossrefPubMedGoogle Scholar
  • 38 Lee JY, Kim JM, Kim IT. et al. Relationship between plasma homocysteine level and glaucomatous retinal nerve fiber layer defect. Curr Eye Res 2017; 42: 918-923 doi:10.1080/02713683.2016.1257728
    CrossrefPubMedGoogle Scholar
  • 39 Mandaviya PR, Stolk L, Heil SG. Homocysteine and DNA methylation: A review of animal and human literature. Mol Genet Metab 2014; 113: 243-252
    CrossrefPubMedGoogle Scholar
  • 40 Alkozi HA, Franco R, Pintor JJ. Epigenetics in the eye: An overview of the most relevant ocular diseases. Front Genet 2017; 8: 144 doi:10.3389/fgene.2017.00144
    CrossrefPubMedGoogle Scholar
  • 41 McDonnell F, Irnaten M, Clark AF. et al. Hypoxia-induced changes in DNA methylation alter RASAL1 and TGFbeta1 expression in human trabecular meshwork cells. PLoS One 2016; 11: e0153354 doi:10.1371/journal.pone.0153354
    CrossrefPubMedGoogle Scholar
  • 42 Jünemann AGM, von Ahsen N, Reulbach U. et al. C677T variant in the methylentetrahydrofolate reductase gene is a genetic risk factor for primary open-angle glaucoma. Am J Ophthalmol 2005; 139: 721-723
    CrossrefPubMedGoogle Scholar
  • 43 Fingert JH, Kwon YH, Moore PA. et al. The C677T variant in the methylenetetrahydrofolate reductase gene is not associated with disease in cohorts of pseudoexfoliation glaucoma and primary open-angle glaucoma patients from Iowa. Ophthalmic Genet 2006; 27: 39-41
    CrossrefPubMedGoogle Scholar
  • 44 Zetterberg M, Tasa G, Palmér MS. et al. Methylenetetrahydrofolate reductase genetic polymorphisms in patients with primary open-angle glaucoma. Ophthalmic Genet 2007; 28: 47-50
    CrossrefPubMedGoogle Scholar
  • 45 Fan BJ, Chen T, Grosskreutz C. et al. Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma. Mol Vis 2008; 14: 2484-2491
    PubMedGoogle Scholar
  • 46 Kamburoglu G, Gumus K, Kadayifcilar S. et al. Plasma homocysteine, vitamin B12 and folate levels in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2006; 244: 565-569
    CrossrefPubMedGoogle Scholar
  • 47 Ukinc K, Ersoz HO, Karahan C. et al. Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as a novel risk factor for diabetic nephropathy. Endocrine 2009; 36: 255-261
    CrossrefPubMedGoogle Scholar
  • 48 Klein BE, Knudtson MD, Tsai MY. et al. The relation of markers of inflammation and endothelial dysfunction to the prevalence and progression of diabetic retinopathy: Wisconsin epidemiologic study of diabetic retinopathy. Arch Ophthalmol 2009; 127: 1175-1182
    CrossrefPubMedGoogle Scholar
  • 49 Coral K, Angayarkanni N, Gomathy N. et al. Homocysteine levels in the vitreous of proliferative diabetic retinopathy and rhegmatogenous retinal detachment: its modulating role on lysyl oxidase. Invest Ophthalmol Vis Sci 2009; 50: 3607-3612
    CrossrefPubMedGoogle Scholar
  • 50 Ganapathy PS, Roon P, Moister TK. et al. Diabetes accelerates retinal neuronal cell death in a mouse model of endogenous hyperhomocysteinemia. Ophthalmol Eye Dis 2009; 1: 3-11
    PubMedGoogle Scholar
  • 51 Bolander-Gouaille C. PS on homocysteine as a risk factor of cardiovascular disease. Lakartidningen 2000; 97: 2786-2787
    PubMedGoogle Scholar
  • 52 Quigley HA. Open-angle glaucoma. N Engl J Med 1993; 328: 1097-1106
    CrossrefPubMedGoogle Scholar
  • 53 Martí-Carvajal AJ, Solà I, Lathyris D. et al. Homocysteine-lowering interventions for preventing cardiovascular events (Review). Cochrane Database Syst Rev 2017; (08) CD006612 DOI: 10.1002/14651858.CD006612.pub5.
    CrossrefPubMedGoogle Scholar
  • 54 Park JH, Saposnik G, Ovbiagele B. et al. Effect of B-vitamins on stroke risk among individuals with vascular disease who are not on antiplatelets: a meta-analysis. Int J Stroke 2016; 11: 206-211
    CrossrefPubMedGoogle Scholar
  • 55 Seshadri S. Homocysteine and the risk of dementia. Clin Chem 2012; 58: 1059-1060
    CrossrefPubMedGoogle Scholar