Increased level of platelet P-selectin in nonarteritic anterior ischemic optic neuropathy

  • Valeria Nagy
  • Bence Kolozsvari
  • Zsuzsa Balogh
  • Adrienne Csutak
  • Marta Kasza
  • Bela NagyJr
  • Laszlo Kardos
  • Andras Berta
  • Gyorgy Pfliegler
Neurophthalmology

Abstract

Purpose

P-selectin receptor is expressed in platelets and endothelial cells in a cell-activation-dependent manner. Platelet P-selectin (CD62) levels may become elevated in a number of vasoocclusive diseases, including arteriosclerosis, atherothrombosis, and diabetes mellitus (DM). Nonarteritic anterior ischemic optic neuropathy (NAION) is associated with a sudden loss of vision due to the vascular insufficiency of ciliary arteries supplying the optic nerve. In this study, our aim was to investigate the presence of increased platelet reactivity in the development of NAION.

Methods

Twenty-one NAION patients, 39 healthy control subjects, and 44 patients suffering from diabetes mellitus (DM) were examined in our case-control, pilot study. Platelet activation was investigated by flow cytometric analysis of the mean fluorescence intensity (MFI) of CD62 on platelets. These results were compared among the different study groups.

Results

NAION patients showed considerably although not signifactly (p = 0.2017) higher P-selectin MFI values (71.98 ± 40.30) versus healthy subjects (55.48 ± 20.95), insulin-dependent DM patients (50.02 ± 13.08), and non-insulin-dependent DM subjects (54.72 ± 24.74). However, logistic regression analysis resulted in a statistically significant adjusted effect on the odds of NAION when CD62 MFI values were logarithmically transformed (OR: 3.86, 95 % CI: 1.10 to 13.53, p = 0.0346).

Conclusion

Elevated platelet CD62 positivity may be related to NAION, suggesting a possible role of enlarged platelet activity in the generation of this type of ischemic optic neuropathy.

Keywords

Nonarteritic anterior ischemic optic neuropathy (NAION) Arteriae ciliares posteriores breves P-selectin Mean fluorescence intensity Flow cytometry 

References

  1. 1.
    Kappelmayer J, Nagy B Jr, Miszti-Blasius K, Hevessy Z, Setiadi H (2004) The emerging value of P-selectin as a disease marker. Clin Chem Lab Med 42:475–486PubMedCrossRefGoogle Scholar
  2. 2.
    Furie B, Furie BC (2004) Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol Med 10:171–178PubMedCrossRefGoogle Scholar
  3. 3.
    Andre P, Hartwell D, Hrachovinova I, Saffaripour S, Wagner DD (2000) Pro-coagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci U S A 97:13835–13840PubMedCrossRefGoogle Scholar
  4. 4.
    Michelson AD, Barnard MR, Hechtman HB, MacGregor H, Connolly RJ, Loscalzo J, Valeri CR (1996) In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Natl Acad Sci U S A 93:11877–11882PubMedCrossRefGoogle Scholar
  5. 5.
    Amrani DL, Stojanovic L, Mosesson MN, Shalev Y, Mosesson MW (1995) Development of a whole platelet ELISA to detect circulating activated platelets. J Lab Clin Med 126:603–611PubMedGoogle Scholar
  6. 6.
    Minamino T, Kitakaze M, Asanuma H, Ueda Y, Koretsune Y, Kuzuya T, Hori M (1999) Plasma adenosine levels and platelet activation in patients with atrial fibrillation. Am J Cardiol 83:194–198PubMedCrossRefGoogle Scholar
  7. 7.
    Nagy B Jr, Csongradi E, Bhattoa HP, Balogh I, Blasko G, Paragh G, Kappelmayer J, Kaplar M (2007) Investigation of Thr715Pro P-selectin gene polymorphism and soluble P-selectin levels in type 2 diabetes mellitus. Thromb Haemost 98:186–191PubMedGoogle Scholar
  8. 8.
    Marquardt L, Ruf A, Mansmann U, Winter R, Schuler M, Buggle F, Mayer H, Grau AJ (2002) Course of platelet activation markers after ischemic stroke. Stroke 33:2570–2574PubMedCrossRefGoogle Scholar
  9. 9.
    Burger PC, Wagner DD (2003) Platelet P-selectin facilitates atherosclerotic lesion development. Blood 101:2661–2666PubMedCrossRefGoogle Scholar
  10. 10.
    Jilma B, Fasching P, Ruthner C, Rumplmayr A, Ruzicka S, Kapiotis S, Wagner OF, Eichler HG (1996) Elevated circulating P-selectin in insulin dependent diabetes mellitus. Thromb Haemost 76:328–332PubMedGoogle Scholar
  11. 11.
    Chong BH, Murray B, Berndt MC, Dunlop LC, Brighton T, Chesterman CN (1994) Plasma P-selectin is increased in thrombotic consumptive platelet disorders. Blood 83:1535–1541PubMedGoogle Scholar
  12. 12.
    Katayama M, Handa M, Araki Y, Ambo H, Kawai Y, Watanabe K, Ikeda Y (1993) Soluble P-selectin is present in normal circulation and its plasma level is elevated in patients with thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. Br J Haematol 84:702–710PubMedCrossRefGoogle Scholar
  13. 13.
    Chung I, Choudhury A, Patel J, Lip GY (2009) Soluble, platelet-bound, and total P-selectin as indices of platelet activation in congestive heart failure. Ann Med 41:45–51PubMedCrossRefGoogle Scholar
  14. 14.
    Nagy V, Facsko A, Takacs L, Balazs E, Berta A, Balogh I, Edes I, Czuriga I, Pfliegler G (2004) Activated protein C resistance in anterior ischaemic optic neuropathy. Acta Ophthalmol Scand 82:140–143PubMedCrossRefGoogle Scholar
  15. 15.
    Nagy V, Steiber Z, Takacs L, Vereb G, Berta A, Bereczky Z, Pfliegler G (2006) Trombophilic screening for nonarteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol 244:3–8PubMedCrossRefGoogle Scholar
  16. 16.
    Hayreh SS (1974) Anterior ischaemic optic neuropathy. I. Terminology and pathogenesis. Br J Ophthalmol 58:955–963PubMedCrossRefGoogle Scholar
  17. 17.
    Hayreh SS, Joos KM, Podhajsky PA, Long CR (1994) Systemic diseases associated with nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 118:766–780PubMedGoogle Scholar
  18. 18.
    Hayreh SS, Podhajsky PA, Zimmerman B (1997) Nonarteritic anterior ischemic optic neuropathy: time of onset of visual loss. Am J Ophthalmol 124:641–647PubMedGoogle Scholar
  19. 19.
    Beck RW, Servais GE, Hayreh SS (1987) Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. Ophthalmology 94:1503–1508PubMedGoogle Scholar
  20. 20.
    Beri M, Klugman MR, Kohler JA, Hayreh SS (1987) Anterior ischemic optic neuropathy. VII. Incidence of bilaterality and various influencing factors. Ophthalmology 94:1020–1028PubMedGoogle Scholar
  21. 21.
    Mojon DS, Hedges TR 3rd, Ehrenberg B, Karam EZ, Goldblum D, Abou-Chebl A, Gugger M, Mathis J (2002) Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol 120:601–605PubMedGoogle Scholar
  22. 22.
    Salomon O, Huna-Baron R, Kurtz S, Steinberg DM, Moisseiev J, Rosenberg N, Yassur I, Vidne O, Zivelin A, Gitel S, Davidson J, Ravid B, Seligsohn U (1999) Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy. Ophthalmology 106:739–742PubMedCrossRefGoogle Scholar
  23. 23.
    Salomon O, Rosenberg N, Steinberg DM, Huna-Baron R, Moisseiev J, Dardik R, Goldan O, Kurtz S, Ifrah A, Seligsohn U (2004) Nonarteritic anterior ischemic optic neuropathy is associated with a specific platelet polymorphism located on the glycoprotein Ibalpha gene. Ophthalmology 111:184–188PubMedCrossRefGoogle Scholar
  24. 24.
    Hayreh SS, Podhajsky PA, Zimmerman B (1998) Ocular manifestations of giant cell arteritis. Am J Ophthalmol 125:509–520PubMedCrossRefGoogle Scholar
  25. 25.
    Hollander JE, Muttreja MR, Dalesandro MR, Shofer FS (1999) Risk stratification of emergency department patients with acute coronary syndromes using P-selectin. J Am Coll Cardiol 34:95–105PubMedCrossRefGoogle Scholar
  26. 26.
    Robless PA, Okonko D, Lintott P, Mansfield AO, Mikhailidis DP, Stansby GP (2003) Increased platelet aggregation and activation in peripheral arterial disease. Eur J Vasc Endovasc Surg 25:16–22PubMedCrossRefGoogle Scholar
  27. 27.
    Weikert U, Kuhl U, Schultheiss HP, Rauch U (2002) Platelet activation is increased in patients with cardiomyopathy: myocardial inflammation and platelet reactivity. Platelets 13:487–491PubMedCrossRefGoogle Scholar
  28. 28.
    Zeiger F, Stephan S, Hoheisel G, Pfeiffer D, Ruehlmann C, Koksch M (2000) P-Selectin expression, platelet aggregates, and platelet-derived microparticle formation are increased in peripheral arterial disease. Blood Coagul Fibrinolysis 11:723–728PubMedCrossRefGoogle Scholar
  29. 29.
    Body R, Pemberton P, Ali F, McDowell G, Carley S, Smith A, Mackway-Jones K (2011) Low soluble P-selectin may facilitate early exclusion of acute myocardial infarction. Clin Chim Acta 412:614–618PubMedCrossRefGoogle Scholar
  30. 30.
    Grau AJ, Ruf A, Vogt A, Lichy C, Buggle F, Patscheke H, Hacke W (1998) Increased fraction of circulating activated platelets in acute and previous cerebrovascular ischemia. Thromb Haemost 80:298–301PubMedGoogle Scholar
  31. 31.
    Zeller JA, Tschoepe D, Kessler C (1999) Circulating platelets show increased activation in patients with acute cerebral ischemia. Thromb Haemost 81:373–377PubMedGoogle Scholar
  32. 32.
    Turkoz Y, Evereklioglu C, Ozkiris A, Mistik S, Borlu M, Ozerol IH, Duygulu F, Ilhan O (2005) Serum levels of soluble P-selectin are increased and associated with disease activity in patients with Behcet’s syndrome. Mediat Inflamm 2005:237–241CrossRefGoogle Scholar
  33. 33.
    Kupersmith MJ, Frohman L, Sanderson M, Jacobs J, Hirschfeld J, Ku C, Warren FA (1997) Aspirin reduces the incidence of second eye NAION: a retrospective study. J Neuroophthalmol 17:250–253PubMedCrossRefGoogle Scholar
  34. 34.
    Newman NJ, Scherer R, Langenberg P, Kelman S, Feldon S, Kaufman D, Dickersin K, Ischemic Optic Neuropathy Decompression Trial Research Group (2002) The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol 134:317–328PubMedCrossRefGoogle Scholar
  35. 35.
    Atkins EJ, Bruce BB, Newman NJ, Biousse V (2010) Treatment of nonarteritic anterior ischemic optic neuropathy. Surv Ophthalmol 55:47–63PubMedCrossRefGoogle Scholar
  36. 36.
    Klinkhardt U, Bauersachs R, Adams J, Graff J, Lindhoff-Last E, Harder S (2003) Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease. Clin Pharmacol Ther 73:232–241PubMedCrossRefGoogle Scholar
  37. 37.
    Moshfegh K, Redondo M, Julmy F, Wuillemin WA, Gebauer MU, Haeberli A, Meyer BJ (2000) Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 36:699–705PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Valeria Nagy
    • 1
  • Bence Kolozsvari
    • 1
  • Zsuzsa Balogh
    • 1
  • Adrienne Csutak
    • 1
  • Marta Kasza
    • 2
  • Bela NagyJr
    • 3
  • Laszlo Kardos
    • 4
  • Andras Berta
    • 1
  • Gyorgy Pfliegler
    • 5
  1. 1.Department of Ophthalmology, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  2. 2.Department of OphthalmologyHungarian Military HospitalBudapestHungary
  3. 3.Department of Laboratory Medicine, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  4. 4.Kenezy Hospital — Institute of InfectologyDebrecenHungary
  5. 5.Division of Rare Diseases, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary

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