Advertisement

Elevated lipocalin-2 level in aqueous humor of patients with central retinal vein occlusion

  • Yaran Koban
  • Seda Sahin
  • Fatih Boy
  • Fatih Kara
Original Paper
  • 62 Downloads

Abstract

Purpose

To assess the concentrations of lipocalin-2 (LCN2) in the serum and the aqueous humor of patients with central retinal vein occlusion (CRVO).

Methods

The concentrations of LCN2 in the serum and aqueous humor of 16 cataract patients and 16 patients with CRVO with macular edema were compared. Collection of aqueous samples was conducted in the operating theater under sterile conditions and just prior to intravitreal ranibizumab injection or cataract surgery. LCN2 levels in serum and aqueous humor samples were measured using a commercial kit (human lipocalin-2/NGAL PicoKine ELISA Kit, MyBioSource Inc., USA; Catalog No: MBS175829) based on standard sandwich enzyme-linked immunosorbent assay technology.

Results

The concentrations of LCN2 in the aqueous humors of the CRVO group were higher than those of the control group (p = 0.021). There was no significant difference in serum LCN2 level between the two groups (p = 0.463).

Conclusions

Concentrations of LCN2 in aqueous humor are increased in CRVO. LCN2 may be part of a pro-catabolic phenotype, and it may play an important role in the dreaded complications of CRVO, such as macular edema, macular ischemia, and neovascularization, which lead to blindness.

Keywords

Aqueous humor Lipocalin-2 Macular edema Matrix metalloproteinase Retinal vein occlusion 

Notes

Compliance with ethical standards

Conflict of interest

Authors do not have any financial interest in any products mentioned in this article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Hatz K, Martinez M (2016) Retinal vein occlusion: an interdisciplinary approach. Ther Umsch 73:85–89CrossRefPubMedGoogle Scholar
  2. 2.
    Campochiaro PA (2012) Anti-vascular endothelial growth factor treatment for retinal vein occlusions. Ophthalmologica 227:30–35CrossRefPubMedGoogle Scholar
  3. 3.
    Campa C, Alivernini G, Bolletta E, Parodi MB, Perri P (2016) Anti-VEGF therapy for retinal vein occlusions. Curr Drug Targets 17:328–336CrossRefPubMedGoogle Scholar
  4. 4.
    Deobhakta A, Chang LK (2013) Inflammation in retinal vein occlusion. Int J Inflam P 438412Google Scholar
  5. 5.
    Noma H, Funatsu H, Mimura T, Harino S, Hori S (2009) Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Ophthalmology 116:87–93CrossRefPubMedGoogle Scholar
  6. 6.
    Koss M, Pfister M, Rothweiler F, Rejdak R, Ribeiro R, Cinatl J, Schubert R, Kohnen T, Koch F (2013) Correlation from undiluted vitreous cytokines of untreated central retinal vein occlusion with spectral domain optical coherence tomography. Open Ophthalmol J 7:11–17CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Abella V, Scotece M, Conde J, Gómez R, Lois A, Pino J, Gómez-Reino JJ, Lago F, Mobasheri A, Gualillo O (2015) The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases. Biomarkers 20:565–571CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee S, Park JY, Lee WH, Kim H, Park HC, Mori K, Suk K (2009) Lipocalin-2 is an autocrine mediator of reactive astrocytosis. J Neurosci 29:234–249CrossRefPubMedGoogle Scholar
  9. 9.
    Cowland JB, Borregaard N (1997) Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase associated lipocalin from humans. Genomics 45:17–23CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang J, Wu Y, Zhang Y, Leroith D, Bernlohr DA, Chen X (2008) The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Mol Endocrinol 2:1416–1426CrossRefGoogle Scholar
  11. 11.
    Valapala M, Edwards M, Hose S, Grebe R, Bhutto IA, Cano M, Berger T, Mak TW, Wawrousek E, Handa JT, Lutty GA, Samuel Zigler J, Jr Sinha D (2014) Increased Lipocalin-2 in the retinal pigment epithelium of Cryba1 cKO mice is associated with a chronic inflammatory response. Aging Cell 13:1091–1094CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Parmar T, Parmar VM, Arai E, Sahu B, Perusek L, Maeda A (2016) Acute stress responses are early molecular events of retinal degeneration in Abca4-/-Rdh8-/- mice after light exposure. Investig Ophthalmol Vis Sci 57:3257–3267CrossRefGoogle Scholar
  13. 13.
    Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432:917–921CrossRefPubMedGoogle Scholar
  14. 14.
    Marques F, Rodrigues AJ, Sousa JC, Coppola G, Geschwind DH, Sousa N, Correia-Neves M, Palha JA (2008) Lipocalin 2 is a choroid plexus acute-phase protein. J Cereb Blood Flow Metab 28:450–455CrossRefPubMedGoogle Scholar
  15. 15.
    Leng X, Wu Y, Arlinghaus RB (2011) Relationships of lipocalin 2 with breast tumorigenesis and metastasis. J Cell Physiol 226:309–314CrossRefPubMedGoogle Scholar
  16. 16.
    Barrera-Chimal J, Bobadilla NA (2012) Are recently reported biomarkers helpful for early and accurate diagnosis of acute kidney injury? Biomarkers 17:385–393CrossRefPubMedGoogle Scholar
  17. 17.
    Naudé PJ, Mommersteeg PM, Zijlstra WP, Gouweleeuw L, Kupper N, Eisel UL, Kop WJ, Schoemaker RG (2014) Neutrophil gelatinase-associated lipocalin and depression in patients with chronic heart failure. Brain Behav Immun 38:59–65CrossRefPubMedGoogle Scholar
  18. 18.
    Xiao Y, Xu A, Hui X, Zhou P, Li X, Zhong H, Tang W, Huang G, Zhou Z (2013) Circulating lipocalin-2 and retinol-binding protein 4 are associated with intimamedia thickness and subclinical atherosclerosis in patients with type 2 diabetes. PLoS ONE 8:e66607CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Salom D, Sanz-Marco E, Mullor JL, Lopez-Prats MJ, Garcia-Delpech S, Udaondo P, Millan JM, Arevalo JF, Diaz-Llopis M (2010) Aqueous humor neutrophil gelatinase-associated lipocalin levels in patients with idiopathic acute anterior uveitis. Mol Vis 16:1448–1452PubMedPubMedCentralGoogle Scholar
  20. 20.
    Agudo M, Pérez-Marín MC, Lönngren U, Sobrado P, Conesa A, Cánovas I, Salinas-Navarro M, Miralles-Imperial J, Hallböök F, Vidal-Sanz M (2008) Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush. Mol Vis 14:1050–1063PubMedPubMedCentralGoogle Scholar
  21. 21.
    Guo Y, Johnson EC, Cepurna WO, Dyck JA, Doser T, Morrison JC (2011) Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model. Investig Ophthalmol Vis Sci 52:1460–1473CrossRefGoogle Scholar
  22. 22.
    Hangai M, Yoshimura N, Yoshida M, Yabuuchi K, Honda Y (1995) Interleukin-1 gene expression in transient retinal ischemia in the rat. Investig Ophthalmol Vis Sci 36:571–578Google Scholar
  23. 23.
    Zhao M, Bai Y, Xie W, Shi X, Li F, Yang F, Sun Y, Huang L, Li X (2015) Interleukin-1β level is increased in vitreous of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). PLoS ONE 10:e0125150CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cowland JB, Sorensen OE, Sehested M, Borregaard N (2003) Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1β, but not by TNF-α. J Immunol 171:6630–6639CrossRefPubMedGoogle Scholar
  25. 25.
    Sommer G, Weise S, Kralisch S, Lossner U, Bluher M, Stumvoll M, Fasshauer M (2009) Lipocalin-2 is induced by interleukin-1β in murine adipocytes in vitro. J Cell Biochem 106:103–108CrossRefPubMedGoogle Scholar
  26. 26.
    Veeriah V, Zanniti A, Paone R, Chatterjee S, Rucci N, Teti A, Capulli M (2016) Interleukin-1β, lipocalin 2 and nitric oxide synthase 2 are mechano-responsive mediators of mouse and human endothelial cell-osteoblast crosstalk. Sci Rep 6:29880CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Jin M, Kim JH, Jang E, Lee YM, Soo Han H, Woo DK, Park DH, Kook H, Suk K (2014) Lipocalin-2 deficiency attenuates neuroinflammation and brain injury after transient middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 34:1306–1314CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Tawfik A, Gnana-Prakasam JP, Smith SB, Ganapathy V (2014) Deletion of hemojuvelin, an iron-regulatory protein, in mice results in abnormal angiogenesis and vasculogenesis in retina along with reactive gliosis. Investig Ophthalmol Vis Sci 55:3616–3625CrossRefGoogle Scholar
  29. 29.
    Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J (2002) An iron delivery pathway mediated by a lipocalin. Mol Cell 10:1045–1056CrossRefPubMedGoogle Scholar
  30. 30.
    Yan L, Borregaard N, Kjeldsen L, Moses MA (2001) The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL. J Biol Chem 276:37258–37265CrossRefPubMedGoogle Scholar
  31. 31.
    Ilhan A, Tas A, Yolcu U, Gundogan FC (2015) Pharmacotherapy for treatment of retinal vein occlusion. Expert Opin Pharmacother 16:447–448PubMedGoogle Scholar
  32. 32.
    Kwon JW, Choi JA, Jee D (2016) Matrix metalloproteinase-1 and matrix metalloproteinase-9 in the aqueous humor of diabetic macular edema patients. PLoS ONE 11:e0159720CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Tuuminen R, Loukovaara S (2014) High intravitreal TGF-β1 and MMP-9 levels in eyes with retinal vein occlusion. Eye 28:1095–1099CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Ophthalmology, Faculty of MedicineKafkas UniversityKarsTurkey
  2. 2.Department of Biochemistry, Faculty of MedicineKafkas UniversityKarsTurkey

Personalised recommendations