Skip to main content

Advertisement

SpringerLink
Log in

The effect of previous surgery and topical eye drops for primary open-angle glaucoma on cytokine expression in aqueous humor

  • Glaucoma
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate cytokine expression in the aqueous humor of patients with primary open-angle glaucoma (POAG) after previous glaucomatous and/or cataract surgery, and to determine the effect of intraocular pressure (IOP)-lowering eye drops on cytokine expression.

Methods

This prospective consecutive case study included 32 eyes diagnosed with POAG (19 with previous surgery and 13 without previous surgery, treated with topical antiglaucoma medication) and 12 eyes without signs of glaucoma. The Luminex 200 multiplex bead immunoassay was used to measure 27 cytokines in aqueous humor.

Results

Eyes suffering from POAG, with previous surgery, had significantly elevated concentrations of IL-6, IL-8, CCL2, CXCL9, and HGF, and a significantly lower concentration of CCL5, compared to POAG eyes without previous surgery, treated only with topical antiglaucoma medication. When compared with cataract controls, eyes with POAG and previous surgery had significantly elevated levels of G-CSF, IL-8, IL-12, CXCL10, and HGF, and significantly decreased concentrations of IL-17, CCL5, and VEGF in aqueous humor. In a comparison between POAG eyes without previous surgery and cataract controls, the cataract control eyes had significantly higher levels of IL-6 and CCL2, as the only significant difference.

Conclusions

POAG is associated with an aqueous inflammatory response in the aqueous humor, which is significantly elevated in eyes with previous surgery. In contrast, preoperative IOP-lowering eye drops did not significantly alter the anterior chamber milieu. The results of the current study indicate that filtration surgery has a higher success rate in eyes that have not experienced previous surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Maier PC, Funk J, Schwarzer G, Antes G, Falck-Ytter YT (2005) Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials. BMJ 331(7509):134

    Article  PubMed Central  PubMed  Google Scholar 

  2. Broadway DC, Grierson I, Hitchings RA (1998) Local effects of previous conjunctival incisional surgery and the subsequent outcome of filtration surgery. Am J Ophthalmol 125(6):805–818

    Article  CAS  PubMed  Google Scholar 

  3. Law SK, Shih K, Tran DH, Coleman AL, Caprioli J (2009) Long-term outcomes of repeat vs initial trabeculectomy in open-angle glaucoma. Am J Ophthalmol 148(5):685–695, e681

    Article  PubMed  Google Scholar 

  4. Takihara Y, Inatani M, Seto T, Iwao K, Iwao M, Inoue T, Kasaoka N, Murakami A, Futa R, Tanihara H (2011) Trabeculectomy with mitomycin for open-angle glaucoma in phakic vs pseudophakic eyes after phacoemulsification. Arch Ophthalmol 129(2):152–157

    Article  PubMed  Google Scholar 

  5. Joseph JP, Grierson I, Hitchings RA (1989) Chemotactic activity of aqueous humor. A cause of failure of trabeculectomies? Arch Ophthalmol 107(1):69–74

    Article  CAS  PubMed  Google Scholar 

  6. Broadway DC, Grierson I, O'Brien C, Hitchings RA (1994) Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery. Arch Ophthalmol 112(11):1446–1454

    Article  CAS  PubMed  Google Scholar 

  7. Sherwood MB, Grierson I, Millar L, Hitchings RA (1989) Long-term morphologic effects of antiglaucoma drugs on the conjunctiva and Tenon's capsule in glaucomatous patients. Ophthalmology 96(3):327–335

    Article  CAS  PubMed  Google Scholar 

  8. Nuzzi R, Vercelli A, Finazzo C, Cracco C (1995) Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study. Graefes Arch Clin Exp Ophthalmol 233(3):154–162

    Article  CAS  PubMed  Google Scholar 

  9. Baudouin C, Pisella PJ, Fillacier K, Goldschild M, Becquet F, De Saint JM, Bechetoille A (1999) Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology 106(3):556–563

    Article  CAS  PubMed  Google Scholar 

  10. Chua J, Vania M, Cheung CM, Ang M, Chee SP, Yang H, Li J, Wong TT (2012) Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol Vis 18:431–438

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Chen KH, Wu CC, Roy S, Lee SM, Liu JH (1999) Increased interleukin-6 in aqueous humor of neovascular glaucoma. Invest Ophthalmol Vis Sci 40(11):2627–2632

    CAS  PubMed  Google Scholar 

  12. Kuchtey J, Rezaei KA, Jaru-Ampornpan P, Sternberg P Jr, Kuchtey RW (2010) Multiplex cytokine analysis reveals elevated concentration of interleukin-8 in glaucomatous aqueous humor. Invest Ophthalmol Vis Sci 51(12):6441–6447

    Article  PubMed Central  PubMed  Google Scholar 

  13. Balaiya S, Edwards J, Tillis T, Khetpal V, Chalam KV (2011) Tumor necrosis factor-alpha (TNF-alpha) levels in aqueous humor of primary open angle glaucoma. Clin Ophthalmol 5:553–556

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Hu DN, Ritch R, Liebmann J, Liu Y, Cheng B, Hu MS (2002) Vascular endothelial growth factor is increased in aqueous humor of glaucomatous eyes. J Glaucoma 11(5):406–410

    Article  PubMed  Google Scholar 

  15. Inoue T, Kawaji T, Inatani M, Kameda T, Yoshimura N, Tanihara H (2012) Simultaneous increases in multiple proinflammatory cytokines in the aqueous humor in pseudophakic glaucomatous eyes. J Cataract Refract Surg 38(8):1389–1397

    Article  PubMed  Google Scholar 

  16. Shima C, Adachi Y, Minamino K, Okigaki M, Shi M, Imai Y, Yanai S, Takahashi K, Ikehara S (2012) Neuroprotective effects of granulocyte colony-stimulating factor on ischemia-reperfusion injury of the retina. Ophthalmic Res 48(4):199–207

    Article  CAS  PubMed  Google Scholar 

  17. Tsai RK, Chang CH, Sheu MM, Huang ZL (2010) Anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush are PI3K/AKT-dependent. Exp Eye Res 90(5):537–545

    Article  CAS  PubMed  Google Scholar 

  18. Cvenkel B, Kopitar AN, Ihan A (2010) Inflammatory molecules in aqueous humour and on ocular surface and glaucoma surgery outcome. Mediat Inflamm 2010:939602

    Article  Google Scholar 

  19. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354(6):610–621

    Article  CAS  PubMed  Google Scholar 

  20. Keeley EC, Mehrad B, Strieter RM (2008) Chemokines as mediators of neovascularization. Arterioscler Thromb Vasc Biol 28(11):1928–1936

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Takai Y, Tanito M, Ohira A (2012) Multiplex cytokine analysis of aqueous humor in eyes with primary open-angle glaucoma, exfoliation glaucoma, and cataract. Invest Ophthalmol Vis Sci 53(1):241–247

    Article  CAS  PubMed  Google Scholar 

  22. Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P, Gonzalez P (2009) Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol 47(1):198–204

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Shifera AS, Trivedi S, Chau P, Bonnemaison LH, Iguchi R, Alvarado JA (2010) Constitutive secretion of chemokines by cultured human trabecular meshwork cells. Exp Eye Res 91(1):42–47

    Article  CAS  PubMed  Google Scholar 

  24. Thirumangalakudi L, Yin L, Rao HV, Grammas P (2007) IL-8 induces expression of matrix metalloproteinases, cell cycle and pro-apoptotic proteins, and cell death in cultured neurons. J Alzheimers Dis 11(3):305–311

    CAS  PubMed  Google Scholar 

  25. Goczalik I, Ulbricht E, Hollborn M, Raap M, Uhlmann S, Weick M, Pannicke T, Wiedemann P, Bringmann A, Reichenbach A, Francke M (2008) Expression of CXCL8, CXCR1, and CXCR2 in neurons and glial cells of the human and rabbit retina. Invest Ophthalmol Vis Sci 49(10):4578–4589

    Article  PubMed  Google Scholar 

  26. Broadway DC, Lyons CJ, McGillivray BC (1998) Anterior segment dysgenesis and congenital glaucoma associated with partial trisomy of chromosome 1 (1q32-qter). J AAPOS 2(3):188–190

    Article  CAS  PubMed  Google Scholar 

  27. Hong KH, Ryu J, Han KH (2005) Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood 105(4):1405–1407

    Article  CAS  PubMed  Google Scholar 

  28. Jo N, Wu GS, Rao NA (2003) Upregulation of chemokine expression in the retinal vasculature in ischemia-reperfusion injury. Invest Ophthalmol Vis Sci 44(9):4054–4060

    Article  PubMed  Google Scholar 

  29. Meleth AD, Agron E, Chan CC, Reed GF, Arora K, Byrnes G, Csaky KG, Ferris FL 3rd, Chew EY (2005) Serum inflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 46(11):4295–4301

    Article  PubMed  Google Scholar 

  30. Nakazawa T, Hisatomi T, Nakazawa C, Noda K, Maruyama K, She H, Matsubara A, Miyahara S, Nakao S, Yin Y, Benowitz L, Hafezi-Moghadam A, Miller JW (2007) Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. Proc Natl Acad Sci U S A 104(7):2425–2430

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Murdoch C, Finn A (2000) Chemokine receptors and their role in inflammation and infectious diseases. Blood 95(10):3032–3043

    CAS  PubMed  Google Scholar 

  32. Birchmeier C, Gherardi E (1998) Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol 8(10):404–410

    Article  CAS  PubMed  Google Scholar 

  33. Borowiak M, Garratt AN, Wustefeld T, Strehle M, Trautwein C, Birchmeier C (2004) Met provides essential signals for liver regeneration. Proc Natl Acad Sci U S A 101(29):10608–10613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Hu DN, Ritch R (2001) Hepatocyte growth factor is increased in the aqueous humor of glaucomatous eyes. J Glaucoma 10(3):152–157

    Article  CAS  PubMed  Google Scholar 

  35. Tonges L, Ostendorf T, Lamballe F, Genestine M, Dono R, Koch JC, Bahr M, Maina F, Lingor P (2011) Hepatocyte growth factor protects retinal ganglion cells by increasing neuronal survival and axonal regeneration in vitro and in vivo. J Neurochem 117(5):892–903

    Article  PubMed  Google Scholar 

  36. Crane IJ, Kuppner MC, McKillop Smith S, Knott RM, Forrester JV (1998) Cytokine regulation of RANTES production by human retinal pigment epithelial cells. Cell Immunol 184(1):37–44

    Article  CAS  PubMed  Google Scholar 

  37. Khodarev NN, Yu J, Labay E, Darga T, Brown CK, Mauceri HJ, Yassari R, Gupta N, Weichselbaum RR (2003) Tumour-endothelium interactions in co-culture: coordinated changes of gene expression profiles and phenotypic properties of endothelial cells. J Cell Sci 116(Pt 6):1013–1022

    Article  CAS  PubMed  Google Scholar 

  38. Yamagami S, Miyazaki D, Ono SJ, Dana MR (1999) Differential chemokine gene expression in corneal transplant rejection. Invest Ophthalmol Vis Sci 40(12):2892–2897

    CAS  PubMed  Google Scholar 

  39. Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361(9):888–898

    Article  CAS  PubMed  Google Scholar 

  40. Kuiper JJ, Mutis T, De Jager W, De Groot-Mijnes JD, Rothova A (2011) Intraocular interleukin-17 and proinflammatory cytokines in HLA-A29-associated birdshot chorioretinopathy. Am J Ophthalmol 152(2):177–182, e171

    Article  CAS  PubMed  Google Scholar 

  41. Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE (2007) TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13(6):711–718

    Article  CAS  PubMed  Google Scholar 

  42. Colin J (2007) The role of NSAIDs in the management of postoperative ophthalmic inflammation. Drugs 67(9):1291–1308

    Article  CAS  PubMed  Google Scholar 

  43. Fechtner RD, Khouri AS, Zimmerman TJ, Bullock J, Feldman R, Kulkarni P, Michael AJ, Realini T, Warwar R (1998) Anterior uveitis associated with latanoprost. Am J Ophthalmol 126(1):37–41

    Article  CAS  PubMed  Google Scholar 

  44. Byles DB, Frith P, Salmon JF (2000) Anterior uveitis as a side effect of topical brimonidine. Am J Ophthalmol 130(3):287–291

    Article  CAS  PubMed  Google Scholar 

  45. Kapin MA, Yanni JM, Brady MT, McDonough TJ, Flanagan JG, Rawji MH, Dahlin DC, Sanders ME, Gamache DA (2003) Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac. Inflammation 27(5):281–291

    Article  CAS  PubMed  Google Scholar 

  46. Flach AJ (1992) Cyclo-oxygenase inhibitors in ophthalmology. Surv Ophthalmol 36(4):259–284

    Article  CAS  PubMed  Google Scholar 

  47. Flach AJ (1993) Nonsteroidal anti-inflammatory drugs in ophthalmology. Int Ophthalmol Clin 33(4):1–7

    Article  CAS  PubMed  Google Scholar 

  48. Roberts CW, Brennan KM (1995) A comparison of topical diclofenac with prednisolone for postcataract inflammation. Arch Ophthalmol 113(6):725–727

    Article  CAS  PubMed  Google Scholar 

  49. Costagliola C, Dell'Omo R, Romano MR, Rinaldi M, Zeppa L, Parmeggiani F (2009) Pharmacotherapy of intraocular pressure: part I. Parasympathomimetic, sympathomimetic and sympatholytics. Expert Opin Pharmacother 10(16):2663–2677

    Article  CAS  PubMed  Google Scholar 

  50. Burke J, Schwartz M (1996) Preclinical evaluation of brimonidine. Surv Ophthalmol 41(Suppl 1):S9–S18

    Article  PubMed  Google Scholar 

  51. Saylor M, McLoon LK, Harrison AR, Lee MS (2009) Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review. Arch Ophthalmol 127(4):402–406

    Article  CAS  PubMed  Google Scholar 

  52. Stamper RL, Wigginton SA, Higginbotham EJ (2002) Primary drug treatment for glaucoma: beta-blockers versus other medications. Surv Ophthalmol 47(1):63–73

    Article  PubMed  Google Scholar 

  53. Akingbehin T, Villada JR (1991) Metipranolol-associated granulomatous anterior uveitis. Br J Ophthalmol 75(9):519–523

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Moorthy RS, Valluri S, Jampol LM (1998) Drug-induced uveitis. Surv Ophthalmol 42(6):557–570

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Martina Becker supported this study with her technical expertise.

Funding

This study was not supported by a grant.

Competing Interests Statement

The authors have no proprietary or commercial interest in any materials discussed in this article. The authors have full control of all primary data, and agree to allow Graefe's Archive for Clinical and Experimental Ophthalmology to review the data if requested.

Contribution Statement

Lisa A. Engel invented the study design, collected data, performed statistical analysis, and wrote the paper. Philipp S. Muether performed the Luminex measurements and reviewed the manuscript. Sascha Fauser invented the study design and reviewed the manuscript. Arno Hueber invented the study design, performed the surgery, participated in writing the paper, and reviewed the manuscript. This manuscript has been proofread and edited by a native English speaker.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    Lisa A. Engel, Philipp S. Muether, Sascha Fauser & Arno Hueber

Authors
  1. Lisa A. Engel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philipp S. Muether
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sascha Fauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arno Hueber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lisa A. Engel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Engel, L.A., Muether, P.S., Fauser, S. et al. The effect of previous surgery and topical eye drops for primary open-angle glaucoma on cytokine expression in aqueous humor. Graefes Arch Clin Exp Ophthalmol 252, 791–799 (2014). https://doi.org/10.1007/s00417-014-2607-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-014-2607-5

Keywords

Search

Navigation