Skip to main content

Advertisement

SpringerLink
Log in

Angiogenic and inflammatory biomarker levels in aqueous humor and vitreous of neovascular glaucoma and proliferative diabetic retinopathy

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To explore the relationships between the aqueous and vitreous levels of vascular endothelial growth factor-A (VEGF-A), interleukin-8 (IL-8), placental growth factor (PlGF) and erythropoietin (EPO) in proliferative diabetic retinopathy (PDR) and neovascular glaucoma (NVG).

Methods

Aqueous and vitreous samples were obtained from patients with PDR and NVG during surgery. Aqueous and vitreous concentrations of VEGF-A, IL-8, PlGF and EPO were measured via enzyme-linked immunosorbent assay.

Results

No correlation between the aqueous and vitreous levels of VEGF-A, IL-8, PlGF or EPO was found in both the PDR and the NVG eyes. Aqueous VEGF-A was significantly higher in the NVG group (317.55 ± 36.25 pg/ml, n = 15) than that in the PDR group (256.23 ± 46.11 pg/ml, n = 17, P < 0.001). The level of VEGF-A in aqueous (317.55 ± 36.25 pg/ml, n = 15) was significantly higher than that in vitreous (224.74 ± 60.32 pg/ml, n = 15, P < 0.001) in NVG patients. The level of IL-8 in aqueous (76.55 ± 10.88 pg/ml, n = 17) was significantly higher than that in vitreous (63.55 ± 10.74 pg/ml, n = 17, P = 0.001) in PDR patients. The level of EPO in aqueous (18.62 ± 2.87 mIU/ml, n = 15) was significantly higher than that in vitreous (15.97 ± 3.11 mIU/ml, n = 15, P = 0.022) in NVG patients. The ratio of aqueous versus vitreous for VEGF-A was significantly higher in the NVG group (1.475 ± 0.289, n = 15) than that in the PDR group (0.996 ± 0.227, n = 17, P < 0.001).

Conclusion

Aqueous levels of VEGF-A, IL-8, PlGF and EPO do not correlate with vitreous levels of those proteins. The relationship between protein levels in aqueous humor and vitreous might be dependent on different disease status or protein types investigated.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kovacs K, Marra KV, Yu G, Wagley S, Ma J, Teague GC, Nandakumar N, Lashkari K, Arroyo JG (2015) Angiogenic and inflammatory vitreous biomarkers associated with increasing levels of retinal ischemia. Investig Ophthalmol Vis Sci 56(11):6523–6530

    Article  CAS  Google Scholar 

  2. Hayreh SS (2007) Neovascular glaucoma. Prog Retin Eye Res 26(5):470–485

    Article  Google Scholar 

  3. Rodrigues GB, Abe RY, Zangalli C, Sodre SL, Donini FA, Costa DC, Leite A, Felix JP, Torigoe M, Diniz-Filho A, de Almeida HG (2016) Neovascular glaucoma: a review. Int J Retina Vitr 2:26

    Article  Google Scholar 

  4. Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y, Ueno A, Hata Y, Yoshida H, Ishibashi T (2009) Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS ONE 4(12):e8158. https://doi.org/10.1371/journal.pone.0008158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen S, Zhou M, Wang W, Wu H, Yu X, Huang W, Gao X, Wang J, Li X, Du S et al (2015) Levels of angiogenesis-related vascular endothelial growth factor family in neovascular glaucoma eyes. Acta Ophthalmol 93(7):e556–e560

    Article  CAS  Google Scholar 

  6. Mitamura Y, Tashimo A, Nakamura Y, Tagawa H, Ohtsuka K, Mizue Y, Nishihira J (2002) Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetes Care 25(12):2352

    Article  Google Scholar 

  7. Okawada H, Saito Y, Iwabuchi S, Kosuge S, Takahashi H, Onda H, Kito M (2018) Relationship between vascular endothelial growth factor and macular edema in retinal vein branch obstruction. Clin Ophthalmol 12:1379–1382. https://doi.org/10.2147/opth.s159109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Funatsu H, Yamashita H, Noma H, Mimura T, Nakamura S, Sakata K, Hori S (2005) Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients. Graefes Arch Clin Exp Ophthalmol 243(1):3–8

    Article  CAS  Google Scholar 

  9. Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Hirayama T, Tamura H, Yamashita H, Minamoto A et al (2008) Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye 22(1):42–48

    Article  CAS  Google Scholar 

  10. Ecker SM, Hines JC, Pfahler SM, Glaser BM (2011) Aqueous cytokine and growth factor levels do not reliably reflect those levels found in the vitreous. Mol Vis 17:2856–2863

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Kim YG, Hong S, Lee CS, Kang SY, Seong GJ, Ma KT, Kim CY (2009) Level of vascular endothelial growth factor in aqueous humor and surgical results of ahmed glaucoma valve implantation in patients with neovascular glaucoma. J Glaucoma 18(6):443–447. https://doi.org/10.1097/ijg.0b013e3181895e5c

    Article  PubMed  Google Scholar 

  12. Kim M, Lee C, Payne R, Yue BY, Chang JH, Ying H (2015) Angiogenesis in glaucoma filtration surgery and neovascular glaucoma: a review. Surv Ophthalmol 60(6):524–535

    Article  Google Scholar 

  13. Rusnak S, Vrzalova J, Sobotova M, Hecova L, Ricarova R, Topolcan O (2015) The measurement of intraocular biomarkers in various stages of proliferative diabetic retinopathy using multiplex xMAP technology. J Ophthalmol 2015:424783. https://doi.org/10.1155/2015/424783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Noma H, Funatsu H, Mimura T, Harino S, Hori S (2010) Aqueous humor levels of vasoactive molecules correlate with vitreous levels and macular edema in central retinal vein occlusion. Eur J Ophthalmol 20(2):402–409

    Article  Google Scholar 

  15. Chalam KV, Brar VS, Murthy RK (2014) Human ciliary epithelium as a source of synthesis and secretion of vascular endothelial growth factor in neovascular glaucoma. JAMA Ophthalmol 132(11):1350–1354

    Article  Google Scholar 

  16. Zhou M, Wang J, Wang W, Huang W, Ding X, Zhang X (2016) Placenta growth factor in eyes with neovascular glaucoma is decreased after intravitreal ranibizumab injection. PLoS ONE 11(1):e0146993. https://doi.org/10.1371/journal.pone.0146993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dewerchin M, Carmeliet P (2012) PlGF: a multitasking cytokine with disease-restricted activity. Cold Spring Harb Perspect Med 2(8):a011056. https://doi.org/10.1101/cshperspect.a011056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yoshida A, Yoshida S, Khalil AK, Ishibashi T, Inomata H (1998) Role of NF-kappaB-mediated interleukin-8 expression in intraocular neovascularization. Investig Ophthalmol Vis Sci 39(7):1097–1106

    CAS  Google Scholar 

  19. Lee TH, Avraham H, Lee SH, Avraham S (2002) Vascular endothelial growth factor modulates neutrophil transendothelial migration via up-regulation of interleukin-8 in human brain microvascular endothelial cells. J Biol Chem 277(12):10445–10451

    Article  CAS  Google Scholar 

  20. Chono I, Miyazaki D, Miyake H, Komatsu N, Ehara F, Nagase D, Kawamoto Y, Shimizu Y, Ideta R, Inoue Y (2018) High interleukin-8 level in aqueous humor is associated with poor prognosis in eyes with open angle glaucoma and neovascular glaucoma. Sci Rep 8(1):14533. https://doi.org/10.1038/s41598-018-32725-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Petrovic MG, Korosec P, Kosnik M, Hawlina M (2007) Vitreous levels of interleukin-8 in patients with proliferative diabetic retinopathy. Am J Ophthalmol 143(1):175–176

    Article  Google Scholar 

  22. Shirley Ding SL, Leow SN, Munisvaradass R, Koh EH, Bastion ML, Then KY, Kumar S, Mok PL (2016) Revisiting the role of erythropoietin for treatment of ocular disorders. Eye 30(10):1293–1309

    Article  CAS  Google Scholar 

  23. Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck K-H (2002) Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 64:326–333

    Article  CAS  Google Scholar 

  24. Ergorul C, Ray A, Huang W, Wang DY, Ben Y, Cantuti-Castelvetri I, Grosskreutz CL (2010) Hypoxia inducible factor-1α (HIF-1α) and some HIF-1 target genes are elevated in experimental glaucoma. J Mol Neurosci 42(2):183–191

    Article  CAS  Google Scholar 

  25. Beirão JM, Moreira LM, Oliveira JC, Menéres MJ, Pessoa BB, Matos ME, Costa PP, Torres PA, Beirão IB (2014) Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30 M familial amyloid polyneuropathy. Mol Vis 20:970–976

    PubMed  PubMed Central  Google Scholar 

  26. Nassiri N, Majdi M, Mehrjardi HZ, Shakiba Y, Haghnegahdar M, Heidari AB, Djalilian AR, Mirahmadian M (2012) Erythropoietin levels in aqueous humor of patients with glaucoma. Mol Vis 18:1991–1995

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhou M, Chen S, Wang W, Huang W, Cheng B, Ding X, Zhang X (2013) Levels of erythropoietin and vascular endothelial growth factor in surgery-required advanced neovascular glaucoma eyes before and after intravitreal injection of bevacizumab. Investig Ophthalmol Vis Sci 54(6):3874–3879

    Article  CAS  Google Scholar 

  28. Inomata Y, Hirata A, Takahashi E, Kawaji T, Fukushima M, Tanihara H (2004) Elevated erythropoietin in vitreous with ischemic retinal diseases. Neuroreport 15:877–879

    Article  CAS  Google Scholar 

  29. Katsura Y, Okano T, Matsuno K, Osako M, Kure M, Watanabe T, Iwaki Y, Noritake M, Kosano H, Nishigori H, Matsuoka T (2005) Erythropoietin is highly elevated in vitreous fluid of patients with proliferative diabetic retinopathy. Diabetes Care 28:2252–2254

    Article  CAS  Google Scholar 

  30. Kase S, Saito W, Ohgami K, Yoshida K, Furudate N, Saito A, Yokoi M, Kase M, Ohno S (2007) Expression of erythropoietin receptor in human epiretinal membrane of proliferative diabetic retinopathy. Br J Ophthalmol 91(10):1376–1378

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by National Natural Science Foundation of China (Grant No. BWS12J019).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, China-Japan Friendship Hospital, Yinghua Donglu, Chaoyang District, Beijing, 100029, China

    Chuan Sun, Hongsong Zhang, Jingjing Jiang & Zhijun Wang

  2. Department of Neurosurgery, The 306th Hospital of PLA, Beijing, China

    Chuang Nie & Jianwen Gu

  3. Department of Ophthalmology, The 306th Hospital of PLA, AnXiang BeiLi, Chaoyang District, Beijing, 100101, China

    Yuxin Li & Ling Luo

Authors
  1. Chuan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongsong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jingjing Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuxin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chuang Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianwen Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ling Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhijun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ling Luo or Zhijun Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, C., Zhang, H., Jiang, J. et al. Angiogenic and inflammatory biomarker levels in aqueous humor and vitreous of neovascular glaucoma and proliferative diabetic retinopathy. Int Ophthalmol 40, 467–475 (2020). https://doi.org/10.1007/s10792-019-01207-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-019-01207-4

Keywords

Search

Navigation