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International Ophthalmology

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01-02-2020 | Glaucoma | Original Paper

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

Authors: Chuan Sun, Hongsong Zhang, Jingjing Jiang, Yuxin Li, Chuang Nie, Jianwen Gu, Ling Luo, Zhijun Wang

Published in: International Ophthalmology | Issue 2/2020

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.

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):6523–6530CrossRef

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

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 2:26CrossRef

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 CrossRefPubMedPubMedCentral

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–e560CrossRef

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):2352CrossRef

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 CrossRefPubMedPubMedCentral

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):3–8CrossRef

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):42–48CrossRef

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 17:2856–2863PubMedPubMedCentral

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 CrossRefPubMed

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):524–535CrossRef

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 CrossRefPubMedPubMedCentral

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):402–409CrossRef

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):1350–1354CrossRef

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

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

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):10445–10451CrossRef

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 CrossRefPubMedPubMedCentral

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):175–176CrossRef

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):1293–1309CrossRef

23.

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

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):183–191CrossRef

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 20:970–976PubMedPubMedCentral

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 18:1991–1995PubMedPubMedCentral

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):3874–3879CrossRef

28.

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

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 28:2252–2254CrossRef

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):1376–1378CrossRef

Title: Angiogenic and inflammatory biomarker levels in aqueous humor and vitreous of neovascular glaucoma and proliferative diabetic retinopathy
Authors: Chuan Sun
Hongsong Zhang
Jingjing Jiang
Yuxin Li
Chuang Nie
Jianwen Gu
Ling Luo
Zhijun Wang
Publication date: 01-02-2020
Publisher: Springer Netherlands
Keywords: Glaucoma
Erythropoietin
Erythropoietin
Diabetic Retinopathy
Diabetic Retinopathy
Epoetin alfa
Published in: International Ophthalmology / Issue 2/2020
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-019-01207-4

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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