Association between Aqueous Cytokines and Diabetic Retinopathy Stage

Hailiang Wu, De-Kuang Hwang, Xudong Song, Yong Tao, Hailiang Wu, De-Kuang Hwang, Xudong Song, Yong Tao

Abstract

Purpose: To measure the concentrations of various cytokines in the aqueous humor from patients with different stages of diabetic retinopathy.

Methods: All selected cataract patients were categorized into 4 groups: the control group (patients without diabetes), nonretinopathy (NDR) group (diabetic patients without retinopathy), nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. The aqueous concentrations of interleukin- (IL-) 1β, IL-2, IL-4, IL-5, IL-6, IL-10, interferon-γ, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) from patients were measured using the cytometric bead array technique.

Results: In this study, 10, 22, 15, and 14 patients were included in the control, NDR, NPDR, and PDR groups, respectively. No difference was observed in the aqueous concentrations of all cytokines between the control group and the NDR group. By contrast, comparison of these groups revealed that the aqueous concentrations of most inflammatory cytokines were significantly higher in the PDR and NPDR groups. In addition, the concentrations of IL-2, IL-5, and VEGF were higher in the PDR group than those in the NPDR group.

Conclusions: Aqueous concentrations of various cytokines increased with the severity of patients' diabetic retinopathy. This finding implies that these cytokines might play a role in the progression of diabetic retinopathy.

Figures

Figure 1
Figure 1
Aqueous concentration of interleukin-1β. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 2
Figure 2
Aqueous concentration of interleukin-2. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 3
Figure 3
Aqueous concentration of interleukin-4. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 4
Figure 4
Aqueous concentration of interleukin-5. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 5
Figure 5
Aqueous concentration of interleukin-6. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 6
Figure 6
Aqueous concentration of interleukin-10. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 7
Figure 7
Aqueous concentration of interferon- (IFN-) γ. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 8
Figure 8
Aqueous concentration of tumor necrosis factor- (TNF-) α. Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.
Figure 9
Figure 9
Aqueous concentration of vascular endothelial growth factor (VEGF). Control: patients without diabetes; NDR: nondiabetic retinopathy; NPDR: nonproliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy.

References

    1. Zhi Z. Prevention and treatment of diabetic retinopathy: progress, challenges and future prospects. Chinese Journal of Ocular Fundus Diseases. 2012;28(3):209–213.
    1. Simó R., Hernández C. Novel approaches for treating diabetic retinopathy based on recent pathogenic evidence. Progress in Retinal and eye Research. 2015;48(9):160–180. doi: 10.1016/j.preteyeres.2015.04.003.
    1. Stitt A. W., Curtis T. M., Chen M., et al. The progress in understanding and treatment of diabetic retinopathy. Progress in Retinal and eye Research. 2016;51(3):156–186. doi: 10.1016/j.preteyeres.2015.08.001.
    1. Xie M., Hu A., Luo Y., Sun W., Hu X., Tang S. Interleukin-4 and melatonin ameliorate high glucose and interleukin-1beta stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells. Molecular Vision. 2014;20(6):921–928.
    1. Zhang X. L., Sun W. T. Investigation of VEGF and IGF-1 concentration in aqueous humor of patients with diabetic retinopathy. Internatonal Journal of Ophthalmology. 2008;8(5):951–953.
    1. Zhou L., Beuerman R. W. Tear analysis in ocular surface diseases. Progress in Retinal and eye Research. 2012;31(6):527–550. doi: 10.1016/j.preteyeres.2012.06.002.
    1. Chen R., Lowe L., Wilson J. D., et al. Simultaneous quantification of six human cytokines in a single sample using microparticle-based flow cytometric technology. Clinical Chemistry. 1999;45(9):1693–1694.
    1. Rajamani U., Jialal I. Hyperglycemia induces Toll-like receptor-2 and-4 expression and activity in human microvascular retinal endothelial cells: implications for diabetic retinopathy. Journal of Diabetes Research. 2014;2014:15. doi: 10.1155/2014/790902.790902
    1. Hang H., Yuan S., Yang Q., Yuan D., Liu Q. Multiplex bead array assay of plasma cytokines in type 2 diabetes mellitus with diabetic retinopathy. Molecular Vision. 2014;20(4):1137–1145.
    1. Tang J., Kern T. S. Inflammation in diabetic retinopathy. Progress in Retinal and eye Research. 2011;30(5):343–358. doi: 10.1016/j.preteyeres.2011.05.002.
    1. Ongkosuwito J. V., Feron E. J., Van Doornik C., et al. Analysis of immunoregulatory cytokines in ocular fluid samples from patients with uveitis. Investigative Ophthalmology & Visual Science. 1998;39(13):2659–2665.
    1. Cheung C. M. G., Vania M., Ang M., Chee S. P., Li J. Comparison of aqueous humor cytokine and chemokine levels in diabetic patients with and without retinopathy. Molecular Vision. 2012;18(4):830–837.
    1. Hu L., Li D.-H., Chen H. Related factors of prevention in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases. 2011;27(3):210–213.
    1. Scuderi S., D’amico A. G., Federico C., et al. Different retinal expression patterns of IL-1α, IL-1β, and their receptors in a rat model of type 1 STZ-induced diabetes. Journal of Molecular Neuroscience. 2015;56(2):431–439. doi: 10.1007/s12031-015-0505-x.
    1. Endo H., Naito T., Asahara T., Kajima M., Shiota H. Cytokines in the vitreous fluid of patients with proliferative diabetic retinopathy—vascular endothelial growth factor and platelet-derived growth factor are elevated in proliferative diabetic retinopathy. Nippon Ganka Gakkai Zasshi. 2000;104(10):711–716.
    1. Johnsen-Soriano S., Sancho-Tello M., Arnal E., et al. IL-2 and IFN-gamma in the retina of diabetic rats. Graefe's Archive for Clinical and Experimental Ophthalmology. 2010;248(7):985–990. doi: 10.1007/s00417-009-1289-x.
    1. Tang S., Le-Ruppert K. C. Activated T lymphocytes in epiretinal membranes from eyes of patients with proliferative diabetic retinopathy. Graefe's Archive for Clinical and Experimental Ophthalmology. 1995;233(1):21–25. doi: 10.1007/BF00177781.
    1. Wang X., Wang W., Xu J., Le Q. Effect of rapamycin and interleukin-2 on regulatory CD4+ CD25+ Foxp3+ T cells in mice after allogenic corneal transplantation. Transplantation Proceedings. 2013;45(2):528–537. doi: 10.1016/j.transproceed.2012.06.064.
    1. Trenn G., Takayama H., Hu-Li J., Paul W. E., Sitkovsky M. V. B cell stimulatory factor 1 (IL-4) enhances the development of cytotoxic T cells from Lyt-2+ resting murine T lymphocytes. The Journal of Immunology. 1988;140(4):1101–1106.
    1. Lee W. J., Kang M. H., Seong M., Cho H. Y. Comparison of aqueous concentrations of angiogenic and inflammatory cytokines in diabetic macular oedema and macular oedema due to branch retinal vein occlusion. British Journal of Ophthalmology. 2012;96(11):1426–1430. doi: 10.1136/bjophthalmol-2012-301913.
    1. Korthagen N. M., van Bilsen K., Swagemakers S. M., et al. Retinal pigment epithelial cells display specific transcriptional responses upon TNF-α stimulation. British Journal of Ophthalmology. 2015;99(5):700–704. doi: 10.1136/bjophthalmol-2014-306309.
    1. Demircan N., Safran B., Soylu M., Ozcan A. A., Sizmaz S. Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye. 2006;20(12):1366–1369. doi: 10.1038/sj.eye.6702138.
    1. Koleva-Georgieva D. N., Sivkova N. P., Terzieva D. Serum inflammatory cytokines IL-1β, IL-6, TNF-α and VEGF have influence on the development of diabetic retinopathy. Folia Medica. 2011;53(2):44–50.
    1. Kwon S. H., Shin J. P., Kim I. T., Park D. H. Aqueous levels of angiopoietin-like 4 and semaphorin 3E correlate with nonperfusion area and macular volume in diabetic retinopathy. Ophthalmology. 2015;122(5):968–975. doi: 10.1016/j.ophtha.2015.01.007.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi