Background: Diabetic retinopathy (DR) is a common complication of diabetes mellitus and a major cause of vision loss in the working age population. Its pathogenesis is poorly understood but may involve low grade chronic inflammation and angiogenesis. The aim of this study was to evaluate the relationship between serum levels of one inflammatory (IL-6) and angiogenic cytokine (VEGF-A) with the presence and severity of DR in type 2 diabetic mellitus patients. Methods: From January to June 2019, we conducted a cross-sectional analytical study on 84 patients out of which 31 developed DR and 53 did not. All patients underwent complete ophthalmological examination and laboratory analysis for IL-6 and VEGF-A with ELISA Technique. We studied the relation of IL-6 and VEGF-A with the presence and severity of DR, HBA1c, the duration of diabetes. Results: The group with DR had statistically significant higher levels of VEGF-A compared to the control group (390.5 pg/ml vs. 173.1 pg/ml; p = 0.007). There was no significant difference in IL-6 levels between both groups (42.8 pg/ml vs. 31.7 pg/ml; p = 0.10). Equally there was no association between these 2 cytokines and macular oedema or with the severity of DR. The level of IL-6 was associated to the balance of diabetes (p = 0.006) although VEGF-A was not (p = 0.15). Moreover, Il-6 (p = 0.31) and VEGF-A (p = 0.24) were not linked to the duration of diabetes. Conclusion: Serum concentrations of VEGF-A have an effect on the development of DR. They correlate with the presence of the disease but IL-6 does not. However, IL-6 was associated to the balance of diabetes. These 2 biomarkers may play a role in the pathophysiology of diabetes and the diabetic retinopathy. Findings on Il-6 and VEGF-A may therefore contribute to the development of the diagnosis tools and caretaking of diabetes and diabetic retinopathy.
References
[1]
Cho, N.H., Shaw, J.E., Karuranga, S., Huang, Y., da Rocha Fernandes, J.D., Ohlrogge, A.W. and Malanda, B. (2018) IDF Diabetes Atlas: Global Estimates of Diabetes Prevalence for 2017 and Projections for 2045. Diabetes Research and Clinical Practice, 138, 271-281. https://doi.org/10.1016/j.diabres.2018.02.023
[2]
Yau, J.W.Y., Rogers, S.L., Kawasaki, R., Lamoureux, E.L., Kowalski, J.W., Bek, T., Chen, S.-J., Dekker, J.M., Fletcher, A., Grauslund, J., Haffner, S., Hamman, R.F., Ikram, M.K., Kayama, T., Klein, B.E.K., Klein, R., Krishnaiah, S., Mayurasakorn, K., O’Hare, J.P., Orchard, T.J., Porta, M., Rema, M., Roy, M.S., Sharma, T., Shaw, J., Taylor, H., Tielsch, J.M., Varma, R., Wang, J.J., Wang, N., West, S., Xu, L., Yasuda, M., Zhang, X., Mitchell, P. and Wong, T.Y. (2012) Global Prevalence and Major Risk Factors of Diabetic Retinopathy. Diabetes Care, 35, 556-564. https://doi.org/10.2337/dc11-1909
[3]
Bourne, R.R.A., Stevens, G.A., White, R.A., Smith, J.L., Flaxman, S.R., Price, H., Jonas, J.B., Keeffe, J., Leasher, J., Naidoo, K., Pesudovs, K., Resnikoff, S. and Taylor, H.R. (2013) Causes of Vision Loss Worldwide, 1990-2010: A Systematic Analysis. The Lancet Global Health, 1, e339-e349. https://doi.org/10.1016/S2214-109X(13)70113-X
[4]
Klein, B.E.K. (2007) Overview of Epidemiologic Studies of Diabetic Retinopathy. Ophthalmic Epidemiology, 14, 179-183. https://doi.org/10.1080/09286580701396720
[5]
Jingi, A.M., Noubiap, J.J.N., Ellong, A., Bigna, J.J.R. and Mvogo, C.E. (2014) Epidemiology and Treatment Outcomes of Diabetic Retinopathy in a Diabetic Population from Cameroon. BMC Ophthalmology, 14, 19. https://doi.org/10.1186/1471-2415-14-19
[6]
Lawan, A. and Mohammed, T. (2012) Pattern of Diabetic Retinopathy in Kano, Nigeria. Annals of African Medicine, 11, 75. https://doi.org/10.4103/1596-3519.93528
[7]
Rotchford, A.P. and Rotchford, K.M. (2002) Diabetes in Rural South Africa—An Assessment of Care and Complications. South African Medical Journal, 92, 536-541.
[8]
Simó, R. and Hernández, C. (2015) Novel Approaches for Treating Diabetic Retinopathy Based on Recent Pathogenic Evidence. Progress in Retinal and Eye Research, 48, 160-180. https://doi.org/10.1016/j.preteyeres.2015.04.003
[9]
Stitt, A.W., Curtis, T.M., Chen, M., Medina, R.J., McKay, G.J., Jenkins, A., Gardiner, T.A., Lyons, T.J., Hammes, H.-P., Simó, R. and Lois, N. (2016) The Progress in Understanding and Treatment of Diabetic Retinopathy. Progress in Retinal and Eye Research, 51, 156-186. https://doi.org/10.1016/j.preteyeres.2015.08.001
[10]
Aiello, L.P. (2005) Angiogenic Pathways in Diabetic Retinopathy. The New England Journal of Medicine, 353, 839-841. https://doi.org/10.1056/NEJMe058142
[11]
Murugeswari, P., Shukla, D., Rajendran, A., Kim, R., Namperumalsamy, P. and Muthukkaruppan, V. (2008) Proinflammatory Cytokines and Angiogenic and Anti-Angiogenic Factors in Vitreous of Patients with Proliferative Diabetic Retinopathy and Eales’ Disease. Retina, 28, 817. https://doi.org/10.1097/IAE.0b013e31816576d5
[12]
Zhou, J., Wang, S. and Xia, X. (2012) Role of Intravitreal Inflammatory Cytokines and Angiogenic Factors in Proliferative Diabetic Retinopathy. Current Eye Research, 37, 416-420. https://doi.org/10.3109/02713683.2012.661114
[13]
Gupta, N., Mansoor, S., Sharma, A., Sapkal, A., Sheth, J., Falatoonzadeh, P. and Kenney, M.C. (2013) Diabetic Retinopathy and VEGF. The Open Ophthalmology Journal, 7, 4. https://doi.org/10.2174/1874364101307010004
[14]
Koleva-Georgieva, D.N., Sivkova, N.P. and Terzieva, D. (2011) Serum Inflammatory Cytokines IL-1β, IL-6, TNF-α and VEGF Have Influence on the Development of Diabetic Retinopathy. Folia Medica (Plovdiv), 53, 44-50. https://doi.org/10.2478/v10153-010-0036-8
[15]
Doganay, S., Evereklioglu, C., Er, H., Türkoz, Y., Sevinc, A., Mehmet, N. and Savli, H. (2002) Comparison of Serum NO, TNF-α, IL-1β, sIL-2R, IL-6 and IL-8 Levels with Grades of Retinopathy in Patients with Diabetes Mellitus. Eye, 16, 163. https://doi.org/10.1038/sj/eye/6700095
[16]
Wilkinson, C.P., Ferris, F.L., Klein, R.E., Lee, P.P., Agardh, C.D., Davis, M., Dills, D., Kampik, A., Pararajasegaram, R., Verdaguer, J.T., Global Diabetic Retinopathy Project Group (2003) Proposed International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scales. Ophthalmology, 110, 1677-1682. https://doi.org/10.1016/S0161-6420(03)00475-5
[17]
Brownlee, M. (2005) The Pathobiology of Diabetic Complications: A Unifying Mechanism. Diabetes, 54, 1615-1625. https://doi.org/10.2337/diabetes.54.6.1615
[18]
Zehetner, C., Kirchmair, R., Kralinger, M. and Kieselbach, G. (2013) Correlation of Vascular Endothelial Growth Factor Plasma Levels and Glycemic Control in Patients with Diabetic Retinopathy. Acta Ophthalmologica, 91, e470-e473. https://doi.org/10.1111/aos.12081
[19]
Simo, R. and Hernandez, C. (2008) Intravitreous Anti-VEGF for Diabetic Retinopathy: Hopes and Fears for a New Therapeutic Strategy. Diabetologia, 51, 1574. https://doi.org/10.1007/s00125-008-0989-9
[20]
Antonetti, D.A., Barber, A.J., Hollinger, L.A., Wolpert, E.B. and Gardner, T.W. (1999) Vascular Endothelial Growth Factor Induces Rapid Phosphorylation of Tight Junction Proteins Occludin and Zonula Occluden 1. A Potential Mechanism for Vascular Permeability in Diabetic Retinopathy and Tumors. The Journal of Biological Chemistry, 274, 23463-23467. https://doi.org/10.1074/jbc.274.33.23463
[21]
Le, D.S.N.T., Miles, R., Savage, P.J., Cornell, E., Tracy, R.P., Knowler, W.C. and Krakoff, J. (2008) The Association of Plasma Fibrinogen Concentration with Diabetic Microvascular Complications in Young Adults with Early-Onset of Type 2 Diabetes. Diabetes Research and Clinical Practice, 82, 317-323. https://doi.org/10.1016/j.diabres.2008.08.019
[22]
Lee, I.G., Chae, S.L. and Kim, J.C. (2006) Involvement of Circulating Endothelial Progenitor Cells and Vasculogenic Factors in the Pathogenesis of Diabetic Retinopathy. Eye (London, England), 20, 546-552. https://doi.org/10.1038/sj.eye.6701920
[23]
Ozturk, B.T., Bozkurt, B., Kerimoglu, H., Okka, M., Kamis, U. and Gunduz, K. (2009) Effect of Serum Cytokines and VEGF Levels on Diabetic Retinopathy and Macular Thickness. Molecular Vision, 15, 1906-1914.
[24]
Zhou, Z., Ju, H., Sun, M. and Chen, H. (2019) Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis. Disease Markers, 2019, Article ID: 9401628. https://doi.org/10.1155/2019/9401628
[25]
Mahdy, R.A. and Nada, W.M. (2011) Evaluation of the Role of Vascular Endothelial Growth Factor in Diabetic Retinopathy. Ophthalmic Research, 45, 87-91. https://doi.org/10.1159/000317062
