DOI: 10.25881/20728255_2025_20_4_S1_70

Authors

Zenkin N.S., Petrachkov D.V., Baryshev K.V., Panova A.D. , Subbot A.M.

Research Institute of Eye Diseases named after M.M. Krasnov, Moscow

Abstract

Introduction. Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes mellitus, in whose pathogenesis chronic inflammation and pathological angiogenesis play a key role. Studying the local cytokine profile of the vitreous body allows us to identify specific mediators involved in the development of the disease.

Objective. To conduct a comparative analysis of the concentrations of a wide range of cytokines in the vitreous body of patients with PDR and in the control group to identify an imbalance of key mediators of inflammation and angiogenesis.

Methods. The study analyzed vitreous samples obtained from nine patients with PDR and seven control patients (idiopathic epiretinal membranes). Cytokine concentrations were determined using a multiplex enzyme-linked immunosorbent assay (Bio-Plex Pro Human Cytokine 27-plex Assay). Statistical data processing was performed using GraphPad Prism software. The nonparametric Mann-Whitney U test was used to compare groups. Statistical significance was established at p < 0.05.

Results. Patients with PDR showed statistically significant increases in concentrations of proinflammatory and proangiogenic mediators compared to the control group. The most pronounced increases were noted for IL-8 (6.7-fold), MCP-1 (3.2-fold), and eotaxin (2.3-fold). Levels of IL-6, IL-1β, IL-4, IL-13, IFN-γ, IL-12(p70), and the growth factors VEGF and PDGF-BB were also significantly increased.

Conclusion. These data confirm the central role of local inflammation in the pathogenesis of PDR. The vitreous cytokine profile in PDR is a complex mixture of proinflammatory, proangiogenic, and regulatory signals. The results support the development of therapeutic strategies aimed not only at inhibiting angiogenesis (anti-VEGF therapy) but also at modulating the inflammatory component of the disease.

Keywords: proliferative diabetic retinopathy, vitreous body, cytokines, angiogenesis, inflammation.

References

1. Konovalova, K., Shishkin, M., Fayzrakhmanov, R., Saraeva, S., & Pavlovsky, O. (2025). The Role of Cytokines in the Pathogenesis of Proliferative Diabetic Retinopathy. Point of View. East–West, 12(2), 43–48. doi: 10.25276/2410-1257-2025-2-43-50.

2. Koskela UE, Kuusisto SM, Nissinen AE, Savolainen MJ, Liinamaa MJ. High vitreous concentration of IL-6 and IL-8, but not of adhesion molecules in relation to plasma concentrations in proliferative diabetic retinopathy. Ophthalmic Res. 2013;49(2):108-14

3. Taghavi Y, Hassanshahi G, Kounis NG, Koniari I, Khorramdelazad H. Monocyte chemoattractant protein-1 (MCP-1/CCL2) in diabetic retinopathy: latest evidence and clinical considerations. J Cell Commun Signal. 2019 Dec;13(4):451-462. doi: 10.1007/s12079-018-00500-8. Epub 2019 Jan 3. PMID: 30607767.

4. Mason RH, Minaker SA, Lahaie Luna G, Bapat P, Farahvash A, Garg A, Bhambra N, Muni RH. Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: a systematic review and meta-analysis. Eye (Lond). 2022 Jun 7. doi: 10.1038/s41433-022-02127-x.

5. Yoshida S, Kobayashi Y, Nakama T, Zhou Y, Ishikawa K, Arita R, Nakao S, Miyazaki M, Sassa Y, Oshima Y, Izuhara K, Kono T, Ishibashi T. Increased expression of M-CSF and IL-13 in vitreous of patients with proliferative diabetic retinopathy: implications for M2 macrophage-involving fibrovascular membrane formation. Br J Ophthalmol. 2015 May;99(5):629-34. doi: 10.1136/bjophthalmol-2014-305860.

6. Burgos R, Simó R, Audí L, Mateo C, Mesa J, García-Ramírez M, Carrascosa A. Vitreous levels of vascular endothelial growth factor are not influenced by its serum concentrations in diabetic retinopathy. Diabetologia. 1997 Sep;40(9):1107-9. doi: 10.1007/s001250050794.

7. Freyberger H, Bröcker M, Yakut H, Hammer J, Effert R, Schifferdecker E, Schatz H, Derwahl M. Increased levels of platelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy. Exp Clin Endocrinol Diabetes. 2000;108(2):106-9. doi: 10.1055/s-2000-5803. PMID: 10826517.

8. Loporchio DF, Tam EK, Cho J, Chung J, Jun GR, Xia W, Fiorello MG, Siegel NH, Ness S, Stein TD, Subramanian ML. Cytokine Levels in Human Vitreous in Proliferative Diabetic Retinopathy. Cells. 2021 Apr 30;10(5):1069. doi: 10.3390/cells10051069. PMID: 33946446; PMCID: PMC8147162.

9. Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology. 2003 Sep;110(9):1690-6. doi: 10.1016/S0161-6420(03)00568-2. PMID: 13129863.

10. Kuo, C.Y.J., Murphy, R., Rupenthal, I.D. et al. Correlation between the progression of diabetic retinopathy and inflammasome biomarkers in vitreous and serum – a systematic review. BMC Ophthalmol 22, 238 (2022). doi: 10.1186/s12886-022-02439-2

11. Demircan N, Safran BG, Soylu M, Ozcan AA, Sizmaz S. Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye (Lond). 2006 Dec;20(12):1366-9. doi: 10.1038/sj.eye.6702138. Epub 2005 Nov 11. PMID: 16284605.

12. Takeuchi M, Sato T, Sakurai Y, Taguchi M, Harimoto K, et al. (2017) Association between aqueous humor and vitreous fluid levels of Th17 cell-related cytokines in patients with proliferative diabetic retinopathy. PLOS ONE 12(5): e0178230. doi: 10.1371/journal.pone.0178230.

13. Zhou, Y., Yoshida, S., Kubo, Y. et al. Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy. Sci Rep 6, 28140 (2016). doi: 10.1038/srep28140

14. Petrachkov, D. V. The Effect of Intraoperative Use of Angiogenesis Inhibitors on the Results and Frequency of Complications in Surgical Treatment of Proliferative Diabetic Retinopathy / D. V. Petrachkov, V. M. Filippov, and S. Sh. Balkar // Vestnik Oftalmologii. – 2025. – Vol. 141, No. 2. – Pp. 44-50. – DOI 10.17116/oftalma202514102144.

For citation

Zenkin N.S., Petrachkov D.V., Baryshev K.V., Panova A.D. , Subbot A.M. The state of the cytokine profile of the vitreous body in proliferative diabetic retinopathy. Bulletin of Pirogov National Medical & Surgical Center. 2025;20(4,supplement):70-73. (In Russ.) https://doi.org/10.25881/20728255_2025_20_4_S1_70