Features of the aqueous humor proteome in patients with primary open-angle glaucoma and its changes during treatment with neuropeptides

Purpose of the work was to study aqueous humor (AH) proteome in patients with primary open-angle glaucoma (POAG) and evaluate its changes during treatment with neuropeptides.

Material and methods. AH samples were collected during surgery from 80 patients, divided into the main (n = 52, aged 75 (71,5; 78) yrs) and control groups (n = 28, aged 76 (74; 78) yrs). Subgroup 1 of the main group consisted of patients (n = 31) with developed and advanced stages of simple and pseudoexfoliative POAG. Subgroup 2 of the main group included patients (n = 21) with simple and pseudoexfoliative forms of POAG, who received a 10-day course of intramuscular injections of a complex of neuropeptides before surgery. The control group consisted of patients with age-related and complicated forms of cataract. In addition to routine and specialized ophthalmological examination, an analysis of the proteomic profile of the AH was performed using the Cytokine/ Chemokine/ Growth Factor Convenience 45-Plex Human Panel 1 multiplex panel (ThermoFisher scientific, USA).

Results. The study of 45 biomarkers revealed changes in 13 of them (28.9 %) in patients with POAG compared with the control group. In addition, statistically significant differences were obtained in 2 of these 13 cytokines (15.4 %) after a course of neuroprotective treatment.

Conclusion. The shifts in the cytokine system revealed as a result of proteomic mapping of the AH indicate their role in the implementation of systemic mechanisms of glaucoma development and progression as modulators of the chronic inflammatory component. The detected changes in the Eotaxin protein apparently reflect involutional shifts characteristic of patients with age-related changes in the retina. It is necessary to continue research to determine the risk factors for the development of POAG at the stage of preclinical changes, the development and implementation of an accessible method for early non-invasive diagnosis, as well as personalized therapy.

1. Baevskij R.M. Forecasting conditions on the verge of normality and pathology Moscow: Medicine. 1979 (In Russ.).

2. Nesterov A.P. Primary glaucoma. Moscow: Medicine. 1973 (In Russ.).

3. Weinreb RN, Friedman DS, Fetchtner RD, et al. Risk assessment in the management of patients with ocular hypertension. Am J Ophthalmol. 2004; 138 (3): 458–67. doi: 10.1016/j.ajo.2004.04.054

4. Onishchenko A.L., Kolbasko A.V., Isakov I.N., Shirina M.A. Study on causes of ophthalmologists’ inertia in glaucoma treatment. Russian Annals of Ophthalmology. 2013; 129 (6): 58–61 (In Russ.).

5. Movsisyan A.B., Kuroedov A.V., Arkharov M.A., et al. Epidemiological analysis primary open-angle glaucoma incidence and prevalence in Russia. Russian journal of clinical ophthalmology. 2022; 22 (1): 3–10 (In Russ.). doi: 10.32364/2311-7729-2022-22-1-3-10

6. Egorov E.A., Kuroyedov A.V., eds. Glaucoma. National Guidelines Moscow: GEOTAR-Media. 2023 (In Russ.).

7. Neroev V.V., Mikhaylova L.A., Malishevskaya T.N., et al. Glaucoma epidemiology in the Russian Federation. Russian ophthalmological journal. 2024; 17 (3): 7–12 (In Russ.). doi: 10.21516/2072-0076-2024-17-3-7-12

8. Fomin N.E., Kuroyedov A.V. Diagnostics of glaucoma before clinical manifestations. Clinical ophthalmology. 2020; 20 (3): 152–8 (In Russ.). doi: 10.32364/2311-7729-2020-20-3-152-158

9. Krylova A.A., Zakharchuk A.V., Krivosheina O.I., et al. Perspectives of proteomic analysis in ophthalmology. Russian journal of clinical ophthalmology. 2023; 23 (4): 213–8 (In Russ.). doi: 10.32364/2311-7729-2023-23-4-7

10. Fernández-Vega Cueto A, Álvarez L, García M, et al. Candidate glaucoma biomarkers: from proteins to metabolites, and the pitfalls to clinical applications. Biology (Basel). 2021; 10 (8): 763. doi: 10.3390/biology10080763

11. Iomdina EN, Tikhomirova NK, Bessmertny AM et al. Alterations in proteome of human sclera associated with primary open angle glaucoma involve proteins participating in regulation of the extracellular matrix. Molecular Vision. 2020; 26: 623–40. http://www.molvis.org/molvis/v26/623

12. Lee SH, Jung JH, Park TK, et al. Proteome alterations in the aqueous humor reflect structural and functional phenotypes in patients with advanced normal-tension glaucoma. Sci Rep. 2022; 12: 1221. https://doi.org/10.1038/s41598-022-05273-0

13. Hubens WHG, Mohren RJC, Liesenborghs I, et al. The aqueous humor proteome of primary open angle glaucoma: An extensive review. Exp Eye Res. 2020; 197: 108077. doi: 10.1016/j.exer.2020.108077

14. Samokhina N.I., Kochergin S.A., Alekseev I.B. Diagnostic value of proteomic analysis of the fluid of the anterior chamber of the eye in cataracts, primary open-angle glaucoma and pseudoexfoliative syndrome. Russian journal of clinical ophthalmology. 2017; 1: 13–7 (In Russ.). doi: 10.21689/2311-7729-2017-17-1-13-17

15. Samokhina N.I. Possibilities of using proteomic analysis in the diagnosis of ophthalmopathology (literature review). Point of view. East — West. 2015; 1: 260–2 (In Russ.).

16. Erichev V.P., Petrov S.Yu., Subbot A.M., et al. The role of cytokines in the pathogenesis of eye diseases. National journal of glaucoma. 2017; 16 (1): 87–101 (In Russ.).

17. Starikova D.I., Churnosov M.I. Modern concepts of the molecular basis of etiopathogenesis of primary open-angle glaucoma. Fyodorov journal of ophthalmic surgery. 2017; 3: 80–3 (In Russ.).

18. Senile cataract. Clinical recommendations. URL https://cr.minzdrav.gov.ru/view-cr/284_2 (access date: 05/01/2025) (In Russ.).

19. Mo FM, Proia AD, Johnson WH, et al. Interferon γ–Inducible Protein-10 (IP-10) and Eotaxin as biomarkers in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2010; 51: 4226–36. doi: 10.1167/iovs.09-3910

20. Liu B, Chen H, Johns TG, Neufeld AH. Epidermal growth factor receptor activation: an upstream signal for transition of quiescent astrocytes into reactive astrocytes after neural injury. J Neurosci. 2006; 26 (28): 7532–40. doi: 10.1523/JNEUROSCI.1004-06.2006

21. Hu DN, Ritch R. Hepatocyte growth factor is increased in the aqueous humor of glaucomatous eyes. J Glaucoma. 2001; 10 (3): 152–7. doi: 10.1097/00061198-200106000-00002

22. Biletskaya V.A., Lipatov D.V., Frolov M.A., et al. Investigation of biomarkers in the moisture of the anterior chamber of the eye and vitreous body in patients with neovascular glaucoma and diabetes mellitus. National journal of Glaucoma. 2022; 21 (1): 15–21 (In Russ.). doi: 10.53432/2078-4104-2022-21-1-15-21

23. Spraque AH, Khalil RA. Inflammatory cytokines in vascular dysfunc- tion and vascular disease. Biochem Pharmacol. 2009; 78 (6): 539–52. doi.org/10.1016/j.bcp.2009.04.029

24. Chono I, Miyazaki D, Miyake H, et al. High interleukin-8 level in aqueous humor is associated with poor prognosis in eyes with open angle glaucoma and neovascular glaucoma. Sci Rep. 2018; 8: 14533. doi: 10.1038/s41598-018-32725-3

25. Zhou X, Li F, Kong L, Tomita H, et al. Involvement of inflammation, degradation, and apoptosis in a mouse model of glaucoma. J Biol Chem. 2005; 280 (35): 31240–8. doi: 10.1074/jbc.M502641200

26. Dufour JH, Dziejman M, Liu MT, et al. IFN-gamma-inducible protein 10 (IP10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol. 2002; 168 (7): 3195-204.

27. Lv J, Gao R, Wang Y, et al. Protective effect of leukemia inhibitory factor on the retinal injury induced by acute ocular hypertension in rats. Exp Ther Med. 2022; 25 (1): 19. doi: 10.3892/etm.2022.11717

28. Zhang Y, Zhao G. Association between monocyte chemotactic protein 1 variants and age-related macular degeneration onset among Chinese people. Med Sci Monit. 2020;26: e921584. doi: 10.12659/MSM.921584

29. Tamhane M, Cabrera-Ghayouri S, Abelian G, Viswanath V. Review of biomarkers in ocular matrices: Challenges and opportunities. Pharm Res. 2019; 36 (3): 40. doi: 10.1007/s11095-019-2569-8

30. Marquez-Curtis LA, Janowska-Wieczorek A. Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 axis. Biomed Res Int. 2013; 2013: 561098. doi: 10.1155/2013/561098

31. Johnson TV, Bull ND, Martin KR. Stem cell therapy for glaucoma: possibilities and practicalities. Expert Rev Ophthalmol. 2011; 6 (2): 165–74. doi: 10.1586/eop.11.3