Aqueous Humor Levels of Cytokines and Growth Factors in Patients with Congenital Aniridia

Purpose. To study the concentration of cytokines and growth factors in the aqueous humor of patients with congenital aniridia.

Patients and methods. The study comprised 10 patients (10 eyes) with congenital aniridia and 10 patients (10 eyes) with agerelated cataract. Aqueous humor was collected at the beginning of routine cataract surgery before the primary incision was created. A concentration of 27 cytokines and the transforming growth factor-β2 (TGF- β2) was determined using a Bio-Plex Pro™ Human Cytokine 27-plex Assay and Bio-Plex Pro™ and TGFβ 3-plex Assay kit by flow-through fluorometry on a Bio-Rad MAGPIX (Luminex Corp. Austin). Intergroup comparisons were conducted using the Mann-Whitney U test.

Results. A comparative analysis showed a statistically significant increase in the concentration of IL-7 (p = 0.004), IL-15 (p = 0.008) and a decrease in the content of IL-9 (p = 0.008), IL-10 (p = 0.034) and GM-CSF (p = 0.045) in patients with congenital aniridia compared with the age-related cataract group. Inflammatory mediators (IL-1β, IL-6, IL-8, IL-12, IL-17A, MCP-1) and vascular endothelial growth factor (VEGF) in the aniridia group did not statistically differ from the comparison group.

Conclusion. Statistically significant difference was detected in IL-7, IL-9, IL-10, IL-15, GM-CSF concentrations in the aqueous humor in patients with congenital aniridia when comparing to non aniridic patients with age-related cataract. The other cytokines with proinflammatory, angiogenic and profibrotic properties did not significantly differ from the comparison group. 

1. Brauner S.C., Walton D.S., Chen T.C. Aniridia. Int Ophthalmol Clin. 2008;48(2):79–85.

2. Hingorani M., Hanson I., van Heyningen V. Aniridia. Eur J Hum Genet. 2012;20(10):1011–1017. DOI: 10.1038/ejhg.2012.100

3. Tsai J.H., Freeman J.M., Chan C.C., Schwartz G.S., Derby E.A., Petersen M.R., Holland E.J. A progressive anterior fibrosis syndrome in patients with postsurgical congenital aniridia. Am J Ophthalmol. 2005;140(6):1075–1079.

4. Wang Y., Riemann C.D., Duncan M.K. Dysregulation of canonical Wnt signaling may result in aniridia fibrosis syndrome (AFS). Invest Ophthalmol Vis Sci. 2017;58(8):2043–2043.

5. Edén U., Riise R., Tornqvist K. Corneal involvement in aniridia. Cornea. 2010;29(10):1096–1102. DOI: 10.1097/ICO.0b013e3181d20493

6. Wang Y., Riemann С.D., Duncan М.К. Molecular mechanisms of aniridia fibrosis syndrome (AFS). Invest Ophthalmol Vis Sci. 2015;56(7):897.

7. Zandi S., Tappeiner C., Pfister I.B., Despont A., Rieben R., Garweg J.G. Vitreal cytokine profile differences between eyes with epiretinal membranes or macular holes. Invest Ophthalmol Vis Sci. 2016;57:6320–6326. DOI: 10.1167/iovs.16‑20657

8. Friedlander M. Fibrosis and diseases of the eye. J Clin Invest. 2007;117:576–586.

9. Yu‑Wai‑Man C., Khaw P.T. Personalized medicine in ocular fibrosis: myth or future biomarkers. Adv Wound Care. 2016;5:390–402. DOI: 10.1089/wound.2015.0677

10. de Iongh R.U., Wederell E., Lovicu F.J., McAvoy J.W. Transforming growth factor‑beta‑induced epithelial‑mesenchymal transition in the lens: a model for cataract formation. Cells Tissues Organs. 2005;179:43–55.

11. Saika S. TGF‑beta pathobiology in the eye. Lab Invest. 2006;86:106–115.

12. Wang K., Read A.T., Sulchek T., Ethier C.R. Trabecular meshwork stiffness in glaucoma. Exp Eye Res. 2017;158:3–12. DOI: 10.1016/j.exer.2016.07.011

13. Braunger B.M., Fuchshofer R., Tamm E.R. The aqueous humor outflow pathways in glaucoma: A unifying concept of disease mechanisms and causative treatment. Eur J Pharm Biopharm. 2015;95:173–181. DOI: 10.1016/j.ejpb.2015.04.029

14. Chernykh V.V., Konenkov V.I., Orlov N.B., Ermakova O.V., Khodzhaev N.S., Trunov A.N. Features of the content of transforming growth factors — beta 1, 2, 3 (TGF‑β1, TGF‑β2, TGF‑β3) in intraocular fluid in primary open‑angle glaucoma. Fyodorov Journal of Ophthalmic Surgery = Ophthal'mochirurgia. 2019;2:13–17 (In Russ.). DOI: 10.25276/0235‑4160‑2019‑2‑13‑17

15. Iolyeva M., Aebischer D., Proulx S.T., Willrodt A.H., Ecoiffier T., Häner S., Bouchaud G., Krieg C., Onder L., Ludewig B., Santambrogio L., Boyman O., Chen L., Finke D., Halin C. Interleukin‑7 is produced by afferent lymphatic vessels and supports lymphatic drainage. Blood. 2013;122(13):P. 2271–2281. DOI: 10.1182/blood‑2013‑01‑478073

16. Chernykh V.V., Konenkov V.I., Ermakova O.V., Orlov N.B., Obukhova O.O., Eremina A.V., Trunov A.N. Сontent of cytokines and growth factors in the intraocular fluid of patients with primary open‑angle glaucoma. Bulletin of Siberian Medicine = Bull'eten sibirskoy medicini. 2019;18(1):257–265 (In Russ.). DOI: 10.20538/1682‑0363‑2019‑1‑257–265

17. Chernykh V.V., Borodin Y.I., Bgatova N.P., Trunov A.N., Khodjayev N.S., Druzhinin I.B., Eremina A.V., Pozhidaeva A.A., Konenkov V.I. The role of the lymphatic system in the uveoscleral outflow of aqueous humor. Fyodorov Journal of Ophthalmic Surgery = Ophthal'mochirurgia. 2015;2:74–79 (In Russ.).

18. Ma A., Koka R., Burkett P. Diverse functions of IL‑2, IL‑15, and IL‑7 in lymphoid homeostasis. Annu Rev Immunol. 2006;24(1):657–679.

19. Trunov A.N., Chernych D.V., Eremina A.V., Chernych V.V. Cytokines and growth factors in the pathogenesis of proliferative diabetic retinopathy. Fyodorov Journal of Ophthalmic Surgery = Ophthal'mochirurgia. 2017;1:93–97 (In Russ.).