THE ROLE OF ENDOTHELIN-1, HIF1α, HIF2α IN RETINAL VEIN OCCLUSION

The problem of development and course of retinal venous occlusions (RVO) is relevant for today. The etiology of development of the RVO is multifaceted, and has not been fully studied. One of the main reasons for the decline in vision is the development of macular edema. The main problem in the treatment of macular edema is the difficulty in predicting increased visual acuity when disease is combined with retinal ischemia. One of the risk factors for the development of ischemia is endothelial dysfunction, whose important markers are endothelin-1 and hypoxia-inducible factors (HIF1α, HIF2α). Aim of the study was to evaluate the effect of the systemic level of endothelin-1 and hypoxia factors on the course of retinal venous occlusions. Material and methods. Content of the main markers of endothelial dysfunction (endothelin-1, HIF1α, HIF2α) was measured in 137 patients with RVO, among them 59 patients with central retinal vein occlusion and 78 - with central retinal vein branch occlusion. The average age of the patients was 73.35 ± 7.6 years. The level of markers of endothelial dysfunction was determined in serum by ELISA. Results and discussion. A statistically significant increase in endothelin-1 content in patients with optic nerve edema ( p = 0.018) was found. There were no statistically significant data on the effect on the course of the RVO of hypoxia factors HIF1 α and HIF2 α. Conclusion. Assessment of main markers indices of endothelial dysfunction can be used for understanding the etiology of RVO development and the correct tactics of the patients’ treatment forming.

HIF2ɑ, retinal vein occlusions, macular edema, endothelial dysfunction, Endothelin-1 (ET-1), HIF1α, HIF2 α

1. Bradshaw S.E., Gala S., Nanavaty M., Shah A., Mwamburi M., Kefalas P. Systematic literature review of treatments for management of complications of ischemic central retinal vein occlusion // BMC Ophthalmol. 2016. 16. 104.

2. Cheung N., Klein R., Wang J.J., Cotch M.F., Islam A.F., Klein B.E., Cushman M., Wong T.Y. Traditional and novel cardiovascular risk factors for retinal vein occlusion: the multiethnic study of atherosclerosis // Invest. Ophthalmol. Vis. Sci. 2008. 49. (10). 4297-4302.

3. Cugati S., Jie J.W., Rochtchina E., Mitchell P. Ten-year incidence of retinal vein occlusion in an older population: the blue mountains eye study // Arch. Ophthalmol. 2006. 124. (5). 726-732.

4. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor // Endocr. Rev. 1997. 18. 4-25.

5. Kida T., Flammer J., Oku H., Morishita S., Fukumoto M., Suzuki H., Konieczka K., Ikeda T. Suppressed endothelin-1 by anti-VEGF therapy is important for patients with BRVO-related macular edema to improve their vision // EPMA J. 2016. 7. (1). 18.

6. Kida T., Morishita S., Kakurai K., Suzuki H., Oku H., Ikeda T. Treatment of systemic hypertension is important for improvement of macular edema associated with retinal vein occlusion // Clin. Ophthalmol. 2014. 8. 955-958.

7. Marti H.H., Risau W. Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors // Proc. Natl. Acad. Sci. USA. 1998. 95. 15809-15814.

8. Matsuura A., Yamochi W., Hirata K.-I., Kawashima S., Yokoyama M. Stimulatory interaction between vascular endothelial growth factor and endothelin-1 on each gene expression // Hypertension. 1998. 32. (1). 89-95.

9. McIntosh R.L., Rogers S.L., Lim L., Cheung N., Wang J.J., Mitchell P., Kowalski J.W., Nguyen H.P., Wong T.Y. Natural history of central retinal vein occlusion: an evidence-based systematic review // Ophthalmology. 2010. 117. (6). 1113.e15-1123.e15.

10. Monacci W.T., Merrill M.J., Oldfield E.H. Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues // Am. J. Physiol. 1993. 264. C995-C1002.

11. Ozkaya A., Alkin Z., Yesilkaya C. Ranibizumab in macular edema secondary to retinal vein occlusion in a real life practice: a retrospective case series // Beyoglu Eye J. 2016. 1. 5-9.

12. Rogers S., McIntosh R.L., Cheung N., Lim L., Wang J.J., Mitchell P., Kowalski J.W., Nguyen H., Wong T.Y. The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia // Ophthalmology. 2010. 117. (2). 13-319 e311.

13. Salvatore S., Vingolo E.M. Endothelin-1 role in human eye: a review // J. Ophthalmol. 2010. 2010. 354645.

14. Stangos A.N., Petropoulos I.K., Pournaras J.A., Mendrinos E., Pournaras C.J. The vasodilatory effect of juxta-arteriolar microinjection of endothelin A receptor inhibitor in healthy and acute branch retinal vein occlusion minipig retinas // Invest. Ophthalmol. Vis. Sci. 2010. 51. (4). 2185-2190.

15. Wang G.L, Jiang B.-H., Rue E.A., Semenza G.L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension // Proc. Natl. Acad. Sci. USA. 1995. 92. 5510-5514.