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The effect of intravitreally administered angiogenesis inhibitor on the concentration of angiotensin-converting enzyme in the blood serum and lacrimal fluid in patients with diabetic macular edema

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Abstract


BACKGROUND: Diabetic retinopathy (DR) is one of the more serious complications of diabetes and the main cause of blindness among working-age individuals. In recent years, information has emerged on the possible role of the renin-angiotensin system (RAS) in the pathogenesis of DR, and DR’s possible connection with the system of pro-angiogenic factors.

AIM: To study the impact of anti-angiogenic therapy on systemic and local concentrations of angiotensin-converting enzyme (ACE), a key component of RAS, for patients with diabetic macular edema (DME).

MATERIAL AND METHODS: The concentration of ACE in the lacrimal fluid and blood serum in 10 patients (20 eyes) with DME was determined before and after intravitreal injection (IVI) of ranibizumab. The comparison group consisted of 7 patients (14 eyes) with age-related macular degeneration (AMD). The control group consisted of 10 healthy individuals (20 eyes). All groups were comparable in age and sex. The concentration of ACE was determined by enzyme immunoassay. The main group was examined four times: before IVI of ranibizumab, and then one week, two weeks and one month after IVI of ranibizumab. The comparison group was examined before, and then one week after, IVI of ranibizumab.

RESULTS: In patients with DME, there was an initial 1.8-fold increase in the concentration of ACE in the lacrimal fluid of both eyes. A week after IVI of ranibizumab, the concentration of ACE in the lacrimal fluid began to decrease, reaching the control level after two weeks, and remaining there one month after IVI of ranibizumab. Initially, the concentration of ACE in the blood serum in patients with DME was 2.2 times lower than the control level. After IVI of ranibizumab there was an increase in the concentration of ACE in the blood serum, but by the end of the observation, the indicators continued to remain well below the control level. In patients with AMD, the initial concentration of ACE in the lacrimal fluids was not elevated; the concentration of ACE in the lacrimal fluids decreased 1.4 times one week after IVI of ranibizumab. The concentration of ACE in the blood serum of the patients with AMD was initially 25% lower than the control level, and essentially did not change after IVI of ranibizumab.

СONCLUSIONS: Changes in the concentration of ACE in patients with DME may be a new prognostic criterion for the development of DME for patients with diabetes. These changes in the concentration of ACE, in the context of antiangiogenic therapy, indicate an interaction between the renin-angiotensin and angiogenic systems. Similar changes that were observed after IVI of ranibizumab in patients with AMD confirm the mutual influence of these two systems.

The data presented in this study open up prospects for finding new pathways of pathogenic therapy for diabetic macular edema and diabetes.


Vladimir V. Neroev

Moscow Helmholtz Research Institute of Eye Diseases

Email: sekr@igb.ru
ORCID iD: 0000-0002-8480-0894
SPIN-code: 5214-4134

Russian Federation, 14/19 Sadovaya-Chernogryazskaya street, 105062, Moscow

MD, PhD, Professor

Natalia B. Chesnokova

Moscow Helmholtz Research Institute of Eye Diseases

Email: nchesnokova2012@yandex.ru
ORCID iD: 0000-0002-7856-8005
SPIN-code: 8705-7248

Russian Federation, 14/19 Sadovaya-Chernogryazskaya street, 105062, Moscow

MD, PhD, Professor

Tatiana D. Okhotsimskaya

Moscow Helmholtz Research Institute of Eye Diseases

Author for correspondence.
Email: tata123@inbox.ru
ORCID iD: 0000-0003-1121-4314
SPIN-code: 9917-7103

Russian Federation, 14/19 Sadovaya-Chernogryazskaya street, 105062, Moscow

MD, PhD

Marina V. Ryabina

Moscow Helmholtz Research Institute of Eye Diseases

Email: mryabina@yandex.ru
ORCID iD: 0000-0001-7961-8695
SPIN-code: 6928-5676

Russian Federation, 14/19 Sadovaya-Chernogryazskaya street, 105062, Moscow

MD, PhD

Victoria. A. Fadeeva

Moscow Helmholtz Research Institute of Eye Diseases

Email: vika.fadeeva.90@mail.ru
ORCID iD: 0000-0003-4460-2620
SPIN-code: 3305-2647

Russian Federation, 14/19 Sadovaya-Chernogryazskaya street, 105062, Moscow

MD

Tatiana А. Pavlenko

Moscow Helmholtz Research Institute of Eye Diseases

Email: tanya1975_@inbox.ru
ORCID iD: 0000-0001-8032-4248
SPIN-code: 7940-3050

Russian Federation, 14/19 Sadovaya-Chernogryazskaya street, 105062, Moscow

MD, PhD

Olga V. Beznos

Moscow Helmholtz Research Institute of Eye Diseases

Email: olval2011@mail.ru
ORCID iD: 0000-0001-7557-4955
SPIN-code: 7894-5162

Russian Federation, 14/19 Sadovaya-Chernogryazskaya street, 105062, Moscow

MD

  1. International Diabetes Federation. IDF diabetes atlas. 7th. Brussels: IDF; 2015.
  2. Solomon SD, Chew E, Duh EJ, et al. Diabetic Retinopathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017;40(3):412-418. doi: https://doi.org/10.2337/dc16-2641
  3. Бикбов М.М., Файзрахманов Р.Р., Зайнуллин Р.М. и др. Макулярный отек как проявление диабетической ретинопатии. // Сахарный диабет. – 2017. – Т. 20. – №4. – С. 263-269. [Bikbov MM, Fayzrakhmanov RR, Zaynullin RM, at al. Macular oedema as manifestation of diabetic retinopathy. Diabetes mellitus. 2017;20(4):263-269. (In Russ.)] doi: https://doi.org/10.14341/DM8328
  4. Danser AH, Derkx FH, Admiraal PJ, et al. Angiotensin levels in the eye. Invest Ophthalmol Vis Sci. 1994;35(3):1008-1018.
  5. Wagner J, Jan Danser AH, Derkx FH, et al. Demonstration of renin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular renin-angiotensin system. Br J Ophthalmol. 1996;80(2):159-163. doi: https://doi.org/10.1136/bjo.80.2.159.
  6. White AJ, Cheruvu SC, Sarris M, et al. Expression of classical components of the renin-angiotensin system in the human eye. J Renin Angiotensin Aldosterone Syst. 2015;16(1):59-66. doi: https://doi.org/10.1177/1470320314549791
  7. Nath M, Chandra P, Halder N, et al. Involvement of Renin-Angiotensin System in Retinopathy of Prematurity – A Possible Target for Therapeutic Intervention. PLoS One. 2016;11(12):e0168809. doi: https://doi.org/10.1371/journal.pone.0168809
  8. Kim JH, Kim JH, Yu YS, et al. Blockade of angiotensin II attenuates VEGF-mediated blood-retinal barrier breakdown in diabetic retinopathy. J Cereb Blood Flow Metab. 2009;29(3):621-628. doi: https://doi.org/10.1038/jcbfm.2008.154
  9. Haque R, Iuvone PM, He L, et al. Prorenin receptor (PRR)-mediated NADPH oxidase (Nox) signaling regulates VEGF synthesis under hyperglycemic condition in ARPE-19 cells. J Recept Signal Transduct Res. 2017;37(6):560-568. doi: https://doi.org/10.1080/10799893.2017.1369120
  10. Wang B, Wang F, Zhang Y, et al. Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2015;3(4):263-274. doi: https://doi.org/10.1016/s2213-8587(14)70256-6
  11. Behl T, Kotwani A. Potential of angiotensin II receptor blockers in the treatment of diabetic retinopathy. Life Sci. 2017;176:1-9. doi: https://doi.org/10.1016/j.lfs.2017.03.020
  12. Fogli S, Del Re M, Rofi E, et al. Clinical pharmacology of intravitreal anti-VEGF drugs. Eye (Lond). 2018;32(6):1010-1020. doi: https://doi.org/10.1038/s41433-018-0021-7
  13. Зуева М.В., Слепова О.С., Гундорова Р.А., и др. Классификация окуло-окулярных реакций при тяжелой механической травме глаза по данным электрофизиологических и иммунологических исследований. // Рефракционная хирургия и офтальмология. – 2007. – Т. 7. – №1. – С. 35-41. [Zueva MV, Slepova OS, Gundorova RA, et al. The classification of oculo-ocular reactions after severe mechanical ocular trauma by the data of electrophysiological and immunological examinations. Refraktsionnaya khirurgiya i oftal’mologiya. 2007;7(1):35-41. (In Russ.)]
  14. Ola MS, Alhomida AS, Ferrario CM, Ahmad S. Role of Tissue Renin-angiotensin System and the Chymase/angiotensin-( 1-12) Axis in the Pathogenesis of Diabetic Retinopathy. Curr Med Chem. 2017;24(28):3104-3114. doi: https://doi.org/10.2174/0929867324666170407141955
  15. Qian X, Lin L, Zong Y, et al. Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice. Graefes Arch Clin Exp Ophthalmol. 2018;256(3):525-534. doi: https://doi.org/10.1007/s00417-017-3866-8
  16. Choudhary R, Kapoor MS, Singh A, Bodakhe SH. Therapeutic targets of renin-angiotensin system in ocular disorders. J Curr Ophthalmol. 2017;29(1):7-16. doi: https://doi.org/10.1016/j.joco.2016.09.009
  17. Нероев В.В., Чеснокова Н.Б., Охоцимская Т.Д., и др. Активность ангиотензин-превращающего фермента в крови и слезе у пациентов с диабетической ретинопатией // Вестник офтальмологии. – 2006. – Т. 122. – №3. – С. 11-14. [Neroev VV, Chesnokova NB, Okhotsimskaia TD, at al. Activity of angiotensin-converting enzyme in the blood and tear of patients with diabetic retinopathy. Annals of ophtalmology. 2006;122(3):11-14 (In Russ.)]
  18. Danilov SM, Lunsdorf H, Akinbi HT, et al. Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding. Sci Rep. 2016;6:34913. doi: https://doi.org/10.1038/srep34913
  19. Campbell DJ. Neprilysin Inhibitors and Bradykinin. Front Med (Lausanne). 2018;5:257. doi: https://doi.org/10.3389/fmed.2018.00257

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Copyright (c) 2019 Neroev V.V., Chesnokova N.B., Okhotsimskaya T.D., Ryabina M.V., Fadeeva V.A., Pavlenko T.А., Beznos O.V.

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