IMMUNOCORRECTIVE EFFECTS OF TRICOR FENOFIBRATE IN THE TREATMENT OF THE EARLY AND INTERMEDIATE STAGES OF AGE-RELATED MACULAR DEGENERATION



Cite item

Full Text

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment, blindness and disability in the elderly. Treatment of end-stage AMD is extremely limited and requires invasive interventions. Currently, there is an active search for remedies aimed at preventing the degenerative process in the retina in the early stages of the disease. AMD is a multifactorial pathology, has common mechanisms with diseases associated with aging, metabolic shifts and hemodynamic disorders. The study of the effects of drugs already used to correct these disorders in the general clinic may also be of interest to ophthalmologists. The aim of the work was to study the dynamics of inflammatory markers of activation of the vascular endothelium and cytokines of the immune response in the tear fluid (TF) of patients with initial and intermediate stages of AMD against the background of the use of Tricor fenofibrate. 65 people were examined, divided into three groups according to the AREDS classification: group I - 20 people with early AMD (AREDS2), group II - 16 patients with intermediate AMD (AREDS3), 29 healthy elderly people without ophthalmopathology entered the age control group (AREDS1- risk group). Patients of groups I and II received Tricor at a dose of 145 mg once a day for 9 months. Tear fluid (TF) was taken twice: before and immediately after the completion of the course of treatment. The determination of sICAM-1, sVCAM-1, sE-, sP-selectin and MCP-1/CCL2 in CS was performed by flow cytometry using a self-constructed multiplex panel from compatible simplex test kits Human FlowCytomixTM Simplex (Bender MedSystem GmbH, Germany); IL-1ß, IL-2 IL-6 TNFa was determined within the framework of the Human Flow CytomixTM 15 Flex system (Bender MedSystem GmbH, Germany). Data processing was performed in the FlowCytomix Pro v 6.0 package (Bender Med Systems GmbH, Germany). According to the results of the study, a significant effect of Tricor fenofibrate was found on the initially high levels of local production of IL-1β, IL-2, IL-6, MCP-1/CCL2 and sICAM-1 in the AREDS2 group, which indicated a direct anti-inflammatory, vasoprotective effect in the treatment of the initial stage of AMD; a similar effect of the drug, but less pronounced, noted in the AREDS3 group. The ophthalmological examination data also indicated stabilization of visual functions and the clinical picture of the fundus, improvement of intraocular blood circulation in patients of the main groups. Thus, the use of Tricor can help prevent the degenerative process in the retina in the early stages of AMD development.

About the authors

Наталья Балацкая

Helmholtz National Medical Research Center of Eye Diseases

Email: balnat07@rambler.ru
ORCID iD: 0000-0001-8007-6643

105062, Moscow, Russian Federation, Sadovaya-Chernogryazskaya str., 14/19.

Russian Federation, 105062, Moscow, Russian Federation, Sadovaya-Chernogryazskaya str., 14/19.

Irina Gennadievna Kulikova

Helmholtz National Medical Research Center of Eye Diseases

Author for correspondence.
Email: ig-kulikova@yandex.ru

Biologist of the Department of Immunology and Virology of the Helmholtz National Medical Research Center of Eye Diseases, 

Russian Federation, 105062, Moscow, Russian Federation, Sadovaya-Chernogryazskaya str., 14/19.

Ekaterina Alexandrovna Eremeeva

Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia

Email: balnat07@rambler.ru

PhD (Medicine), Eye Physician, Outpatient Department for Adults, Helmholtz Research Institute for Ocular Diseases

Russian Federation, 105062, Moscow, Russian Federation, Sadovaya-Chernogryazskaya str., 14/19.

Alexander Evgenievich Andryushin

Helmholtz National Medical Research Center of Eye Diseases

Email: gradmalexander@gmail.ru

Researcher of the Department of Immunology and Virology of the Helmholtz National Medical Research Center of Eye Diseases

Russian Federation, 105062, Moscow, Russian Federation, Sadovaya-Chernogryazskaya str., 14/19.

References

  1. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high- dose supplementation with vitamins C and E, betacarotene, and zinc for age-related macular degeneration and vision loss: AREDS. Arch. Ophthalmol., 2001, Vol. 119, pp. 1417-1436. doi:0.1001/archopht.119.10.1417.
  2. Chakravarthy U., Wong T.Y., Fletcher A., Piault E., Evans C., Zlateva G., Buggage R., Pleil A., Mitchell P. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmology, 2010, Vol. 10, no. 31. doi: 10.1186/1471-2415-10-31.
  3. Chen Q., Jiang N., Zhang Y., Ye S., Liang X., Wang X., Lin X., Zong R., Chen H., Liu Z. Fenofibrate Inhibits Subretinal Fibrosis Through Suppressing TGF-β-Smad2/3 signaling and Wnt signaling in Neovascular Age-Related Macular Degeneration. Front Pharmacol., 2020, Vol.11, P. 580884. doi: 10.3389/fphar.2020.580884.
  4. Dunbar H.M.P., Behning С., Abdirahman А., Higgins В.Е., Binns А.М., Terheyden J.H., Zakaria N., Poor S., Finger R. P., Leal S., Holz F. G, Schmid M., Crabb D.P., Rubin G. S., Luhmann U.F.O. Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration: A MACUSTAR Study Report. JAMA Ophthalmol., 2022, Vol.140, no8, pp.780–789. doi: 10.1001/jamaophthalmol.2022.2113.
  5. Grabacka M., Pierzchalska M., Płonka P.M., Pierzchalski P. The Role of PPAR Alpha in the Modulation of Innate Immunity. Int J Mol Sci., 2021, Vol. 22(19), P.10545. doi: 10.3390/ijms221910545.
  6. Grimes K. R., Aloney A., Skondra D., Chhablani J. Effects of systemic drugs on the development and progression of age-related macular degeneration. Surv. Ophthalmol., 2023, Vol.68, no 3, pp.332-346. doi: 10.1016/j.survophthal.2023.01.007.
  7. Jin L., Hua H., Ji Y., Jia Z., Peng M., Huang S. Anti-inflammatory role of fenofibrate in treating diseases. Biomol Biomed., 2023, Vol.23, no 3, pp. 376-391. doi: 10.17305/bb.2022.8534.
  8. Lim L.S., Mitchell P., Seddon J.M., Holz F.G., Wong T.Y. Age-related macular degeneration. Lancet, 2012, Vol.379, no 9827, pp.1728-1738. doi: 10.1016/S0140-6736(12)60282-7.
  9. Moran E., Ding L., Wang Z., Cheng R., Chen Q., Moore R., et al. Protective and antioxidant effects of PPARα in the ischemic retina // Invest. Ophthalmol. Vis. Sci., 2014, Vol.55, pp. 4568–4576. doi: 10.1167/iovs.13-13127
  10. Rosa J. G. S., Disner G.R., Pinto F. J., Lima C., Lopes-Ferreira M. Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives. Int. J. Mol. Sci., 2023, Vol.24, no17, P.13079. doi: 10.3390/ijms241713079
  11. Roubeix C., Sahel J.A., Guillonneau X., Delarasse C., Sennlaub F. [On the inflammatory origins of AMD]. Med Sci (Paris), 2020, Vol. 36, no10, pp.886-892. doi: 10.1051/medsci/2020159
  12. Sacks F. M. After the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: implications for fenofibrate. Am J Cardiol., 2008, Vol.102, no12A, pp.34L-40L. doi: 10.1016/j.amjcard.2008.09.073.
  13. Simo R., Hernandez С. Fenofibrate for diabetic retinopathy.Lancet, 2007, Vol. 70, no 9600, pp.1667-1668. doi: 10.1016/S0140-6736(07)61608-0.
  14. The ACCORD Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med., 2010, Vol. 363, no3, pp. 233-244. doi: 10.1056/NEJMoa1001288.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) Балацкая Н., Kulikova I.G., Eremeeva E.A., Andryushin A.E.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № 77 - 11525 от 04.01.2002.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies