Neuroprotective properties of Na+/H+-exchanger isoform-1 inhibitor in experimental POAG

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.9.10058

Abstract

Introduction: Worldwide glaucoma is the leading cause of irreversible vision loss. The processes associated with the loss of retinal ganglion cells are multifactorial and have much in common with neurodegenerative diseases. Therefore the search for means to prevent the death of retinal neurons is an important task of modern pharmacology.

Materials and Methods: The study was conducted on male Wistar rats. Glaucoma was modeled by injecting a 1% solution of hyaluronic acid into the anterior chamber of the eye. The IOP level was recorded on the 0th, 63rd and 73rd days of the experiment. The effectiveness of the drugs was evaluated based on the results of ophthalmoscopy, electroretinography, followed by the determination of gene expression.

Results and Discussion: In the group with RU-1355 correction, the fundus picture improved; the index in the group was 18.0% lower compared to the model. The introduction of the RU-1355 compound provided an increase in the a-wave amplitude by 18.1%, and b-wave amplitude by 39.0% relative to the group with pathology. The most pronounced effect was observed on the expression level of BDNF, Bcl-2, Caspase 3 and NF-κB p65, which indicates that the compound has the capacity to influence the slowdown of the apoptosis process through an increase in the neurotrophic factor and the anti-apoptotic factor Bcl-2.

Conclusion: RU-1355 has neuroprotective properties, which was expressed by a decrease in ophthalmoscopic manifestations, preservation of the b-wave amplitude of the electroretinogram and the influence on gene expression of factors involved in apoptosis and neuroprotection. Based on the pharmacological activity of the RU-1355 compound in relation to POAG, further study of its action against other retinal diseases is promising.

Graphical Abstract

Keywords:

intraocular pressure, retinal ganglion cells, glaucoma, neurodegeneration, ophthalmoscopy, retina, electroretinography

References

Baudouin C, Kolko M, Melik-Parsadaniantz S, Messmer EM (2021) Inflammation in glaucoma: from the back to the front of the eye, and beyond. Progress in Retinal and Eye Research 83: 100916. https://doi.org/10.1016/j.preteyeres.2020.100916 [PubMed]

Beykin G, Norcia AM, Srinivasan VJ, Dubra A, Goldberg JL (2021) Discovery and clinical translation of novel glaucoma biomarkers. Progress in Retinal and Eye Research 80: 100875. https://doi.org/10.1016/j.preteyeres.2020.100875 [PubMed] [PMC]

Boia R, Ruzafa N, Aires ID, Pereiro X, Ambrósio AF, Vecino E, Santiago AR (2020) Neuroprotective strategies for retinal ganglion cell degeneration: current status and challenges ahead. International Journal of Molecular Sciences 21(7): 2262. https://doi.org/10.3390/ijms21072262 [PubMed] [PMC]

Dolzhikov AA, Shevchenko OA, Pobeda AS, Peresypkina AA, Dolzhikova IN, Zhunusov NS, Lugovskoy SS (2020) Review of a new concept of glaucoma pathogenesis based on the glymphatic theory of cerebrospinal fluid circulation. Research Results in Pharmacology 6(3): 1–7. https://doi.org/10.3897/rrpharmacology.6.53634

Downs JC (2015) Optic nerve head biomechanics in aging and disease. Experimental Eye Research 133: 19–29. https://doi.org/10.1016/j.exer.2015.02.011 [PubMed] [PMC]

Fan J, Dawson TM, Dawson VL (2017) Cell death mechanisms of neurodegeneration. Advances in Neurobiology 15: 403–425. https://doi.org/10.1007/978-3-319-57193-5_16 [PubMed]

Kalatanova AV, Pobeda AS, Abasheva DA, Dolzhikov AA, Peresypkina AA, Pokrovskii MV (2021) Electroretinography in evaluation of neuroprotective effect in an experimental model of glaucoma. Bulletin of Ophthalmology [Vestnik Oftalmologii] 137(3): 86–92.https://doi.org/10.17116/oftalma202113703186 [PubMed] [in Russian]

Monteiro MC, Coleman MD, Hill EJ, Prediger RD, Maia CS (2017) Neuroprotection in neurodegenerative disease: from basic science to clinical applications. Oxidative Medicine and Cellular Longevity: 2949102. https://doi.org/10.1155/2017/2949102 [PubMed] [PMC]

Moreno MC, Marcos HJ, Oscar Croxatto J, Sande PH, Campanelli J, Jaliffa CO, Benozzi J, Rosenstein RE (2005) A new experimental model of glaucoma in rats through intracameral injections of hyaluronic acid. Experimental Eye Research 81(1): 71–80.https://doi.org/10.1016/j.exer.2005.01.008 [PubMed]

Naumenko LV, Taran AS, Sokolova EV, Govorova YuA, Ozerov AA (2021) Effect of quinazoline derivatives – Na+/H+ exchanger inhibitors on intraocular pressure. Bulletin of Medical Science [Byulleten' Medicinskoj Nauki] 3(23): 79–82. https://doi.org/10.31684/254184752021379 [in Russian]

Ovsyankina NV (2022) The effect of new 4,6-diphenylpyrimidine derivatives on the sodium-hydrogen exchange of rabbit platelets in vitro. Mechnikov Readings-2022: Materials of the 95thAll-Russian Scientific and Practical Student Conference with International Participation, Saint-Petersburg. Vol. Part II: 224–225. [in Russian]

Perfilova VN, Gurova NA, Popova TA, Vishnevskaja VV, Ozerov AA, Kustova MV, Ovsjankina NV (2019) Effect of NHE-1 inhibitors zoniporide and VMA-1321 on the level of lipid peroxidation products and enzymes of the antioxidant system in the heart mitochondria of animals with chronic heart failure. Bulletin of Volgograd State Medical University [Vestnik Volgogradskogo Gosudarstvennogo Meditsinskogo Universiteta] 3(71): 62–65. https://doi.org/10.19163/1994-9480-2019-3(71)-62-65 [in Russian]

Pitts KM, Neeson CE, Hall NE, Lin JB, Falah HK, Wang SL, Lo KT, Song CE, Margeta MA, Solá-Del Valle DA (2022) Neurodegeneration markers galectin-3 and apolipoprotein e are elevated in the aqueous humor of eyes with glaucoma. Translational Vision Science & Technology 1(11): 1. https://doi.org/10.1167/tvst.11.11.1 [PubMed] [PMС]

Pobeda AS, Kalatanova AV, Abashev DA, Dolzhikov AA, Solovev NV, Shchurovskaya KV, Chernyaeva SS, Kolesnik IM (2021) Study to elucidate the pharmacological activity of retinalamin in a rat model of ischemic retinopathy. Research Results in Pharmacology 7(2): 39–48. https://doi.org/10.3897/rrpharmacology.7.67390

Pobeda AS, Soloviev NV, Chernyaeva SS, Efimenko SV (2022) Changes in gene expression in the retina during intravitreal injection of NMQ4. Russian National Ophthalmological Forum 2: 432–433. [in Russian]

Pobeda AS, Soloviev NV, Pokrovskii MV, Skachilova SYa, Efimenko SV, Simakina EA, Bashuk VV, Proskurina OV, Dolzhikov AA, Nesterova NI (2023) The effect of new 3-hydroxypyridine derivatives on NMDA-induced retinal neurodegeneration. Experimental and Clinical Pharmacology 86(3): 11–16. https://doi.org/10.30906/0869-2092-2023-86-3-11-16 [in Russian]

Qu J, Wang D, Grosskreutz CL (2010) Mechanisms of retinal ganglion cell injury and defense in glaucoma. Experimental Eye Research 91(1): 48–53. https://doi.org/10.1016/j.exer.2011.07.014 [PubMed] [PMC]

Shchurovskaya KV, Pobeda AS, Pokrovskii MV, Solovev NV, Kulikovskaya VA, Peresypkina AA, Shutov VI, Puchenkova OA, Shabalin AA (2021) Protective effect of asialized erythropoietin in modelling of retinal ischemia-reperfusion. Journal of Research in Medical And Dental Science 9(8): 286–290.

Spasov A, Ozerov A, Vassiliev P, Kosolapov V, Gurova N, Kucheryavenko A, Naumenko L, Babkov D, Sirotenko V, Taran A, Litvinov R, Borisov A, Klochkov V, Merezhkina D, Miroshnikov M, Uskov G, Ovsyankina N (2021) Synthesis and multifaceted pharmacological activity of novel quinazoline NHE-1 inhibitors. Scientific Reports 11: 24380. https://doi.org/10.1038/s41598-021-03722-w [PubMed] [PMC]

Spasov AA, Muravyeva VYu, Gurova NA, Ovsyankina NV (2022) Neurotropic effects of sodium-hydrogen exchanger isoform 1 inhibitors. Medicinal Bulletin [Meditsinskii Vestnik] 23(1): 30–37. [in Russian]

Author Contribution

Anna S. Pobeda, Belgorod National Research University

PhD in Biological Sciences, Associate Professor of Department of Pharmacology and Clinical Pharmacology; e-mail: pobeda@bsu.edu.ru; ORCID IDhttps://orcid.org/0000-0002-0541-8946 . The author took part in conceptualization and direction development of the research, generation of key aims and objectives conducting experimental work, analysing the material, writing, and editing the text of the article.

Alexander A. Spasov, Volgograd State Medical University

Doctor Habil. of Medical Sciences, Full Professor, Member of the Russian Academy of Sciences, Head of the Department of Pharmacology and Bioinformatics; e-mail: aspasov@mail.ru; ORCID ID: https://orcid.org/0000-0002-7185-4826. The author consulted on the research idea, concept, and design of the study.

Olga N. Zhukovskaya , Research Institute of Physical and Organic Chemistry, Southern Federal University

PhD in Chemical Sciences, Researcher in the Laboratory of Organic Synthesis; e-mail: zhukowskaia.ol@yandex.ru; ORCID ID: https://orcid.org/0000-0003-0865-6656. The author took part in synthesis of the substances and consulted on the research idea.

Kristina V. Shchurovskaya , Regional State Budgetary Institution of Healthcare "Children's Regional Clinical Hospital"

MD, ophthalmologist; e-mail: kristinka-i@yandex.ru. The author took part in conducting experimental work and analysing the material.

Nikolai V. Solovev , OOO Diagnosticheskiy tsentr "Zreniye"

MD, ophthalmologist;  e-mail: morkovkapro@mail.ru. The author took part in conducting experimental work and analysing the material.

Valentina A. Kulikovskaya , Regional State Budgetary Institution of Healthcare "Belgorod Regional Clinical Hospital of St. Joasaph"

MD, ophthalmologist; e-mail: Valentina.kulikovskaya@gmail.com. The author took part in conducting experimental work and analysing the material.

Vladimir M. Pokrovsky , Belgorod State National Research University

Junior researcher of the Scientific Research Institute of Pharmacology of Living Systems; e-mail: vmpokrovsky@yandex.ru; ORCID ID: https://orcid.org/0000-0003-3138-2075. The author took part in the experimental work, analysis of the material and editing the manuscript.

Evgeny A. Patrakhanov , Belgorod State National Research University

Junior researcher of the Research Institute of Pharmacology of Living Systems; e-mail: pateval7@gmail.com; ORCID ID https://orcid.org/0000-0002-8415-4562. The author took part in the experimental work, analysis of the material, and editing the manuscript.

Anastasia V. Turpakova , Belgorod State National Research University

4th-year student at the Medical Institute; e-mail: 1516173@bsu.edu.ru. The author took part in conducting experimental work.

Anna I. Ustinova , Belgorod State National Research University

6th- year student at the Medical Institute; e-mail: 1303025@bsu.edu.ru. The author took part in conducting experimental work.

Downloads

Published

21-12-2023

How to Cite

Pobeda AS, Spasov AA, Zhukovskaya ON, Shchurovskaya KV, Solovev NV, Kulikovskaya VA, Pokrovsky VM, Patrakhanov EA, Turpakova AV, Ustinova AI (2023) Neuroprotective properties of Na+/H+-exchanger isoform-1 inhibitor in experimental POAG. Research Results in Pharmacology 9(4): 75–83. https://doi.org/10.18413/rrpharmacology.9.10058

Issue

Section

Experimental Pharmacology

Most read articles by the same author(s)

<< < 1 2