Skip to main content
Log in

Mitochondrial Antioxidant SkQ1 Improves Hypothermic Preservation of the Cornea

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Diseases of the cornea are a frequent cause of blindness worldwide. Keratoplasty is an efficient method for treating severely damaged cornea. The functional competence of corneal endothelial cells is crucial for successful grafting, which requires improving the media for the hypothermic cornea preservation, as well as developing the methods for the evaluation of the corneal functional properties. The transport of water and ions by the corneal endothelium is important for the viability and optic properties of the cornea. We studied the impact of SkQ1 on the equilibrium sodium concentration in the endothelial cells after hypothermic preservation of pig cornea at 4C for 1, 5, and 10 days in standard Eusol-C solution. The intracellular sodium concentration in the endothelial cells was assayed using the fluorescent dye Sodium Green; the images were analyzed with the custom-designed CytoDynamics computer program. The concentrations of sodium in the pig corneal endothelium significantly increased after 10 days of hypothermic preservation, while addition of 1.0 nM SkQ1 to the preservation medium decreased the equilibrium concentration of intracellular sodium (at 37C). After 10 days of hypothermic preservation, the permeability of the plasma membrane for sodium decreased in the control cells, but not in the cells preserved in the presence of 1 nM SkQ1. Therefore, SkQ1 increased the ability of endothelial cells to restore the intracellular sodium concentration, which makes SkQ1 a promising agent for facilitating retention of the functional competence of endothelial cells during cold preservation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

Abbreviations

AOI:

area of interest

[Na+]I :

intracellular sodium ion concentration

SkQ1:

10-(6′-plastoquinonyl) decyltriphenylphosphonium

References

  1. Maghsoudlou, P., Sood, G., and Akhondi, H. (2020) Cornea transplantation, in StatPearls [Internet], StatPearlsPublishing, Treasure Island (FL).

  2. Bourne, W. M. (1998) Clinical estimation of corneal endothelial pump function, Trans. Am. Ophthalmol. Soc., 96, 229-239.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Riley, M. V., Winkler, B. S., and Starnes, C. A. (1998) Regulation of corneal endothelial barrier function by adenosine, cyclic AMP, and protein kinases, Invest. Ophthalmol. Vis. Sci., 39, 2076.

    CAS  PubMed  Google Scholar 

  4. Bonanno, J. A. (2012) Molecular mechanisms underlying the corneal endothelial pump, Exp. Eye Res., 95, 2-7, https://doi.org/10.1016/j.exer.2011.06.004.

    Article  CAS  PubMed  Google Scholar 

  5. Schmedt, T., Silva, M. M., Ziaei, A., and Jurkunas, U. (2012) Molecular bases of corneal endothelial dystrophies, Exp. Eye Res., 95, 24-34, https://doi.org/10.1016/j.exer.2011.08.002.

    Article  CAS  PubMed  Google Scholar 

  6. Kuang, K., Li, Y., Yiming, M., Sánchez, J. M., Iserovich, P., et al. (2004) Intracellular [Na+], Na+ pathways, and fluid transport in cultured bovine corneal endothelial cells, Exp. Eye. Res., 79, 93-103, https://doi.org/10.1016/j.exer.2004.02.014.

    Article  CAS  PubMed  Google Scholar 

  7. Riley, M., Winkler, B., Czajkowski, C., and Peters, M. (1995) The roles of bicarbonate and CO2 in transendothelial fluid movement and control of corneal thickness, Invest. Ophthalmol. Vis. Sci., 36, 103-112.

    CAS  PubMed  Google Scholar 

  8. Bonanno, J. A. (2003) Identity and regulation of ion transport mechanisms in the corneal endothelium, Prog. Retin Eye Res., 22, 69-94, https://doi.org/10.1016/s1350-9462(02)00059-9.

    Article  CAS  PubMed  Google Scholar 

  9. Bonanno, J. A., Guan, Y., Jelamskii, S., and Kang, X. J. (1999) Apical and basolateral CO2-HCO3- permeability in cultured bovine corneal endothelial cells, Am. J. Physiol., 277, C545-C553, https://doi.org/10.1152/ajpcell.1999.277.3.C545.

    Article  CAS  PubMed  Google Scholar 

  10. Baturina, G. S., Pal’chikova, I. G., Konev, A. A., Smirnov, E. S., Katkova, L. E., et al. (2018) Examining effects of hypothermic conservation on sodium level in corneal graft endothelial cells [in Russian], Vavilovskiy Zhurnal Genetiki i Selektsii, 22, 433-437, https://doi.org/10.18699/VJ18.379.

    Article  Google Scholar 

  11. Baturina, G. S., Katkova, L. E., Pal’chikova, I. G., Solenov, E. I., and Iskakov, I. A. (2019) New approaches to examining functional activity of endothelial cells in corneal preparations [in Russian], Sovremennye Tekhnologii v Oftal'mologii, 5, 262-265, https://doi.org/10.25276/2312-4911-2019-5-262-265.

    Article  Google Scholar 

  12. Wei, Y., Troger, A., Spahiu, V., Perekhvatova, N., et al. (2019) The role of SKQ1 (Visomitin) in inflammation and wound healing of the ocular surface, Ophthalmol. Ther., 8, 63-73, https://doi.org/10.1007/s40123-018-0158-2.

    Article  PubMed  Google Scholar 

  13. Brzheskiy, V. V., Efimova, E. L., Vorontsova, T. N., Alekseev, V. N., gusarevich, O. G., et al. (2015) Results of a multicenter, randomized, double-masked, placebo-controlled clinical study of the efficacy and safety of Visomitin eye drops in patients with dry eye syndrome, Adv. Ther., 32, 1263-1279, https://doi.org/10.1007/s12325-015-0273-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Silachev, D. N., Plotnikov, E. Y., Pevzner, I. B., Zorova, L. D., Balakireva, A. V., et al. (2018) Neuroprotective effects of mitochondria-targeted plastoquinone in a rat model of neonatal hypoxic-ischemic brain injury, Molecules, 23, 1871, https://doi.org/10.3390/molecules23081871.

    Article  CAS  PubMed Central  Google Scholar 

  15. Solenov, E. I. (2008) Cell volume and sodium content in rat kidney collecting duct principal cells during hypotonic shock, J. Biophys., 2008, 420963, https://doi.org/10.1155/2008/420963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ilyaskin, A. V., Karpov, D. I., Medvedev, D. A., Ershov, A. P., Baturina, G. S., et al. (2014) Quantitative estimation of transmembrane ion transport in rat renal collecting duct principal cells, Gen. Physiol. Biophys., 33, 13-28, https://doi.org/10.4149/gpb_2013063.

    Article  CAS  PubMed  Google Scholar 

  17. Ilyackin, A. V., Batupina, G. C., Medvedev, D. A., Epshov, A. P., Colenov, E. I. (2011) Examining reaction of renal collecting duct main cells to hypotonic shock. Experiment and mathematical modeling [in Russian], Biofizika, 56, 550-560, https://doi.org/10.1134/S0006350911030092.

    Article  Google Scholar 

  18. Palchikova, I. G., Smirnov, E. S., and Konev, A. A. (2017) Analyses of DNA image cytometry uncertainty caused by diffractive blurring, Appl. Mech. Mater., 870, 369-374, https://doi.org/10.4028/www.scientific.net/AMM.870.369.

    Article  Google Scholar 

  19. Winslow, J. L., Cooper, R. L., and Atwood, H. L. (2002) Intracellular ionic concentration by calibration from fluorescence indicator emission spectra, its relationship to the K(d), F(min), F(max) formula, and use with Na-Green for presynaptic sodium, J. Neurosci. Methods., 118, 163-175, https://doi.org/10.1016/s0165-0270(02)00100-0.

    Article  PubMed  Google Scholar 

  20. Maycock, N. J., and Marshall, J. (2014) Genomics of corneal wound healing: a review of the literature, Acta Ophthalmol., 92, e170-e184, https://doi.org/10.1111/aos.12227.

    Article  PubMed  Google Scholar 

  21. Edelhauser, H. F. (2000) The resiliency of the corneal endothelium to refractive and intraocular surgery, Cornea, 19, 263–273, https://doi.org/10.1097/00003226-200005000-00002.

    Article  Google Scholar 

  22. Joyce, N. C. (2003) Proliferative capacity of the corneal endothelium, Prog. Retin. Eye Res., 22, 359-389, https://doi.org/10.1016/s1350-9462(02)00065-4.

    Article  CAS  PubMed  Google Scholar 

  23. Vianna, L. M., Li, H. D., Holiman, J. D., Stoeger, C., Belfort, R. Jr., and Jun, A. S. (2016) Characterization of cryopreserved primary human corneal endothelial cells cultured in human serum-supplemented media, Arq. Bras. Oftalmol., 79, 37-41, https://doi.org/10.5935/0004-2749.20160011.

    Article  PubMed  Google Scholar 

  24. Ptushenko, V. V., Solovchenko, A. E., Bychkov, A. Y., Chivkunova, O. B., Golovin, A. V., et al. (2019) Cationic penetrating antioxidants switch off Mn cluster of photosystem II in situ, Photosynth. Res., 142, 229-240, https://doi.org/10.1007/s11120-019-00657-2.

    Article  CAS  PubMed  Google Scholar 

  25. Rokitskaya, T. I., Murphy, M. P., Skulachev, V. P., and Antonenko, Y. N. (2016) Ubiquinol and plastoquinol triphenylphosphonium conjugates can carry electrons through phospholipid membranes, Bioelectrochemistry, 111, 23-30, https://doi.org/10.1016/j.bioelechem.2016.04.009.

    Article  CAS  PubMed  Google Scholar 

  26. Antonenko, Y. N., Avetisyan, A. V., Bakeeva, L. E., Chernyak, B. V., Chertkov, V. A., et al. (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies, Biochemistry (Moscow), 73, 1273-1287, https://doi.org/10.1134/s0006297908120018.

    Article  CAS  Google Scholar 

  27. Saretzki, G., Murphy, M. P., and von Zglinicki, T. (2003) MitoQ counteracts telomere shortening and elongateslifespan of fibroblasts under mild oxidative stress, Aging Cell, 2, 141-143, https://doi.org/10.1046/j.1474-9728.2003.00040.x.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Russian Foundation for Basic Research (projects nos. 19-08-00874 and 20-015-00147-a) and State Assignment (project no. 0259-2021-0016).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evgeniy I. Solenov.

Ethics declarations

The authors declare no conflict of interests. All applicable international, nation-wide, and/or institutional guidelines for animal care and use have been followed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baturina, G.S., Katkova, L.E., Palchikova, I.G. et al. Mitochondrial Antioxidant SkQ1 Improves Hypothermic Preservation of the Cornea. Biochemistry Moscow 86, 382–388 (2021). https://doi.org/10.1134/S0006297921030135

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297921030135

Keywords

Navigation