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Inflammatory Metabolites of Arachidonic Acid in Tear Fluid in UV-Induced Corneal Damage

  • D. V. ChistyakovEmail author
  • N. V. Azbukina
  • S. V. Goriainov
  • V. V. Chistyakov
  • O. S. Gancharova
  • V. V. Tiulina
  • V. E. Baksheeva
  • E. N. Iomdina
  • P. P. Philippov
  • M. G. Sergeeva
  • I. I. Senin
  • E. Yu. ZerniiEmail author
Article
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Abstract

The ultraviolet (UV) B-induced damage of the eye surface of experimental animals (rabbits) includes total loss of corneal epithelium, apoptosis of keratocytes and stromal edema. These changes are accompanied by clinically and histologically manifested corneal inflammation, neutrophil infiltration, and exudation of the anterior chamber of the eye. According to results of mass spectrometric analysis, the UV-induced corneal damage is associated with pronounced changes in the tear lipid composition, including a decrease in the amount of arachidonic acid and prostaglandin E2 and an increase in the concentrations of prostaglandin D2 and its derivative 15d-PGJ2. In addition, it is accompanied by changes in the levels of hydroxyeicosate tetraenic acids, including a decrease of 12-HETE and an increase of 5-HETE. These changes suggest activation of metabolic pathways involving 5-lipoxygenase, 12-lipoxygenase, cyclooxygenases 1 and 2, and prostaglandin D synthase. These findings contribute to understanding mechanisms of UV-induced keratitis and point to feasibility of selective anti-inflammatory therapy for improving corneal regeneration after iatrogenic UV damage.

Keyword

s: UV-induced corneal damage keratocyte apoptosis keratitis tear film eicosanoids prostaglandin E2 prostaglandin D2 15d-PGJ2 5-HETE 12-HETE 

Notes

FUNDING

This work was supported by the Russian Science Foundation, (project no. 16-15-00255; setting up a model of corneal UV damage in experimental animals (rabbits), clinical and histological analysis of normal and damaged cornea, collection and processing of tea samples from experimental animals, and identification of arachidonic acid metabolites present in it, analysis of the data obtained) and the PFUR program “5-100” (development of a mass spectrometric analysis method for arachidonic acid metabolites in rabbit tears).

COMPLIANCE WITH ETHICAL STANDARDS

All animal experiments were carried out in accordance with the recommendations of the 8th edition of the National Research Council, and also of the Statement for the Use of Animals in Ophthalmic and Visual Research of the Association for Research in Vision and Ophthalmology (ARVO). The protocol of this study was approved by the Committee on Bioethics of the Belozersky Institute of Physico-Chemical Biology (Moscow State University, protocol no. 1/2016).

REFERENCES

  1. 1.
    Cejkova, J., Stipek, S., Crkovska, J., Ardan, T., Platenik, J., Cejka, C., and Midelfart, A., Physiol. Res., 2004, vol. 53, pp. 1–10.Google Scholar
  2. 2.
    Trokel, S.L., Srinivasan, R., and Braren, B., Am. J. Ophthalmol., 1983, vol. 96, pp. 710–715.CrossRefGoogle Scholar
  3. 3.
    Glaucoma Laser Trial Research Group, Am. J. Ophthalmol., 1995, vol. 120, pp. 718–731.Google Scholar
  4. 4.
    Carlson, K.H., Bourne, W.M., McLaren, J.W., and Brubaker, R.F., Exp. Eye Res., 1988, vol. 47, pp. 27–41.CrossRefGoogle Scholar
  5. 5.
    Zinflou, C. and Rochette, P.J., Free Radic. Biol. Med., 2017, vol. 108, pp. 118–128.  https://doi.org/10.1016/j.freeradbiomed.2017.03.022 CrossRefGoogle Scholar
  6. 6.
    Ibrahim, O.M., Kojima, T., Wakamatsu, T.H., Dogru, M., Matsumoto, Y., Ogawa, Y., Ogawa, J., Negishi, K., Shimazaki, J., Sakamoto, Y., Sasaki, H., and Tsubota, K., Invest. Ophthalmol. Vis. Sci., 2012, vol. 53, pp. 2403–2413.  https://doi.org/10.1167/iovs.11-6863 CrossRefGoogle Scholar
  7. 7.
    Zernii, E.Y., Baksheeva, V.E., Yani, E.V., Philippov, P.P., and Senin, I.I., Curr. Med. Chem., 2019, vol. 26, no. 3, pp. 517–545. https://doi.org/10.2174/0929867324666170609080920 CrossRefGoogle Scholar
  8. 8.
    Zernii, E.Y., Gancharova, O.S., Baksheeva, V.E., Golovastova, M.O., Kabanova, E.I., Savchenko, M.S., Tiulina, V.V., Sotnikova, L.F., Zamyatnin, A.A., Jr., Philippov, P.P., Senin, I.I., Oxid. Med. Cell. Longev., 2017, vol. 2017, 9281519.  https://doi.org/10.1155/2017/9281519 CrossRefGoogle Scholar
  9. 9.
    Walter, S.D., Gronert, K., McClellan, A.L., Levitt, R.C., Sarantopoulos, K.D., and Galor, A., Invest. Ophthalmol. Vis. Sci., 2016, vol. 57, pp. 2472–2478.  https://doi.org/10.1167/iovs.16-19131 CrossRefGoogle Scholar
  10. 10.
    Funk, C.D., Science, 2001, vol. 294, pp. 1871–1875.  https://doi.org/10.1126/science.294.5548.1871 CrossRefGoogle Scholar
  11. 11.
    Tripathi, T. and Alizadeh, H., Inflamm. Cell Signal., 2014, vol. 1, e301.  https://doi.org/10.14800/ics.301 Google Scholar
  12. 12.
    Chistyakov, D.V., Azbukina, N.V., Astakhova, A.A., Goriainov, S.V., Chistyakov, V.V., and Sergeeva, M.G., Int. J. Mol. Sci., 2018, vol. 19.  https://doi.org/10.3390/ijms19092793
  13. 13.
    Chistyakov, D.V., Grabeklis, S., Goriainov, S.V., Chistyakov, V.V., Sergeeva, M.G., and Reiser, G., Biochem. Biophys. Res. Commun., 2018, vol. 500, pp. 204–210.  https://doi.org/10.1016/j.bbrc.2018.04.040 CrossRefGoogle Scholar
  14. 14.
    Tiulina, V., Zernii, E., Baksheeva, V., Gancharova, O., Kabanova, E., Sotnikova, L., Zamyatnin, A., Philippov, P., and Senin, I., FEBS Open Bio, 2018, vol. 8, pp. 215–215.Google Scholar
  15. 15.
    Zernii, E.Y., Baksheeva, V.E., Kabanova, E.I., Tiulina, V.V., Golovastova, M.O., Gancharova, O.S., Savchenko, M.S., Sotikova, L.F., Zamyatnin, A.A., Filippov, P.P., and Senin, I.I., Bull. Exper. Biol. Med., 2018, vol. 165, pp. 269–271.  https://doi.org/10.1007/s10517-018-4145-3 CrossRefGoogle Scholar
  16. 16.
    Zernii, E.Y., Golovastova, M.O., Baksheeva, V.E., Kabanova, E.I., Ishutina, I.E., Gancharova, O.S., Gusev, A.E., Savchenko, M.S., Loboda, A.P., Sotnikova, L.F., Zamyatnin, A.A., Philippov, P.P., and Senin, I.I., Biochemistry (Moscow), 2016, vol. 81, pp. 1549–1557.  https://doi.org/10.1134/S0006297916120166 Google Scholar
  17. 17.
    Zernii, E.Y., Gancharova, O.S., Ishutina, I.E., Baksheeva, V.E., Golovastova, M.O., Kabanova, E.I., Savchenko, M.S., Serebryakova, M.V., Sotnikova, L.F., Zamyatnin, A.A., Philippov, P.P., and Senin, I.I., Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 2017, vol. 11, pp. 186–193.  https://doi.org/10.1134/S1990750817020123 Google Scholar
  18. 18.
    Shimmura, S., Masumizu, T., Nakai, Y., Urayama, K., Shimazaki, J., Bissen-Miyajima, H., Kohno, M., and Tsubota, K., Invest. Ophthalmol. Vis. Sci., 1999, vol. 40, pp. 1245–1249.Google Scholar
  19. 19.
    Sergeeva M.G. and Varfolomeeva A.T., Kaskad arakhidonovoi kisloty (The Arachidonic Acid Cascade), Moscow: Narodnoye obrazovanie, 2006. ISBN: 5-87953-228-3. Google Scholar
  20. 20.
    Ambaw, Y.A., Chao, C., Ji, S., Raida, M., Torta, F., Wenk, M.R., and Tong, L., Sci. Rep., 2018, vol. 8, 11296.  https://doi.org/10.1038/s41598-018-29568-3 CrossRefGoogle Scholar
  21. 21.
    Doucette, L.P. and Walter, M.A., Ophthalmic Genet., 2017, vol. 38, pp. 108–116.  https://doi.org/10.3109/13816810.2016.1164193 CrossRefGoogle Scholar
  22. 22.
    Csukas, S., Paterson, C.A., Brown, K., and Bhattacherjee, P., Invest. Ophthalmol. Vis. Sci., 1990, vol. 31, pp. 382–387.Google Scholar
  23. 23.
    Jung, W.K., Lee, C.M., Lee, D.S., Na, G., Lee, D.Y., Choi, I., Park, S.G., Seo, S.K., Yang, J.W., Choi, J.S., Lee, Y.M., Park, W.S., and Choi, I.W., Int. J. Mol. Med., 2014, vol. 33, pp. 449–456.  https://doi.org/10.3892/ijmm.2013.1588 CrossRefGoogle Scholar
  24. 24.
    Mieyal, P.A., Dunn, M.W., and Schwartzman, M.L., Invest. Ophthalmol. Vis. Sci., 2001, vol. 42, pp. 328–332.Google Scholar
  25. 25.
    Mastyugin, V., Aversa, E., Bonazzi, A., Vafaes, C., Mieyal, P., and Schwartzman, M.L., J. Pharmacol. Exp. Ther., 1999, vol. 289, pp. 1611–1619.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • D. V. Chistyakov
    • 1
    Email author
  • N. V. Azbukina
    • 1
  • S. V. Goriainov
    • 2
  • V. V. Chistyakov
    • 2
  • O. S. Gancharova
    • 1
  • V. V. Tiulina
    • 1
  • V. E. Baksheeva
    • 1
  • E. N. Iomdina
    • 3
  • P. P. Philippov
    • 1
  • M. G. Sergeeva
    • 1
  • I. I. Senin
    • 1
  • E. Yu. Zernii
    • 1
    • 4
    Email author
  1. 1.Belozersky Institute of Physico-Chemical Biology, Moscow State UniversityMoscowRussia
  2. 2.Peoples’ Friendship University of Russia (PFUR)MoscowRussia
  3. 3.Moscow Helmholtz Research Institute of Eye DiseasesMoscowRussia
  4. 4.Sechenov First Moscow State Medical University, Institute of Molecular MedicineMoscowRussia

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