Physical and chemical analysis of the lipofuscin granule bisretinoid photodestruction products from retinal pigment epithelium cells of the eye

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Abstract

In this work, the mechanisms of formation of the bisretinoid oxidation products in lipofuscin granules isolated from the retinal pigment epithelium cells of the human eye have been studied. The physico-chemical characteristics of the bisretinoid photooxidation products are described. The methods of IR spectroscopy, Raman spectroscopy, fluorescence spectroscopy, scanning confocal microscopy, time-of-flight mass spectrometry of secondary ions (TOF.SIMS) and HPLC were used for the study. The properties of the products of photooxidation and degradation of the fluorophore of lipofuscin granules, including synthetic N-retinylidene-N-retinylethanolamine (A2E), are described in detail. It has been shown that the products of oxidative degradation of lipofuscin granules are similar to the products of photooxidation of the main bisretinoid of lipofuscin granules – A2E. These data are important both for understanding the mechanisms of formation of cytotoxic products in lipofuscin granules and for establishing their chemical nature.

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About the authors

M. A. Yakovleva

Emanuel Institute of Biochemical Physics RAS

Author for correspondence.
Email: lina.invers@gmail.com
Russian Federation, Moscow

A. A. Vasin

Semenov Federal Research Center for Chemical Physics RAS

Email: lina.invers@gmail.com
Russian Federation, Moscow

A. E. Dontsov

Emanuel Institute of Biochemical Physics RAS

Email: lina.invers@gmail.com
Russian Federation, Moscow

A. A. Gulin

Semenov Federal Research Center for Chemical Physics RAS

Email: lina.invers@gmail.com
Russian Federation, Moscow

A. V. Aybush

Semenov Federal Research Center for Chemical Physics RAS

Email: lina.invers@gmail.com
Russian Federation, Moscow

A. A. Astafiev

Semenov Federal Research Center for Chemical Physics RAS

Email: lina.invers@gmail.com
Russian Federation, Moscow

A. M. Shakhov

Semenov Federal Research Center for Chemical Physics RAS

Email: lina.invers@gmail.com
Russian Federation, Moscow

T. B. Feldman

Emanuel Institute of Biochemical Physics RAS; Lomonosov Moscow State University

Email: lina.invers@gmail.com
Russian Federation, Moscow; Moscow

M. A. Ostrovsky

Emanuel Institute of Biochemical Physics RAS; Lomonosov Moscow State University

Email: lina.invers@gmail.com
Russian Federation, Moscow; Moscow

References

  1. M. Zetterberg, Maturitas. 83, 19 (2016).
  2. L. Nivison-Smith, R. Milston, M. Madigan, M. Kalloniatis, Optom. Vis. Sci. 91, 832 (2014).
  3. C.R. Fisher, D.A. Ferrington, Investig. Ophthalmol. Visual Sci. 59, 41 (2018).
  4. Yu.S. Petronyuk, N. N. Trofimova, P.P. Zak et al., Russian Journal of Phys. Chem. B. 16(1), 97-102 (2022). https://doi.org/10.1134/S1990793122010249
  5. Y. Ruan, S. Jiang, A. Gericke, Int. J. Mol. Sci. 2021. 22, 1296 (2021). https://doi.org/10.3390/ijms22031296
  6. I.K. Larin, Russian Journal of Physical Chemistry B. 17, 244–250 (2023). https://doi.org/10.1134/s1990793123010074
  7. F.G. Holz, F. Schütt, J. Kopitz, G.E. Eldred, F.E. Kruse, H.E. Völcker, M. Cantz, Investig. Ophthalmol. Visual Sci. 40, 737 (1999).
  8. L. Adler IV, C. Chen, Y. Koutalos, Exp. Eye Res. 155, 121 (2017).
  9. M. Boulton, A. Dontsov, J. Jarvis-Evans, M. Ostrovsky, D. Svistunenko, J. Photochem. Photobiol. B Biol. 19, 201 (1993). https://doi.org/10.1016/1011-1344(93)87085-2
  10. L.E. Lamb, J.D. Simon, Photochem. Photobiol. 79, 127 (2004).
  11. J.R. Sparrow, S.R. Kim, A.M. Cuervo, U. Bandhyopadhyayand, Adv. Exp. Med. Biol. 613, 393 (2008). https://doi.org/10.1007/978-0-387-74904-4_46
  12. Y. Wu, E. Yanase, X. Feng, M.M. Siegel, J.R. Sparrow, Proc. Natl. Acad. Sci. USA. 107, 7275 (2010).
  13. S. Ben-Shabat, Y. Itagaki, S. Jockusch, J.R. Sparrow, N.J. Turro, K. Nakanishi, Angew. Chem. Int. Ed. 41, 814 (2002).
  14. T.B. Feldman, M.A. Yakovleva, P.M. Arbukhanova, S.A. Borzenok, A.S. Kononikhin, I.A. Popov, E.N. Nikolaev, M.A. Ostrovsky, Anal. Bioanal. Chem. 407, 1075 (2015).
  15. M.A. Yakovleva, A.E. Dontsov, N.N. Trofimova, N.L. Sakina, A.S. Kononikhin, A.V. Aybush, T.B. Feldman, M.A. Ostrovsky, Int. J. Mol. Sci. 23 (1), 222 (2022). https://doi.org/10.3390/ijms23010222
  16. T.B. Feldman, M.A. Yakovleva, A.V. Larichev, P.M. Arbukhanova, A.Sh. Radchenko, S.A. Borzenok, V.A. Kuzmin, M.A. Ostrovsky, Eye. 32, 1440 (2018). https://doi.org/10.1038/s41433-018-0109-0
  17. F.G. Holz, S. Schmitz-Valckenberg, R.F. Spaide, A.C. Bird, Atlas of Fundus Autofluorescence Imaging. Berlin-Heidelberg: Springer–Verlag, 2007. P. 342.
  18. D. Schweitzer, E.R. Gaillard, J. Dillon, R.F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, C. Biskup, Investig. Ophthalmol. Visual Sci. 53 (7), 3376 (2012). https://doi.org/10.1167/iovs.11-8970
  19. D. Schweitzer, S. Quick, S. Schenke, M. Klemm, S. Gehlert, M. Hammer, S. Jentsch, J. Fischer, Ophthalmology. 106, 714 (2009). https://doi.org/10.1007/s00347-009-1975-4
  20. J. Folch, M. Lees, G.H. Sloane Stanley, J. Biol. Chem. 226, 497 (1957).
  21. C.A. Parish, M. Hashimoto, K. Nakanishi, J. Dillon, J. Sparrow, Proc. Natl. Acad. Sci. USA. 95, 14609 (1998).
  22. Z. Wang, L.M.M. Keller, J. Dillon, E.R. Gaillard, Photochem. Photobiol. 82, 1251 (2006).
  23. T. Feldman, D. Ostrovskiy, M. Yakovleva, A. Dontsov, S. Borzenok, M. Ostrovsky, Int. J. Mol. Sci. 23, 12234 (2022). https://doi.org/10.3390/ijms232012234
  24. A. Dontsov, M. Yakovleva, N. Trofimova, N. Sakina, A. Gulin, A. Aybush, F. Gostev, A. Vasin, T. Feldman, M. Ostrovsky, Int. J. Mol. Sci. 23 (3), 1534 (2022). https://doi.org/10.3390/ijms23031534
  25. W.F. Razumov, Russian Journal of Physical Chemistry B. 17(1), 36 (2023). https://doi.org/10.1134/S199079312301027X
  26. M.A. Yakovleva, A.Sh. Radchenko, A.A. Kostyukov et al., Russian Journal of Physical Chemistry B. 16(1), 90-96 (2022). https://doi.org/10.1134/S199079312201033X
  27. M.A. Yakovleva, A.Sh. Radchenko, T.B. Feldman, A.A. Kostyukov, P.M. Arbukhanova, S.A. Borzenok, V.A. Kuzmin, M.A. Ostrovsky, Photochem. Photobiol. Sci. 19, 920 (2020). https://doi.org/10.1039/C9PP00406H

Supplementary files

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2. Fig. 1. a – Fluorescence spectra of chloroform extracts from suspensions of native lipofuscin granules (1) and irradiated with visible light (2) with a wavelength of 488 nm; b – chromatograms of chloroform extract from LG suspension: 1 – non-irradiated LG, 2 – LG after irradiation with visible light. Detection – by absorption at a wavelength of 430 nm.

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3. Fig. 2. 3D fluorescence spectra: a – fluorescence profiles of A2E; b – fluorescence profiles of A2E irradiated with visible light; c – fluorescence profiles of LG suspension; g – fluorescence profiles of LG suspension irradiated with visible light; d – fluorescence profiles of chloroform extract of LG; e – fluorescence profiles of chloroform extract of LG irradiated with visible light.

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4. Fig. 3. Raman spectra of samples before (black spectrum) and after exposure to visible light (gray spectrum): a – suspension of lipofuscin granules, b – chloroform extracts from LG, c – synthetic A2E.

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5. Fig. 4. IR spectra of samples before (black spectrum) and after exposure to visible light (gray spectrum): a – suspension of lipofuscin granules, b – chloroform extracts from LG, c – synthetic A2E.

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6. Fig. 5. Histograms of mass spectrometric data before (dark columns) and after exposure to light (light columns) on the studied samples: a – LG suspension, b – chloroform extracts from LG, c – synthetic A2E. For clarity, the ion intensities were normalized to the corresponding average ion intensity of the dark sample.

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