Biochemistry (Moscow)

, Volume 83, Issue 12–13, pp 1563–1574 | Cite as

Iatrogenic Damage of Eye Tissues: Current Problems and Possible Solutions

  • V. E. Baksheeva
  • O. S. Gancharova
  • V. V. Tiulina
  • E. N. Iomdina
  • A. A. ZamyatninJr.
  • P. P. Philippov
  • E. Yu. ZerniiEmail author
  • I. I. Senin


Visual system is at high risk of iatrogenic damage. Laser ocular surgery, the use of powerful illumination devices in diagnostics and surgical treatment of eye diseases, as well as long surgeries under general anesthesia provoke the development of chronic degenerative changes in eye tissues, primarily in the cornea and the retina. Despite the existence of approaches for prevention and treatment of these complications, the efficacy of these approaches is often limited. Here, we review the mechanisms of iatrogenic damage to eye tissues at the cellular and biochemical levels. It is well recognized that oxidative stress is one of the main factors hindering regeneration of eye tissues after injuries and, thereby, aggravating iatrogenic eye disorders. It is accompanied by the downregulation of low–molecular–weight antioxidants and antioxidant enzymes, as well as changes in the expression and redox status of proteins in the damaged tissue. In this regard, antioxidant therapy, in particular, the use of highly effective mitochondria–targeted antioxidants such as SkQ1, is considered as a promising approach to the prevention of iatrogenesis. Recent findings indicate that the most efficient protection of eye tissues from the iatrogenic injury is achieved by preventive use of these antioxidants. In addition to preventing corneal and retinal cell death induced by oxidative stress, SkQ1 contributes to the restoration of innate antioxidant defense of these tissues and suppresses local inflammatory response. Since the timing of routine medical manipulations is usually known in advance, iatrogenic damage to the ocular tissues can be successfully prevented using mitochondria–targeted therapy.


iatrogenesis general anesthesia perioperative dry eye syndrome laser eye surgery photochemical damage to the retina mitochondria–targeted antioxidants SkQ1 



photochemical retinal damage


perioperative dry eye syndrome


reactive oxygen species


retinal pigment epithelium


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  1. 1.
    Gomes, J. A. P., Azar, D. T., Baudouin, C., Efron, N., Hirayama, M., Horwath–Winter, J., Kim, T., Mehta, J. S., Messmer, E. M., Pepose, J. S., Sangwan, V. S., Weiner, A. L., Wilson, S. E., and Wolffsohn, J. S. (2017) TFOS DEWS II iatrogenic report, Ocul. Surf., 15, 511–538.CrossRefPubMedGoogle Scholar
  2. 2.
    Malafa, M. M., Coleman, J. E., Bowman, R. W., and Rohrich, R. J. (2016) Perioperative corneal abrasion: updated guidelines for prevention and management, Plast. Reconstr. Surg., 137, 790e–798e.CrossRefPubMedGoogle Scholar
  3. 3.
    Wolffe, M. (2016) How safe is the light during ophthalmic diagnosis and surgery, Eye (Lond.), 30, 186–188.CrossRefGoogle Scholar
  4. 4.
    Iomdina, E. N., Tarutta, E. P., Ignat’eva, N. Yu., Kostanyan, I. A., Minkevich, N. I., Shehter, A. B., Danilov, N. A., Kvaatsheliya, N. G., and Cherhisheva, S. G. (2008) Current achievements in basic studies of the pathogenesis of progressing myopia, Ross. Oftalmol. Zh., 1, 7–12.Google Scholar
  5. 5.
    Batra, Y. K., and Bali, I. M. (1977) Corneal abrasions during general anesthesia, Anesth. Analg., 56, 363–365.CrossRefPubMedGoogle Scholar
  6. 6.
    Glickman, R. D. (2002) Phototoxicity to the retina: mechanisms of damage, Int. J. Toxicol., 21, 473–490.CrossRefPubMedGoogle Scholar
  7. 7.
    Zernii, E. Y., Baksheeva, V. E., Iomdina, E. N., Averina, O. A., Permyakov, S. E., Philippov, P. P., Zamyatnin, A. A., and Senin, I. I. (2016) Rabbit models of ocular diseases: new relevance for classical approaches, CNS Neurol. Disord. Drug Targets, 15, 267–291.CrossRefPubMedGoogle Scholar
  8. 8.
    Buddi, R., Lin, B., Atilano, S. R., Zorapapel, N. C., Kenney, M. C., and Brown, D. J. (2002) Evidence of oxidative stress in human corneal diseases, J. Histochem. Cytochem., 50, 341–351.CrossRefPubMedGoogle Scholar
  9. 9.
    Moreno, M. C., Campanelli, J., Sande, P., Saenz, D. A., Sarmiento, M. I. K., and Rosenstein, R. E. (2004) Retinal oxidative stress induced by high intraocular pressure, Free Radic. Biol. Med., 37, 803–812.CrossRefPubMedGoogle Scholar
  10. 10.
    Gandhi, S., and Jain, S. (2014) The Anatomy and Physiology of Cornea, Keratoprostheses and Artificial Corneas: Fundamentals and Surgical Applications, Springer, Berlin–Heidelberg, pp. 19–25.Google Scholar
  11. 11.
    Kolozsvari, L., Nogradi, A., Hopp, B., and Bor, Z. (2002) UV absorbance of the human cornea in the 240–to 400–nm range, Invest. Ophthalmol. Vis. Sci., 43, 2165–2168.PubMedGoogle Scholar
  12. 12.
    Chen, Y., Mehta, G., and Vasiliou, V. (2009) Antioxidant defenses in the ocular surface, Ocul. Surf., 7, 176–185.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Fini, M. (1999) Keratocyte and fibroblast phenotypes in the repairing cornea, Prog. Retin. Eye Res., 18, 529–551.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhang, W., Li, H., Ogando, D. G., Li, S., Feng, M., Price, F. W., Jr., Tennessen, J. M., and Bonanno, J. A. (2017) Glutaminolysis is essential for energy production and ion transport in human corneal endothelium, EBioMedicine, 16, 292–301.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kim, K. M., Shin, Y.–T., and Kim, H. K. (2012) Effect of autologous platelet–rich plasma on persistent corneal epithelial defect after infectious keratitis, Jpn. J. Ophthalmol., 56, 544–550.CrossRefPubMedGoogle Scholar
  16. 16.
    Baudouin, C. (2001) The pathology of dry eye, Surv. Ophthalmol., 45, S211–S220.CrossRefPubMedGoogle Scholar
  17. 17.
    Zernii, E. Yu., 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., Jr., Philippov, P. P., and Senin, I. I. (2016) Alterations in tear biochemistry associated with chronic dry eye syndrome in postanesthetic period, Biochemistry (Moscow), 81, 1549–1557.CrossRefGoogle Scholar
  18. 18.
    Zernii, E. Yu., Baksheeva, V. E., Kabanova, E. I., Tulina, V. V., Golovastova, M. O., Gancharova, O. S., Savchenko, M. S., Sotikova, L. F., Zamyatnin, A. A., Jr., Filippov, P. P., and Senin, I. I. (2018) Effect of general anesthesia duration on recovery of secretion and biochemical properties of tear fluid in the post–anesthetic period, Bull. Exp. Biol. Med., 165, 269–271.CrossRefPubMedGoogle Scholar
  19. 19.
    Yu, H.–D., Chou, A.–H., Yang, M.–W., and Chang, C.–J. (2010) An analysis of perioperative eye injuries after nonocular surgery, Acta Anaesthesiol. Taiwan, 48, 122–129.CrossRefPubMedGoogle Scholar
  20. 20.
    Orlin, S. E., Kurata, F. K., Krupin, T., Schneider, M., and Glendrange, R. R. (1989) Ocular lubricants and corneal injury during anesthesia, Anesth. Analg., 69, 384–385.CrossRefPubMedGoogle Scholar
  21. 21.
    Zeev, M. S.–B., Miller, D. D., and Latkany, R. (2014) Diagnosis of dry eye disease and emerging technologies, Clin. Ophthalmol., 8, 581–590.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Grover, V. K., Kumar, K. V. W., Sharma, S., Sethi, N., and Grewal, S. P. S. (1999) Comparison of methods of eye protection under general anesthesia, Survey Anesthesiol., 43, 75–76.CrossRefGoogle Scholar
  23. 23.
    Wolkoff, P., Nojgaard, J. K., Troiano, P., and Piccoli, B. (2005) Eye complaints in the office environment: precorneal tear film integrity influenced by eye blinking efficiency, Occup. Environ. Med., 62, 4–12.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Mastropasqua, L., Ciancaglini, M., Di Tano, G., Carpineto, P., Lobefalo, L., Loffredo, B., Bosco, D., Columbaro, M., and Falcieri, E. (1998) Ultrastructural changes in rat cornea after prolonged hypobaric hypoxia, J. Submicrosc. Cytol. Pathol., 30, 285–293.PubMedGoogle Scholar
  25. 25.
    Zernii, E. Yu., Gancharova, O. S., Ishytina, I. E., Baksheeva, V. E., Golovastova, M. O., Kabanova, E. I., Savchenko, M. S., Serebryakova, M. V., Sotikova, L. F., Zamyatnin, A. A., Jr., Filippov, P. P., and Senin, I. I. (2017) Mechanisms of perioperative corneal abrasions: alterations in the tear film proteome, Biochemistry (Moscow) Suppl. Ser. B: Biomed. Chem., 11, 186–193.CrossRefGoogle Scholar
  26. 26.
    Fullard, R. J., and Snyder, C. (1990) Protein levels in non–stimulated and stimulated tears of normal human subjects, Invest. Ophthalmol. Vis. Sci., 31, 1119–1126.PubMedGoogle Scholar
  27. 27.
    Seitz, B., Rozsival, P., Feuermannova, A., Langenbucher, A., and Naumann, G. O. H. (2003) Penetrating keratoplasty for iatrogenic keratoconus after repeat myopic laser in situ keratomileusis: histologic findings and literature review, J. Cataract Refract. Surg., 29, 2217–2224.CrossRefPubMedGoogle Scholar
  28. 28.
    Wang, L., Moss, H., Ventura, B. V., Padilha, H., Hester, C., and Koch, D. D. (2013) Advances in refractive surgery, Asia Pac. J. Ophthalmol. (Phila), 2, 317–327.CrossRefGoogle Scholar
  29. 29.
    Levitt, A. E., Galor, A., Weiss, J. S., Felix, E. R., Martin, E. R., Patin, D. J., Sarantopoulos, K. D., and Levitt, R. C. (2015) Chronic dry eye symptoms after lasik: parallels and lessons to be learned from other persistent post–operative pain disorders, Mol. Pain, 11,21.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Cejkova, J., Stipek, S., Crkovska, J., Ardan, T., Platenik, J., Cejka, C., and Midelfart, A. (2004) UV rays, the prooxidant/antioxidant imbalance in the cornea and oxidative eye damage, Physiol. Res., 53, 1–10.PubMedGoogle Scholar
  31. 31.
    Leonardi, A., Tavolato, M., Curnow, S. J., Fregona, I. A., Violato, D., and Alio, J. L. (2009) Cytokine and chemokine levels in tears and in corneal fibroblast cultures before and after excimer laser treatment, J. Cataract Refract. Surg., 35, 240–247.CrossRefPubMedGoogle Scholar
  32. 32.
    Kochevar, I. E. (1989) Cytotoxicity and mutagenicity of excimer laser radiation, Lasers Surg. Med., 9, 440–445.CrossRefPubMedGoogle Scholar
  33. 33.
    Bilgihan, K., Bilgihan, A., Adiguzel, U., Sezer, C., Yis, O., Akyol, G., and Hasanreisoglu, B. (2002) Keratocyte apoptosis and corneal antioxidant enzyme activities after refractive corneal surgery, Eye, 16, 63–68.CrossRefPubMedGoogle Scholar
  34. 34.
    Riley, M. V., Susan, S., Peters, M. I., and Schwartz, C. A. (1987) The effects of UV–B irradiation on the corneal endothelium, Curr. Eye Res., 6, 1021–1033.CrossRefPubMedGoogle Scholar
  35. 35.
    Carubelli, R., Nordquist, R. E., and Rowsey, J. J. (1990) Role of active oxygen species in corneal ulceration. Effect of hydrogen peroxide generated in situ, Cornea, 9, 161–169.CrossRefPubMedGoogle Scholar
  36. 36.
    Ng, S. K., Wood, J. P., Chidlow, G., Han, G., Kittipassorn, T., Peet, D. J., and Casson, R. J. (2015) Cancer–like metabolism of the mammalian retina, Clin. Exp. Ophthalmol., 43, 367–376.CrossRefPubMedGoogle Scholar
  37. 37.
    Fletcher, A. E. (2008) Sunlight exposure, antioxidants, and age–related macular degeneration, Arch. Ophthalmol., 126, 1396–1403.PubMedGoogle Scholar
  38. 38.
    Winkler, B. S. (2008) An hypothesis to account for the renewal of outer segments in rod and cone photoreceptor cells: renewal as a surrogate antioxidant, Invest. Ophthalmol. Vis. Sci., 49, 3259–3261.CrossRefPubMedGoogle Scholar
  39. 39.
    Wu, J., Seregard, S., and Algvere, P. V. (2006) Photochemical damage of the retina, Surv. Ophthalmol., 51, 461–481.CrossRefPubMedGoogle Scholar
  40. 40.
    Van den Biesen, P. R., Berenschot, T., Verdaasdonk, R. M., van Weelden, H., and van Norren, D. (2000) Endoillumination during vitrectomy and phototoxicity thresholds, Br. J. Ophthalmol., 84, 1372–1375.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kuhn, F., Morris, R., and Massey, M. (1991) Photic retinal injury from endoillumination during vitrectomy, Am. J. Ophthalmol., 111, 42–46.CrossRefPubMedGoogle Scholar
  42. 42.
    McDonald, H. R., and Irvine, A. R. (1983) Light–induced maculopathy from the operating microscope in extracapsular cataract extraction and intraocular lens implantation, Ophthalmology, 90, 945–951.CrossRefPubMedGoogle Scholar
  43. 43.
    Michels, M., and Sternberg, P., Jr. (1990) Operating micro–scope–induced retinal phototoxicity: pathophysiology, clinical manifestations and prevention, Surv. Ophthalmol., 34, 237–252.CrossRefGoogle Scholar
  44. 44.
    Postel, E. A., Pulido, J. S., Byrnes, G. A., Heier, J., Waterhouse, W., Han, D. P., Mieler, W. F., Guse, C., and Wipplinger, W. (1998) Long–term follow–up of iatrogenic phototoxicity, Arch. Ophthalmol., 116, 753–757.CrossRefPubMedGoogle Scholar
  45. 45.
    Tso, M. O., Fine, B. S., and Zimmerman, L. E. (1972) Photic maculopathy produced by the indirect ophthalmo–scope. 1. Clinical and histopathologic study, Am. J. Ophthalmol., 73, 686–699.CrossRefGoogle Scholar
  46. 46.
    Tso, M. O., and Woodford, B. J. (1983) Effect of photic injury on the retinal tissues, Ophthalmology, 90, 952–963.CrossRefPubMedGoogle Scholar
  47. 47.
    Delori, F. C., Webb, R. H., and Sliney, D. H. (2007) Maximum permissible exposures for ocular safety (ansi 2000), with emphasis on ophthalmic devices, J. Opt. Soc. Am., 24, 1250–1265.Google Scholar
  48. 48.
    Glickman, R. D., Jacques, S. L., Schwartz, J. A., Rodriguez, T., Lam, K.–W., and Buhr, G. (1996) Photodisruption increases the free–radical reactivity of melanosomes isolated from retinal pigment epithelium, in Laser–Tissue Interaction VII, Proc. SPIE (Jacques, S. I., ed.), Vol. 2681, SPIE, Bellingham (WA), pp. 460–467.CrossRefGoogle Scholar
  49. 49.
    Van Norren, D., and Vos, J. J. (2016) Light damage to the retina: an historical approach, Eye, 30, 169–172.CrossRefPubMedGoogle Scholar
  50. 50.
    Grignolo, A., Orzalesi, N., Castellazzo, R., and Vittone, P. (1969) Retinal damage by visible light in albino rats, Ophthalmologica, 157, 43–59.CrossRefPubMedGoogle Scholar
  51. 51.
    Bush, R. A., Reme, C. E., and Malnoe, A. (1991) Light damage in the rat retina: the effect of dietary deprivation of n–3 fatty acids on acute structural alterations, Exp. Eye Res., 53, 741–752.CrossRefPubMedGoogle Scholar
  52. 52.
    Pautler, E. L., Morita, M., and Beezley, D. (1990) Hemoprotein(s) mediate blue light damage in the retinal pigment epithelium, Photochem. Photobiol., 51, 599–605.CrossRefPubMedGoogle Scholar
  53. 53.
    Demontis, G. C., Longoni, B., and Marchiafava, P. L. (2002) Molecular steps involved in light–induced oxidative damage to retinal rods, Invest. Ophthalmol. Vis. Sci., 43, 2421–2427.PubMedGoogle Scholar
  54. 54.
    Van Norren, D., and Theo, G. M. (2011) The action spectrum of photochemical damage to the retina: a review of monochromatic threshold data, Photochem. Photobiol., 87, 747–753.CrossRefPubMedGoogle Scholar
  55. 55.
    Ham, W. T., Jr., Mueller, H. A., and Sliney, D. H. (1976) Retinal sensitivity to damage from short wavelength light, Nature, 260, 153–155.CrossRefPubMedGoogle Scholar
  56. 56.
    Kremers, J. J., and van Norren, D. (1989) Retinal damage in macaque after white light exposures lasting ten minutes to twelve hours, Invest. Ophthalmol. Vis. Sci., 30, 1032–1040.PubMedGoogle Scholar
  57. 57.
    Sykes, S. M., Robison, W. G., Jr., Waxler, M., and Kuwabara, T. (1981) Damage to the monkey retina by broad–spectrum fluorescent light, Invest. Ophthalmol. Vis. Sci., 20, 425–434.PubMedGoogle Scholar
  58. 58.
    Ben–Shabat, S., Parish, C. A., Vollmer, H. R., Itagaki, Y., Fishkin, N., Nakanishi, K., and Sparrow, J. R. (2001) Biosynthetic studies of a2e, a major fluorophore of retinal pigment epithelial lipofuscin, J. Biol. Chem., 277, 7183–7190.Google Scholar
  59. 59.
    Organisciak, D. T., Wang, H. M., and Kou A. L. (1984) Ascorbate and glutathione levels in the developing normal and dystrophic rat retina: effect of intense light exposure, Curr. Eye Res., 3, 257–267.CrossRefPubMedGoogle Scholar
  60. 60.
    Hunter, J. J., Morgan, J. I. W., Merigan, W. H., Sliney, D. H., Sparrow, J. R., and Williams, D. R. (2012) The susceptibility of the retina to photochemical damage from visible light, Prog. Retin. Eye Res., 31, 28–42.CrossRefPubMedGoogle Scholar
  61. 61.
    Pawlak, A., Rozanowska, M., Zareba, M., Lamb, L. E., Simon, J. D., and Sarna, T. (2002) Action spectra for the photoconsumption of oxygen by human ocular lipofuscin and lipofuscin extracts, Arch. Biochem. Biophys., 403, 59–62.CrossRefPubMedGoogle Scholar
  62. 62.
    Wolf, G. (2003) Lipofuscin and macular degeneration, Nutr. Rev., 61, 342–346.CrossRefPubMedGoogle Scholar
  63. 63.
    Chen, Y., Sawada, O., Kohno, H., Le, Y.–Z., Subauste, C., Maeda, T., and Maeda, A. (2013) Autophagy protects the retina from light–induced degeneration, J. Biol. Chem., 288, 7506–7518.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Thumann, G., Bartz–Schmidt, K. U., Kociok, N., Kayatz, P., Heimann, K., and Schraermeyer, U. (1999) Retinal damage by light in the golden hamster: an ultrastructural study in the retinal pigment epithelium and bruch’s membrane, J. Photochem. Photobiol. B, 49, 104–111.CrossRefPubMedGoogle Scholar
  65. 65.
    Hao, W., Wenzel, A., Obin, M. S., Chen, C. K., Brill, E., Krasnoperova, N. V., Eversole–Cire, P., Kleyner, Y., Taylor, A., Simon, M. I., Grimm, C., Reme, C. E., and Lem, J. (2002) Evidence for two apoptotic pathways in light–induced retinal degeneration, Nat. Genet., 32, 254–260.CrossRefPubMedGoogle Scholar
  66. 66.
    Organisciak, D. T., and Vaughan, D. K. (2010) Retinal light damage: mechanisms and protection, Prog. Retin. Eye Res., 29, 113–134.CrossRefPubMedGoogle Scholar
  67. 67.
    Wenzel, A., Grimm, C., Samardzija, M., and Reme, C. E. (2005) Molecular mechanisms of light–induced photore–ceptor apoptosis and neuroprotection for retinal degeneration, Prog. Retin. Eye Res., 24, 275–306.CrossRefPubMedGoogle Scholar
  68. 68.
    Lieven, C. J., Ribich, J. D., Crowe, M. E., and Levin, L. A. (2012) Redox proteomic identification of visual arrestin dimerization in photoreceptor degeneration after photic injury, Invest. Ophthalmol. Vis. Sci., 53, 3990–3998.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Zernii, E. Y., Nazipova, A. A., Gancharova, O. S., Kazakov, A. S., Serebryakova, M. V., Zinchenko, D. V., Tikhomirova, N. K., Senin, I. I., Philippov, P. P., Permyakov, E. A., and Permyakov, S. E. (2015) Light–induced disulfide dimerization of recoverin under ex vivo and in vivo conditions, Free Radic. Biol. Med., 83, 283–295.CrossRefPubMedGoogle Scholar
  70. 70.
    Grixti, A., Sadri, M., and Watts, M. T. (2013) Corneal protection during general anesthesia for nonocular surgery, Ocul. Surf., 11, 109–118.CrossRefPubMedGoogle Scholar
  71. 71.
    Hrazdirova, V., Navratilova, B., and Ventrubova, R. (1990) Use of contact lenses during general anesthesia, Cesk. Oftalmol., 46, 223–229.PubMedGoogle Scholar
  72. 72.
    Boggild–Madsen, N. B., Bundgarrd–Nielsen, P., Hammer, U., and Jakobsen, B. (1981) Comparison of eye protection with methylcellulose and paraffin ointments during general anaesthesia, Can. Anaesth. Soc. J., 28, 575–578.CrossRefPubMedGoogle Scholar
  73. 73.
    White, E., and Crosse, M. M. (1998) The aetiology and prevention of peri–operative corneal abrasions, Anaesthesia, 53, 157–161.CrossRefPubMedGoogle Scholar
  74. 74.
    Cross, D. A., and Krupin, T. (1977) Implications of the effects of general anesthesia on basal tear production, Anesth. Analg., 56, 35–37.CrossRefPubMedGoogle Scholar
  75. 75.
    Cuddihy, P. J., and Whittet, H. (2005) Eye observation and corneal protection during endonasal surgery, J. Laryngol. Otol., 119, 556–557.CrossRefPubMedGoogle Scholar
  76. 76.
    Ganidagli, S., Cengi, M., Becerik, C., Oguz, H., and Kilic, A. (2004) Eye protection during general anaesthesia: comparison of four different methods, Eur. J. Anaesthesiol., 21, 665–667.CrossRefPubMedGoogle Scholar
  77. 77.
    Manecke, G. R., Jr., Tannenbaum, D. P., and McCoy, B. E. (2000) Severe bilateral corneal injury attributed to a preservative–containing eye lubricant, Anesthesiology, 93, 1545–1546.CrossRefPubMedGoogle Scholar
  78. 78.
    Zernii, E. Y., Baksheeva, V. E., Yani, E. V., Philippov, P. P., and Senin, I. I. (2017) Therapeutic proteins for treatment of corneal epithelial defects, Curr. Med. Chem., doi: 10.2174/0929867324666170609080920.Google Scholar
  79. 79.
    Brzheskiy, V. V., Efimova, E. L., Vorontsova, T. N., Alekseev, V. N., Gusarevich, O. G., Shaidurova, K. N., Ryabtseva, A. A., Andryukhina, O. M., Kamenskikh, T. G., Sumarokova, E. S., Miljudin, E. S., Egorov, E. A., Lebedev, O. I., Surov, A. V., Korol, A. R., Nasinnyk, I. O., Bezditko, P. A., Muzhychuk, O. P., Vygodin, V. A., Yani, E. V., Savchenko, A. Y., Karger, E. M., Fedorkin, O. N., Mironov, A. N., Ostapenko, V., Popeko, N. A., Skulachev, V. P., and Skulachev, M. V. (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.PubMedGoogle Scholar
  80. 80.
    Blades, K. J., Patel, S., and Aidoo, K. E. (2001) Oral antioxidant therapy for marginal dry eye, Eur. J. Clin. Nutr., 55, 589–597.CrossRefPubMedGoogle Scholar
  81. 81.
    Xie, W. (2016) Recent advances in laser in situ keratomileusis–associated dry eye, Clin. Exp. Optom., 99, 107–112.CrossRefPubMedGoogle Scholar
  82. 82.
    Kornilovskiy, I. M., Sultanova, A. I., and Burtsev, A. A. (2016) Riboflavin photoprotection with cross–linking effect in photorefractive ablation of the cornea, Vestnik Oftalmol., 132, 37–41.CrossRefGoogle Scholar
  83. 83.
    McKay, T. B., and Karamichos, D. (2017) Quercetin and the ocular surface: what we know and where we are going, Exp. Biol. Med. (Maywood), 242, 565–572.CrossRefGoogle Scholar
  84. 84.
    Ciuffi, M., Pisanello, M., Pagliai, G., Raimondi, L., Franchi–Micheli, S., Cantore, M., Mazzetti, L., and Failli, P. (2003) Antioxidant protection in cultured corneal cells and whole corneas submitted to UV–B exposure, J. Photochem. Photobiol. B, 71, 59–68.CrossRefPubMedGoogle Scholar
  85. 85.
    Hammond, B. R., Johnson, B. A., and George, E. R. (2014) Oxidative photodegradation of ocular tissues: beneficial effects of filtering and exogenous antioxidants, Exp. Eye Res., 129, 135–150.CrossRefPubMedGoogle Scholar
  86. 86.
    Gueven, N., Nadikudi, M., Daniel, A., and Chhetri, J. (2017) Targeting mitochondrial function to treat optic neuropathy, Mitochondrion, 36, 7–14.CrossRefPubMedGoogle Scholar
  87. 87.
    Zueva, M. V., and Ivanina, T. A. (1980) Damaging effect of visual light on the retina in experiment (electrophysiological and electron microscopy studies), Vestnik Oftalmol., 4, 48–51.Google Scholar
  88. 88.
    Bhagavan, H. N., and Chopra, R. K. (2007) Plasma coenzyme q10 response to oral ingestion of coenzyme Q10 formulations, Mitochondrion, 7 (Suppl.), S78–88.CrossRefPubMedGoogle Scholar
  89. 89.
    Manach, C., Williamson, G., Morand, C., Scalbert, A., and Remesy, C. (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies, Am. J. Clin. Nutr., 81, 230S–242S.CrossRefPubMedGoogle Scholar
  90. 90.
    Gueven, N., Woolley, K., and Smith, J. (2015) Border between natural product and drug: comparison of the related benzoquinones idebenone and coenzyme Q10, Redox Biol., 4, 289–295.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Blagosklonny, M. V., Campisi, J., Sinclair, D. A., Bartke, A., Blasco, M. A., Bonner, W. M., Bohr, V. A., Brosh, R. M., Jr., Brunet, A., Depinho, R. A., Donehower, L. A., Finch, C. E., Finkel, T., Gorospe, M., Gudkov, A. V., Hall, M. N., Hekimi, S., Helfand, S. L., Karlseder, J., Kenyon, C., Kroemer, G., Longo, V., Nussenzweig, A., Osiewacz, H. D., Peeper, D. S., Rando, T. A., Rudolph, K. L., Sassone–Corsi, P., Serrano, M., Sharpless, N. E., Skulachev, V. P., Tilly, J. L., Tower, J., Verdin, E., and Vijg, J. (2010) Impact papers on aging in 2009, Aging (Albany NY), 2, 111–121.CrossRefPubMedCentralGoogle Scholar
  92. 92.
    Skulachev, V. P., Anisimov, V. N., Antonenko, Y. N., Bakeeva, L. E., Chernyak, B. V., Erichev, V. P., Filenko, O. F., Kalinina, N. I., Kapelko, V. I., Kolosova, N. G., Kopnin, B. P., Korshunova, G. A., Lichinitser, M. R., Obukhova, L. A., Pasyukova, E. G., Pisarenko, O. I., Roginsky, V. A., Ruuge, E. K., Senin, I. I., Severina, I. I., Skulachev, M. V., Spivak, I. M., Tashlitsky, V. N., Tkachuk, V. A., Vyssokikh, M. Y., Yaguzhinsky, L. S., and Zorov, D. B. (2009) An attempt to prevent senescence: a mitochondrial approach, Biochim. Biophys. Acta, 1787, 437–461.CrossRefPubMedGoogle Scholar
  93. 93.
    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., and Senin, I. I. (2017) Mitochondria–targeted antioxidant SkQ1 prevents anesthesia–induced dry eye syndrome, Oxid. Med. Cell. Longev., 2017, 9281519.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Vallabh, N. A., Romano, V., and Willoughby, C. E. (2017) Mitochondrial dysfunction and oxidative stress in corneal disease, Mitochondrion, 36, 103–113.CrossRefPubMedGoogle Scholar
  95. 95.
    Linton, J. D., Holzhausen, L. C., Babai, N., Song, H., Miyagishima, K. J., Stearns, G. W., Lindsay, K., Wei, J., Chertov, A. O., Peters, T. A., Caffe, R., Pluk, H., Seeliger, M. W., Tanimoto, N., Fong, K., Bolton, L., Kuok, D. L., Sweet, I. R., Bartoletti, T. M., Radu, R. A., Travis, G. H., Zagotta, W. N., Townes–Anderson, E., Parker, E., Van der Zee, C. E., Sampath, A. P., Sokolov, M., Thoreson, W. B., and Hurley, J. B. (2010) Flow of energy in the outer retina in darkness and in light, Proc. Natl. Acad. Sci. USA, 107, 8599–8604.CrossRefPubMedGoogle Scholar
  96. 96.
    Sacca, S. C., Roszkowska, A. M., and Izzotti, A. (2013) Environmental light and endogenous antioxidants as the main determinants of non–cancer ocular diseases, Mutat. Res., 752, 153–171.CrossRefPubMedGoogle Scholar
  97. 97.
    Shimmura, S., Tadano, K., and Tsubota, K. (2004) UV dose–dependent caspase activation in a corneal epithelial cell line, Curr. Eye Res., 28, 85–92.CrossRefPubMedGoogle Scholar
  98. 98.
    Sacca, S. C., Cutolo, C. A., Ferrari, D., Corazza, P., and Traverso, C. E. (2018) The eye, oxidative damage and polyunsaturated fatty acids, Nutrients, 10, E668.PubMedGoogle Scholar
  99. 99.
    Specht, S., Organisciak, D. T., Darrow, R. M., and Leffak, M. (2000) Continuing damage to rat retinal DNA during darkness following light exposure, Photochem. Photobiol., 71, 559–566.CrossRefPubMedGoogle Scholar
  100. 100.
    Roginsky, V., Barsukova, T., Loshadkin, D., and Pliss, E. (2003) Substituted p–hydroquinones as inhibitors of lipid peroxidation, Chem. Phys. Lipids, 125, 49–58.CrossRefPubMedGoogle Scholar
  101. 101.
    Antonenko, Y. N., Avetisyan, A. V., Bakeeva, L. E., Chernyak, B. V., Chertkov, V. A., Domnina, L. V., Ivanova, O. Y., Izyumov, D. S., Khailova, L. S., Klishin, S. S., Korshunova, G. A., Lyamzaev, K. G., Muntyan, M. S., Nepryakhina, O. K., Pashkovskaya, A. A., Pletjushkina, O. Y., Pustovidko, A. V., Roginsky, V. A., Rokitskaya, T. I., Ruuge, E. K., Saprunova, V. B., Severina, I. I., Simonyan, R. A., Skulachev, I. V., Skulachev, M. V., Sumbatyan, N. V., Sviryaeva, I. V., Tashlitsky, V. N., Vassiliev, J. M., Vyssokikh, M. Y., Yaguzhinsky, L. S., Zamyatnin, A. A., Jr., and Skulachev, V. P. (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, 1273–1278.CrossRefGoogle Scholar
  102. 102.
    Anisimov, V. N., Bakeeva, L. E., Egormin, P. A., Filenko, O. F., Isakova, E. F., Manskikh, V. N., Mikhelson, V. M., Panteleeva, A. A., Pasyukova, E. G., Pilipenko, D. I., Piskunova, T. S., Popovich, I. G., Roshchina, N. V., Rybina, O. Y., Saprunova, V. B., Samoylova, T. A., Semenchenko, A. V., Skulachev, M. V., Spivak, I. M., Tsybul’ko, E. A., Tyndyk, M. L., Vyssokikh, M. Y., Yurova, M. N., Zabezhinsky, M. A., and Skulachev, V. P. (2008) Mitochondria–targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 pro-longs lifespan and prevents development of traits of senescence, Biochemistry (Moscow), 73, 1329–1342.CrossRefGoogle Scholar
  103. 103.
    Neroev, V. V., Archipova, M. M., Bakeeva, L. E., Fursova, A. Zh., Grigorian, E. N., Grishanova, A. Y., Iomdina, E. N., Ivashchenko, Zh. N., Katargina, L. A., Khoroshilova–Maslova, I. P., Kilina, O. V., Kolosova, N. G., Kopenkin, E. P., Korshunov, S. S., Kovaleva, N. A., Novikova, Y. P., Philippov, P. P., Pilipenko, D. I., Robustova, O. V., Saprunova, V. B., Senin, I. I., Skulachev, M. V., Sotnikova, L. F., Stefanova, N. A., Tikhomirova, N. K., Tsapenko, I. V., Shchipanova, A. I., Zinovkin, R. A., and Skulachev, V. P. (2008) Mitochondria–targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age–related eye disease. SkQ1 returns vision to blind animals, Biochemistry (Moscow), 73, 1317–1328.CrossRefGoogle Scholar
  104. 104.
    Machemer, R., and Laqua, H. (1975) Pigment epithelium proliferation in retinal detachment (massive periretinal proliferation), Am. J. Ophthalmol., 80, 1–23.CrossRefPubMedGoogle Scholar
  105. 105.
    Yang, Y., Karakhanova, S., Soltek, S., Werner, J., Philippov, P. P., and Bazhin, A. V. (2012) In vivo immunoregulatory properties of the novel mitochondria–targeted antioxidant SkQ1, Mol. Immunol., 52, 19–29.CrossRefPubMedGoogle Scholar
  106. 106.
    Demianenko, I. A., Vasilieva, T. V., Domnina, L. V., Dugina, V. B., Egorov, M. V., Ivanova, O. Y., Ilinskaya, O. P., Pletjushkina, O. Y., Popova, E. N., Sakharov, I. Y., Fedorov, A. V., and Chernyak, B. V. (2010) Novel mito–chondria–targeted antioxidants, “Skulachev–ion” derivatives, accelerate dermal wound healing in animals, Biochemistry (Moscow), 75, 274–280.Google Scholar
  107. 107.
    Demyanenko, I. A., Zakharova, V. V., Ilyinskaya, O. P., Vasilieva, T. V., Fedorov, A. V., Manskikh, V. N., Zinovkin, R. A., Pletjushkina, O. Y., Chernyak, B. V., Skulachev, V. P., and Popova, E. N. (2017) Mitochondria–targeted antioxidant SkQ1 improves dermal wound healing in genetically diabetic mice, Oxid. Med. Cell. Longev., 2017, 6408278.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Demyanenko, I. A., Popova, E. N., Zakharova, V. V., Ilyinskaya, O. P., Vasilieva, T. V., Romashchenko, V. P., Fedorov, A. V., Manskikh, V. N., Skulachev, M. V., Zinovkin, R. A., Pletjushkina, O. Y., Skulachev, V. P., and Chernyak, B. V. (2015) Mitochondria–targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice, Aging (Albany NY), 7, 475–485.CrossRefGoogle Scholar
  109. 109.
    Voronkova, Ya. G., Popova, T. N., Agarkov, A. A., and Zinovkin, R. A. (2015) Effect of SkQ1 on activity of the glutathione system and NADPH–generating enzymes in an experimental model of hyperglycemia, Biochemistry (Moscow), 80, 1614–1621.CrossRefGoogle Scholar
  110. 110.
    Tiulina, V., Zernii, E., Baksheeva, V., Gancharova, O., Kabanova, E., Sotnikova, L., Zamyatnin, A., Philippov, P., and Senin, I. (2018) Mitochondria–targeted antioxidant SkQ1 improves corneal healing after UV–induced damage in rabbits, FEBS Open Bio, 8,215.Google Scholar
  111. 111.
    Novikova, Yu. P., Gancharova, O. S., Eichler, O. V., Philippov, P. P., and Grigoryan, E. N. (2014) Preventive and therapeutic effects of SkQ1–containing Visomitin eye drops against light–induced retinal degeneration, Biochemistry (Moscow), 79, 1101–1110.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • V. E. Baksheeva
    • 1
  • O. S. Gancharova
    • 1
  • V. V. Tiulina
    • 1
  • E. N. Iomdina
    • 2
  • A. A. ZamyatninJr.
    • 1
    • 3
  • P. P. Philippov
    • 1
  • E. Yu. Zernii
    • 1
    • 3
    Email author
  • I. I. Senin
    • 1
  1. 1.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Moscow Helmholtz Research Institute of Eye DiseasesMoscowRussia
  3. 3.Institute of Molecular MedicineSechenov First Moscow State Medical UniversityMoscowRussia

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