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The Coenzyme Q10 as an antiapoptotic countermeasure for retinal lesions onboard the International Space Station

Matteo Lulli1*, Francesca Cialdai2, Leonardo Vignali2, Monica Monici2, Sara Luzzi3, Alessandro Cicconi3, Stefano Cacchione3, Alberto Magi4, Michele Balsamo5, Marco Vukich5, Gianluca Neri5, Alessandro Donati5 and Sergio Capaccioli6
  • 1 Università degli Studi di Firenze, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Italy
  • 2 Università degli Studi di Firenze, Italy
  • 3 Dipartimento di Biologia e Biotecnologie Charles Darwin, Sapienza Università di Roma, Italy
  • 4 Department of Experimental and Clinical Medicine, University of Florence, Italy
  • 5 Kayser (Italy), Italy
  • 6 Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, Italy

Health of astronauts operating in the International Space Station (ISS) is a major concern for Space Agencies. In addition to a variety of intrinsic environmental issues, the astronauts are exposed for some months to damaging effects of microgravity and low level of high energy solar and cosmic radiation entering the ISS, which ultimate outcome at cellular level is apoptosis (1). Eye, and especially the retina, is one of the most critical and sensitive districts of astronaut organism. Several in vitro and in vivo studies in the retina have shown that microgravity and cosmic radiation generate reactive oxygen species (ROS), which in turn damage retinal cells and induce apoptosis as well as inflammatory response (2-9). Since effective prevention strategies have been scarce so far, we aimed to find pharmacological countermeasures within the CORM project funded by the Italian Space Agency, exploiting the antiapoptotic activity of the Coenzyme Q10 (CoQ10), the unique lipid soluble antioxidant synthesized endogenously. We have previously demonstrated that CoQ10 inhibits apoptosis of corneal keratocytes subjected to excimer laser irradiation (10, 11) and that this was due to its ability to hinder mitochondrial depolarization (12). Successively, we demonstrated that CoQ10 inhibits retinal cells apoptosis induced by radiation both in vitro and in vivo (13) and, if applied as eye drops on the cornea, it reaches the retina protecting the retinal layers from excitotoxicity-induced apoptosis (14). Therefore, we considered CoQ10 as a promising countermeasure to prevent retinal damages elicited by microgravity and cosmic radiation (Figure 1). The CORM project involved two experimental phases. The first was the demonstration of CoQ10 ability to counteract radiation- and simulated microgravity-induced alterations of the human retinal pigment epithelial ARPE-19 and mouse retinal ganglion RGC-5 cells. The second was the execution onboard the ISS in the frame of the ASI VITA mission of an experiment driven by the Italian astronaut of the European Space Agency (ESA) Paolo Nespoli. The experiment has been primed at the Kennedy Space Center (FL, USA) inside specific hardware developed by Kayser Italia integrated in the Kubik incubator of ESA, launched to the ISS by the SpaceX-12 vehicle and recovered to the Earth with the same vehicle. ARPE-19 cells treated and not treated with CoQ10 have been subjected to space environment onboard the ISS for 72h. Once back to the Earth, the following parameters have been evaluated: apoptosis rate, cytoskeleton morphology, telomere length and integrity, RNA and DNA whole sequence. Experiments on ground revealed that CoQ10 prevents simulated microgravity-induced apoptosis and cytoskeleton alterations in ARPE-19 and RGC-5 cells, and lowers X-radiation-induced accumulation of telomere-induced foci (TIF) as well as senescence promotion in ARPE-19 cells (5). The results obtained in the CORM project will reveal the damaging effect of the ISS environment on human retinal cells and could qualify CoQ10 as an effective countermeasure. Obviously, this may have a major impact on the Earth to treat different human retinopathies, ranging from glaucoma to age-related macular degeneration, characterized by apoptotic cell death.

Figure 1
Image

Acknowledgements

This research has been supported by the Agenzia Spaziale Italiana (Contract Number 2016-6-U.0 (CORM), PI Matteo Lulli). ASI has coordinated the program and has provided the access to the ISS and to the onboard resources thanks to the Memorandum of Understanding between ASI and NASA for the design, development, operation, and utilization of three mini pressurized logistic modules for the International Space Station.

References

1. J. S. Alwood et al., From the bench to exploration medicine: NASA life sciences translational research for human exploration and habitation missions. NPJ Microgravity 3, 5 (2017). 2. X. W. Mao et al., Spaceflight environment induces mitochondrial oxidative damage in ocular tissue. Radiat Res 180, 340-350 (2013). 3. X. W. Mao et al., Acute Effect of Low-Dose Space Radiation on Mouse Retina and Retinal Endothelial Cells. Radiat Res 190, 45-52 (2018). 4. H. W. Zhao et al., Effect of long-term weightlessness on retina and optic nerve in tail-suspension rats. Int J Ophthalmol 9, 825-830 (2016). 5. M. Lulli et al., The Coenzyme Q10 (CoQ10) as Countermeasure for Retinal Damage Onboard the International Space Station: the CORM Project. Microgravity Science and Technology, (2018). 6. J. Tombran-Tink, C. J. Barnstable, Space flight environment induces degeneration in the retina of rat neonates. Adv Exp Med Biol 572, 417-424 (2006). 7. C. Cingolani et al., Retinal degeneration from oxidative damage. Free Radic Biol Med 40, 660-669 (2006). 8. J. E. Roberts et al., Simulated microgravity induced damage in human retinal pigment epithelial cells. Mol Vis 12, 633-638 (2006). 9. T. H. Mader et al., Intraocular pressure and retinal vascular changes during transient exposure to microgravity. Am J Ophthalmol 115, 347-350 (1993). 10. R. Brancato et al., Prevention of corneal keratocyte apoptosis after argon fluoride excimer laser irradiation with the free radical scavenger ubiquinone Q10. Eur J Ophthalmol 10, 32-38 (2000). 11. R. Brancato et al., Concomitant effect of topical ubiquinone Q10 and vitamin E to prevent keratocyte apoptosis after excimer laser photoablation in rabbits. J Refract Surg 18, 135-139 (2002). 12. L. Papucci et al., Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J Biol Chem 278, 28220-28228 (2003). 13. M. Lulli et al., Coenzyme Q10 protects retinal cells from apoptosis induced by radiation in vitro and in vivo. J Radiati Res 53, 695-703 (2012). 14. M. Lulli et al., Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage. Investigative Ophthalmology and Visual Science 53, 8295-8302 (2012).

Keywords: Coenzyme Q10 (CoQ10), Retina, Microgravity (μg), Apoptosis, ISS, antioxidant

Conference: 39th ISGP Meeting & ESA Life Sciences Meeting, Noordwijk, Netherlands, 18 Jun - 22 Jun, 2018.

Presentation Type: Extended abstract

Topic: Astronaut health

Citation: Lulli M, Cialdai F, Vignali L, Monici M, Luzzi S, Cicconi A, Cacchione S, Magi A, Balsamo M, Vukich M, Neri G, Donati A and Capaccioli S (2019). The Coenzyme Q10 as an antiapoptotic countermeasure for retinal lesions onboard the International Space Station. Front. Physiol. Conference Abstract: 39th ISGP Meeting & ESA Life Sciences Meeting. doi: 10.3389/conf.fphys.2018.26.00036

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Received: 02 Dec 2018; Published Online: 16 Jan 2019.

* Correspondence: Dr. Matteo Lulli, Università degli Studi di Firenze, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Florence, Italy, matteo.lulli@unifi.it