Effect of space flight on the behavior of human retinal pigment epithelial ARPE-19 cells and evaluation of coenzyme Q10 treatment.

Francesca Cialdai,Davide Bolognini,Alberto Magi,Monica Monici,Gianluca Neri,Michele Balsamo,Alessandro Donati,Leonardo Vignali,Sergio Capaccioli,Marco Vukich,Stefano Cacchione,Matteo Lulli,Nicola Iannotti

doi:10.1007/s00018-021-03989-2

Abstract

Astronauts on board the International Space Station (ISS) are exposed to the damaging effects of microgravity and cosmic radiation. One of the most critical and sensitive districts of an organism is the eye, particularly the retina, and > 50% of astronauts develop a complex of alterations designated as spaceflight-associated neuro-ocular syndrome. However, the pathogenesis of this condition is not clearly understood. In the current study, we aimed to explore the cellular and molecular effects induced in the human retinal pigment ARPE-19 cell line by their transfer to and 3-day stay on board the ISS in the context of an experiment funded by the Agenzia Spaziale Italiana. Treatment of cells on board the ISS with the well-known bioenergetic, antioxidant, and antiapoptotic coenzyme Q10 was also evaluated. In the ground control experiment, the cells were exposed to the same conditions as on the ISS, with the exception of microgravity and radiation. The transfer of ARPE-19 retinal cells to the ISS and their living on board for 3days did not affect cell viability or apoptosis but induced cytoskeleton remodeling consisting of vimentin redistribution from the cellular boundaries to the perinuclear area, underlining the collapse of the network of intermediate vimentin filaments under unloading conditions. The morphological changes endured by ARPE-19 cells grown on board the ISS were associated with changes in the transcriptomic profile related to the cellular response to the space environment and were consistent with cell dysfunction adaptations. In addition, the results obtained from ARPE-19 cells treated with coenzyme Q10 indicated its potential to increase cell resistance to damage.

Highlights

Space radiations and microgravity present in spacecraft and Space Stations in orbit around the Earth cause several time-dependent health alterations in astronauts both during their missions and after their return on the Earth
We investigated the impact of the space environment on human retinal pigment epithelial cells
We found that the transfer of ARPE-19 cells from Cape Canaveral to the International Space Station (ISS) and three day incubation on board did not affect their proliferation rate nor led them to apoptosis with respect to on ground controls

Summary

Introduction

Space exploration has entered a new phase in which NASA, ESA and other national space agencies are working together to plan long-term space missions in order, for example, to create lunar bases and reach other space destinations such as Mars. A basic principle of pharmacological research is that the most valid rational basis for identifying tools capable of blocking or inhibiting a pathological process is the knowledge of its pathogenic mechanisms. This principle applies to the variety of damages and health impairments known to be endured by astronauts during their long duration space missions

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