Activation of the visual system by space radiation: A novel study on Ca2+ signalling in ex-vivo rabbit eyes exposed to visible light, X-rays and high-energy protons

Space radiation interactions with the visual system have been the subject of many investigations, starting from astronauts reporting the perception of light flashes (visual illusions in absence of light stimuli). These perceptions have been attributed to single-ion hits, able to induce an electrophysiological response in the eye. Searching for a more general mechanism of radiation interaction with cortical neuronal networks and with sensory systems, a valuable hypothesis is that of the perturbation to calcium (Ca²⁺) homeostasis. We here report results on radiation-induced perturbation of Ca²⁺ signalling obtained with an ex-vivo whole rabbit eye model. Surgically enucleated eyes (from animals intended for human consumption) were kept in viable conditions and exposed to visible light (varying the duration of the exposure), to kilovoltage X-rays (reference radiation, dose range 10-200 mGy) and to 230 MeV protons (representative of the main component of space radiation, dose range 10-20 mGy). After extraction of the vitreous humor, sample stability and homogeneity in the animal population and organ conditions were verified by measuring the concentration of biogenic polyamines, while eye integrity was tested by measuring the lactate dehydrogenase (LDH) enzymatic activity. The activation of the visual response is attributed to a change in the Ca²⁺ concentration (expressed μg calcium/μg amines) comparing, for each animal, the left eye used as a control and the right eye exposed to light or ionizing radiation. The vitrectomy was conducted immediately after the exposure. A significant increase in Ca²⁺ concentration was measured after white light exposure with a duration longer than 1 min, with a saturation to a ∼150 % relative change for exposure durations of 3 and 5 min. The model was therefore validated for the visual system activation by light, but no increase in Ca²⁺ concentration was found for ionizing radiation exposures in the investigated dose ranges. Only at the highest X-ray dose of 200 mGy, eyes were severely damaged, as demonstrated by the drastic increase in LDH activity. Based on these findings, the limitations of the study are critically discussed, and improvement strategies are suggested, also considering the rapid kinetics of the perturbation that might hinder the measurement of small ionizing radiation-induced transient Ca²⁺ changes.