Experiments in Space Provide Insight into Aging-related Diseases of the Eye

By Eunice Marpaung (6/29/15)

A health care worker walks into a corridor in the hospital and immediately steps back when she sees the familiar yellow and black fan-like symbol that warns her of a nearby radiation source. But she has already been exposed to small doses of radiation every day of her life, at work, at home, and outdoors. With the increasing use of technology in medicine and daily living, our exposure to radiation has only increased with time.

Xiao Wen Mao, MD, an associate research professor in the Department of Basic Sciences, Division of Radiation Research at Loma Linda University, investigates the effects of radiation on individual molecules in the cell. As a research physician, she is particularly interested in how the molecules are damaged.

Mao has found on a specific organ —the eye. She is interested in molecular changes in the eye because they may explain why our eyes develop diseases, such as macular degeneration, cataracts, and diabetic retinopathy, with increasing age.

“There are different levels of radiation exposure,” she explains. “Higher dose exposure happens during radiation therapy. Low-dose radiation happens in relation to occupational radiation exposure, medical procedures, and frequent-flyer risks.” Low-dose exposure also increases outside of the Earth’s atmosphere, which makes spaceflight a great model for radiation-induced changes in the eye.

“Astronauts on space missions are exposed to levels of low-dose radiation that are above those typically encountered on Earth, and each exposure could contribute to degeneration in an incremental manner. More than 30% of the astronauts returning from space shuttle missions or the International Space Station are diagnosed with eye problems. At present, we know little about the pathophysiology associated with environmental conditions of space travel, including risk of low-dose radiation exposure in the eyes,” describes Mao.

Since many astronauts are coming back to Earth with vision difficulties, NASA is particularly interested in her work. In fact, in 2013, Mao was granted funding from NASA for ground-based research in this area. Interestingly, the changes in the astronauts’ eyes are similar to age-related changes in vision experienced by Earth-bound humans. With this evidence, Mao compares long-term spaceflight to accelerated aging, which potentially allows her research to be broadly applied to symptoms of aging.

Proton radiation is the most abundant form of radiation in space. In her experiments, Mao exposes mouse eyes to increasing increments of proton radiation to observe blood vessel changes in the eyes. Using advanced imaging and other techniques that Mao and her team have developed, they observe vasculature changes in the eyes of the mice as a result of radiation exposure. With increasing exposure to radiation, eyes lose more retinal endothelial cells that are required to maintain the retina and are critical for vision.

Mao also conducts space simulation experiments in her lab. Mice are put in a space-like environment with hind limb unloading to simulate fluid shifts in microgravity and low-dose radiation conditions. After the mice have “returned” from the space simulation, Mao investigates their brains, vasculature, stress levels, and behavior.

She will also conduct a spaceflight study which was funded by NASA in 2014. The objectives of this project are to use in-orbit flight animals to evaluate retinal microvascular and tissue remodeling that impact visual function and to identify factors and cellular mechanisms that trigger space environment-induced ocular structure and function. Mice will be sent into space, specifically to the International Space Station, where they will be housed from 30 days to six months. Eyes from these mice will be evaluated with physiological and functional endpoints in space and after returning to Earth. She and her team will assess spaceflight-induced oxidative stress, retinal vascular remodeling, mitochondrial associated-cell injury, and mitochondrial integrity in the retina assessing neuropathology by using stereological and automated image analyses, non-invasive magnetic resonance diffusion tensor imaging, and visual electroretinography.

A mechanism that Mao proposes to explain radiation-induced changes is the overproduction of reactive oxygen species (ROS), which have been correlated with symptoms of aging. Radiation causes more ROS to form than usual, leading to increased oxidative stress. Because mitochondria are involved in generating energy for cellular function, this critical organelle is particularly sensitive to oxidative stress. With unique, integrative, and advanced imaging and complex “omics” technology, Mao and her team aim to determine if oxidative damage in the retina is mediated through photoreceptor mitochondrial ROS production that leads to retinal degeneration.

Understanding molecular mechanisms helps researchers like Mao find specific countermeasures. She has already tested a potential radioprotectant called metalloporphyrin (MP). In Mao’s real and simulated space studies, MP is injected into the mice before they are placed in the space environment. The mice are then observed to see if MP protected them from the usual abnormal changes in eye physiology. She has observed that with the use of such radioprotectants, the cataracts that develop in the mice are less opaque.

“With the information from our space studies, we can find mechanisms for ground-based diseases,” says Mao. Further research may result in the discovery of countermeasures for age-related eye diseases on Earth. Even after exposure to radiation, whether in a clinical setting or daily life, there may be ways to avoid or reverse changes that happen in the eye. There may be a way to reduce the effects of normal radiation exposure on how we see the world around us. There may be a way to save our sight.