Usually when we think about our eyes, we think about the things our eyes are doing when we’re awake – such as the things we see. But what happens when our eyes are closed, such as when we’re sleeping? In fact, we sleep for about one-third of our lives, which means that our eyes are closed for one-third of the time, as well. So, what is happening during that time to our eyes? Cameron Postnikoff, a fifth-year doctoral student in the UAB Vision Science Graduate Program, is interested in this very question. In particular, he’s interested in understanding what happens to the ocular surface during sleep, which is the outermost surface of the eye.

The surface of the eye is dynamic

When our eyes are open, the surface of the eye is in regular contact with the world around us, including the particles, allergens and bacteria that float through the air. As a result, the eye’s surface is constantly changing: new particles move in and out, we blink frequently and tears regularly move across the eye’s surface. Postnikoff likens this to a daytime coffee shop, a dynamic place where there is a steady flow of patrons moving in and out. But when the eye is closed, such as when we’re sleeping, the tear flow slows down, blinking stops, and things begin to accumulate. If the open eye is a bustling, daytime coffee shop, the closed eye is a “nightclub,” where “everyone comes together and collects.” And among the things that collect on the eye’s surface are products-related inflammation, such as inflammatory proteins, inflammatory lipids and inflammatory cells.

Natural eye inflammation during sleep

So why is there inflammation on the eye’s surface while we sleep? Researchers hypothesize that inflammation may have several purposes. For example, inflammation could help to regulate the levels of bacteria on the eye that accumulate over the course of the day. Another hypothesis is that inflammation provides additional oxygen to our eyes during sleep, which is a time that our eyes can’t receive oxygen from the air. Or, inflammation could serve some sort of maintenance process that helps to regenerate and repair the surface of the eye.

Neutrophils, the underdog of inflammatory cells

Postnikoff’s research focuses on a particular type of inflammatory cell: neutrophils. Neutrophils are white blood cells that exist within the body to help control infection. They find and attack bacteria by killing it (degranulation), eating it (phagocytosis) or immobilizing it (NETosis). They are one of the first cells to travel to the site of infection, but are often short-lived. As Postnikoff describes, “I think of neutrophils as sort of like the underdog of immune cells,” underappreciated but serving an important purpose. In fact, his research shows that the number of neutrophils on the eye’s surface changes dramatically across the night as we sleep. During the first hour of sleep, the eye can accumulate up to 500,000 neutrophils. Throughout the night, this number increases to approximately 1 million. This is 5 times the concentration of neutrophils in the blood system! This sharp and rapid increase suggests that there’s an “active and strong, forceful recruitment of [neutrophils] to the ocular surface.” As a result, the overall immune environment of the eye is radically different when we sleep compared to when we’re awake.

Implications for disease

Inflammation during sleep may play a role in disease of the eye’s surface. By looking closely at the proteins on the surface of the neutrophil (the membrane receptors), researchers can determine whether the cell is active, passive, inflammatory or less inflammatory. Researchers can also examine whether the amount and types of membrane receptors are different in individuals with eye disease. Interestingly, neutrophils that accumulate during sleep in individuals with dry eyes contain about twice as many membrane receptors that are inflammatory compared to healthy individuals. This suggests that the inflammatory process is abnormal in some way in dry eye disease. Additionally, it suggests potential treatment. For example, Postnikoff’s research lab is currently conducting clinical trials to examine whether rinsing the eyes in the morning can change the inflammatory environment of the eye and be therapeutic. This could offer a better transition between the closed eye and open eye environments. As Postnikoff describes, it’s possible that “if you rinse [the neutrophils] off, it can help transition that night club into a coffee shop so that you’re ready to go for the rest of the day.”