The summer sun shone high over the Lions of Illinois Eye Research Institute. Inside, ophthalmology researcher Maximilian McCann examined cells extracted from an eyeball's gelatinous insides, as he'd been doing on and off for the last five years.

McCann, a UIC postdoctoral researcher in the College of Medicine, studies proliferative diabetic retinopathy, an advanced complication of diabetes that disrupts vision and can lead to blindness.

Now, in the lab, he paused. Something didn't add up. Had he made a mistake, or a discovery?

Just the facts

McCann originally set out to explore the how and why of proliferative diabetic retinopathy with an open mind, allowing curiosity to take the helm and facts to chart the course. In science, this learning-for-learning's-sake approach is called basic research, and it has advanced our knowledge of everything from penicillin to particle physics.

"My goal is to help every patient who experiences blindness as a result of proliferative diabetic retinopathy," McCann said. "Currently, not even our best treatment strategies can do that. So starting at the beginning seemed like the way to go."

Proliferative diabetic retinopathy happens when high blood sugar damages blood vessels and cuts off blood flow to the retina, where rods and cones translate light into images we see. In proliferative diabetic retinopathy, the eye is starved for a new energy source, so it grows new blood vessels, which spiderweb into the eyeball's jellylike interior, or vitreous.

These new, unimproved pathological vessels are weak. They're prone to leakage and even hemorrhaging, thereby impairing vision. Leaking fluid causes the retina to swell, which impairs both the processing of visual information and its relay to the brain, and leaked blood can cause a person to see spots. Built-up scar tissue from hemorrhaging and healing can pull the retina out of position, leading to permanent blindness.

But how does the big picture translate to individuals? To answer this question, McCann turned to the expert eyewitnesses: the patients.

The game's afoot - or a retina

Currently, the most common course of action to treat proliferative diabetic retinopathy involves surgically removing the offending blood vessels. This treatment can't reverse vision loss, but it's still a researcher's dream.

"Blood vessels from proliferative diabetic retinopathy patients are discarded after the surgery," said Andrius Kazlauskas, a professor in the College of Medicine and the study's senior author. "In this project, we transformed a surgical byproduct into an information-packed document."

Working with doctors, residents and nurses at UI Health, Kazlauskas and McCann analyzed the blood vessels removed from consenting patients with proliferative diabetic retinopathy. They extracted the endothelial cells, or the cells that wallpaper the vessels' interior.

Much to the researchers' surprise, a few patients' samples included no endothelial cells at all. Instead, immune cells were the dominant cell type in the surgical specimens.

"We had two groups of patients, and one was different than the other," Kazlauskas said. "That's when our basic research became a mystery."

Elementary, my dear endothelial cell

Why were some patients' ocular blood vessels overrun with immune cells?

At first, the researchers didn't know.

"We were like detectives driving our cars very slowly, looking for clues out the window, letting the evidence guide us step by step," Kazlauskas said.

The researchers pored over published research from their peers, trying to find something that might explain their result. Finally, they did: evidence that immune cells like the ones they'd observed had cleared away sick blood vessels - and their endothelial cells - in mice.

"That was the big surprise," McCann said. "Previously, it wasn't thought that the human eye has any sort of defense against pathological blood vessels. Nobody had observed these results in patients before."

Back to the basics

Kazlauskas and McCann will continue in the spirit of open-ended basic research.

"We started with a blank slate, and now we've gathered clues. From here, we can follow the evidence to find what comes next," Kazlauskas said.

Ultimately, the researchers hope that their discovery will inform better treatments for proliferative diabetic retinopathy. For now, their next step is determining whether the immune-endothelial cell swap is causative or coincidental.

This study appears in Signal Transduction and Targeted Therapy.

This research received funding from the National Institutes of Health.

Additional UIC authors include Basma Baccouche, Yueru Li, Priti Roy, Neil Sheth, Jennifer I. Lim, William F. Mieler, Felix Y. Chau, Lawrence J. Ulanski, R. V. Paul Chan, Monique Munro, Robert A. Hyde, Caitlin Berek, Anna Ong, Sudeshna De, Barbara Siedlecki, Ru-Ik Chee, Yannek I. Leiderman and Michael J. Heiferman.