Collaboration yields new ocular disease target

Scientists now have a clearer idea of the importance of a particular protein in normal eye function thanks to a collaboration by scientists at the Dean McGee Eye Institute and OMRF. The research could help improve understanding and treatment of vision-impairing diseases like diabetic retinopathy and age-related macular degeneration.

The project focused on the role a protein called caveolin-1 plays in eye disease.

“Research into several ocular diseases points to this protein, but little work had been done on its role in normal eye function,” said OMRF scientist Rheal Towner, Ph.D., who worked with scientists at DMEI on the research.

Project leader Michael Elliott, Ph.D., of DMEI, said that by “knocking out” or removing the gene that makes the protein, they were able to examine mice that lacked caveolin-1. What they found surprised them.

“We thought the protein might have a direct effect on the retina, but instead, it seems to regulate the environment in which the retina lives,” said Elliott. “The right environment is vital for proper function, so caveolin-1 might be a useful therapeutic for repairing some diseases that involve eye structure.”

Ocular diseases like diabetic retinopathy and age-related macular degeneration could be affected by the discovery, he said.

Towner examined the eyes of mice missing the gene to make the protein and compared them with those of “normal” mice in OMRF’s Advanced Magnetic Resonance Center Imaging Facility.

Their research, recently published in the Journal of Biological Chemistry, shows that caveolin-1 plays a vital role in healthy eye function, especially in the blood-retinal barrier.

“The blood-retinal barrier acts as a shield to keep unwanted substances out of the retina and is important for preventing injury and disease,” said Towner. “We discovered that when caveolin-1 was missing, the barrier couldn’t be maintained.”

Eyes without the protein also had trouble adapting to changes in lighting, Towner said.

Using the state-of-the-art functional MRI facilities at OMRF, scientists were able to view the thickness of the barrier down to 100 microns, or 1/254th of an inch, allowing a much closer look at the structure of the eye.

“As the technology becomes more sophisticated, we’re able to delve deeper into the physical makeup of biological structures than we ever have before,” Towner said.

The next step in the research will be to investigate if caveolin-1 therapy could repair deficits in the eye’s structure, Elliott said.