Gene changes linked to increased eye pressure may have implications for glaucoma therapy

University of North Carolina at Chapel Hill scientists have discovered that increased pressure within the eye alters a set of genes normally involved in preventing hardening of tissue.

Increased eye pressure often occurs in glaucoma, a blinding eye disease that affects about 70 million people worldwide, and the new findings may have implications for treating this disease. The study currently appears in the online October issue of the Journal of Cellular Physiology.

“Pressure is required in the eye to keep its shape, and this pressure is maintained in the front part of the eye by a fluid, the aqueous humor,” said Dr. Teresa Borrás, the paper’s senior author and professor of ophthalmology in UNC’s School of Medicine. From 1997 to 2002, Borrás held a Research to Prevent Blindness Jules and Doris Stein Professorship Award.

The aqueous humor is created by the ciliary body, a tissue beneath the eye’s iris. The fluid flows around the iris and out through the trabecular meshwork, or TM, a spongy tissue that provides resistance and maintains the pressure, Borrás said.

Often in glaucoma, the TM stops working and fluid builds up within the eye, causing pressure inside the eye to rise. When this happens, the optic nerve in the back of the eye can become squeezed. As this is the area that carries the visual signals from eye to brain, vision loss can occur, Borrás said.

In earlier studies, Borrás and her research group had shown that a greater outflow of fluid occurred when researchers artificially increased the pressure in human donor eyes.

“It was like the TM had a homeostatic counteracting mechanism that could sense an increase in pressure and open up a little bit, to help move the fluid out of the eye,” said Borrás.

However, it was unclear how the TM achieved this pressure regulation. This study was aimed at measuring what genes were turned on or off in the TM after the pressure was increased, Borrás added.

The UNC scientists knew that the homeostatic mechanism would involve sensing and triggering other genes. They were not surprised that most of the genes that were turned on fell into the group responsible for the cell signaling processes, Borrás said.

But unexpectedly, the genes switched on included two known from previous work to be involved in bone physiology: matrix Gla protein (MGP) and perlecan. In addition, the gene for spectrin, a protein that alters cell shape, was switched off.

MGP prevents the hardening of cartilage to bone, and perlecan has been implicated in allowing tissue to withstand compression, Borrás said. Spectrin helps maintain cell shape. Thus, when spectrin is switched off, cells are more easily deformed.

“It appears that these proteins help keep the TM soft, which would make the outflow of fluid easier and help to maintain normal pressure,” said Borrás.

The research team now is trying to better understand the role of these proteins in the regulation of pressure by the TM. “Our goal is to determine if one of these proteins can be used to treat glaucoma,” said Borrás.