Understanding how pressure is regulated in the eye could lead to new treatments for glaucoma

Scientists in the University of Arizona Department of Physiology have identified a potential molecular mechanism that may hold the key to understanding how pressure is regulated in the eye.

Funded by a $2.3 million five-year grant from the National Institutes of Health (NIH) National Eye Institute, this research could help to develop future treatments for glaucoma and other diseases.

Glaucoma is an incurable disease caused by improper drainage of the aqueous humor (the fluid that nourishes the eye). The imbalance of fluid inflow and outflow elevates the intraocular pressure (the fluid pressure inside the eye), eventually damaging the optic nerve, causing progressive vision loss.

Current treatments focus on lowering eye pressure with eyedrops and oral medications. However, these drugs lose their effectiveness over time. More than 3 million Americans suffer from glaucoma, the second-leading cause of blindness in the United States.

In response to this major health issue, Nicholas Delamere, PhD, professor and head of the Department of Physiology at the UArizona College of Medicine - Tucson and his research team have discovered a specific "mechanosensitive ion channel," TRPV4, which they believe senses and helps regulate pressure inside the eye.

Mechanosensitive channels (MS channels) are proteins found in most cell membranes that open a conductance pore in response to mechanical stress.

The size of each cell in the body is determined by the regulation of the amount of fluid that flows in and out of the cell itself. Cells continually swell and shrink to maintain their appropriate dimensions. Pressure-sensing mechanisms control the correct amount of fluid in each cell, but exactly what signal tells the cell to switch from input to output of these fluids to keep the precise amount of pressure remains a mystery, Dr. Delamere explained.

"Like a cell, the eyeball needs the correct amount of fluid formation and drainage to keep its proper size to stay plump and healthy. You have to keep the eye inflated like a basketball, but like a basketball, it can become overinflated," he said. "We still don't really know how the eye knows to keep the pressure balanced on a safe level. Glaucoma is an example when the pressure-sensing mechanism stops working and the pressure rises too high, causing all kinds of damage."

Cells feel the stretch and strain of mechanical forces caused by pressure. Recent studies have found when cells are stretched or strained, certain pores in the membrane will open and that is a signal for the cell to react. Dr. Delamere's research is focused on finding the "ion channel" - the switch that responds to pressure in the eye. This specific switch has never been looked at before.

If the findings prove true, it means we have another piece of the puzzle on how the eye regulates. If we understand how it works properly, we get a ticket to understanding when it doesn't work and how we can prevent that. Understanding these ion channels and the signaling that determines the proper regulating of fluid also could be important in understanding blood pressure regulation and the growth of cancer cells. You have a target mechanism for the development of new drugs."

Nicholas Delamere, PhD, professor and head of the Department of Physiology at the UArizona College of Medicine - Tucson

"Glaucoma is a health care problem with major implications for millions of people," said UArizona President Robert C. Robbins, MD. "Dr. Delamere and his team of researchers have identified a mechanism that may control cellular pressure regulation, a discovery that could lead to new treatments and a better understanding of this issue."