A unique international study that is unusual because it points to a mechanical feature of cells as a cause of disease suggests glaucoma arises when certain cells in the eye become stiff and impede drainage of fluid, causing pressure to build up. Treatments that target this stiffness could lead to a cure for glaucoma, say the researchers.
Glaucoma – a group of conditions that damage the optic nerve – is the second leading cause of blindness globally, after cataracts. It is caused by build-up of fluid in the eye, resulting in high pressure.
According to the US volunteer organization Prevent Blindness, there are currently over 2.7 million Americans aged 40 and older living with open-angle glaucoma – the kind that primarily affects people of African or European origin.
For 150 years, scientists have been trying to discover what causes the blockage that stops the aqueous humor – the clear fluid that nourishes the eye and maintains pressure inside the eyeball – from draining properly, causing pressure to build up, which, in turn, damages the optic nerve at the back of the eye.
Now, a unique study led by Mark Johnson, a professor of biomedical engineering and mechanical engineering at Northwestern University in Evanston, IL, reveals that the cause of the blockage is a fault in the endothelial cells that line the canal – known as Schlemm’s canal – through which the fluid drains from the eye.
The researchers describe their findings in the Proceedings of the National Academy of Sciences (PNAS).
The porous cells lining the walls of Schlemm’s canal help control the drainage of fluid from the eye. If, however, they become too stiff, it is more difficult for them to form pores, which impedes the flow of fluid out of the eye, and so builds up pressure.
This is what Prof. Johnson and colleagues discovered when they compared cultured endothelial cells isolated from the inner walls of Schlemm’s canals of healthy eyes and eyes affected by glaucoma.
For their study, they compared the cells from healthy and diseased eyes using “atomic force microscopy, optical magnetic twisting cytometry, and a unique cell perfusion apparatus.”
But the stiffness problem appears to be more than a straightforward mechanical fault in the plumbing of the eye. The researchers also found stiffness correlated with an “enhanced sensitivity to the mechanical microenvironment” of the cells, and this included changes in key genes.
Thus, they suggest the lining of the Schlemm’s canal is a dynamic material that responds and adapts to mechanical strain, using pore formation as a way to control the resistance to aqueous humor outflow. However, in eyes affected by glaucoma, this dynamic, responsive process becomes impaired.
Prof. Johnson, who is also a professor of ophthalmology, says drugs that target the stiffness of the cells lining the Schlemm’s canal could lead to a cure for glaucoma. He adds:
“The work appears to be one of the first times that the methods of mechanobiology – the study of the mechanical characteristics of cells – have been used to show that dysfunctional cell mechanics lies at the heart of a disease process.”
In June 2014, a group of engineers at the University of Washington in Seattle reported they are designing a sensor that can be implanted in the eye to monitor pressure. They hope their permanent implant will be able to continuously monitor hard-to-measure changes in eye pressure.