Glaucoma cure may lie in targeting 'stiff cells' that impede fluid drainage
Date: Sep-15-2014A 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.
Researchers say drugs that target the stiffness of the cells lining the Schlemm's canal could lead to a cure for glaucoma.
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.
Blockage in canal that drains the eye caused by faulty cells lining the walls
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."
Cell stiffness likely part of a dynamic process involving genes that respond to changes
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.
Written by Catharine Paddock PhD
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Courtesy: Medical News Today
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