Georgia Tech
Glaucoma is the second leading cause of blindness. Nearly 4
million Americans have the disorder, which affects 70 million worldwide. There
is no cure and no early symptoms. Once vision is lost, it’s permanent.
New findings at Georgia Tech, published in January during Glaucoma
Awareness Month, explore one of the many molecular origins of glaucoma and
advance research dedicated to fighting the disease.
Glaucoma is typically triggered when fluid is unable to
circulate freely through the eye’s trabecular meshwork (TM) tissue. Intraocular
pressure rises and damages the retina and optic nerve, which causes vision loss.
In certain cases of glaucoma, this blockage results from a build-up of the
protein myocilin. Georgia Tech Chemistry and Biochemistry Assistant Professor
Raquel Lieberman focused on examining the structural properties of these myocilin
deposits.
“We were surprised to discover that both genetically defected
as well as normal, or wild-type (WT), myocilin are readily triggered to produce
very stable fibrous residue containing a pathogenic material called amyloid,”
said Lieberman, whose work was published in the most recent Journal of Molecular Biology.
Amyloid formation, in which a protein is converted from its
normal form into fibers, is recognized as a major contributor to numerous
non-ocular disorders, including Alzheimer’s, certain forms of diabetes and Mad
Cow disease (in cattle). Scientists are currently studying ways to destroy
amyloid fibrils as an option for treating these diseases. Further research,
based on Lieberman’s findings, could potentially result in drugs that prevent
or stop myocilin amyloid formation or destroy existing fibrils in glaucoma
patients.
Until this point, amyloids linked to glaucoma had been
restricted to the retinal area. In those cases, amyloids kill retina cells,
leading to vision loss, but don’t affect intraocular pressure.
“The amyloid-containing myocilin deposits we discovered kill
cells that maintain the integrity of TM tissue,” said Lieberman. “In addition
to debris from dead cells, the fibrils themselves may also form an obstruction
in the TM tissue. Together, these mechanisms may hasten the increase of
intraocular pressure that impairs vision.”
Together with her research team, Lieberman produced WT and
genetically defected myocilin variants that had been documented in patients who
develop glaucoma in childhood or early adulthood. The experiments were
conducted in collaboration with Georgia Tech Biology Professor Ingeborg Schmidt-Krey
and Stanford Genetics Professor Douglas Vollrath. Three Georgia Tech
students also participated in the research: Susan Orwig (Ph.D. graduate,
Chemistry and Biochemistry), Chris Perry (current undergraduate, Biochemistry)
and Laura Kim (master's graduate, Biology).
The National Institutes of Health (award number
R01EY021205 from the National Eye Institute) funded the research. The content
is solely the responsibility of the authors and does not necessarily represent
the official views of the National Eye Institute or the National Institutes of
Health.