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goal of my research is to improve glaucoma diagnosis and treatment
through a basic understanding of how glaucoma develops, and how
drugs and
other therapies affect the cells of the eye. Aqueous humor, a clear
nutrient fluid that bathes and supports the ocular tissues, is produced
by the ciliary body,
and it is drained through the trabecular meshwork and Schlemm's
canal. In glaucoma, drainage is insufficient to balance aqueous
production, and fluid
pressure can build up until the optic nerve is damaged.
Cellular Studies.
The research program in our laboratory is focused on the cellular
mechanisms involved in the development and treatment of glaucoma.
Together with Collin Murphy, PhD, and Johnnie Underwood Hu, PhD,
we are investigating aqueous outflow with a model using flow meters
to measure
the rate at which fluid moves across cells cultured from the tissues
of the trabecular meshwork and Schlemm's canal. This approach has
led to a better
understanding of how certain drugs and hormones affect aqueous outflow.
Drug Studies.
Epinephrine, a commonly used glaucoma medication, improves aqueous
outflow by shrinking the outflow cells to enlarge the spaces
between them, which improves fluid movement. Steroids, on the other
hand, which decrease aqueous outflow in certain patients and produce
"steroid
glaucoma," reduce the spaces between cells so that fluid cannot
get through.
We have determined that steroids increase the number of tight junctions
by inducing synthesis of a specific cell junction protein called
ZO-1. When the
cultured cells are exposed to the steroid, but production of ZO-1
is suppressed using an antisense oligonucleotide inhibitor, the
steroid effect on fluid flow
is also suppressed and fluid flow in the cell module is increased.
We are currently investigating the possibility of using such oligonucleotides
in glaucoma
therapy.
Other Research.
We
have used the cell culture flow meter model to examine the role
of specific wound-healing factors, such as those produced by
macrophage cells, which improve aqueous flow following injury. Insights
from this model are being tested in animal experiments to determine
their
therapeutic applicability. Other research projects include detection
of herpes simplex virus in irido-corneal-endothelial syndrome;
endocyclophotocoagulation (ECP) laser treatment; and the ultrasound
biomicroscope.
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