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Vision Correction
Fall 2010
Newsletter

JORGE A. ALVARADO, M.D.

Professor of Ophthalmology and Physiology
 


Research Summary

Glaucoma

Untreated glaucoma is one of the leading causes of blindness in the U.S., with enormous economic and social costs. Yet the exact mechanisms of the
development of the disease are not known, and the means by which specific therapies work are not well understood.

The 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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