FUNDING PERIOD: APRIL 1, 2005 – MARCH 31, 2007

Raymond Chuen-Chung Chang, Ph.D.
The University of Hong Kong
Hong Kong, China
Project: Microglia/Microphages and Neuroprotection in Glaucoma

Glaucoma is a chronic disease in which the neurons, called retinal ganglion cells, undergo degeneration. Another trait of developing glaucoma is an increase of pressure within the eyes. Recently, a novel approach was proposed to utilize our body immunity to protect neurons in the eyes. Dr. Chang’s study aims to define which factors or what conditions for the activation of innate immune cells can lead these cells to elicit protective effects. He will also study how a Chinese medicine, Chinese Wolfberry, exhibits protective effects to neurons in the eyes via mild activation of innate immune cells. Knowledge of how body immunity exerts protective effects to neurons in the eyes will hopefully pave a new road for therapeutic intervention against loss of vision in glaucoma.

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Deepak Edward, M.D.
University of Illinois at Chicago
Chicago, IL
Project: In Vivo Study of Femtosecond Laser Ablation

The current procedure for reducing eye pressure is to make an opening in the trabecular meshwork to allow the aqueous humor to flow more freely into the Schlemm’s canal. A common form of this procedure is known as laser trabecular ablation, or LTA. This procedure involves long pulse durations that can cause collateral damage, including inflammation and scarring, and eventually leads to closure of the incision. Dr. Edward plans to study the results of a new technique using an ultrafast Titanium Sapphire laser, which has been found to overcome all of the aforementioned problems. By studying changes in the treated eye over a period of up to two months, Dr. Edward hopes to better understand the interplay between mechanical effects of the laser and the biologic response that might occur during wound healing.

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Dorette Ellis, Ph.D.
University of Florida
Gainesville, FL
Project: The Role of sGC Activators as Ocular Hypotensive Agents

Researchers have shown that topical application of nitric oxide to rabbit and monkey eyes causes significant decreases in intraocular pressure. This would suggest that nitric oxide could be used to treat high intraocular pressure in glaucoma. However, higher doses of nitric oxide are less effective than lower doses and constant use of some nitric oxide donors result in tolerance. Nitric oxide binds to its target enzyme called soluble guanylate cyclase causing the formation of cGMP, and subsequent activation of other proteins and effects. There are gaps in our knowledge about the involvement of nitric oxide and soluble guanylate cyclase, and the role of nitric oxide in glaucoma. A better understanding of the interaction between soluble guanylate cyclase activators, their target enzyme, and down stream effectors will lead to new strategies in the treatment of glaucoma.

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Haiyan Gong, M.D., Ph.D.
Boston University School of Medicine
Boston, MA
Project: Can Wash-Out be Induced in the Human Eye to Reduce IOP?

In order to be transparent so that vision is possible, some of the tissues of the eye have no blood supply. These tissues depend upon a clear nutritive fluid called aqueous humor in order to survive. Used aqueous humor leaves the eye through a specially designed filtration tissue known as the trabecular meshwork. The finest mesh of this filer is called the juxtacanalicular region (JCT). After flowing through the JCT, used aqueous humor passes through the inner wall lining cells of Schlemm’s canal and into the veins leaving the eye. Disruption of connectivity between the inner wall of Schlemm’s canal and the JCT is predicted to increase aqueous humor outflow facility and may lead to the development of novel therapeutic agents for the treatment of the elevated pressure associated with glaucoma.

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Cynthia L. Grosskreutz, M.D., Ph.D.
Massachusetts Eye and Ear Infirmary
Boston, MA
Project: Heat Shock Proteins in Experimental Glaucoma

Heat shock proteins (HSP) are a group of highly conserved proteins that act in a coordinated response to environmental and physiological stress. It has been recently observed that one member of this protein family, HSP27, is elevated in certain genetic models of glaucoma. Dr. Grosskreutz hopes to discover whether experimentally increasing HSP27 levels in the eye will prevent neuronal death in the retina in glaucoma. She will apply this gene therapy to increase and decrease HSP27 levels in the retina and record changes. Together, these results will provide important new information regarding the role of heat shock proteins in retinal ganglion cell death in glaucoma, and provide clues to new neuroprotective treatment approaches for this blinding disease.

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Paul Kaufman, M.D.
University of Wisconsin Medical School
Madison, WI
Project: A.G.E. Crosslink Breakers for Ocular Disorders

Dr. Kaufman will determine whether the crosslink breaker compound, alagebrium, can alter intraocular pressure, improve the ease with which fluid passes out of the eye (outflow facility) via the conventional outflow pathways, and improve the ability to focus in response to a pharmacologic stimulus. Completion of these studies will clarify whether crosslink breaker compounds have any promise for further development as therapies for primary open angle glaucoma or presbyopia, the age-related loss of focal ability. This type of therapy would target a different pathway than all other glaucoma therapeutics and create the first pharmacologic therapy for presbyopia.

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David Mackey, M.D.
Royal Victorian Eye & Ear Hospital
East Melbourne, Australia
Project: Ophthalmic Examination of Dizygotic Twins in Queensland

Glaucoma is thought to have a major genetic component. Several genes have been identified, but so far these only accounts for 5% of glaucoma cases. Twin studies are an important tool for determining the relative contribution of genes or environment in any measure. If there is very little genetic component, then identical twins will vary as much as non identical twins. Dr. Mackey will analyze pressure, refraction, optic nerve, corneal thickness and many other measures in his study, and then compare all the numerical measurements of the twins with their DNA markers to discover where similar twins consistently have similar DNA markers. Discovering the genes that cause glaucoma will enable other family members to be tested and predict who is at high risk or low risk of developing glaucoma. This will allow better early screening for glaucoma and potentially lead to the development of new treatments.

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Catherine McCarty, Ph.D., M.P.H.
Marshfield Clinic Research Foundation
Marshfield, WI
Project: A Population-Based Study of Pharmacogenetics and Glaucoma

Beta-blockers are a common class of medication used to lower intraocular pressure. Interestingly, this same class of medications is used orally to treat high blood pressure, and genetics have been shown to play a role in how a person responds to this medication. Dr. McCarty believes that genetics is also associated with how a person responds to a prescription for medication to lower intraocular pressure. Her goal is to ultimately improve treatment of patients with glaucoma and ocular hypertension. In the future this study may lead to an assessment as to whether prescription medications based on genotype would improve cost effectiveness and preserve visual function in people with glaucoma and intraocular hypertension.

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