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MOST COMMON EYE DISEASES , , AND INFECTIOUS DISEASES

Research and educational programs are essential to find cures for the most common causes of blindness, macular degeneration and glaucoma, which are currently irreversible, and infectious and inflammatory eye diseases, which have reached epidemic proportions worldwide. To combat these eye conditions, affecting millions of Americans and individuals around the world, UCSF is making a commitment toward medical breakthroughs. That Man May See seeks anchor gifts as well as seed funding for studies leading to the detection, treatment, and potential eradication of these eye disorders.

UCSF faculty and research teams work steadily to uncover new therapies and procedures to relieve the burden of blindness and vision loss. Current studies include plans to better diagnose and treat early stages of macular degeneration and research that has uncovered a potential role for the immune system in glaucoma. UCSF is a world leader in the research and treatment of infectious and inflammatory diseases of the eye, including , ocular diseases due to the herpes viruses, and AIDS-associated ocular infections, as well as corneal ulcers and trachoma.

Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of visual loss in America for those 60 years and older. One in three adults over 75 will suffer from AMD. Otherwise healthy people lose the ability to read and drive, and are at risk for early loss of an independent life.

Visual loss in AMD is usually caused by growth of abnormal blood vessels underneath the macula, a small area in the back of the eye where central vision is located. Current treatments address the late stages of AMD and, for the most part, only minimally postpone loss of vision. With the exception of antioxidant vitamins, there are no effective treatments for early AMD. An innovative team of scientists from UCSF is developing new imaging technology that could provide the breakthrough needed to combat AMD. In addition, UCSF researchers are developing improved diagnostic measures leading to greater understanding of the pathogenesis and cellular mechanisms of retinal degenerations.

Glaucoma

Glaucoma is recognized as the leading cause of irreversible blindness. It affects over three million people in the United States alone and nearly 70 million people worldwide. Glaucoma is a silent blinding disease, given this title because it usually does not cause pain or central vision loss until advanced stages.

Of all the diseases treated by ophthalmic medical professionals, glaucoma may be the most challenging one. Studies under way at UCSF could very well transform this particular field of medicine and how the disease is treated in the future. Working with teams of world-class investigators, researchers are seeking to develop specific glaucoma therapies that may lead to the

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discovery of a cure for glaucoma. These investigators have already uncovered a previously unrecognized role for the immune system in glaucoma that could lead to radically new treatment strategies.

Infectious Diseases of the Eye

Through UCSF’s Francis I. Proctor Foundation for Research in , teams of clinician scientists work toward the prevention and treatment of infectious and inflammatory eye diseases. Recognized as the preeminent center for this discipline, the Proctor Foundation is dedicated to research, training, and application of this research to the prevention of blindness worldwide.

Teams of medical researchers with experience in the medical and surgical management of infectious and inflammatory ocular disease demonstrate particular interest in high-risk keratoplasty, extraction in patients with uveitis, ocular disease due to the herpes viruses, and AIDS-associated ocular infections.

Two programs of significant magnitude are under way in South India to battle corneal ulcers and in Ethiopia toward the elimination of trachoma.

Examples of UCSF Ophthalmology Faculty Research Related to Macular Degeneration

Daniel M. Schwartz, MD The innovative collaboration among UCSF, California Institute of Technology (Caltech), and the University of Medicine and Dentistry of New Jersey (UMDNJ) is focused on developing a novel therapy to diagnose and treat macular degeneration early in the course of the disease, before visual loss has occurred. In early AMD, there is progressive accumulation of lipids (fats) in Bruch’s membrane, a thin tissue layer that lies between the and its blood supply. Presumably, as these fats accumulate and block transport across Bruch’s membrane, retinal nutrition is impaired. Inadequate delivery of oxygen and nutrients to the retina eventually stimulates growth of abnormal blood vessels (neovascularization), which bleed and cause severe visual loss. The team includes recent Nobel Prize recipient Robert Grubbs, PhD.

Robert B. Bhisitkul, MD, PhD Dr. Bhisitkul is studying the underlying mechanisms of photoreceptor cell dysfunction and death as well as the development of abnormal blood vessels under the macula. His research has progressed to clinical trials using synthetic molecules to block abnormal blood vessel development.

Eugene de Juan, Jr., MD Dr. de Juan has made prodigious contributions to his areas of major research interest that include severe vitreoretinal disease, pigmentosa, macular degeneration, and vitreoretinal surgical instrument development. He has published over 200 scholarly, peer-reviewed journal articles and amassed more than 40 issued patents. Dr. de Juan is initiating several clinical trials at UCSF leading to potential novel treatments for retinal disorders.

Jacque L. Duncan, MD, and Matthew M. LaVail, PhD Drs. Duncan and LaVail work in the area of (RP) and AMD, loss of vision as a result of photoreceptor cell degeneration and death. Treatments that can prevent photo-

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receptor degeneration in experimental models of retinal degenerations may be effective in preventing degeneration in both RP and AMD. This work investigates novel treatments to preserve retinal function. Dr. LaVail’s research demonstrated that subretinal and intravitreal injection of various growth factors protect the retina from degenerating in several models of inherited retinal degenerations. His research is designed to further investigate the retinal func- tional response to ribozyme therapy in different experimental models of dominantly inherited retinal degenerations.

Examples of UCSF Ophthalmology Faculty Research Related to Glaucoma

Robert L. Stamper, MD Head of the glaucoma service at UCSF Department of Ophthalmology, Dr. Stamper has several research interests in the area of glaucoma. He is using a form of electroencephalogram to plot the extent of peripheral vision. This new technology, called the multifocal visual-evoked potential, requires less patient input and is less frustrating than the currently used computerized visual field. Dr. Stamper has just completed a four-year multicenter study of a new drug that treats glaucoma, not by lowering the pressure but by strengthening the ’s ability to withstand pressure. Results of this totally new idea in glaucoma therapy should be available shortly. Finally, Dr. Stamper is helping to develop innovative ways of surgically managing glaucoma.

Jorge A. Alvarado, MD Dr. Alvarado’s work examines the cellular basis for the development of glaucoma and the role that the body’s immune system plays in the control of eye pressure, a key element to glaucoma. Dr. Alvarado’s lab has uncovered the role that monocytes play in the regulation of eye pressure, and this discovery suggests intriguing new methods for regulating eye pressure and treating glaucoma.

Douglas B. Gould, PhD The major goals of Dr. Gould’s research program are to understand the cellular processes that lead from COL4A1 gene mutations (and other basement membrane components) to human diseases. COL4A1, a type of collagen, affects eye development and also predisposes mice to brain hemorrhages – a condition that exists in humans as well. Dr. Gould is using multiple approaches to dissect genetic interactions and to test mechanistic hypotheses. Understanding basic disease mechanisms could help people with COL4A1 mutations, and potentially others, reduce the risk of stroke and retain their vision into old age.

Jeanette Hyer, PhD Dr. Hyer’s lab works on the development of the anterior portion of the eye (the , , , and ), how that complicated structure forms, and what has gone wrong when it does not form correctly. An understanding of how these tissues originally develop will aid in learning how they might be reformed and reengineered in the future, perhaps using an individual’s own retinal stem cells (stem cell populations have been found within both the iris and corneal tissue).

Shan C. Lin, MD One of Dr. Lin’s research efforts focuses on the American Chinese Eye Study. The study reaches out to members of this community, beginning with residents of San Francisco’s Chinatown, who are less likely to seek out vision care due to financial or cultural issues. Results of this research

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effort can help Bay Area residents and also serve to effect diagnostic tools and treatment worldwide.

David W. Sretavan, MD, PhD Dr. Sretavan and his team have a number of different projects in the lab. They are linked by a fundamental interest in the processes of nerve cells called axons. Axons are key to information processing in the eye and in the brain, and axonal damage from injury or disease has irreversible consequences for vision. Specific studies include basic mechanisms of retinal ganglion cell axon damage in glaucoma, and novel methods using micro- and nanoscale devices for axon micro- repair.

Erik M. Ullian, PhD Dr. Ullian’s laboratory is focused on several genetic and signaling mechanisms that regulate retinal neuron survival, morphology, and function. Dr. Ullian aims to understand the basic biological mechanisms that regulate neuronal function and survival. This work is relevant to a variety of diseases and conditions where neurons become sick or do not function normally, as in glaucoma.

Examples of UCSF Ophthalmology Faculty Research Related to Infectious Diseases

Todd P. Margolis, MD, PhD Director of the Proctor Foundation is Todd Margolis, MD, PhD. His clinical experience is in the medical and surgical management of infectious and inflammatory ocular disease with a particular interest in high-risk keratoplasty, cataract extraction in patients with uveitis, ocular disease due to the herpes viruses, and AIDS-associated ocular infections.

Dr. Margolis’s clinical research is aimed at understanding the pathogenic mechanisms leading to atypical presentations of ocular infections. This work dovetails closely with his laboratory research, providing valuable clinical samples and raising important questions that can be addressed at the laboratory bench.

Nisha Acharya, MD Dr. Nisha Acharya is participating in a study that evaluates whether adding steroids to the treatment for will improve clinical outcomes. Dr. Acharya’s research also assesses whether bacterial subtypes and resistance factors will affect treatment outcomes. She is co-director of the uveitis service at the Francis I. Proctor Foundation.

Thomas M. Lietman, MD Dr. Tom Lietman leads continued studies in the Gurage area in the Ethiopian highlands southwest of Addis Ababa that have revealed that up to 80% of the village children have active trachoma infections, a prevalence higher than anywhere else in the world. Dr. Lietman’s team has monitored the treatment of 100,000 of these children in the past four years in an attempt to develop a cost-effective, feasible way of eradicating the disease worldwide. It is estimated that 80 million individuals in the developing world are currently in need of treatment for trachoma and its complications.