FAST FACTS • Director of Glaucoma Service (1987 to present), Professor (1996 to present), Vice-Chairman (2001 to present), Frederick C. Blodi Chair (2006 to present), Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City • Member of the Board of Directors for the American Board of Ophthalmology, 2006 to 2014 • Delivered 10 named lectures including the 5th American Glaucoma Society Clinician-Scientist Lecture, 2004 • Recipient of Research to Prevent Blindness' Lew R. Wasserman Award, 2004 • An author on the first article describing the myocilin gene as the cause for juvenile open-angle glaucoma and 3% to 5% of adult-onset primary open-angle glaucoma.1,2 Also an author on the initial descriptions of the PITX23 and FOXC14 genes for Axenfeld-Rieger syndrome 1. What influenced you as a public health physician in Alaska to become an ophthalmologist? I had gone to Alaska to serve the 2 years that I owed to the US Public Health Service. At the time, my plan was to return to the University of Pittsburgh to do an orthopedic surgery residency. I enjoyed my work and the Native American people so much, however, that I extended my stay to 6 years. I spent 4 of them with the Indian Health Service in Bethel and Ketchikan and 2 years with the Arctic Laboratory of the Centers for Disease Control in Anchorage. While working with Eskimos, I was struck by the prevalence of uveitis and acute angle-closure glaucoma in this population, and I developed an interest in eye diseases. One of the visiting ophthalmologists from Anchorage, Thomas Morrison, MD, traveled to hospitals in remote Alaskan towns. His enthusiasm for ophthalmology was infectious and inspired me to abandon orthopedics and change my focus to ophthalmology. 2. How did you encounter the pedigree that led to the discovery of the GLC1A and myocilin glaucoma gene? Like many things in life, it was a combination of good fortune and hard work. An astute patient presented to the University of Iowa in 1986 and asked if he could have glaucoma filtering surgery. He had noted that members of his family affected with glaucoma had gone blind at very young ages. He had also determined that medical therapy and laser therapy did not work for members of his family but that those who had undergone trabeculectomy had generally done well. With his help, we tracked down about 60 of his family members in Illinois, Wisconsin, and Georgia, and we were able to find enough affected individuals to perform a linkage analysis. We were fortunate to begin our glaucoma genetics research with such an amazing family, both because of the number of affected individuals and because of their motivation for finding an answer. The timing was also lucky because this family presented when Edwin Stone, MD, PhD, had just begun to set up a laboratory at the University of Iowa—while he was still a resident. Our work together on this family has led to a long and enjoyable collaboration on genetics projects. Approximately one third of the resources of the Stone laboratory are directed at glaucoma projects, and our newest faculty member, John Fingert, MD, PhD, a glaucoma specialist and molecular geneticist, will help to accelerate our glaucoma genetics program further. 3. What inspired your interest in genetics, and what advice would you give to a young ophthalmologist who is similarly inclined? I had no background in genetics. My interest in this line of research developed after I joined the faculty at the University of Iowa. As I mentioned, we had the great fortune to study a very large family, which ultimately led to the GLC1A genetic locus for glaucoma and the myocilin gene. Our success with that family made me appreciate the potential for genetic research, and I began learning what I could about molecular genetic approaches to studying diseases. I kept looking for families or individuals who might lead to new genetic discoveries. For example, I saw a young child with congenital glaucoma and a host of other genetic abnormalities caused by a chromosomal translocation. A colleague in the Sheffield laboratory, Darryl Nishimura, PhD, was able to find the genes disrupted by this break, and this single child led to the discovery of the FKHL7 (now FOXC1) gene that causes Axenfeld-Rieger syndrome as well as cardiac valve disease. As our work has become better known, I have had other glaucoma specialists contact me with interesting families that we have studied, most recently a family with dominant excavation of the optic nerve head. I would advise young academic ophthalmologists to take advantage of the opportunities that arise in their environment. For clinicians like me who do not have doctoral training in a particular area, it can be rewarding to form a collaborative relationship with somebody who has the scientific background to make significant advances. In my case, this connection is in molecular genetics because of Dr. Stone and Val Sheffield, MD, PhD. For others, it might be in blood flow, wound healing, or whatever opportunity presents itself in their particular institution. It is wonderful to be a part of a large collaborative group that is working together in the search for new knowledge. It is also helpful for bench researchers to collaborate with clinicians, who have access to the patients and know the questions that need to be answered. 4. What is the current clinical use for genetic testing in glaucoma, and what do you predict for the future? Genetic testing is not yet often helpful in glaucoma, but that is certain to change. I currently do myocilin testing in individuals who have open-angle glaucoma at an early age with high IOPs and a strong family history for the disease. I also perform genetic testing if individuals have features of a disease with known genes such as aniridia, Axenfeld-Rieger syndrome, or primary congenital glaucoma. My colleagues and I have established a nonprofit genetic testing center that currently looks for myocilin mutations and, in the future, will test for the anterior segment developmental genes (CYP1B1, PAX6, PITX2, FOXC1). The goal of this center is to provide low-cost testing for all known eye-related genes. These tests are available at http://carverlab.org. I believe that the future will find us making presymptomatic diagnoses based on genetic testing and customizing therapy based on our knowledge of molecular pathways. 5. Why do you think that Iowa City and the University of Iowa have developed into a mecca for ophthalmology? I feel fortunate to be a member of the Department of Ophthalmology at the University of Iowa. It has a long tradition of excellence in clinical care, teaching, and scholarship. I was excited to join a department with tremendous scholars: Frederick Blodi, MD; H. Stanley Thompson, MD; Sohan Hayreh, MD; William Scott, MD; Jay Krachmer, MD; and others. Many new clinician-scientists have followed in their wake. For me, the most important aspect of our department is the sense of collegiality and camaraderie. Anyone in the department will happily help anyone else at any time for any reason on either a clinical or an academic issue. The strong sense of teamwork and the joy of working together create an ideal environment. As a department, we also make education a high priority, and we tend to attract faculty members who love to teach and residents and fellows who love to learn. We still have department-wide rounds every morning. They provide a forum for discussing interesting cases and new research ideas. They also keep communication open among all members of the department. 1. Stone EM, Fingert JH, Alward WL, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275:668-670. 2. Alward WL, Fingert JH, Coote MA, et al. Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A). N Engl J Med. 1998;338:1022-1027. 3. Semina EV, Reiter R, Leysens NJ, et al. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RGS, involved in Rieger syndrome. Nat Genet. 1996;14:392-399. 4. Nishimura DY, Swidereski RE, Alward WL, et al. The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25. Nat Genet. 1998;19:140147.