• Professor of Ophthalmology and Visual Sciences as well as Affiliate Professor of Veterinary Science, Animal Health, and Biomedical Sciences at University of Wisconsin Medical School in Madison
• Co-Chair of Advocacy Planning; Member of the Board of Trustees of ARVO and the Board of Governors of the ARVO Foundation; and Past President (1997 to 1998) and current Executive Vice President of ARVO. Completing term as President of the International Society for Eye Research
• President and Director of Ocular Physiology Research and Education Foundation, Inc.
• Recipient of ARVO Special Recognition Award and AAO Honor Award, both in 1999
• Former member of the National Advisory Eye Council of the NIH
• Former Chair of the Scientific Advisory Committee of the Glaucoma Research Foundation
• Author of more than 250 peer-reviewed publications and several textbooks, including the 10th edition of Adler's Physiology of the Eye
1. How have your studies and collaborative work with premier researchers affected the growth and direction of your own research?
Collaborations are the cornerstones of my work. Science has become evermore complex and interdisciplinary, and no one person or laboratory can bring to bear all the needed techniques for the most informative, cutting-edge work. Marrying physiology, structural biology, and cell/molecular biology requires close collaboration among several laboratories, and I have been blessed with wonderful co-investigators. The important thing is that we bring different scientific expertise and even different viewpoints to bear on a problem. We all “play better” as a result, we all learn, and we do things that none of us can do individually. I give special recognition to Drs. Ernst Bárány, Johannes Rohen, Elke Lutjen-Drecoll, Anders Bill, Ernst Tamm, Benny Geiger, Robert Weinreb, Laszlo Bito, Rosario Hernandez, and Jon Polansky, among others. The length and breadth of the list explains why a collaborative approach has been so successful. That many of these colleagues live and work outside the US illustrates the globalization of scientific research, as well as the disappearance of boundaries fostered by improvements in communication technology. The recent “roadmap” for the future of biomedical research articulated by NIH Director Elias Zerhouni, MD,1 essentially adopts this collaborative approach but on a much larger scale, of course.
2. What are the benefits and drawbacks of collaborative research?
The addition of laboratories to a project multiplies geometrically the complexity of getting things done. The quality, quantity, and novelty of what is accomplished far outweighs the complexity factor, however. For me, the personal interactions have been especially rewarding and have resulted in close friendships—personal as well as scientific—that have spanned decades.
3. Based upon your involvement with the National Eye Institute Advisory Council, what are your thoughts regarding research directions in the US?
My Council service ended nearly 10 years ago, but I have remained deeply interested in policy directions and decisions. I think that research has become more cellular, molecular, genetic, and interdisciplinary, which are all positive developments. There is a danger, however, that we may forget how necessary it remains that the classical techniques of physiology, pharmacology, and morphology—along with live-animal studies—not be lost in the rush toward the newer, “sexier” technologies. Ultimately, the insights that come from the cellular and molecular work need to be translated into the whole tissue, organ, and animal before they can be applied to human disease. Our basic science colleagues and our policy-makers sometimes forget this fact. The techniques and approaches are complementary, not competitive.
4. How has thinking on aqueous humor dynamics/outflow changed, and what effect has research in this area had on glaucoma management?
Investigators and practitioners realize now that uveoscleral outflow is important to both the eye's normal physiological defense mechanisms and as a therapeutic target for glaucoma. The first class of compounds to really exploit this pathway therapeutically, the prostaglandin F2 alpha analogues, has revolutionized our treatment of glaucoma. The justifiable burst of enthusiasm in this area, however, has drawn attention away from the fact that we still understand neither the basic pathophysiological mechanism in the trabecular meshwork that leads to elevated outflow resistance and IOP nor what regulates normal outflow resistance. We are getting closer to such understanding and to better therapies directed at this target tissue, but we could move a lot more quickly if people focused their attention on this area. We still do not have an effective, well-tolerated, patient-friendly drug for this pathway, and yet we have never been closer to having the scientific knowledge needed to develop such drugs. There is a lesson for the pharmaceutical industry here. Further, our improved knowledge of the biology of both outflow pathways (uveoscleral and trabecular) and the concomitant development of molecular genetic technology has led to the real possibility of gene-therapy approaches to manipulating aqueous outflow, both as stand-alone therapies and in conjunction with more classical drug-based approaches and even surgery.
5. What are your thoughts on the role of genetics in glaucoma, and how will research in this area impact the field in the next
10 years?
I am not a gene hunter. Although gene hunting is important in understanding the basis for many diseases, including at least some forms of glaucoma, genetic therapies for disease do not necessarily require an understanding of the genetic basis of the disease. One can manipulate various cellular and physiological pathways genetically to therapeutic advantage even though those particular pathways may not be part of the disease pathophysiology. One can upregulate a specific gene to enhance the outflow of aqueous humor by a particular mechanism even though there is nothing wrong with that mechanism. An analogy might be to reduce disturbing noise by noise-cancellation headphones; the source of the noise remains, but the resulting annoyance and discomfort have been eliminated. I do think we will see at least the beginnings of this approach to glaucoma therapy—both in terms of aqueous humor dynamics and direct protection of the optic nerve—within the next decade.
1. NIH Roadmap page. National Institutes of Health Web site. Available at: http://nihroadmap.nih.gov. Accessed December 18, 2003.
