The Eyes Have It

By Dr. Charles Chappell '64

During the years since he graduated from Hendrix as a biology major, Dr. Joe G. Hollyfield '60 has achieved recognition as one of the preeminent researchers in the United States into the causes of eye diseases. Having earned his Ph.D. in developmental biology at the University of Texas in 1966 and then completed post-doctoral studies in the Netherlands, Dr. Hollyfield taught and conducted research first at Columbia University College of Physicians and Surgeons in New York City and later at Baylor College of Medicine in Houston, Texas. In 1995, he became the Director of Research at the Cole Eye Institute, Cleveland Clinic Lerner College of Medicine, in Cleveland, Ohio, and he is now also the inaugural holder of the Gund Professorship in Ophthalmology Research at the same institution.

Throughout his career as a researcher, Dr. Hollyfield has maintained close ties with his undergraduate alma mater. Along with his wife Mary Rayborn, herself an eminent eye researcher with whom he often collaborates, Dr. Hollyfield has given lectures on the eye and conducted laboratory exercises in Professor Emeritus Dr. Arthur Johnson's histology class; has supervised Hendrix students in summer laboratory projects; and has donated two research microscopes to the Department of Biology. Dr. Hollyfield serves as a member of the Hendrix Board of Trustees, and in 1991 the College named him a Distinguished Alumnus.

Dr. Hollyfield specializes in the investigation of retinal diseases that cause loss of vision, with an emphasis on macular degeneration, a leading cause of blindness, especially in older adults. His extensive and varied scholarly activities have resulted in the publication of more than 200 peer-reviewed articles and 14 volumes of the proceedings of biennial conferences on eye research. Since 1991, Dr. Hollyfield has been the editor-in-chief of the journal Experimental Eye Research.

In February 2012, Dr. Hollyfield kindly responded to a series of questions about his lengthy and productive career as a scientific researcher.

CC: What experiences at Hendrix influenced you to choose a career in scientific research?

JH: There were a series of events that led me to the laboratory. I always loved nature and the outdoors, so my parents weren't surprised when I told them I would major in biology. Dr. Arthur A. Johnson was my adviser, and I was aware that he had a research interest in nematodes and spent summers in Minnesota collecting specimens. I also remember a discussion in one of my classes taught by Mr. Albert Raymond about graduate school and what was required to complete a Ph.D. thesis.

I did get a solid background in biology at Hendrix, but I only began to realize this as I prepared for my final oral exam, which was required for biology majors during the final semester of their senior year. As I began to review my lecture notes from each of the courses taken along with some additional reading, the interrelatedness of all these different courses began to take shape. To revisit all this information and have the opportunity to integrate all the coursework for my major was an important exercise for me.

Dr. Johnson helped guide me to a job with the Food and Drug Administration that I began a few weeks after graduation. I started in the St. Louis office, was transferred to Dallas and managed to work for the FDA for about eight months before Uncle Sam discovered that I was no longer a student. When I received my induction notice, I made a hasty visit to my draft board office in El Dorado, where I learned that my 1A status would be returned to a student deferment if I were in graduate school. My parents had moved from El Dorado to Monroe, La., during my junior year at Hendrix, which gave me Louisiana residency status. I also discovered that any resident of Louisiana with a bachelor's degree could enroll in the graduate school at Louisiana State University in Baton Rouge. I had to move quickly, but entered graduate school in the Department of Zoology at LSU and my draft board reestablished my student deferment. I also secured a part-time job in one of the research labs.

CC: Explain your current interest in retinal diseases, particularly macular degeneration

JH: My current studies are the result of the natural evolution of my research interest. My Ph.D. thesis involved an analysis of the stem cell lineage of red blood cells in the frog, Rana pipiens. I discovered that there was a complete replacement of the red blood cell population at metamorphosis, when the tadpole became a frog. During my last year in Austin while exploring sources of support for a postdoctoral fellowship I discovered a private foundation named Fight for Sight. One of the requirements for applying for their fellowship program was that the project be in some area of eye research. In one of the background articles I read for my thesis, I learned that there were fundamental molecular changes in the photoreceptors of the retina that also took place at metamorphosis. I proposed in my Fight for Sight application that these differences might be related to cell replacement, as I had discovered for the red blood cells. I moved from retinal developmental to cell biology studies of photoreceptors and the subjacent retinal pigment epithelium in 1978-1980 after moving to the Cullen Eye Institute at Baylor College of Medicine in Houston. My lab was using a frog retina culture preparation for experimental studies at the time. I was approached by a clinical colleague who asked if I had any use for a normal human eye that was being removed from a cancer patient with a large facial/orbital tumor. We quickly set up a series of culture studies using human retina from this initial donation. The results from this early work were so promising that it prompted me to establish a relationship with the local eye bank to develop a source of additional human eye tissues with short postmortem times. With their help we were able to secure eye tissue quite frequently, allowing us to develop a second line of research using only human retinal tissue. I also found it much easier to obtain grant support to study human tissue rather than the frog retina. As we accumulated more and more human eye tissue from donors of all ages, it was possible to study changes in the retina during aging. This in turn led to questions about age-related macular degeneration (AMD). It was because of this line of research that I was recruited to the Cleveland Clinic to establish a research program focused on AMD.

CC: What do you predict for the future of research into retinal disease?

JH: Most of the diseases of the retina have a genetic basis. We now know of mutations in over 150 genes that cause specific forms of retinal degeneration. While it is estimated that about an equal number of genes remain to be discovered, I expect that much of the future efforts will be focused on translational studies that try to use our knowledge coming from many decades of discovery research to formulate ways allowing the prevention of many of these blinding genetic diseases. Gene therapy, the replacement of defective genes, is already under way with some success. But not every genetic disease involves the same metabolic pathway, so it is unlikely that there will be a "panacea," allowing one breakthrough treatment to have an impact on all blinding diseases. I am confident that many of these devastating diseases can be prevented, although much more focused effort is needed.

CC: What advice do you have for Hendrix students who may be considering careers in scientific research?

JH: Scientific research is not for everyone. At least for me, it has required intense focus, persistence and a lot of hard work. But scientific research also offers an enormous amount of freedom and the opportunity to continue to grow to one's maximum intellectual potential. To pursue the unknown in a laboratory is an enormous privilege. It is probably one of the few careers that allows one to pose a question, develop a hypothesis, plan experiments to test the hypothesis, collect and analyze the data, and continue on to wherever the data may lead. In a research environment there is always something new; a new idea to explore, a bright new student, an outstanding postdoctoral fellow. But it does require a full commitment and an enormous amount of hard work. I tell my students and laboratory staff that the word "labor" in "laboratory" is there for a reason!

The driving motivation for most academic researchers is the process of discovery. There is nothing quite like a true Eureka moment when Mother Nature finally gives up her secret that has long been elusive and required the right set of experiments to fully understand. For me, this has been an extremely rewarding career.