To end, I will very briefly discuss a treatment that has a profound neuroprotective effect against DBA/2J glaucoma. We serendipitously uncovered this effect during the course of experiments to understand the role of bone marrow genotype in the pigment-dispersion phenotype (discussed earlier). When DBA/2J mice receive high-dose irradiation accompanied by syngeneic bone marrow administration at 5 to 8 weeks of age, they are protected from glaucoma out to the oldest age assessed (14 months). The treatment has no detected effect on the iris disease or IOP.
136 Glaucoma is prevented in most animals
(Fig. 7) . Therefore, a single treatment at 5 to 8 weeks of age has long-lasting benefit and places the animals in a state that is resistant to neurodegeneration until they are at least 14 months of age. Because of the timing of IOP elevation in DBA/2J mice, the neurodegeneration is delayed at least for 3 to 5 months after the neurodegenerative signals arise.
We are not aware of any other neuroprotective effects this substantial. Because bone marrow genotype is not changed, it is not the causative agent. A recent associative study, suggests a protective effect of high-dose radiation without bone marrow transfer in a human population. In an epidemiologic study of atom bomb survivors, radiation appeared to protect against glaucoma.
137 The glaucoma was self-reported and so more detailed examinations are needed. Together with our experiments, however, these data suggest that high-dose radiation is neuroprotective and that our finding may not be unique to DBA/2J mice. Considerable effort is needed to understand this effect and a variety of possible mechanisms must be assessed.
136 It is important to determine whether this treatment protects against other forms of glaucoma. With increased understanding, it may be possible to eliminate the need for radiation but maintain the beneficial effect. In conclusion, this discovery provides an exciting new tool for research into mechanisms of neuroprotection in glaucoma and possibly other diseases.
It is a great honor to receive the Cogan Award, and I am indebted to my family, mentors, colleagues, friends, and everyone who has helped and guided me throughout the years. I owe a special thank you to everyone who has worked in my laboratory. Your efforts resulted in this award and allowed us to make new discoveries. I especially thank Richard Smith who is a wonderful colleague and friend, my postdoctoral fellows Michael Anderson, Douglas Gould, and Richard Libby, who were responsible for much of the work I discussed, and Robert Ritch for his overflowing enthusiasm and open mind. I thank my former teachers and mentors for nurturing and expanding my interests: Jerome Den Hollander, Dennis Phillips, John Rees, Rima Rozen, Lesley Southerns, Charles Scriver, and Oliver Smithies; Abbot Clark and Robert Nickells for frequent discussions and collaborations; the organizers and faculty of the National Eye Institute–funded “Fundamental Issues in Vision Research” Course at Woods Hole; and individuals who provided encouragement and support as I began to consider working on glaucoma and who have encouraged and supported me during this time (alphabetically): Ruben Adler, Lee Alward, Ben Barres, David Beebe, Joseph and Barbara Cohen, Muriel Davisson, John Dowling, Thomas Freddo, Sharon Freedman, Achim Gossler, Brigid Hogan, Paul Kaufman, Barbara Knowles, Lesley Kozak, Bruce Ksander, Eric Lander, Edward Leiter, Brian Link, Richard Masland, Larry Mobraaten, James Morgan, John Morrison, Robert Nussbaum, Timothy O’Brien, Ken Paigen, David Papermaster, Elio Raviola, Thomas Roderick, Derry Roopenian, Carla Shatz, John Schimenti, David Serreze, Val Scott, Leonard Schultz, Val Sheffield, William Sly, the late J. Wayne Streilein, John Sundberg, Martin Wax, Alan Whitmore, Janey Wiggs, Cookie Willems, and Don Zack. I acknowledge my collaborators, colleagues at The Jackson Laboratory and The Howard Hughes Medical Institute, and the help and support of Norman Hawes and the “eye group” headed by John Heckenlively and Bo Chang. In addition, I thank my assistant Felicia Farley and The Jackson Laboratory Scientific/Administrative Services, including Jennifer Torrance who prepared the figures. It is not possible to list everyone, but I thank you all.