Simon John sees things differently.
The Jackson Laboratory professor and Howard Hughes Medical Investigator studies glaucoma. The common perception of this eye disease, which is one of the leading causes of blindness, is that it affects older people and is caused by increased fluid pressure. But according to Dr. John, there’s more to glaucoma than meets the eye.
“Glaucoma is certainly more common in the aging population, but it’s important to bear in mind that all segments of the population are affected,” he said in his rich Welsh accent, “including newborn children. And some of the disease cases in the very young are particularly nasty and can affect the patients throughout their lives.”
Dr. John noted that the primary tool today for detecting and diagnosing glaucoma is determining elevated intraocular eye pressure (IOP). However, what causes blindness is not the pressure itself but rather damage to the nerve that connects the eye to the brain.
“Current treatments aren’t adequate,” Dr. John said. “They’re all aimed at lowering the IOP, and they’re not effective in all patients. If we can identify the genes that are associated with the risk of developing glaucoma, this would suggest new pathways and targets for treatment.”
Dr. John’s interest in the eye as a research subject goes back to his postdoctoral days at the University of North Carolina, working in the laboratory of 2007 Nobel Laureate Oliver Smithies. “I’d always been intrigued by the eye as an organ—the different kinds of tissues, the fact that it’s part of the brain, the amazing natural optics.” Dr. Smithies’ lab at the time was studying cardiovascular peptides. “Some people had found these peptides in the eye, but no one knew what they were doing there. So I thought I’d look at them and see if they’re important in ocular pressure.”
Noting that no one was experimentally investigating glaucoma using mice, Dr. John decided that he could “make a difference” by focusing his research on glaucoma, a disease that affects about 70 million people worldwide. “Mice represent the most powerful mammalian system to study diseases as complex as glaucoma,” he said.
Glaucoma is typically a progressive and insidious disease; with no obvious symptoms, it’s usually discovered only after substantial visual loss has occurred. “Therefore,” he said, “diagnosis and early detection are the key things we have to work out—that’s where genetics comes in, as instrumental in being able to assess genetic risk.”
But studying glaucoma in mouse models is easier said than done: Imagine the tiny amount of intraocular fluid in a mouse eye. “When I first started, there weren’t techniques to measure mouse eye pressure, so we had to invent them,” he said, adding with a laugh, ”it was a very risky way to start a lab, but there’s a lot of fun in inventing.”
That spirit of innovation and creativity is what brought Dr. John to the attention of the Howard Hughes Medical Institute. HHMI’s prestigious Investigator program funds about 300 of the nation’s most innovative biomedical researchers, allowing them full freedom to explore and even change the boundaries of science.
And Dr. John is fulfilling that ambitious mission, taking glaucoma research into revolutionary new directions. In one experiment using a mouse model genetically susceptible to glaucoma, for example, he and his lab discovered that a full-body radiation treatment actually prevented glaucoma from ever developing in those mice. “We’re now working with a machine that lets us irradiate just the mouse eye, testing to see if you can stop glaucoma that way. It could hold potential for treating humans at risk for the disease, and it’s very exciting.”
Dr. John said what first drew him to The Jackson Laboratory in 1992 was the exceptional collegiality and commitment to supporting scientists, as well as the unsurpassed mouse expertise and resources. “Bar Harbor was also the ideal place for our family,” he noted, referring to his wife Lisa, daughter Emma and son Cai, “and being near the ocean feels like being home in Wales.”
What keeps him working long hours, nights and weekends? Dr. John said he’s partly motivated by sheer love of solving puzzles and understanding how things work. “I’m fascinated by the complexity of glaucoma – figuring out all the many factors that interact and conspire to cause the disease.”
“But more important,” he said, “I’m driven to make a contribution, to help patients and society. And that keeps getting stronger. I get the most heartrending e-mails from a mother who has two children with congenital glaucoma, asking for my help. I tell her I can’t give her medical advice, but it’s hard. Connections like that remind you that people need hope. That keeps me working.”
