Inside the eye’s retina, retinal pigment epithelial cells dutifully tend to the photoreceptors, delivering them nutrients and clearing away their waste.
These essential transportation tasks are two of the many jobs retinal pigment epithelial (RPE) cells perform that are crucial to maintaining vision. The scale of movement is too small to register on standard medical imaging instruments, but detecting material transportation is one way to confirm the RPE cells are healthy and properly functioning.
Since they are often early casualties in vision diseases that result in blindness, such as age-related macular degeneration—with the photoreceptors usually the next to go—monitoring RPE cell function could allow clinicians to diagnose conditions sooner and more precisely, informing personalized treatments.
Jeremy Rogers, an assistant professor of biomedical engineering at the University of Wisconsin-Madison, will use a National Science Foundation CAREER Award to develop an optical instrument that’s tailored to spying RPE cell function on a minute scale by tracking the changes in how light scatters as the cells move around particles. He hopes that by using the five-year, $500,000 grant to build a customized tool called an optical coherence microscope, he also will create a blueprint that could lead to monitoring cellular function in other parts of the eye.
“As we develop expertise in customizing these optical instruments to be able to see dynamics in RPE cells, I think then we can start to look at dynamics in other cell types,” says Rogers, who has previously focused much of his work on using optical techniques to improve cancer screening. “And that really has the potential to be an essential tool for a wider range of vision-related diseases.”
Clinicians can readily image a patient’s retina and diagnose diseases with existing technology like optical coherence tomography that shows regions of different cell types, stacked like a layer cake. But that’s as fine as the resolution gets.
“You can’t see the fine-grain cellular structure and you can’t assess function,” says Rogers. “If we can actually see activity at a cellular scale, there’s opportunity for earlier diagnosis or more accurate, personalized diagnosis, so the treatment options can be more customized to an individual.”
That cellular view could also allow doctors to thoroughly study the effects of treatment—whether through traditional drugs or emerging options like gene therapy or cell replacement using stem cell technology—on an ongoing basis and adjust tactics as needed.
Of course, those scenarios all depend on imaging an actual patient. Rogers will begin by using his customized microscope, which uses light to create images in a manner similar to how an ultrasound machine employs sound waves, to image cultured RPE cells in a dish.
If the technique proves successful, it would offer an alternative to a current labeling method of genetically altering cells to express fluorescent proteins to enable imaging. Instead, the cells would remain in a completely natural state.
“By avoiding that labeling, we can do something that is native contrast that makes it much easier to ensure you have not changed things that are important to the cell,” he says, adding that putting fluorescently labeled cells back into a patient is problematic. “So label-free methods also give you a path toward clinical translation, ultimately.”
As part of the project’s educational activities, Rogers plans to work with staff in the Discovery Building on the UW-Madison campus to create interactive optical demonstrations, both for school field trips to campus and for teachers to replicate in their classrooms. He sees optics and imaging as lending themselves particularly well to community outreach.
“We’re very visual beings,” says Rogers, who’s also a member of the McPherson Eye Research Institute at UW-Madison. “We tend to interpret everything through vision, and that’s part of the reason I think losing our sight can be so devastating. It is exciting to be working on technology that may help to restore that vision.”
Author: Tom Ziemer