Annual Report 2019
• Stopping cancer in its tracks
• SOAR Residency Program lays foundation for independent research careers
> One cell at a time
• Creating a field of molecular surgery to guide new therapies
• Developing cures with stem cells and regenerative medicine
One cell at a time
Focusing on the future of precision health through adaptive optics
Retinal cell death due to glaucoma, diabetic retinopathy, macular degeneration, and a myriad of other conditions leads to irreversible vision loss. Alfredo Dubra, PhD, associate professor of ophthalmology, believes that the best way to mitigate, and ultimately prevent, this vision loss is to monitor retinal health at the cellular level. This is the very definition of precision health, and the Dubra laboratory is devoted to the development of non-invasive imaging technologies to make this a reality.
The key to viewing the retina with microscopic detail is adaptive optics, a technology originally proposed for and demonstrated in astronomical telescopes to capture the sharpest images of planets, stars, and galaxies by correcting optical imperfections caused by the atmosphere. In the same way, Dubra uses adaptive optics to sharpen the view of the living retina by correcting optical imperfections unique to each eye, which allows him to study and monitor individual retinal cells.
“Adaptive optics can be especially beneficial for patients with retinal diseases, because we can use it to detect the most minute changes due to disease progression or even detect disease at its earliest stage before patients experience vision loss,” Dubra said. “This is very exciting, because in collaboration with the specialized clinical team at Byers, this advanced imaging can guide treatment and reduce, or even prevent, vision loss. Also, by being able to image individual cells, we help the basic scientists at the Mary M. and Sash A. Spencer Center for Vision Research at the Byers Eye Institute understand how diseases work, so that they can develop more effective treatments.”
Of equal importance, viewing progress of disease at the microscopic level can dramatically reduce the time spent testing new therapies. This would make new treatment available to patients faster. In addition, shorter testing would reduce costs and make it possible to test more new drugs, which would benefit patients.
Other faculty are using adaptive optics retinal imaging to bridge the gap between animal and human testing. Often, researchers use animals when searching for new therapies, but the modeling of a disease in animals can greatly differ from the human form of the disease. Dubra is working with basic scientists such as Yang Hu, MD, PhD, assistant professor of ophthalmology, and others at the Byers Eye Institute to identify and help develop the best animal models of eye disease in order to develop novel treatments.
Childhood goals launch his career
Dubra, a recent recruit to the Stanford faculty, knew the career he wanted to pursue from an early age. Born and raised in Uruguay, he underwent several strabismus surgeries and eye patching as an infant. The battle with his own amblyopia and hyperopia led him to devote his life’s work to helping others with visual impairments. Dubra began studying physics and optics during his undergraduate and graduate education in Uruguay, where he was first exposed to research in an applied optics group. He then went to London to further his education by obtaining a PhD in physics in 2004 from the Imperial College London, while studying the optics of the eye and the tear film. In 2006, Dubra traveled to the University of Rochester, the birthplace of adaptive optics retinal imaging, to further his training. Five years later, having started his own lab, he advanced the technology to the point that the full cone and rod photoreceptor mosaic, as well as the finest retinal capillaries and even individual blood cells, could be visualized in patients. The visualization of rod photoreceptors was significant, because they are often the starting point for many blinding conditions. After six years at the Medical College of Wisconsin, where he devoted himself to the advancement and dissemination of his technology to research institutions worldwide, Dubra joined Stanford in the fall of 2016.
Discovery leads to new advances
The Dubra lab moved into the newly built Spencer Center for Vision Research in June 2017. At the new location, the lab is part of a unique environment in which clinicians and scientists can work closely, accelerating the pace of research. The team is developing novel instruments to see not only finer details but also microscopic features that are currently not visible by other imaging methods. The team includes computer and vision scientists and electrical and optical engineers, all devoted to the ultimate goal of developing the ability to check the shape and health of each individual retinal cell, so that doctors can avoid vision loss altogether by initiating and personalizing treatment sooner. Central to materializing the benefits of adaptive optics retinal imaging is collaboration with other faculty members at the Byers Eye Institute, including Jeffrey Goldberg, MD, PhD; Hu; Theodore Leng, MD; Heather Moss, MD, PhD; Quan Dong Nguyen, MD, MSc; and Ruwan Silva, MD, MPhil.
Dubra is also widely regarded as one of the most collaborative vision scientists in the world. Instruments created by the Dubra Lab are currently being used at the New York Eye and Ear Infirmary of Mount Sinai; Moorfields Eye Hospital/the University College London; the Medical College of Wisconsin; the National Eye Institute Intramural Research Program; University of California, San Diego; and the University of Pennsylvania. Many of these instruments are used to select candidates for clinical trials, and then to monitor the efficacy of these treatments. Widespread dissemination of Dubra’s technologies are also allowing teams of researchers to study a large number of rare inherited retinal conditions that may soon become curable with gene and/or stem cell therapies.
By KATHRYN SILL
Kathryn Sill is a web and communications specialist for the Byers Eye Institute in the Department of Ophthalmology, at Stanford University School of Medicine. Email her at firstname.lastname@example.org.