Several research groups funded through the NEI Audacious Goals Initiative (AGI) are developing new imaging tools to see the eye and optic nerve in unprecedented detail. The researchers will use these tools to resolve individual nerve cells. They’ll go beyond examining the cells’ anatomy to measuring the cells’ function; asking not only whether the cells look healthy but whether they act healthy. Ultimately, this advanced imaging technology will be used to test the effects of potential regenerative therapies developed through the AGI. For more information about this research and a look at some stunning images of the visual system captured by scientists—past and present—watch NEI’s new video. (link is external)
Five bold projects will develop new technology to noninvasively image cells of the eye in unprecedented detail:
Interferometric Optophysiology of the Human Retina (U01 EY025501 (link is external))
Principal investigator: Austin Roorda (link is external), Ph.D., University of California, Berkeley
Dr. Roorda and colleagues are designing a system to map the interaction of cells in the retina. The system will enable scientists to stimulate individual neurons and observe other cells as they become active in response. Mapping these intricate signaling patterns will help explain how the retina processes visual information before it is sent to the brain, and will be an important tool for monitoring function in regenerated cells. The system will incorporate eye tracking components and adaptive optics, a technology that corrects for distortion imposed by the cornea and lens.
Accelerating Vision Restoration with In-vivo Cellular Imaging of Retinal Function (U01 EY025497 (link is external))
Principal investigator: David Williams (link is external), Ph.D., University of Rochester Center for Visual Science, New York
Dr. Williams’ team is designing an optical system to image responses to light of large numbers of individual cells in the retina. The system uses two main components: a fluorescent marker that can detect cellular calcium fluxes, and two-photon microscopy—which uses infrared light to detect the fluorescent signals without damaging living tissue. The team plans to test their system in collaboration with investigators who are exploring three different approaches to vision restoration: preserving photoreceptors with gene therapy, replacing lost photoreceptors using stem cells, and genetically re-engineering cells other than photoreceptors to respond to light.
A Two-photon Ophthalmoscope for Human Retinal Imaging and Functional Testing (U01 EY025451 (link is external))
Principal investigator: Krzysztof Palczewski (link is external), Ph.D., Case Western Reserve University, Cleveland
Dr. Palczewski and colleagues are pursuing a tool to visually monitor vitamin A derivatives in the retina. Vitamin A derivatives help power the light-sensitive machinery inside photoreceptors. Many inherited diseases of the retina involve mutations that affect the retina’s ability to utilize or recycle vitamin A. Dr. Palczewski’s team will develop a two-photon microscope capable of measuring the metabolism and distribution of vitamin A derivatives within photoreceptors, at baseline in various retinal diseases and in response to potential therapies.
Imaging Optic Nerve Function and Pathology (U01 EY025500 (link is external))
Principal investigators: Sheng-Kwei Song (link is external), Ph.D., and Yong Wang (link is external), Ph.D., Washington University, St. Louis
Drs. Song and Wang are adapting two technologies—diffusion basis spectrum imaging and diffusion functional magnetic resonance imaging—to noninvasively visualize the optic nerve. Although this bundle of fibers originates in the retina, most of the optic nerve resides deep within the brain, out of reach of most devices used to see into the eye. Optic nerve damage, a consequence of glaucoma and other optic neuropathies, is currently irreversible. This system could be used to monitor how a patient’s optic nerve responds to a potential new therapy throughout the course of treatment and without the need for biopsy.
Platform Technologies for Microscopic Retinal Imaging: Development and Translation (U01 EY025477 (link is external))
Principal investigators: Alfredo Dubra (link is external), Ph.D., and Joseph Carroll (link is external), Ph.D., Medical College of Wisconsin, Milwaukee
With collaborators at several research institutions, Drs. Dubra and Carroll will develop a suite of core technologies that will advance and increase the usability of next-generation retinal cameras. The suite will include real-time eye motion stabilization, image resolution doubling, a tunable lens to improve the focusing of all colors of light, and high-throughput methods for testing the function of individual cells.
An external Scientific Oversight Committee (ESOC) has been appointed to help investigators reach their proposed milestones. The ESOC members include:
- Chris Xu, Ph.D., Cornell University
- Leonard Levin, M.D., Ph.D., McGill University
- Van Wedeen, M.D., Harvard University
- Stephen Burns, Ph.D., Indiana University