NIH launches research to gaze deeply into your eyes

Five projects pave the way for the audacious goal of restoring vision to the blind.

National Eye Institute

Five bold projects will develop new technology to noninvasively image cells of the eye in unprecedented detail. The National Eye Institute (NEI) announced the awards as part of its Audacious Goals Initiative. NEI has committed $3.8 million to the projects in 2015 and up to $17.9 million over the next five years, pending the availability of funds. NEI is part of the National Institutes of Health.

The NEI Audacious Goals Initiative is a coordinated effort to spur new therapies for blinding diseases. The central audacious goal is to restore vision by regenerating neurons and neural connections in the eye and visual system. Special emphasis is devoted to cells of the retina, including the light-sensitive rod and cone photoreceptors, and the retinal ganglion cells, which connect photoreceptors to the brain via the optic nerve.

“These ambitious projects will give us a window into the visual system,” said NEI Director Paul A. Sieving, M.D., Ph.D. “Tools developed will enhance the study of functional changes in the retina and optic nerve, in real-time and at the cellular level, and will be indispensable when evaluating new regenerative therapies for eye diseases.”

Many causes of incurable blindness affect retinal neurons. Among the hundreds of rare inherited disorders that damage the retina are retinitis pigmentosa and Stargardt disease. Common causes include age-related macular degeneration and glaucoma.

“We have entered the research phase of the Audacious Goals Initiative. Projects in this first round of AGI funding will bridge gaps in current technology, enabling later phases of the initiative,” said Dr. Sieving, who is making a detailed announcement of the grants at the 2015 Association for Research in Vision and Ophthalmology annual meeting.

The five projects include

Interferometric Optophysiology of the Human Retina (U01 EY025501)

Principal investigator: Austin Roorda, 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.

Principal investigator: Austin Roorda, 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)

Principal investigator: David Williams, 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.

Principal investigator: David Williams, 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)

Principal investigator: Krzysztof Palczewski, 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.

Principal investigator: Krzysztof Palczewski, 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)

Principal investigators: Sheng-Kwei Song, Ph.D., and Yong Wang, 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.

Principal investigators: Sheng-Kwei Song, Ph.D., and Yong Wang, 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)

Principal investigators: Alfredo Dubra, Ph.D., and Joseph Carroll, 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.

For more information about these projects and the NEI Audacious Goals Initiative, visit http://www.nei.nih.gov/audacious.

NEI leads the federal government's research on the visual system and eye diseases. NEI supports basic and clinical science programs that result in the development of sight-saving treatments. For more information, visit http://www.nei.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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