Concurrent Structural and Functional Imaging of Retinal Neurons

Lay Summary

Building the Capacity to Detect Visual Problems Early Through Cellular Imaging

Researchers will develop an optical imaging technique designed to detect cellular signs of vision diseases early, when they can be treated most effectively, and test this approach in animal models.

Several serious eye diseases can lead to vision loss and even blindness, and their early detection is crucial to limit damage through available therapies.  Among these diseases are diabetic retinopathy, often an early complication of diabetes, and glaucoma.  While currently available imaging procedures can detect disease-related anatomical changes in the eye, cellular changes may precede these and may therefore provide a means for early diagnosis and treatment to appreciably lessen vision loss.  The University of Alabama investigators recently used near infrared (NIR) light imaging to monitor the functional activity of retinal nerve cells in retinas and eyes removed from laboratory frogs.  This imaging method records signals known as fast intrinsic optical signals (fast IOS), which are small changes in light scattering that occur in neural tissue when nerve cells are stimulated.  Detection of these fast IOS signals, however, is hampered by interference from slow IOS signals.

The investigators hypothesize that these slow IOS signals result from metabolic changes that occur during stimulation of non-neural structures, such as the pigmented cell layer that underlies the layer of neural cells in the retina.  Moreover, they hypothesize that they will be able to eliminate this interference by slow IOS signals by developing a camera-based optical coherent tomography (OCT) imager.  Using the proposed OCT imaging system, the investigators anticipate that they will be able to improve the spatial resolution of retinal recordings and selectively record signals from individual functional layers and cells of the retina with a millisecond temporal resolution.

They will test the OCT imager first on retinas removed from laboratory animals to determine which frequencies of light stimulation are most effective for activating different kinds of nerve cells.  Then they will test OCT imaging of retinas in the laboratory animals.

Abstract

Concurrent Structural and Functional Imaging of Retinal Neurons

We have recently demonstrated the feasibility of using near infrared (NIR) light to image visible light stimulus evoked intrinsic optical signals (IOSs) in isolated amphibian retinas and eyes. Fast IOSs have time courses that are comparable to electrophysiological (i.e., functional) response of the stimulus-activated retina. We hypothesize that further development of the IOS imaging technology will allow concurrent evaluation of morphological structure and physiological function of the human retina, with sub-cellular resolution in three dimensions. Combined structural and functional measurements will lead to improved retinal disease diagnosis, and thus allow better prevention and treatment of visual-threatening diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and other eye diseases that are known to damage retinal photoreceptors and/or post-photoreceptor neurons.

While our long-term goal is to produce a functional imager for clinic applications, the primary objective of this project is to develop a high spatiotemporal resolution light imager, and validate it for three-dimensional (3D) IOS imaging of amphibian (frog) and mammalian (rabbit) animals. Success of the proposed study will build a solid technical foundation to pursue practical applications of the IOS imaging technology for retinal neural diagnosis and evaluation. During this project, we expect to achieve three specific aims as follows:

Aim 1: to develop a high spatiotemporal resolution imager. The proposed NIR light imager will provide sub-cellular resolution in both lateral and axial directions, with a millisecond temporal resolution. Our technical strategy is to construct a fast digital camera-based optical coherence tomography (OCT) imager. Unlike conventional single point scanning OCT, the camera-based OCT will allow simultaneous sampling of multiple retinal points, and thus provide ultrafast imaging speed.

Aim 2: to validate 3D OCT imaging of fast IOSs in isolated animal (frog and rabbit) retinas and eyecups. Successful criterion of this task is to selectively record stimulus-evoked IOSs from individual retinal layers and cells.

Aim 3: to conduct in vivo imaging of fast IOSs in intact mammalian animals (rabbits). Using the OCT imager developed and validated in Aims 1 and 2, we will conduct in vivo IOS imaging of retinal neural activity in anesthetized rabbits. Successful implementation of in vivo IOS imaging will pave the road to using fast IOSs for noninvasive evaluation of retinal neural function in living animals and human patients.