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.