Strategies for treating degenerative retinal diseases are evolving at a rapid pace; however there exist major gaps impeding progress towards the ultimate audacious goal of regenerating neurons in the eye to restore sight. Technologies for monitoring the presence and health of individual photoreceptors and ganglion cells in living animal and human retinae are desperately needed. These tools would provide critical insight into the pathogenesis of a number of retinal and neuro-degenerative diseases; such insight is a requisite first step to developing the appropriate therapeutic approaches for a given patient/disease. Furthermore, improved visualization of cellular structure and function in patients with retinal degenerative diseases will permit scientists and clinicians to more precisely target and monitor the outcome of their therapeutic interventions. We have assembled a multidisciplinary research team uniquely equipped to address this major technological need. Drawing on our extensive experience in developing adaptive optics and retinal imaging tools, we propose to develop and disseminate four complementary platform/enabling technologies. We will leverage our existing collaborative relationships among all five participating sites, synergisic expertise, and access to extensive animal models along with an unrivaled patient population for testing these technologies. The specific technologies we propose to develop are: 1) Real-time retinal motion compensation, allowing retinal cellular-resolution imaging even in cases of extreme involuntary eye motion, like nystagmus; 2) Adaptive longitudinal chromatic aberration correction, allowing multi-wavelength, cellular-resolution retinal imaging; 3) Super- resolution line scanning ophthalmoscopy, to non-invasively image previously inaccessible cells and provide the largest image resolution improvement (> 50%) since the original demonstration of ophthalmic adaptive optics; and 4) High-throughput, opto-physiological method for assessing photoreceptor function with cellular resolution, providing a sensitive biomarker for assessing the function of regenerated/restored cells. A major strength of this application is that through our collaborative network we will validate the utility of these new technologies using regenerative therapies in both pre-clinical and clinical settings. This work will have a significant positive impact by enabling diagnosis of retinal disease and monitoring of retinal structure and function with unprecedented sensitivity and resolution. Finally, the focus of the proposed technologies will be photoreceptor and retinal ganglion cell imaging to explicitly advance the audacious goal, but they will not be limited to assessing any one therapeutic approach or cell type. Rather they will be generalizable and broadly applicable to all retinal cell types, retinal diseases, and therapeutic strategies.
The NEI recently unveiled the audacious goal to 'regenerate neurons and neural connections in the eye and visual system;' central to achieving this goal is developing the ability to monitor the presence and health of individual cells in the living retina. Here we propose to develop and disseminate transformative platform imaging technologies that overcome current barriers and will enable longitudinal, cellular-resolution assessment of retinal structure and function. These technologies can be integrated into nearly all existing ophthalmic imaging devices and will positively impact our ability to diagnose and monitor retinal and neuro-ophthalmic disease pathogenesis on a cellular level and assess therapies that aim to regenerate photoreceptors or retinal ganglion cells.
| Merkle, Conrad William; Chong, Shau Poh; Kho, Aaron Michael et al. (2018) Visible light optical coherence microscopy of the brain with isotropic femtoliter resolution in vivo. Opt Lett 43:198-201 |
| Liu, Jianfei; Jung, HaeWon; Dubra, Alfredo et al. (2018) Cone Photoreceptor Cell Segmentation and Diameter Measurement on Adaptive Optics Images Using Circularly Constrained Active Contour Model. Invest Ophthalmol Vis Sci 59:4639-4652 |
| Chong, Shau Poh; Zhang, Tingwei; Kho, Aaron et al. (2018) Ultrahigh resolution retinal imaging by visible light OCT with longitudinal achromatization. Biomed Opt Express 9:1477-1491 |
| Sredar, Nripun; Fagbemi, Oladipo E; Dubra, Alfredo (2018) Sub-Airy Confocal Adaptive Optics Scanning Ophthalmoscopy. Transl Vis Sci Technol 7:17 |
| Yanoga, Fatoumata; Gentile, Ronald C; Chui, Toco Y P et al. (2018) SILDENAFIL CITRATE INDUCED RETINAL TOXICITY-ELECTRORETINOGRAM, OPTICAL COHERENCE TOMOGRAPHY, AND ADAPTIVE OPTICS FINDINGS. Retin Cases Brief Rep 12 Suppl 1:S33-S40 |
| Morgan, Jessica I W; Vergilio, Grace K; Hsu, Jessica et al. (2018) The Reliability of Cone Density Measurements in the Presence of Rods. Transl Vis Sci Technol 7:21 |
| Tuten, William S; Cooper, Robert F; Tiruveedhula, Pavan et al. (2018) Spatial summation in the human fovea: Do normal optical aberrations and fixational eye movements have an effect? J Vis 18:6 |
| Georgiou, Michalis; Kalitzeos, Angelos; Patterson, Emily J et al. (2018) Adaptive optics imaging of inherited retinal diseases. Br J Ophthalmol 102:1028-1035 |
| Davidson, Benjamin; Kalitzeos, Angelos; Carroll, Joseph et al. (2018) Automatic Cone Photoreceptor Localisation in Healthy and Stargardt Afflicted Retinas Using Deep Learning. Sci Rep 8:7911 |
| Marcos, Susana; Werner, John S; Burns, Stephen A et al. (2017) Vision science and adaptive optics, the state of the field. Vision Res 132:3-33 |
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