Optical imaging of retinal structure and function with cellular resolution

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Optical imaging tools have revolutionized human retinal imaging, providing clinicians with a new view of the retina. Thetranslation of this technology for preclinical imaging has enabled longitudinal studies to understand disease mechanisms andevaluate the effects of therapies that are under development. However, the available tools do not meet the requirements ofresolution and functional imaging capability, and vision scientists still rely heavily on ex vivo histology. The purpose of thisresearch project proposal is to investigate novel technology, integrating three imaging techniques into a single system. Wepropose to use a light source with visible wavelengths for optical coherence tomography (OCT), an imaging technique thatprovides 3D images of the retinal structure. En face images extracted from the high speed OCT system volumes will be usedas an image quality metric in a wavefront-sensorless adaptive optics (WS AO) configuration to increase the lateral resolutionto the limits permitted by the numerical aperture of the eye under investigation. Through appropriate selection of thewavelength range for the OCT, the same light source can be used for excitation of fluorescent reporter molecules in theretina. With the high resolution provided by the WS AO and confocal detection, the 3D location of the fluorescent labels willbe visualized by overlay on the OCT volumetric structural imaging. This multimodal system will be demonstrated through theinvestigation of gene therapy in the retina. A prototype system will be constructed for knowledge translation to acollaborating laboratory to investigate novel treatments for vision loss due to diabetic retinopathy. The impact of this projectis a novel imaging technology that will accelerate the preclinical development of new therapies for diseases causingblindness. The technology developed through this proposal also has strong potential for future translation to human retinalimaging.