Grant: Discovery Grants Program - Individual

At the back of the eye, the retina is comprised of many layers of cells that play important roles in vision. With age and disease, cellular function changes and can lead to cell death, and in extreme cases, blindness. Almost 5.5 million Canadians are a risk of vision loss from existing ocular disorders, many of which impact the retina. Early diagnosis combined with the application of existing or tracking of new treatment strategies are critical to delaying or preventing vision loss and maintaining quality of life for Canadians and people worldwide. To diagnose and monitor retinal disease progression, ophthalmologists and optometrists use cameras that provide large scale pictures of the retina. However, to better understand the changes in individual cells in the retina, my lab can capture cellular-scale images using a custom-built adaptive optics scanning light ophthalmoscope (AOSLO). The overarching purpose of my research program is to create novel imaging tools that provide information on cellular function and that will revolutionize our understanding of the retina and the clinician's ability to diagnose and treat disease. To gain insight into changes in cell function with aging and disease, we combined our AOSLO with two-photon excited fluorescence (TPEF) imaging that enables us to detect signals from molecules involved in cellular metabolism and vision. In humans, this imaging technology has the potential to transform the clinical landscape to monitor cellular changes with retinal and systemic (e.g. diabetes) diseases, long before permanent cell loss or detrimental health consequences. Although highly promising, cellular-scale TPEF imaging in people is not yet feasible and substantial improvements in excitation efficiency, axial resolution and image quality are required prior to translation to humans. Even imaging in animal models, aimed to understand the normal processes of vision or to reveal the mechanisms of retinal degeneration, could greatly benefit from enhanced instrumentation. To address these challenges, three objectives are proposed that aim to provide better imaging in animal models and poise the technology for translation into human retinal imaging. O1. Improve TPEFO efficiency by exploring the effects of excitation polarization. O2. Improve TPEFO axial resolution through confocal imaging. O3. Improve TPEFO image quality with beam shaping. The proposed TPEFO advancements will improve our ability to provide in vivo measures of cell physiology and a means to identify deviations from normal. Through their work on the proposed projects, HQP within my laboratory will gain technical skills in optics, animal research, and image processing. They will benefit from incorporation into a collegial international network of researchers in adaptive optics retinal imaging providing assistance towards thesis completion and opening career pathways. HQP will also be prepared for positions in optical or biomedical engineering.