Exploring Visual Processes with Two-Photon Ophthalmoscopy

ongoing

In vivo methods to objectively assess retinal physiology are rare among existing imaging techniques. To accelerate the diagnosis of progressive outer retinal disease and the development of treatment before vision is seriously impaired, there is a need for such methods that can quantify visual cycle kinetics in the living eye. Two-photon ophthalmoscopy shows potential to provide new information in this regard paired with microscopic resolution of retinal morphology. The technique can noninvasively track the visual cycle via the transient fluorophore all-trans-retinol in rods and cones separately. In this proposal, we aim to establish two-photon ophthalmoscopy as a method to assess outer retina function and to explore its prospect towards clinical application. An adaptive optics scanning laser ophthalmoscope optimized for safe two-photon imaging in the human eye will be developed. With this instrument, we will quantify the visual cycle in rods versus cones in response to stimulation in healthy human subjects. Particularly the cone visual cycle is not yet fully understood and requires further study. Further, the visual experience of subjects exposed to two-photon ophthalmoscopy will be investigated. The technique uses a pulsed laser as imaging source aimed to evoke nonlinear processes in the retina that can potentially be perceived by the subjects. A detailed understanding of these pathways will provide greater insight into the first steps of vision and help to design suitable stimulus paradigms to test visual cycle function. Successful implementation of two-photon ophthalmoscopy in the human eye promises to deepen our knowledge of normal and abnormal visual cycle function and further our understanding of retinal biochemistry in health and disease.