Aberration correction with sensorless adaptive optics for imaging the mouse retina

Small animals, such as mice, are commonly used in biomedical research as models for studying human diseases. Imaging the retina in a living animal can provide valuable insights into the causes and mechanisms of vision loss. However, often imaging in vivo results in low resolution due to optical aberrations that can be caused by the biological tissue in front of the retina. Imaging systems that could non-invasively image the mouse retina with cellular-level resolution would be beneficial to many vision scientists. Adaptive optics (AO) is a technology that was originally developed for astronomers to image through the turbulent atmosphere. AO technology has been extended for microscopy and ophthalmoscopy to restore imaging performance lost due to optical aberrations from biological samples. Often, AO systems employ a wavefront sensor for direct measurement of the aberrations. Alternatively, Sensorless AO (SAO) has been implemented for imaging into tissue with multiple scattering layers, which can confound the optical wavefront measurements from a single imaging plane.In this thesis, I present several imaging systems for imaging the mouse retina with cellular-level resolution by using custom and novel SAO methods. The imaging modalities include Scanning Laser Ophthalmoscopy with fluorescence detection, Optical Coherence Tomography, and Two-Photon Excited Fluorescence imaging. The simple and robust optical designs in this thesis feature wide imaging field of views for navigation and a compactable system layout. Using SAO enables depth-resolved aberration correction in the different layers of the mouse retina. My results demonstrate detailed non-invasive cellular imaging capabilities in the living mouse eye of GFP labelled cells, nerve fibers bundles, volumetric imaging of vasculature, as well as the RPE mosaic of the outer retina.