Cellular Functional Architecture of the Human Cone Photoreceptor Mosaic
Chromatic and high-acuity aspects of vision are mediated by cone photoreceptors, which sample the image relayed by the eye's optics and transduce it into the neural signals that give rise to perception. Our understanding of how individual cones function has largely been gleaned from in vitro electrophysiological preparations, which allow the experimenter to stimulate single receptors while simultaneously recording their outputs. Building upon these findings requires investigating how signals arising from single sensory input neurons are handled downstream by the nervous system, up to and including the perceptual stage. With these goals in mind, the tools to approach these questions in vivo must be developed.
The challenges associated with studying the perceptions arising from single sensory receptors are not trivial--doing so requires an ability to visualize and repeatedly stimulate the receptor of interest, which can be difficult when it is situated within a densely packed array of similar cells that is itself contained within a sensory organ. The eye, however, represents a unique case because the receptor layer can be visualized directly through the transparent cornea and lens. The fidelity of this view is diluted only by optical imperfections in the refractive components of the eye. Advances in ocular imaging that have taken place over the past 20 years now make it possible to overcome these imperfections and image individual photoreceptors in vivo. The series of experiments described in this document involve the development of methods to overcome these obstacles, the application of this technology to study single-cone-driven perception in healthy subjects, and the translation of these tools to the clinical realm, where cone structure and function were studied with micron-scale resolution in patients with retinal disease.