UC Berkeley

Short-wavelength-sensitive cones, known as S-cones, constitute a small fraction (5-10%) of the photoreceptors in the human retina, playing crucial roles in color vision and regulating circadian rhythms. While their distribution is coarse, they hold potential as biomarkers for detecting structural and functional changes in retinal diseases. However, our understanding of S-cone topography remains limited, with only a few studies using histology and high-resolution imaging to explore their foveal distribution and role in supporting spatial resolution, particularly in conditions like Enhanced S-cone Syndrome. This dissertation includes three projects that share a common goal of furthering the understanding of the S-cone topography and function in healthy and diseased eyes.The first study investigated S-cone-mediated acuity in subjects with Enhanced S-cone syndrome (ESCS), serving as a model to elucidate adaptive mechanisms to abnormally distributed photoreceptors during retinal development. By comparing S-cone acuity between ESCS subjects and normal individuals, we identified and validated supernormal S-cone acuity in Enhanced S-cone Syndrome. Our discussion delves into potential retinal re-organization mechanisms, possibly involving the recruitment of elements from the rod pathway to achieve superior S-cone acuity. Subsequently, upon noting fixation displacement mediated by the S-cone pathway during acuity experiments, we embarked on a comprehensive exploration of oculomotor function guided by the S-cone pathway. A consistent superior displacement of the S-cone-mediated preferred retinal locus (PRL) of fixation in six normal subjects was observed. This displacement was also found in saccade landing positions between chromatic (S-cone-mediated) and luminance (L/M-cone-mediated) systems, indicating that the S-cone pathway could mediate its own stimulus detection and saccade initiation. Moreover, the investigation into the human S-cone topography heterogeneity entailed functional mapping of the S-cone-free zone in normal eyes using adaptive optics microperimetry. Macular pigment imaging aided in addressing the pre-receptoral blue filtering effect on S-cone sensitivity. We discussed the interplay between S-cone acuity, S-cone preferred retinal locus displacement, and S-cone scotoma size. These findings collectively demonstrate the utility of adaptive optics imaging and psychophysics in understanding the functional topography of the S-cone pathway, shedding light on its heterogeneity and potential implications for visual function in both normal and pathological conditions.