Assessing Foveal Specializations in Health and Disease - PROJECT SUMMARY Human vision is initiated by photons of light hitting the retina, a light-sensitive tissue lining the inside of the eye. At the center of the human retina is the fovea, a highly specialized region that supports high-acuity vision. The fovea is distinguished by an excavation of the inner retinal layers with a concomitant lack of vasculature, an increased packing of cone photoreceptors, a unique “private-line” circuitry between cones and midget ganglion cells, and a near-absence of rod photoreceptors. Several conditions are known to affect the development of these foveal specializations often resulting in reduced visual function (e.g., achromatopsia, albinism, blue cone monochromacy, and premature birth). To provide the best care for individuals with these conditions whose visual function is negatively affected, it is critically important to understand how variations in foveal morphology lead to a reduction in visual function. Non-invasive clinical imaging tools such as optical coherence tomography (OCT) and OCT angiography provide information about the overall structure of the retina and can be used to detect significant structural changes due to disease or injury. Complementing these clinical tools is adaptive optics scanning light ophthalmoscopy (AOSLO). AOSLO is a non-invasive, in vivo imaging technique that corrects for the eye’s monochromatic aberrations and can provide cellular-resolution imaging of the retina, including resolution of the foveal cone mosaic. AOSLO can also be used to perform psychophysical studies to probe structure-function relationships in the retina. Here, we will use a combination of clinical modalities like OCT along with AOSLO to investigate several developmental specializations of the human fovea in vivo including foveal cone packing and the development of regions which are free of short-wavelength-sensitive cones (S-cones) or rods at the central fovea. Our central hypothesis is that the coordinated development of foveal specializations is disrupted in cases of foveal disease. We will investigate this hypothesis through the work of the following two specific aims: Aim 1) Assess foveal cone topography and function in individuals with a history of premature birth; Aim 2) Examine the relationship of the S-cone sub-mosaic and the rod mosaic. Completion of the proposed research will provide key information about the variability of human foveal specializations in both health and disease. Aim 1 will reveal the organization of the foveal cone mosaic in premature birth, which will help inform the treatment of individuals with a history of premature birth who experience visual dysfunction. Aim 2 will serve as a crucial step towards developing a map of how the interleaving of the photoreceptor mosaics near the fovea affects humans’ high-acuity central vision. This work will also provide several training opportunities through the use of psychophysical testing, application of optics and engineering principles used in non-invasive imaging, and several clinical experiences beyond the laboratory. The training plan put forth in this proposal will enable and support my development as an independent, translational scientist through a blend of basic vision science and clinical application of our scientific findings.
