Retinal Contributions to Vision Loss in Albinism

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The fovea is arguably the most important part of the human retina. The normal fovea is characterized by an excavation of inner retinal layers (leaving behind the foveal pit and a concomitant avascular zone), an increased density of cone photoreceptors with nearly absent rods, and specialized “private line” circuitry between cones and midget retinal ganglion cells. Together, these specializations provide the basis for our high-acuity photopic vision. Patients with albinism have disrupted foveal anatomy, with visual deficits including variably reduced acuity, increased photosensitivity, high refractive errors, nystagmus, and impaired stereopsis. Despite the prevalence of albinism (~1 in 15,000), significant gaps remain in our understanding of the anatomical basis for the visual deficits in albinism. Such gaps not only compromise our ability to develop novel therapeutic strategies for patients with albinism but also fundamentally limit our understanding of how the retina interacts with central visual structures to determine key features of normal visual function. We have formed a multidisciplinary research team whose overall goal is to close these knowledge gaps through execution of the following specific aims: 1) Examine the influence of retinal melanin on visual acuity and the phenotypic spectrum of foveal morphology, 2) Characterize disruptions in foveal post-receptoral circuitry in subjects with albinism, and 3) Map rod photoreceptor mosaic topography in subjects with albinism. By advancing non-invasive imaging approaches that can reveal the physiological basis for visual deficits in albinism on a personalized basis, we gain access to outcome measures for use in emerging therapeutic trials and develop the ability to define the therapeutic potential for individual patients. Clinically, such approaches are broadly applicable to diseases beyond albinism. This work is also expected to have a significant positive impact by increasing our basic understanding of the relationships between melanin, foveal anatomy, photoreceptor topography, retinal circuitry, and visual function. These relationships inform the basic developmental and organizational principles of the human visual system. Importantly, our proposal directly addresses emerging needs outlined in the most recent publication from the National Eye Institute, “Vision Research: Needs, Gaps, & Opportunities”, and incorporates specific program objectives of the NEI Retinal Diseases Panel: (1) Characterize the macula and perifoveal regions of the retina to better understand the predilection of the macula for disease; (2) Improve understanding of the roles of neuronal activity and molecular events in the formation of central visual circuits during development; (3) Continue to develop and apply noninvasive technologies such as fMRI, OCT, adaptive optics, and confocal imaging to better understand retinal function and changes in disease states. Altogether, this project takes a multidisciplinary approach towards elucidating how retinal structures contribute to vision deficits and reduced quality of life in patients suffering from albinism and related vision disorders.