Retinal Versus Cortical Contributions to Vision Loss in Albinism

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DESCRIPTION (provided by applicant): Even though the fovea occupies only 0.02% of the total area of the retina, 40% of primary visual cortex is devoted to processing visual signals that arise there. Thus, it is not surprising that diseases affecting the structure or function of the foea are especially devastating to visually guided behaviors. Yet fundamental gaps remain in our concepts of how the fovea develops, how foveal structure is disrupted during aging and disease, and how the fovea interacts with more central visual system structures to determine key features of visual function. The overall goal of this proposal is to address these issues using a novel combination of noninvasive imaging technologies including functional magnetic resonance imaging (fMRI), optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). Albinism is an inherited disorder characterized by absent or reduced melanin pigment in the eye, and often in the skin and hair, with all types manifesting the visual features of foveal hypoplasia, macular translucency, photosensitivity, refractive errors, nystagmus, impaired stereopsis, altered retinostriate decussation, and reduced visual acuity. These specific retinal and cortical features of albinism make it a perfect "experiment of nature" to examine the knowledge gaps listed above. We propose to do this through the following specific aims: 1) Define the spectrum of foveal morphology in albinism and assess the relationship between pit morphology and retinal melanin, 2) Identify retinal factors contributing t visual deficits in albinism, and 3) Determine the cortical correlates of visual deficits in albinis. The results of this project will provide a more comprehensive understanding of the interrelationships linking melanin, retinal morphology, and cortical organization. This will offer insight into the basis for vision deficits in albinism, which may alter current phenotype/genotype classifications. This work is expected to have a significant positive impact by providing a new framework for understanding and targeting clinical therapies to alleviate the behavioral manifestations of albinism, and by producing sensitive tools for assessing therapeutic outcomes. This proposal directly addresses emerging needs outlined in the National Eye Institute's August 2012 Publication, "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.