Retinal Contributions to Vision Loss in Albinism

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.

Grant Number: 5R01EY033580-04
NIH Institute/Center: NIH
Principal Investigator: Joseph Carroll