The macula is a unique and highly specialized region of the primate retina. It contains the highest densities of rod and cone photoreceptor cells and encompasses the cone-enriched fovea, which mediates high acuity central vision. Unfortunately, loss of central vision is a significant consequence of various retinal degenerations, including cone-rod dystrophies and macular degenerations. For example, vision loss in age-related macular degeneration (AMD), is responsible for about one-half of all registered blindness in the Western world. These degenerations are characterized by dysfunction and, ultimately, death of rod and cone photoreceptors and the overlying retinal pigment epithelial (RPE) cells in the macula. Previous studies have suggested that perifoveal rod photoreceptor loss precedes that of cones in AMD; however, our understanding of the mechanism of macular and foveal cone loss in this process is poor. It appears that cones, especially foveal cones, have a capacity for survival in a region of the retina that has a propensity for degeneration. To understand the functional role of macular and foveal cones in the homeostasis of the normal retina and in the pathobiology of the diseased retina, we believe that it is critical to define the molecular """"""""fingerprint"""""""" of these cells. We hypothesize that differential gene expression by foveal cones defines the unique microenvironment of the macula, including the fovea. Furthermore, some of these genes may contribute to disease susceptibility while others may enhance photoreceptor survival. Thus, the following aims are proposed: (1) Identify genes preferentially expressed in the primate fovea. (2) Characterize fovea-associated/cone-specific genes and identify the proteins they encode. (3) Determine the functional roles of fovea-associated proteins. The central theme of our research program is that differential gene expression in the central millimeter of primate retina (in foveal cone photoreceptors) impacts on the pathology of macular degenerations. Understanding normal foveal cone biology and its alteration in disease will provide the rationale for therapies to prolong photoreceptor survival in macular degeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011286-08
Application #
6518546
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Chin, Hemin R
Project Start
1995-12-04
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
8
Fiscal Year
2002
Total Cost
$385,000
Indirect Cost
Name
Duke University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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Bowes Rickman, Catherine; Ebright, Jessica N; Zavodni, Zachary J et al. (2006) Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE. Invest Ophthalmol Vis Sci 47:2305-16

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