Why Vision Cells Die In Age-Related Macular Degeneration

Jacque Duncan, MD
University of California, San Francisco (San Francisco, CA)
Year Awarded:
2009
Grant Duration:
April 1, 2009 to June 30, 2012
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2009104
Award Type:
Standard
Award Region:
US Northwestern

Relationship Between Fundus Autofluorescence And Cell Survival

Summary

This project will ask whether autofluorescent lesions visible in the macula and genetic risk factors associated with age-related macular degeneration (AMD) correlate with vision loss and progression of disease severity. We will use multiple measures of retinal structure and function to measure disease severity and progression over 1 year. We will correlate these precise measures of AMD disease severity and progression with autofluorescent lesions and genes associated with increased risk of AMD.

Details

Age-related macular degeneration, or AMD, is the leading cause of visual impairment among the elderly in the United States. Although recent research has shown that many genes play a role in determining who gets AMD, the reasons these genes make AMD more likely are not well understood. The present proposal will try to ask why some people are more likely to develop AMD and lose vision because of it, by using new, high-resolution imaging techniques. The cells responsible for central vision will be studied over a one-year period to see how they change. These studies may predict who may be most likely to develop AMD based on their genes and the appearance of their retina, and may provide better understanding of the causes of vision loss in patients with AMD.

Specific Aims:

1. Study vision cell structure with high-resolution images in living eyes.

2. Develop new technology to image individual cells that lie beneath the vision cells using their imaging properties.

3. Correlate vision cell structure and survival with genes associated with increased risk of advanced AMD.

Research Updates

Age-related macular degeneration, or AMD, is the leading cause of blindness among the elderly in the United States. Although recent research has shown that many genes play a role in determining who gets AMD, the reasons why these genes make AMD more likely in some individuals are not well understood. The present proposal will use new, high-resolution imaging techniques to study the retina cells responsible for central vision over a one-year period to see how they change. These studies may predict who may be most likely to develop AMD based on their genes and the appearance of their retina, and may provide better understanding of the causes of vision loss in patients with AMD. In the past 6 months, we have looked at the retina in the eyes of 10 patients with AMD. In two AMD patients, we were not able to obtain clear images of cone cells (i.e. the cells most concentrated in the central retina) largely due to the presence of cataracts. We have also imaged seven non-AMD subjects between the ages of 53 to 72, which should provide insight into how cones change during normal aging. In the coming months, we will continue to build a system to examine cone cells in the UCSF retina clinic. This system will let us see specific cells that lie beneath vision cells and help keep those vision cells alive. Finally, we are studying the genes that increase the risk of AMD, to see how they affect the vision cells in people with AMD and in older individuals without AMD.

Publications

Duncan JL, Talcott KE, Ratnam K, Sundquist SM, Lucero AS, Day S, Zhang Y, Roorda A. Cone structure in retinal degeneration caused by mutations in the peripherin/RDS gene. Investigative Ophthalmology and Visual Sciences, 2011; 52(3):1557-1566. PubMed Icon  Google Scholar Icon

Duncan JL, Ratnam K, Birch DG, Sundquist SM, Lucero AS, Zhang Y, Meltzer M, Smaoui N, Roorda A. Abnormal Cone Structure in Foveal Schisis Cavities in X-Linked Retinoschisis from Mutations in Exon 6 of the RS1 Gene. Invest Ophthalmol Vis Sci. 2011; 52(13):9614-23.  PubMed Icon 

Talcott KE, Ratnam K, Sundquist SM, Lucero AS, Lujan BJ, Tao W, Porco TC, Roorda A, Duncan JL. Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Cone structure in retinal degeneration associated with mutations in the peripherin/RDS gene. PubMed Icon Google Scholar Icon

Duncan JL, Talcott KE, Ratnam K, Sundquist SM, Lucero AS, Day S, Zhang Y, Roorda A. Cone structure in retinal degeneration associated with mutations in the peripherin/RDS gene. Invest Ophthalmol Vis Sci. 2011 Mar 1;52(3):1557-66. Print 2011 Mar. PubMed Icon Google Scholar Icon