Genetics Of Macular Degeneration In Monkeys

Peter Francis, MD, PhD
Oregon Health and Science University (Portland, OR)

Co-Principal Investigators

Martha Neuringer, PhD
Oregon Health and Science University
Year Awarded:
2009
Grant Duration:
April 1, 2009 to March 31, 2011
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2009113
Award Type:
Standard
Award Region:
US Northwestern

Genetic Studies Of A Nonhuman Primate Model For Age-Related Maculopathy

Summary

More complete understanding of the genetic risk factors for age-related macular degeneration (AMD) is essential to the development of better treatments that are optimized for the individual. Nonhuman primates provide a uniquely useful model for AMD because they have a macula, develop age-related maculopathy, and share with humans some of the same genetic risk factors for this disease. We propose to further define genetic factors in macular disease in a large monkey colony so that these animals can be used most effectively to test new therapies and prevention strategies.

Details

Promising new treatments for age-related macular degeneration (AMD) are being developed, but we need to know if they are safe and effective before trying them on human patients. Animals are very valuable for this purpose, and monkeys are potentially the best model for AMD because they have the same kind of eye structure, and older monkeys develop AMD just like humans do. We have a unique, large colony of monkeys with many families that are prone to AMD, and we know that some of the same genes are involved in both their disease and human AMD. If we understand the genetics of their disease better and can define each monkey's genetic profile, these animals can be used to accurately test treatments and ways to prevent the disease, so that better treatments can be made available to patients.

The specific aims of the project are:

1) To examine monkeys with AMD for gene differences in a particular genetic region that is associated with risk for AMD in human patients.

2) To search for changes in six other genes that seem to be related to human AMD to see if they are linked to the risk of AMD in monkeys.

3) To find other new genes in monkeys that are associated with AMD, and also with a type of macular disease that starts early in life.

Research Updates

Drs. Peter Francis, Martha Neuringer, and colleagues have screened a large colony of rhesus monkeys and shown that older members frequently develop signs of age-related macular degeneration (AMD). These researchers have examined the monkey DNA to find genes 'linked' to AMD.  Previously, they showed that two of the same genes that are associated with AMD in humans also are associated with the monkey form of the disease. This was the first study to show that the two species share genetic factors for a common complex disease. They will build upon these results and search for other AMD-associated genes in this monkey population. 

Drs. Francis and Neuringer examined in detail one more AMD gene candidate, finding that in this case the same variation in the genetic code found in humans is not shared by rhesus monkeys.  They found several other genetic variations, but did not identify any that could cause the disease. In addition, they documented a disease similar to AMD in a second species of monkey, the Japanese macaque, and are screening several genes for variations that may be linked to this disease.  Drs. Francis and Neuringer hope that these accurate animal models of AMD will lead to identification of new genetic links, thus strengthening the usefulness of these animals for testing future preventative therapies.

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