Gene therapy for AMD

Jayakrishna Ambati, MD
University of Kentucky Research Foundation (Lexington, KY)
Year Awarded:
Grant Duration:
April 1, 2004 to June 30, 2008
Macular Degeneration
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Southeastern

Adeno-associated viral gene therapy in a novel mouse model of AMD


This project uses viral gene therapy in mice to repair genetic defects that lead to AMD like pathology.


Progress in understanding how AMD develops and the process of developing new drug treatments has been hampered by the absence of good animal models. However, Dr. Ambati's past research has shown that mice with a deletion of their Ccl-2 gene develop a form of ocular pathology similar to human AMD as they age. The development of early (dry) AMD as well as late (wet) AMD in these mice makes this model particularly attractive for scientists investigating the development of the disease and the mechanisms that mediate the progression of dry AMD to the more severe wet form. Dr. Ambati's goal is to replace the function of the deleted Ccl-2 gene in these mice using an adeno-associated virus (AAV) as a vector. By treating one eye with active AAV therapy (which will deliver the Ccl-2 gene) and treating the other eye with a control AAV treatment, Dr. Ambati hopes to gain a better understanding of the molecular mechanisms underlying the development of AMD. These studies could also provide definitive proof that the absence of the Ccl-2 gene is directly responsible for the development of AMD in mice, and will justify an investigation of potential mutations in the Ccl-2 gene in humans with AMD. This in turn could lead to the identification of new therapeutic strategies to prevent blindness and restore sight.


Nozaki, M, Raisler, B.J., Sakurai, E, Sarma, J.V., Barnum, S.R., Lambris, J.D., Chen, Y, Zhang, K, Ambati, B.K., Baffi, J.Z., and Ambati, J. (2006) Drusen complement omponents C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci USA. 103(7):2328-2333. Epub 2006 Feb 1.