Defining the Role of Macrophage Scavenger Receptors in a Novel Mouse Model of AMD

  • Ambati, Jayakrishna (PI)

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Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in the U.S., affecting more than 11 million individuals. Absence of good animal models has limited mechanistic understanding and thwarted development of therapies. We recently reported that mice deficient in the macrophage chemoattractant Ccl-2 gene develop AMD similar to humans. This animal model reproduces most of the salient features of human AMD. As in patients with AMD, inflammatory proteins such as complement components and immunoglobulins are deposited in the eyes of these mice. We have shown that accumulation of these inflammatory deposits results from an inability to recruit scavenger macrophages that normally maintain homeostasis by degrading these toxins, which contribute to the development of AMD. We propose to explore the role of scavenger receptors used by macrophages to clear these deposits to define the molecular mechanisms underlying the development of AMD in Ccl-2 deficient (knockout) mice. Using adeno-associated viral gene therapy, we will rescue the function of the Ccl-2 gene in knockout mice to inhibit development of AMD, and simultaneously eliminate expression of macrophage scavenger receptors using bone marrow transplantation to determine their contribution in preventing the inhibition of AMD induced by gene therapy. Pa2:e2
Effective start/end date12/1/0411/30/07


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