Grants and Contracts Details
Description
Age related macular degeneration (AMD) is the leading cause of blindness over the age of 55 years.
Most blindness in AMD results from invasion of the retina by choroidal neovascularization (CNV). There is
abundant evidence that inflammatory and immunologic mediators play a significant role in the development
of AMD and its progression to choroidal neovascularization, but the exact molecular basis of immune
regulated angiogenesis is still unknown.
Recently I, along with other members of the Macular Degeneration Research Group at the University of
Kentucky, identified the chemokine receptor CCR3 as a unique molecular signature of CNV in an animal
model (Takeda, Baffi, Nature 2009). We have showed that CCR3, previously assigned as an eosinophillmast
cell chemokine receptor involved in allergic responses, was expressed by human choroidal endothelial cells
in CNV tissue specimens excised from patients with active, neovascular AMD. Pharmacological or genetic
targeting of CCR3 or its ligands inhibited injury-induced CNV in mice. Furthermore, targeting CCR3 or its
eotaxin ligands inhibited angiogenesis in vitro and in vivo, and was both superior to and safer than VEGF-A
blockade. Concomitantly, in vivo imaging with CCR3-targeting quantum dots located spontaneous CNV
invisible to standard fluorescein angiography in mice before retinal invasion. These findings establish CCR3
as an ideal diagnostic and therapeutic target for neovascular AMD.
This proposal seeks to further understand the role and impact of resident versus circulating bone
marrow-derived cell contribution to CCR3 function in CNV using multiple molecular, biological, and
genetic approaches, and to create a novel CCR3 bioimaging strategy to visualize the earliest stages of
neovascular AMD.
The potential impact of this proposal is very high as it wifi define the further define the function of
the CCR3/eotaxin axis in the pathogenesis of AMD, and lead to the development of novel CCR3-
targeting diagnostic and therapeutic strategies that can be used in the clinic to detect the subclinical
stages of neovascular AMID, thus preventing progression to the fulminant neovascular stage.
Status | Finished |
---|---|
Effective start/end date | 4/1/10 → 6/25/12 |
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.