MyVisionTest News Archive
Jun 16, 2009
CCR3 is a target for AMD diagnosis and therapy
A research study using laboratory rats has identified the eosinophil/mast cell chemokine receptor CCR3 as a new biologic marker for choroidal neovascularization (CNV) that has strong potential as a new target for therapeutic intervention.
CCR3 is a receptor found on the surface of a variety of cells, including white blood cells, for a chemical messanger ("cytokine") known as eotaxins. CCR3 is most frequently associated with eosinophils and mast cells, white blood cells that plays a major role in allergic reactions. However, recent research has found that eotaxin and its receptor, CCR3, are overexpressed in human atherosclerosis, suggesting that eotaxin participates in vascular inflammation.
The researchers have discovered that CCR3, a molecule implicated in inflammatory processes, is expressed on the surface of CNV vessels in humans but is absent from normal retinal vascular tissue.
"CCR3 chemokine receptor is known to be a key player in the allergic inflammation process, but [these researchers] have now identified CCR3 as a key marker of the CNV process involved in AMD. If researchers can determine why CCR3 is expressed in the CNV of AMD patients, they could further understand AMD disease progression," said Dr. Grace L. Shen, director of the ocular immunology and inflammation program at the National Eye Institute.
The research team was able to detect CCR3 receptors on laser-induced CNV in mice by attaching anti-CCR3 antibodies to tiny semiconductor nanocrystals called "quantum dots" and injecting these into the mice. The antibodies cause the quantum dots to attach to CCR3 on the surface of the choroidal neovascular blood vessels, making them visible with conventional ocular angiography techniques, even before the CNV has penetrated into the retina. Such imaging techniques utilizing CCR3-targeting quantum dots is able to visualize CNV invisible to standard fluorescein angiography.
Furthermore, genetic or pharmacological targeting of CCR3 or eotaxins inhibited the development of laser-induced CNV in mice. The investigators determined that CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment.
CCR3 blockade was more effective at inhibiting CNV development than VEGF-A neutralization. Anti-VEGF drugs, such as Lucentis and Avastin, are the most effective tools currently available to combat CNV. Unlike VEGF-A blockade, CCR3 blockade is not toxic to the mouse retina.
The researchers state that CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.
WHAT IT MEANS TO YOU: CCR3 is a new biomarker for CNV and a potential new therapeutic target. Early detection of CNV, prior even to the lesion entering the subretinal space, could permit therapy to be initiated before vision has been compromised. In this way risk of vision loss from CNV is minimized. Apparently, CNV is dependent upon CCR3 and blocking it causes regression of CNV in much the same way as will blocking VEGF. This has not yet been tested in humans, but is a very promising development.
Read more...
Nature. 2009 Jun 14. [Epub ahead of print]
Tags: wet AMD, animal study, VEGF, CNV, eotaxin
A research study using laboratory rats has identified the eosinophil/mast cell chemokine receptor CCR3 as a new biologic marker for choroidal neovascularization (CNV) that has strong potential as a new target for therapeutic intervention. CCR3 is a receptor found on the surface of a variety of cells, including white blood cells, for a chemical messanger ("cytokine") known as eotaxins. CCR3 is most frequently associated with eosinophils and mast cells, white blood cells that plays a major role in allergic reactions. However, recent research has found that eotaxin and its receptor, CCR3, are overexpressed in human atherosclerosis, suggesting that eotaxin participates in vascular inflammation.
"CCR3 chemokine receptor is known to be a key player in the allergic inflammation process, but [these researchers] have now identified CCR3 as a key marker of the CNV process involved in AMD. If researchers can determine why CCR3 is expressed in the CNV of AMD patients, they could further understand AMD disease progression," said Dr. Grace L. Shen, director of the ocular immunology and inflammation program at the National Eye Institute.
The research team was able to detect CCR3 receptors on laser-induced CNV in mice by attaching anti-CCR3 antibodies to tiny semiconductor nanocrystals called "quantum dots" and injecting these into the mice. The antibodies cause the quantum dots to attach to CCR3 on the surface of the choroidal neovascular blood vessels, making them visible with conventional ocular angiography techniques, even before the CNV has penetrated into the retina. Such imaging techniques utilizing CCR3-targeting quantum dots is able to visualize CNV invisible to standard fluorescein angiography.
Furthermore, genetic or pharmacological targeting of CCR3 or eotaxins inhibited the development of laser-induced CNV in mice. The investigators determined that CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment.
CCR3 blockade was more effective at inhibiting CNV development than VEGF-A neutralization. Anti-VEGF drugs, such as Lucentis and Avastin, are the most effective tools currently available to combat CNV. Unlike VEGF-A blockade, CCR3 blockade is not toxic to the mouse retina.
The researchers state that CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.
WHAT IT MEANS TO YOU: CCR3 is a new biomarker for CNV and a potential new therapeutic target. Early detection of CNV, prior even to the lesion entering the subretinal space, could permit therapy to be initiated before vision has been compromised. In this way risk of vision loss from CNV is minimized. Apparently, CNV is dependent upon CCR3 and blocking it causes regression of CNV in much the same way as will blocking VEGF. This has not yet been tested in humans, but is a very promising development.
Read more...
Nature. 2009 Jun 14. [Epub ahead of print]
