CCR3 Biology and Imaging Applied to CNV in AMD

We are pursuing the combined goals of understanding the role and impact of CCR3 function during blood vessel development in the eye. Further, we are exploiting CCR3 to create images of the earliest stages of neovascular, ‘wet,’ and age-related macular degeneration (AMD). We are achieving this by using multiple molecular, biological, and genetic approaches. The potential impact of this proposal is very high as it will further define the functional relevance of the CCR3/eotaxin “axis” to the clinical development and progression of AMD. This will 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 AMD, thus preventing this disease from progressing into a vision-threatening state.

Age-related macular degeneration (AMD) is a debilitating eye disease that mostly impacts people over the age of 55 years. It is the leading cause of blindness in the industrialized world. It comes in two varieties, “dry” AMD and “wet” AMD. What distinguishes the wet form from the dry form is the growth of new, leaky blood vessels under the retina’s central portion, which is responsible for your vision as it contains your photoreceptors. The wet form of AMD has a more rapid progression of visual decline, leading to difficulties with basic daily activities such as writing, reading, and driving and often leading to legal blindness. There are some medications currently in use that can slow or stop the progression of this form of the disease once it has become symptomatic, however none of these treatments can prevent the initial vision loss associated with this disease.

Recently, our research group identified a molecule called CCR3, located only in AMD-related blood vessels. One of our goals is to determine the origin of these cells using this marker, which contributes to the growth of these abnormal blood vessels in the eye, so we can pick an optimal delivery mechanism for targeting these vessels. The other goal is to develop a minimally invasive novel imaging technique in animal models of AMD that would allow us to detect these blood vessels and diagnose and treat this disease before it causes any damage to the retina that would lead to vision loss.

Once this diagnostic and therapeutic treatment has been developed in animal models and its safety has been confirmed, it can be further tested for efficacy in clinical trials on humans.