Understanding the Link Between Blood Vessels in the Eye and Vision Loss

We will identify the role of a system regulating blood vessels in the eye in polypoidal choroidal vasculopathy, a poorly understood age-related macular degeneration-like disease. We have developed a new mouse model which develops an eye disease very similar to PCV. Using this new model, the support from the BrightFocus foundation will allow us to better understand the processes leading to this disease and identify new therapies:

1. We will use this model to understand how defects in a system controlling blood vessels in the eye cause disease.
2. We will examine changes in gene expression related to disease to identify new targets for therapy.
3. We will use our new model to test a new drug candidate as a potential treatment for PCV.

Age-related macular degeneration (AMD) is a leading cause of adult-onset blindness and is linked to defects in the blood vessels of the eye. Increasingly, it has been appreciated that “wet” or neovascular AMD is actually a group of diseases that differentially impact people of different ethnic backgrounds. Typical wet AMD is most commonly seen in patients of European ancestry, and care for these patients has been revolutionized by discovery of a class of drugs called the VEGF inhibitors. However, wet AMD-like disease in patients of Asian and African ancestry is more commonly associated with polypoidal choroidal vasculopathy (PCV), a member of the pachychoroid disease spectrum. Compared to typical wet AMD, this disease is poorly understood and some studies have shown that treatment with VEGF inhibitors is less effective for these patients.

Recent genetic studies have linked PCV and the related disease central serous chorioretinopathy to defects in the angiopoietin-TEK system which controls blood vessels in the eye. Testing this association experimentally, we have created a new mouse model which develops PCV. This new model will allow us to better understand PCV and identify new therapeutic approaches for translation to the clinic. In one such approach, we will test a new drug targeting the angiopoietin-TEK system to determine its potential as a new treatment for PCV.

We will use a new model of PCV to understand differences between these diseases with the aim of developing specific drugs for PCV.