Summary

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.

Project Details

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. Increasingly, it has been appreciated that “wet” age-related macular degeneration (AMD) is a group of diseases impacting people of different ethnic backgrounds. Typical wet AMD is commonly seen in patients of European ancestry, and treatment has been revolutionized by VEGF inhibitors. However, in patients of Asian and African ancestry, wet AMD-like disease is commonly due to PCV, a related disease. PCV is poorly understood, and VEGF inhibitors may be less effective. We will use a new model of PCV to understand the differences between these diseases with the aim of developing specific drugs for PCV.