TFPI-VLDLR Pathway in Retinal Angiogenesis

Very Low-Density Lipid Receptor deficient mice show blood vessel growth in the eye similar to that seen in AMD. This project examines genes in this molecular pathway to determine how this pathway modulates new blood vessel growth.

Age-related macular degeneration (AMD) is the most common cause of severe and irreversible vision loss in older adults in the US. The key lesion in the eye is abnormal vessel growth in the retina. Although several risk factors have been named, what molecule triggers the abnormal vessel growth is still not clear. A recent study reported that similar abnormal vessel growth was found in the eyes of a mutant mouse that lacks a very low-density lipid receptor (VLDLR). The current proposal is to examine the role of VLDLR as well as its known up- and downstream molecules on abnormal vessel growth in the eye. We will use this mutant mouse model and look for potential differences between the normal control and the mutant mice. We will also use retinal vascular cell culture to determine if VLDLR and related molecules are the key pathways to stimulate abnormal vessel growth. Identifying key molecules responsible for abnormal vessel growth will provide us with new targets to develop a better treatment strategy for AMD.