Publications
Overview
Angiogenesis, the growth of new microvessels, is a double-edged sword: it is essential for normal tissue growth and repair but is also associated with a variety of diseases such as tumorigenesis, neovascular age-related macular degeneration (nAMD), retinopathy of prematurity (ROP), and proliferative diabetic retinopathy (PDR). Pathological angiogenesis (aka neovascularization) typically goes on excessively and produces leaky microvessels. In ocular diseases such as nAMD, ROP, and PDR, blood contents leak out of aberrantly formed microvessels, leading to edema, tissue damage, and blindness at advanced stages. We are studying neovascularization in animal models of nAMD and ROP and exploring therapeutic opportunities.
Current Projects
- Developing novel anti-angiogenesis strategies for nAMD. Currently, nAMD is treated with repetitive intravitreal injections of anti-VEGFA agents, such as Aflibercept (a recombinant VEGFA-binding protein) and Bevacizumab (a monoclonal antibody). However, about one-third of the patients are refractory to these treatments, whereas those who initially respond well may later experience recurrence and other vision-threatening complications. Using novel mouse models, we are improving the long-term safety of anti-VEGFA therapies and developing VEGF-independent anti-angiogenesis strategies.
- Exploring the feasibility of preventing ROP. While anti-VEGFA suppresses neovascularization, it doesn’t address its major cause, i.e., retinal hypoxia due to oxygen-induced capillary loss. Furthermore, in most cases, retinal tissue damage has already occurred at the beginning of anti-VEGFA treatment. Clearly, ROP patients can benefit from addition therapies. We are investigating mechanisms of oxygen-induced capillary obliteration, with the long-term goal of preventing ROP by protecting retinal capillaries during oxygen exposure.
- Repairing lost retinal vascular network. During retinal neovascularization in ROP patients and in the OIR model, microvessels do not efficiently grow towards avascular retinal areas but instead form neovascular tufts that protrude into the vitreous gel. We are studying this phenomenon in the OIR model. These studies are expected to help redirect vascular growth towards avascular retinal areas, thus improving perfusion and alleviating hypoxia.