Summary

Drusen develop as yellow deposits under the retina and are considered to be hallmarks of age-related macular degeneration; this proposal utilizes cutting-edge recombinant antibody technologies to develop novel anti-drusen “nanobody” molecules that have the potential to serve as direct therapeutics and/or drug discovery tools for AMD. Nanobodies can be selected, engineered, and manipulated as genes, then delivered as either genes or proteins to modulate drusen. Since similar reagents are already in human clinical trials for other abnormal protein diseases, translation to clinical ophthalmology is highly feasible.

Project Details

Sometimes the back of the eye accumulates drusen, which are sacs of what appears to be cellular debris. The presence of high numbers of drusen is strongly associated with the "dry" form of macular degeneration, which can cause blindness. The goal of this project is a novel approach to identify and modify therapeutic targets on these drusen. When you get a virus, your body can make antibodies that are very good at getting rid of the virus. We are going to utilize powerful molecular tools to make very small, specialized kinds of antibodies, nanobodies, that can fight the drusen. Once we have these anti-drusen nanobodies, we can use them to design new drugs, and we can engineer the nanobodies for specific tasks, like clearing of the drusen. This interdisciplinary research project is combining the efforts of the lab that first started using small antibody fragments to fight misfolding proteins that damage brain cells in diseases like Alzheimer's and Parkinson's, with a veterinary lab that is using alpacas to make many useful kinds of nanobodies, plus an experienced eye research lab.