Countering Oxidative Stress In The Retina With The Ubiquitin System

Progress Updates

The goal of this BrightFocus-funded project is to explore a novel approach for countering oxidative stress in retinal pigment epithelial (RPE) cells and in photoreceptor visual cells. RPE cells nourish the photoreceptor cells in the retina. In simplest terms, oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the body's ability to eliminate or neutralize ROS. Excessive ROS irreversibly damages cells. RPE cells and photoreceptors are highly susceptible to damage by ROS and mounting clinical and animal studies strongly implicate chronic oxidative stress as a primary contributor to the cause of age-related macular degeneration (AMD).

We have developed a protein-based therapeutic treatment that increases the ability of cells to eliminate ROS and thereby reduces oxidative stress. We are targeting this protein directly to the RPE cells and photoreceptors of mice by sub-retinally injecting (delivering through a needle to a point just under the retina) adeno-associated viruses (AAVs) that express the therapeutic protein. AAVs have been used safely and successfully in eye gene therapy clinical trials. We have made significant progress during the initial phase of this project in 2009. In collaboration with Dr. William Hauswirth (at University of Florida), we have generated highly purified and concentrated AAVs that express our therapeutic protein. Further, we have sub-retinally injected the viruses into mouse eyes to determine how much time it takes for the therapeutic protein to be expressed and to establish a safety profile for expression of the protein in the retina.