Grant: Operating Grant

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. Unfortunately, current treatments only exist for the advanced form of AMD and begin after significant eye damage has already occurred. Chronic inflammation and abnormal formation of new blood vessels play a significant role in this complex multifactorial disease. Our proposal will focus on special enzymes, called proteases that shape the cellular environment in the retina. Abnormal activation of these proteases can cause inflammation by releasing harmful molecules such as tumor necrosis factor (TNF) in the eye. Our group has developed a way to use the proteases so that instead of harmful factors, they release therapeutic factors. It is important that the therapeutic factor is only released when it is needed to minimize any potential side effects in the retina The long term goal of this novel and first-in-class strategy is to have the retinal cells release the engineered therapeutic factors only at the site of inflammation and injury, in timely manner, and only when the injurious processes have reached a certain critical threshold. Our proposed "smart" therapeutic strategy will be positioned in retinal cells in advance of disease, and work as needed to reduce the negative systemic and off-target effects frequently associated with current therapies for eye disease.