Immune Cell Traps in Inflammation and Wet Age-Related Macular Degeneration

This project aims to characterize immune cell inflammatory activity as a potential treatment target in wet age-related macular degeneration.

Immune cells called neutrophils can set “traps” outside the cell to capture invasive pathogens, which neutrophils then destroy without damaging other body cells. In wet, or neovascular, age-related macular degeneration, these traps may trigger an exaggerated inflammatory response that leads to tissue damage. Matthew Rutar, PhD, and his colleagues hypothesize that reactive traps are responsible for triggering this damage and represent a target for treatment.

To explore the role of neutrophil extracellular traps, or NETs, in neovascular age-related macular degeneration, the researchers plan to use lab models and donor tissues. They also will test inhibitors of NET activity using these tools. The candidate inhibitors are first-generation drugs. If the drugs prove effective, Dr. Rutar and his colleagues will have confirmed that NET inhibition could dampen inflammatory damage in age-related macular degeneration. Current therapies are focused on limiting the rogue growth of blood vessels, so identifying new targets related to inflammation offers new opportunities for treatment.

Neutrophils are a critical component of innate immunity, though can also induce exaggerated inflammatory responses and promote tissue damage, including through aberrant activation of NETs. Despite their central role, the activity of neutrophils and NETs are largely unexplored in AMD. This project will bolster our understanding of neutrophil activation in wet AMD, and the specific roles for NETs in this process. Through testing of new first-generation NET inhibitors, the project will also offer a proof-of-principle for NET inhibition in ameliorating AMD.

Presently, there are a few available treatments for mitigating vision loss in wet AMD. Currently available therapies all target the same VEGF mechanism, despite the recognition that inflammation is implicated in wet AMD. The effect of targeting NET activity on retinal inflammation and pathology, explored in this project, will provide a potential framework for new therapies and diagnostics (ie. a blood test) for reducing vision loss in wet AMD.