Activation of Innate Immune Toll-4 Receptor in POAG

Paul Knepper, MD, PhD Children's Memorial Hospital


We have identified a unified signaling pathway based on activation of innate immune system which results in an inflammatory cascade resulting in POAG. We have identified that cell trauma causes low-molecular-weight hyaluronic acid to start the pathway. Prevention of degradation of high-molecular-weight hyaluronic acid by potent hyaluronidase inhibitor could be novel therapy and the first therapy directly aimed at the cause of POAG.

Project Details

Hyaluronic acid is a long-chain sugar polymer that is naturally present at high concentrations in the fluids of the eye and joints. Inflammation and cell damage in the eye will cut hyaluronic acid into smaller pieces (called low molecular weight hyaluronic acids which are pro-inflammatory) and this can tip the balance towards primary open-angle glaucoma (POAG). Dr. Knepper and colleagues will collect and test samples of the aqueous humor (found in the eye cavity in between the cornea and the lens) of people who are either healthy or who have POAG. The results of this study could lead to the design of a drug to prevent the hyaluronic acid from becoming cut into small pieces. This could be the first treatment that targets the underlying cause of POAG, rather than just managing the symptoms of the disease.