Congratulations to Katherine A. Hajjar, MD, Vice Chair for Research and Brine Family Professor of Cell and Developmental Biology in the Department of Pediatrics at Weill Cornell Medicine, on being awarded a grant by the United States Department of Defense to develop treatment for proliferative vitreoretinopathy, a potentially blinding disease that occurs in almost one-half of military personnel who sustain a penetrating wound to the eye.
Proliferative vitreoretinopathy (PVR) occurs in some patients who have had complicated eye surgeries. When there is a tear in the retina, cells inside the eye, known as RPE cells, that normally remain behind the retina, begin to proliferate, move away from their normal position, and migrate to the inner surface of the retina. Over time, these migratory cells form a scar-like membrane that pulls the remaining retina away from the back of the eye, severely compromising vision. PVR is increasing in frequency among military personnel due to the increasing use of explosive devices in modern combat. Unfortunately, however, there is no treatment for this devastating disease.
The project entitled, "The Annexin A2 Pathway in Proliferative Vitreoretinopathy: A New Therapeutic Target" aims to develop a treatment for human PVR by testing the efficacy and safety of two newly developed antibodies in two animal models. In a previous study, Dr. Hajjar's team at Weill Cornell Medicine determined that a protein called annexin A2 allows RPE cells to abandon their normal position and migrate to the surface of the retina in response to injury. This healing-response-gone-wrong leads to the formation of damaging scar tissue. Additionally, the team showed that mice completely lacking a protein called annexin A2, a protein known to enable the migration of normally stationary cells, are resistant to experimental PVR; the study showed that mice lacking A2 had an over 90% reduction in damage to the eye. Their early results indicate that antibodies directed against A2 can prevent PVR in mice. For this project, Dr. Hajjar and team will determine whether blockade of A2 with two newly developed, even higher affinity, antibodies can prevent PVR in two animal models.
If anti-annexin A2 antibodies are effective and safe in this study, the team can then recruit an industrial partner to help conduct subsequent studies that would enable them to submit an application for Investigational New Drug (IND) status. Ultimately, this work could lead to a treatment to prevent PVR that could be given to military personnel or civilians shortly after injury, while arrangements for definitive surgical repair are being made. The team predicts that anti-A2 could be tested in human subjects within several years of completing this project. This pathway could lead to treatment that prevents development of PVR altogether, thereby eliminating the expensive and disheartening short- and long-term disability that it causes.