***************** Institution - Mount Sinai School of Medicine Institution Location - New York, NY Grant: G2015195 Audrey Bernstein, PhD, is an assistant professor in the Departments of Ophthalmology and Pharmacology and Systems Therapeutics at the Icahn School of Medicine at Mount Sinai in New York City. Her post-doctoral training was in the field of ocular wound healing. The overall goals of her research are to investigate how aberrant protein accumulation induces disease states. Specifically, she has elucidated novel molecular pathways that lead to cell surface accumulation of integrins, fibrotic growth factor (TGFß) signaling, and scarring in the cornea. A second field of research is exfoliation syndrome (XFS), the leading identifiable cause of glaucoma, in which protein aggregates accumulate in the eye, leading to elevated intraocular pressure. In both projects, the use of primary patient-derived cells, organ culture, and genetic screening have revealed new targets for therapeutic intervention of ocular disease in which protein accumulation leads to vision loss. Dr. Bernstein serves as an ocular expert reviewer for several study sections, including the National Eye Institute (NEI), The US Department of Veteran’s Affairs, the Medical Research Council (MRC) in the UK, and The Glaucoma Foundation. The National Eye Institute, Research to Prevent Blindness, The MYS Family U.S. Charitable Foundation, and The Glaucoma Foundation also support her research, in addition to BrightFocus Foundation.
"Dr. Robert Ritch at the New York Eye and Ear, a renowned glaucoma specialist, brought my collaborator, Dr. J Mario Wolosin and I, into this important project. Collectively, our deep knowledge of exfoliation glaucoma and the cellular mechanisms that lead to disease, as well as Dr. Ritch’s access to formally discarded human tissue and our expertise in growing and analyzing cells from tissue samples has yielded a very productive translational collaboration. We are extremely excited about the promise of our research. Our goal is to harness what has already been discovered in neurodegenerative diseases that parallel our research on XFS glaucoma and adapt those findings to identify cellular pathways that can be targeted to reverse XFS disease in patients. We are grateful to the BrightFocus donors for their generous and crucial support of our research to cure this blinding disease."
Audrey Bernstein, PhD, is an associate professor in the Departments of Ophthalmology and Pharmacology and Systems Therapeutics at the Icahn School of Medicine at Mount Sinai, New York, NY. Her post-doctoral training was in the field of ocular wound healing.
Our work is focused on two clinically important ocular disorders: scarring and glaucoma. Our studies focus on the involvement of abnormal protein accumulation in both of these ocular pathologies. Specifically, we have elucidated novel intracellular ubiquitin-mediated degradation pathways that control cell-surface integrin expression and subsequent fibrotic growth factor (TGFb) signaling and scarring in the eye. Silencing of specific genes in this pathway prevents scarring and promote regenerative healing.
In exfoliation glaucoma, the leading identifiable cause of open-angle glaucoma, accumulation of protein aggregates in the eye leads to elevated intraocular pressure and subsequent glaucoma. We have discovered that a significant lysosomal/autophagic and mitochondrial defect defines primary cells isolated from the eyes of XFS patients. Our studies suggest that these age-related dysfunctions may be an underlying cause of this blinding disease
In both studies, the use of patient-derived primary cells and organ culture, quantitative confocal microscopy, histology, flow cytometry, lentivirus technology, and genetic screening are utilized to reveal new therapeutic targets to prevent vision loss. Dr. Bernstein’s serves as an ocular expert reviewer for several study sections including the National Eye Institute (NEI), The U.S. Department of Veteran’s Affairs, the Medical Research Council (MRC) in the UK, and The Glaucoma Foundation. Her research has been supported by NEI, Research to Prevent Blindness, The Glaucoma Foundation, BrightFocus Foundation, and the Moise and Chella Safra Foundation, as well as private donations.