Improving Cellular Degradation to Reverse the Effects of Exfolation Syndrome

Audrey Bernstein, PhD
Mount Sinai School of Medicine (New York, NY)

Co-Principal Investigators

J. Mario Wolosin, PhD
Icahn School of Medicine at Mount Sinai (New York, NY)
Year Awarded:
Grant Duration:
July 1, 2015 to June 30, 2016
Award Amount:
Grant Reference ID:
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Award Region:
US Northeastern
Audrey Bernstein, PhD

Exfoliation Syndrome and Lysosomal Disease


In exfoliation syndrome (XFS), the eye starts accumulating protein aggregates that resemble fluffy white deposits. Eventually this debris may block the exit of fluid from the eye, causing a buildup of pressure that is believed to contribute to glaucoma and optic nerve damage. If unchecked, these changes can lead to blindness. We have discovered that cells obtained from XFS eyes may have a problem degrading these protein aggregates, leading to the toxic accumulation of  this form of “cellular trash.” Our project will test methods to accelerate degradation of this cellular waste in order to improve the health of XFS-affected eyes.


Our goal is to reverse the effects of exfoliation syndrome (XFS), the leading identifiable cause of glaucoma.   Our lab is investing the hypothesis that eyes with XFS have a dysfunction in the cellular machinery that would normally degrade these protein aggregates, causing the accumulation of cellular waste that becomes toxic. We are growing cells from tissue derived from XFS patients who have undergone surgery to have the exfoliated tissue removed from their eyes to relieve pressure. These cells are called tenon fibroblasts. We are using the tenon fibroblasts as a model system to investigate methods to accelerate degradation of cellular waste in order to improve the health of XFS-affected cells. 

Inside the cell, lysosomes degrade cellular waste and mitochondria produce the energy to power the cell. Our work links XFS in the eye to lysosomal and mitochondrial age-related malfunction and disease. Recent work in studies of several other age-related diseases, such as age-related macular degeneration (AMD) and Alzheimer’s disease, have found that lysosomal and mitochondrial dysfunction are significant contributors to disease pathology. Since one of the major challenges of XFS research has been a lack of model systems for experimental purposes, our patient-derived cells provide a wealth of opportunity to identify critical pathways that are disrupted in XFS-affected cells.  

Any evidence we are able to demonstrate in support of this central hypothesis will elucidate cellular mechanisms particular to XFS and reveal novel approaches that prevent XFS manifestation in the eye.  The correlation with other age-related diseases opens the door to new therapies for XFS, some of which may already be under development.

About the Researcher

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."

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