Upstate researcher awarded $2.7 million in grants to research eye scarring, glaucoma
Sunlight streams through the lab of Audrey Bernstein, PhD, in Upstate Medical University’s Neuroscience Research Building. The space, quieted by precautions taken due to the COVID-19 pandemic, is likely to become busier as Bernstein expands her team with the help of two new grants, a $1.7 million award from the National Eye Institute (NEI) and a VA Merit Award grant with $1 million direct to her lab and other support for the VA vision community.
The NEI award supports Bernstein’s research into “an intracellular disorder within the eye that can lead to a severe form of glaucoma,” she explained, and the VA award “extends [her] work on a patented therapeutic to prevent scarring in the eye.”
To perform the work proposed in the NEI award, a team of scientists, with whom she has been collaborating for years, will join Bernstein. Their work was supported initially using seed money from the Safra Family, and expanded with funding from the Bright Focus Foundation, The Glaucoma Foundation, and most recently, the Mayer Family Foundation.
Those initial funding sources allowed their research to gain notice, and led to the support from the NEI, said Bernstein, who joined Upstate three years ago from the Icahn School of Medicine at Mount Sinai in New York City.
“There’s a five-year history for this project,” Bernstein said, noting collaborators include Dr. Wolosin from the Icahn School of Medicine at Mount Sinai and Dr. Ritch from New York Eye and Ear Infirmary of Mount Sinai. In addition to the basic science supported by the NEI, the Mayer’s continuing gift will support the discovery of potential drug therapies for exfoliation glaucoma (XFG).
Bernstein’s glaucoma research is focused on proteins that the eye may produce improperly; these proteins can subsequently aggregate, leading to damaging increases in pressure within the eye. The result of the improper aggregation is exfoliation syndrome (XFS), an age-related disease involving deposits of material on the outside of certain cells of the eye, causing XFG.
XFG can progress quickly, Bernstein said. In a 2018 paper she explained that in XFG “cells display many of the functional features observed in cells from other protein aggregate diseases, such as Parkinson’s, Alzheimer’s, Huntington’s and age-related macular degeneration.” Their work, she explained, will be to get to the underlying mechanism of the disease. “The first step to curing this is to find the underlying cause – understanding how this works. Then you can come up with a better treatment.”
The VA Merit Award will expand Bernstein’s ongoing NIH-funded work, which is focused on developing a therapeutic target for scarring in the eye in conjunction with biotech collaborators. The NIH currently funds Bernstein’s foundational basic science part of this work. With the VA award, Bernstein aims to make significant progress on the translational aspects of this work to prevent scarring; in particular, in veterans. Veterans are at higher risk for corneal scars and glaucoma than is the general public, and Bernstein’s work will address the prevention of ocular scarring in Veterans. Her work specifically targets scarring in the cornea, as well as scarring at the surgical site that often occurs as a result of standard glaucoma surgery.
This project is targeted at an enzyme, Ubiquitin Specific Peptidase 10 (USP10), which controls protein aggregation. An increase in this enzyme during healing leads to cell death, immune cell infiltration, and pathological scarring. Reducing the “expression,” or amount, of USP10 prevents scarring in the eye. Such a reduction could result in improved recovery from corneal injuries and glaucoma surgery.
David Amberg, PhD, Upstate’s vice president for research, noted that her R01 from the NEI “is a great accomplishment by Dr. Bernstein and obtaining it reflects the high regard her colleagues have for her and her lab’s work. It is equally, if not even more impressive, that she has simultaneously obtained a VA Merit Award. She joins a small number of Upstate faculty that have received merit awards, the first for the Ophthalmology and Visual Sciences Department at Upstate, and it also reflects the strong relationship Upstate has had with the Syracuse VA for almost 70 years.”
Bernstein expects that, together, the two awards will allow her to hire three more researchers, doubling the size of her lab team.
Caption: Audrey Bernstein, PhD, in her lab in Neuroscience Research Building.