Eye-Brain Research Uncovers Potential New Way to Treat Glaucoma

New research by 2021-24 Alzheimer’s Disease Research (ADR) grantee Oleg Butovsky, PhD (Brigham & Women’s and Harvard) has shown that APOE4, a common gene variant that increases the risk of Alzheimer’s disease, has a very different impact on glaucoma.

In both diseases, immune cells called microglia switch from “normal” to “neurodegenerative,” causing inflammation. However, in a mouse model, APOE4 inhibited an inflammatory protein called galectin-3 and protected against optic nerve damage, even with elevated intraocular pressure.

In the same study, researchers discovered a potential new treatment. They successfully used galactin-3 inhibitors to target the APOE signaling pathway and prevent the destruction of neurons in the eyes of mice with glaucoma (Margeta MA et al, Immunity, 2022).

Galactin-3 inhibitors can be derived from natural sources and are currently in clinical trials for the lung disease pulmonary fibrosis. Moving forward, Dr. Butovsky and colleagues plan to test their efficacy in glaucoma animal models and explore minimally invasive ways to deliver the drug, such as by mouth or in a slow-release gel. They also will explore the patient population in which this approach might prove most useful, such as people with elevated levels of galectin-3 in their biofluids. That could pave the way for clinical trials to test galectin-3 inhibition as a glaucoma therapy.

In addition to identifying a potential new glaucoma therapy, this cross-cutting research involves funding agencies from both the Alzheimer’s and glaucoma research worlds. Dr. Butovsky’s lab is examining how APOE4 shapes the interactions between peripheral immune cells and microglial immune cells in both the brain and eye. Two of the world’s leading Alzheimer’s authorities are coauthors on the report: David Holtzman, MD (Washington U at St. Louis), who co-chairs the BrightFocus ADR Scientific Review Committee (SRC), and Rudolph Tanzi, PhD (Mass General and Harvard), a former ADR grantee and current mentor on an ADR postdoctoral fellowship grant.

Examining the Brain-Eye Connection

In addition to providing funding for this type of cross-disciplinary research, BrightFocus Foundation encourages it in other ways. Three members of the BrightFocus Scientific Affairs team, along with several SRC members and current/former grantees, coauthored the white paper “Solving Neurodegeneration: Common Mechanisms and Strategies for New Treatments,” which bridges ideas in mind and vision research. It stems from a meeting sponsored by BrightFocus, the Glaucoma Research Foundation, and others in March 2021.

Next month, in collaboration with the newly formed International Society for Molecular Neurodegeneration (ISMND) and the Molecular Neurodegeneration journal, BrightFocus will sponsor ISMND 2022, an international conference focused on the molecular mechanisms underlying neurodegenerative diseases to inform advanced diagnosis and innovative therapy.

Since 2017, BrightFocus has sponsored a daylong scientific symposium, “Common Features of Neurodegenerative Disease: Exploring the Eye-Brain Connection and Beyond,” at the International Conference on Alzheimer’s & Parkinson’s Diseases (AD/PD). The next one is coming up in 2023.

Learn more:

• "Solving Neurodegeneration" White Paper Publication Results from Innovative Research Collaboration (Glaucoma Research Foundation news release, 2022)
• “Solving Neurodegeneration: Common Mechanisms and Strategies for New Treatments", (Molecular Neurodegeneration, 2022)
• Cure in Mind, Cure in Sight – Bridging Brain and Eye Research

About BrightFocus Foundation

BrightFocus Foundation is a premier nonprofit funder of research worldwide to defeat Alzheimer’s, macular degeneration, and glaucoma. The organization is currently supporting a $75 million portfolio of 287 scientific projects. BrightFocus shares the latest research findings, expert information, and resources to empower the millions impacted by these diseases. For more information, visit www.brightfocus.org.