Restoring Vision by Targeting Cholesterol Homeostasis: New Research for Demyelinating Eye Disease
Summary
- A research initiative led by scientists at The Miami Project to Cure Paralysis and Bascom Palmer Eye Institute has been recommended for funding by the National Institutes of Health (NIH) through an R21 mechanism.
- The project aims to develop novel therapies for demyelinating eye diseases by restoring cholesterol homeostasis in the visual system.
- If successful, the work could establish cholesterol homeostasis as a therapeutic target in demyelinating eye diseases.
An innovative research initiative led by scientists at the University of Miami Miller School of Medicine’s The Miami Project to Cure Paralysis and Bascom Palmer Eye Institute has been recommended for funding by the National Institutes of Health (NIH) through an R21 mechanism. The project aims to develop novel therapies for demyelinating eye diseases by restoring cholesterol homeostasis in the visual system—a promising new approach to preserving and restoring vision.
Demyelinating eye diseases—conditions that acutely damage the optic nerve—pose a serious threat to visual function. While many of these diseases stem from autoimmune-inflammatory origins, others may arise from isolated inflammatory episodes or trauma. Even in conditions not traditionally classified as demyelinating, such as glaucoma, demyelination plays a critical role in contributing to the impairment of visual dysfunction.
At the heart of these diseases is a cascade of damage: immune-mediated death of oligodendrocytes (OLs) in the optic nerve leads to myelin loss, Wallerian degeneration of axons and, ultimately, retinal ganglion cell (RGC) death. Current treatments are limited to immunosuppressants and anti-inflammatory agents that merely slow disease progression. What’s missing are therapies that actively protect neurons and promote repair—especially remyelination—to preserve vision.
“The two main drivers of our research were the lack of therapeutic options for immune-mediated optic nerve demyelination, which is a major clinical manifestation of multiple sclerosis, and, most importantly, the conviction that our multidisciplinary expertise as a team put us in the ideal position to tackle this complex scientific question,” said Roberta Brambilla, Ph.D., associate professor of neurological surgery at The Miami Project and the Miller School.
Dr. Brambilla collaborated with Daniel Liebl, Ph.D., professor of neurological surgery at the Miami Project to Cure Paralysis, and Abigail Hackam, Ph.D., professor of ophthalmology at Bascom Palmer Eye Institute, in designing the research.
Why Cholesterol Matters
Cholesterol is indispensable for nervous system health. It supports neurite outgrowth, synaptogenesis, intracellular signaling and, crucially, myelination and remyelination. Disruptions in cholesterol homeostasis have been implicated in a range of neurological disorders, including Alzheimer’s disease, multiple sclerosis and traumatic brain injury. In demyelinating eye diseases, both RGCs and OLs—cells that depend heavily on cholesterol—are particularly vulnerable.
Despite this, the role of cholesterol in visual system repair remains underexplored. The Miller School research team aims to change that.
Experimental Approaches to Demyelinating Eye Disease
To test the hypothesis that restoring cholesterol homeostasis can be therapeutic in demyelinating eye disease, the team is using a mouse model of optic neuritis to explore two complementary strategies:
• Redistributing cholesterol with methyl-β-cyclodextrins (mβCDs): These molecules act as cholesterol carriers. When administered to the demyelinated eye, mβCDs can redistribute cholesterol to areas where it is critically needed, supporting cell survival and enabling repair. This approach targets cholesterol imbalance directly and aims to restore the biochemical environment necessary for remyelination.
• Targeting the sterol sensor TMEM97: TMEM97 is a key regulator of cholesterol sensing and trafficking. By inhibiting TMEM97 pharmacologically and through gene-targeting strategies, the researchers aim to enhance neuroprotective and neuroreparative responses.
This dual approach allows modulation of cholesterol dynamics at both the molecular and cellular levels, potentially unlocking new pathways for regeneration.
The two main drivers of our research were the lack of therapeutic options for immune-mediated optic nerve demyelination and, most importantly, the conviction that our multidisciplinary expertise as a team put us in the ideal position to tackle this complex scientific question.
Dr. Roberta Brambilla
“We’re exploring a completely novel mechanism in the treatment of demyelinating eye disease,” said Dr. Brambilla. “The R21 funding mechanism is ideal as it provides a platform to explore cutting-edge approaches.”
Potential Impact for Patients
The implications of this research extend far beyond the lab. If successful, the findings could:
• Establish cholesterol homeostasis as a therapeutic target in demyelinating eye diseases
• Lead to the development of novel treatments that go beyond symptom management to actively restore vision
• Provide insights applicable to other neurodegenerative conditions where cholesterol imbalance plays a role
• Inspire a new generation of neuroprotective strategies rooted in lipid metabolic regulation
This work potentially represents a shift in how we understand and treat optic nerve pathologies. It’s a call to look deeper, not just at the immune response, but at the metabolic foundations of neural health.
Dr. Brambilla, for one, is optimistic about the research.
“Our studies will test the therapeutic efficacy of available pharmacological compounds, one of which (methyl-b-cyclodextrin) is already approved for clinical trials,” she said. “We believe there is a strong potential for translation to the therapy of human disease.”
Microsoft Copilot contributed to this article, which was reviewed and approved by Dr. Brambilla.
Tags: Bascom Palmer Eye Institute, Department of Neurological Surgery, Dr. Roberta Brambilla, eye diseases, neurological surgery, ophthalmology, The Miami Project to Cure Paralysis, vision impairment, vision loss