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Grants > Boosting Neuronal Energy to Improve Vision in Glaucoma Updated On: Ene. 21, 2025
National Glaucoma Research Grant

Boosting Neuronal Energy to Improve Vision in Glaucoma

Protecting & Regenerating the Optic Nerve
Adriana Di Polo, PhD

Principal Investigator

Adriana Di Polo, PhD

University of Montreal Hospital Center (Canada)

Montreal, Québec, Canada

About the Research Project

Program

National Glaucoma Research

Award Type

Standard

Award Amount

$200,000

Active Dates

July 01, 2023 - June 30, 2025

Grant ID

G2023005S

Goals

In this project, researchers aim to use candidate small molecule drugs to prevent mitochondria-related damage to retinal ganglion cells in glaucoma.

Summary

The mitochondria are the cell structures responsible for packaging energy into a form the cell can use. Nerve cells have long extensions called axons that need energy, requiring mitochondria to migrate through them. The retinal ganglion cells are a type of nerve cell that passes visual information to the brain. In glaucoma, movement of mitochondria through the axons of these cells is disrupted, leaving the axons energy depleted and sick. These sick cells also have abnormal calcium buildup, which causes cell damage.

Adriana Di Polo, PhD, plans to test the effects of small molecules that can clear calcium from cells and keep mitochondria healthy and functioning efficiently. The small molecules are members of a class called “mitochondrial uncouplers” because they separate, or uncouple, processes in the mitochondria that normally lead to production of damaging byproducts.

Uncouplers make mitochondria more efficient at packaging energy without producing as many of these harmful molecules. This class of compound is already known to have an excellent safety profile and good accessibility in the body and has proven to be effective against neurodegeneration.

Dr. Di Polo and colleagues anticipate that their findings will show effectiveness of these mitochondrial uncouplers in preventing cell damage, maintaining healthy calcium levels in retinal ganglion cells, and supporting improved vision in glaucoma. If successful, the project is expected to open the door to clinical trials of these drugs in glaucoma.

Unique and Innovative

Current glaucoma drug treatments focus solely on reducing intraocular pressure, albeit with limited success. However, glaucoma is a complex disease, and in addition to high intraocular pressure, multiple factors can contribute to vision loss, including mitochondrial dysfunction and energy deficits. We propose a novel therapeutic approach using mitochondria-specific drugs to increase organelle transport, calcium handling, and boost energy in vulnerable neurons. By targeting mitochondria, our strategy will improve the health of retinal ganglion cells and save vision in glaucoma.

Foreseeable Benefits

Our goal is to develop a mitochondria-centered therapeutic strategy to improve retinal ganglion cell health and restore vision in glaucoma. The proposed experiments will generate a robust pre-clinical dataset on the efficacy of mitochondrial uncouplers to enhance neuronal function. These compounds have an excellent safety profile, good pharmacokinetics, and tolerability, as well as being highly effective against neurodegeneration. The outcome of these studies will serve as a springboard for the design of clinical trials using mitochondrial uncouplers in glaucoma patients.