Boosting Neuronal Energy to Improve Vision in Glaucoma

Project 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.