TGF-β and Glaucoma Progression in a Spontaneous Model

Gillian McLellan, PhD University of Wisconsin


Glaucoma remains a leading cause of vision loss globally, and it is estimated that over 76 million people will be affected by this disease by 2020. There is mounting evidence that a chemical growth factor, transforming growth factor beta (TGF-β), plays an important role in processes that lead to damage to the optic nerve, resulting in vision loss. This research seeks to understand how we might protect the optic nerve from damaging effects of TGF-β and will test a promising new treatment strategy for glaucoma patients by repurposing an existing drug to block TGF-β and preserve vision.

Project Details

A growing body of evidence implicates a chemical growth factor, TGF-β, in damage to the optic nerve at the back of the eye and subsequent loss of vision in glaucoma. The goal of our research is to repurpose an existing drug to target TGF-β to slow or prevent permanent vision loss.

In our first aim, we will assess the ability of an oral medication that affects TGF-β signaling, to prevent progressive damage to the optic nerve. To accomplish this aim, we will study effects of treatment on optic nerve structure and function in a highly relevant large animal model of inherited glaucoma that has many similarities to human disease. 

In our second aim, we will determine the effects of this same medication on expression of different genes and proteins in the eye tissues that are implicated in this scarring process. Our results will aid in confirmation and discovery of genes and pathways that contribute to loss of vision in glaucoma, and will provide insight into how these genes and pathways are modified by therapy.

Our studies will provide proof of concept that an existing drug can be repurposed to target TGF-β, as a complement to conventional treatments, and will accelerate transfer of this innovative strategy to clinical trials in human patients in order to slow or prevent the inexorable vision loss from glaucoma that many people currently face.