TGF-β and Glaucoma Progression in a Spontaneous Model
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.
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.
About the Researcher
Dr. McLellan graduated from Glasgow University Veterinary School in Scotland in 1990 and worked in general veterinary practice for a few years before moving to the University of London, where she completed a PhD, as well as clinical training as a veterinary ophthalmologist, then served as a lecturer in Ophthalmology. In 2000, she moved to the USA and has since held faculty positions at UC-Davis in California; Iowa State University, and at the University of Wisconsin-Madison, where she currently holds a joint faculty position as an assistant professor in the School of Medicine and Public Health and School of Veterinary Medicine. Dr McLellan is board certified as a veterinary ophthalmologist in both North America and Europe and is a former president of the European College of Veterinary Ophthalmologists (ECVO). She currently serves on the editorial board of the journal, Veterinary Ophthalmology, and has co-authored two textbooks as well as over 40 clinical and research papers.
“One Health”: Advancing Animal and Human Health with Science and Compassion
Research in my lab is focused on solving ocular problems that affect animals and humans, with a particular emphasis on glaucoma. By examining the similarities and differences between species in terms of how they respond to glaucoma, we can identify important clues to enhance understanding of disease mechanisms and suggest new treatment strategies for both human and animal patients.
My lab is uniquely positioned to apply the principles of "One Health" to vision research. I have a joint faculty appointment as an assistant professor of Comparative Ophthalmology in both the School of Veterinary Medicine, where I see clinical veterinary patients, teach veterinary students and train residents; and in the Department of Ophthalmology and Visual Sciences in the School of Medicine and Public Health, where my research laboratories are based. A vital component of my research is the strength of collaborative relationships that exist between my laboratory, other members of the U Wisconsin vision research community in the Glaucoma Research Group and the McPherson Eye Research Institute; other clinicians and collaborators in the School of Veterinary Medicine and School of Medicine and Public Health, as well as collaborators in the College of Engineering.
Though my main research focus is comparative glaucoma, in my clinical practice at U Wisconsin Veterinary Care, I treat a full spectrum of eye disorders in veterinary patients spanning a broad range of species. Outside work, my family currently shares our home with three laid-back cats and two hyperactive chinchillas.
First published on: July 20, 2016
Last modified on: June 30, 2019