Targeting the Glutaminolysis Pathway in Glaucoma-Associated Fibrosis

Glaucoma is a group of progressive optic neuropathies and the leading cause of irreversible vision loss worldwide. It is a chronic eye disease, and its major pathological features include fibrosis of the trabecular meshwork, Schlemm's Canal and lamina cribrosa. Central to fibrosis is extracellular matrix (ECM) remodelling and metabolic reprogramming. Glutaminolysis is an alternative energy pathway that has previously been shown to be implicated in the metabolic reprogramming associated with cancer and other fibrotic diseases, facilitating ECM remodelling and cell proliferation. This paper reviews fibrosis, glutaminolysis in the setting of fibrosis, and fibrosis and glutaminolysis in the context of glaucoma. We review the evidence for fibrosis and metabolic reprogramming in oncology and systemic fibrotic diseases, which reveals a predilection for glutaminolysis. We review the current therapies that exist to target these pathways, and find glutaminolysis to be a potential target for future therapies in glaucoma.