Molecules in aqueous humor may lead to biomarker discovery for glaucoma, according to study

Pawan Singh, PhD, assistant professor in the University of Missouri School of Medicine. Image credit: University of Missouri

A discovery concerning molecules in the eye may lead to the identification of a biomarker for the early detection and treatment of glaucoma.^1,2 Researchers from the University of Missouri found that patients with primary open-angle glaucoma (POAG) have less agmatine and thiamine, also known as metabolites, in the aqueous humor in comparison to patients without glaucoma, according to a news release.

The study was published in Investigative Ophthalmology and Visual Science with Monu Monu, PhD, of the Department of Ophthalmology at the University of Missouri as the first author.²

“In several cases, people do not find out they have glaucoma until they are older and their eye pressure is elevated,” Pawan Singh, PhD, an assistant professor in the University of Missouri School of Medicine, said in the release. “Our long-term goal is to see if doctors could 1 day do a simple blood test to check for these biomarkers. If they can, hopefully they will be able to catch the disease much earlier, before vision loss occurs, so patients can receive treatment sooner.”

A total of 29 patients were involved in the study, 19 of which with POAG and 10 without. A targeted metabolomics were performed on these patients, while in vitro neuroprotection studies were performed using a mouse cone photoreceptor cell line (661W) exposed to oxidative stress. Neuroprotective and anti-neuroinflammatory properties were identified in the presence and absence of metabolites as found through electroretinography and quantitative PCR analyses. Of the 135 endogenous metabolites identified, 31 metabolites showed significant dysregulation in POAG.²

Researchers found through metabolite set enrichment analysis that the altered metabolites were associated with dysregulation of multiple key cellular pathways such as glycolysis, pentose phosphate pathway, short-/long-chain fatty acid metabolism, and electron transport chain under glaucomatous conditions. Agmatine, the putative neuromodulator, and thiamine, a vitamin, were found the decrease in patients with POAG, with the intravitreal of extracellular vesicle-mediated topical delivery of both metabolites significantly reducing the inflammatory response and protecting retinal ganglion cell function against neuroinflammatory damage in the retina. Both agmatine and thiamine also protected photoreceptor cells from oxidative stress-induced cell death and attenuated the inflammatory cytokine response, the study authors found.²

“Our results revealed significant metabolic alterations in POAG that affect key cellular functions,” the study authors stated. “Agmatine and thiamine could be potential immunomodulatory or neuroprotective drugs to treat or prevent neuroinflammatory damage to the retina during glaucoma.”

Thus, the release stated that the metabolite has the potential to help stop or slow the progression of vision loss, possibly as future neuroprotective treatment for glaucoma in the form of eye drops or supplements.¹

“Mizzou’s impressive research infrastructure and our collaborative team help make this research possible,” Singh said. “While more work needs to be done, the eye doctors I have spoken to here at Mizzou are very excited about this research, so I am proud and hopeful for the future.”

References:

1. Consiglio B. Mizzou researcher discovers natural molecules that may help glaucoma patients. University of Missouri. August 20, 2025. Accessed August 20, 2025. https://showme.missouri.edu/2025/mizzou-researcher-discovers-natural-molecules-that-may-help-glaucoma-patients/

2. Monu M, Kumar B, Asfiya R, et al. Metabolomic profiling of aqueous humor from glaucoma patients identifies metabolites with anti-inflammatory and neuroprotective potential in mice. Invest Ophthalmol Vis Sci. 2025;66(5):28. doi:10.1167/iovs.66.5.28