Elevated pressure in the eye due to glaucoma is the number two cause of blindness worldwide, however ophthalmologists are currently unable to predict which patients are most likely to suffer vision loss from the disease. Now, researchers from the Washington University School of Medicine in St. Louis, have identified a biomarker which has the potential to help physicians monitor disease progression and assess the effectiveness of glaucoma medications.
The researchers identified this biomarker of cell damage in the eyes by studying rodent models of glaucoma, as well as collecting fluid samples from the eyes of patients with the condition. The details of this study were published in the journal, JCI Insight.
“There hasn’t been a reliable way to predict which patients with glaucoma have a high risk of rapid vision loss,” said Dr. Rajendra S. Apte, principal investigator and the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences. “But we’ve identified a biomarker that seems to correlate with disease severity in patients, and what that marker is measuring is stress to the cells rather than cell death. Other glaucoma tests are measuring cell death, which is not reversible, but if we can identify when cells are under stress, then there’s the potential to save those cells to preserve vision.”
Over 60 million people around the world are affected by glaucoma. Patients often gradually lose peripheral vision, and some central vision, before they begin therapy for the condition. By this point, the glaucoma has advanced to the point that irreparable damage to the eyes has been done.
Current treatments – including topical eye drops – can be effective at reducing optical pressure, however they cannot always prevent ganglion cell death and eventual vision loss. Visual field tests, in which patients press a button every time they see a blinking light in their periphery, are used to monitor glaucoma disease progression, but even this measure can be unreliable.
According to primary study author Dr. Norimitsu Ban, an ophthalmologist and a postdoctoral research associate, elderly patients may perform poorly on the visual field test for reasons other than vision loss. This is why a biomarker of cell damage would be a more accurate and reliable way to monitor glaucoma disease progression.
“We were lucky to be able to identify a gene and are very excited that the same gene seems to be a marker of stress to ganglion cells in the retinas of mice, rats and humans,” said Ban. The biomarker in question is a molecule known as growth differentiation factor 15 (GDF15), which the researchers found increased in concentration as the rodent models grew older and accumulated damage to their optic nerve.
Patients with glaucoma also showed elevated levels of GDF15 in fluid samples collected from their eyes. “That was exciting because comparing the fluid from patients without glaucoma to those with glaucoma, the GDF15 biomarker was significantly elevated in the glaucoma patients,” said Apte. “We also found that higher levels of the molecule were associated with worse functional outcomes, so this biomarker seems to correlate with disease severity.”
According to Apte and Ban, the molecule is likely not the causative agent of cell death, but rather a biomarker of stress in these cells. In the future, the researchers hope to collect more patient samples to study how GDF15 levels vary over time.
“So we are interested in doing a prospective study and sampling fluid from the eye over several months or years to correlate glaucoma progression with levels of this marker,” said Apt. “We’d also like to learn whether levels of GDF15 change after treatment, a particularly important question as we try to develop therapies that preserve vision more effectively in these patients.”