GLP-1R agonists, a popular class of diabetes drugs, may also have a protective effect against glaucoma in diabetic patients, according to a new study published in the British Journal of Ophthalmology.
The researchers examined retrospective data of 1961 diabetic patients who were new users of this class of drugs and matched them to 4371 unexposed control subjects. After 150 days on average, 10 patients in the medicated group were newly diagnosed with glaucoma (0.5%) compared to 58 patients (1.3%) in the control group. These results indicate that GLP-1 receptor agonists could halve a diabetic patient’s risk of developing glaucoma.
The findings are supported by a Penn Medicine study from 2020, which found that GLP-1R agonists reduced neuroinflammation and prevented retinal ganglion cell death in mice. This class of drugs has also shown similarly protective effects against Alzheimer’s and Parkinson’s diseases in animal models, and clinical trials are underway to test the medications against neurodegenerative diseases in humans.
Glaucoma is the second leading cause of blindness worldwide, and people with diabetes are twice as likely to develop the condition.
“It was very encouraging to see that a popular diabetes medication could significantly reduce the risk of developing glaucoma, and our study suggests that these medications warrant further study in this patient population,” said Qi N. Cui, MD, PhD, with Brian VanderBeek, MD, MPH, both assistant professors of Ophthalmology at Penn.
The findings of a new study in rats show that a chemical known to protect nerve cells also slows glaucoma, the leading cause of irreversible blindness.
According to the National Glaucoma Foundation, in the US, over 3 million have glaucoma, with only half being aware of the fact and more than 120 000 are blind from the disease. The World Health Organization estimates that, worldwide, over 60 million individuals suffer from glaucoma.
Led by researchers at NYU Grossman School of Medicine, the study centred on the watery fluid inside the eye on which its function depends. In patients with glaucoma, a buildup of fluid pressure wears down cells in the eyes and the nerves connecting them to the brain.
Previous research that despite eye pressure having been controlled, the condition progressively worsened. The relationship between pressure buildup and impaired vision remains poorly understood
The new study showed that when rats ingested the compound citicoline, optic nerve signals between the brain and eye were almost fully restored. Citicoline is a major source of choline, a building block in the membranes that line nerve cells and enhance nerve cell communication. It is produced in the brain but also commercially produced.
The study confirmed that increased eye pressure levels contributes to nerve damage in glaucoma, but it also showed that citicoline reduced vision loss in rats without reducing pressure levels.
“Our study suggests that citicoline protects against glaucoma through a mechanism different from that of standard treatments that reduce fluid pressure,” said senior author Kevin Chan, PhD, an assistant professor in the Department of Ophthalmology at NYU Langone Health. “Since glaucoma interrupts the connection between the brain and eye, we hope to strengthen it with new types of therapies.”
The findings are helping scientists better understand how glaucoma works and add to past evidence that citicoline may counter the disease, said Chan, also the director of the Neuroimaging and Visual Science Laboratory at NYU Langone. It is known that humans and rodents with glaucoma have lower than normal levels of choline in the brain, but until now, Prof Chan says, there’s been little concrete evidence of the effectiveness of choline supplements as a therapy for glaucoma or why choline occurs in lower levels in glaucoma patients.
Prof Chan and his team tested whether increasing levels of that chemical would slow or even stop the degradation of the optic nerve and other regions of the brain involved in vision. Using a comprehensive study of the eye-brain connection in glaucoma, his team found that giving rats oral doses of citicoline over a three-week period protected nerve tissues and reduced vision loss sustainably even after the treatment stopped for another three weeks.
To simulate glaucoma, the researchers used a clear gel in rats to build up eye pressure mildly without otherwise blocking their vision. Then, the team used MRI imagery to measure the structural integrity and the amount of functional and physiological activity along the visual pathway. To test the clarity of vision of each eye, the researchers tracked the rodents’ visual behaviour .
It was found that for rats with mildly elevated eye pressure, the tissues that connect the eye and brain, including the optic nerve, degraded for up to five weeks after the injury. Nerve structure breakdown in the citicoline-treated rodents slowed by up to 74%, which the researchers said indicates that the chemical had protective effects on nerve cells.
However, more research is necessary before citicoline supplements to treat glaucoma in humans, as commercial drugs have yet to be proven fully effective in clinical trials. The researchers are planning next to look into how choline protects the eye and why it is depleted in glaucoma patients.
Journal information: Yolandi van der Merwe et al, Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control, Neurotherapeutics (2021). DOI: 10.1007/s13311-021-01033-6
