Reducing internal eye pressure—or intraocular pressure (IOP)—with medicated eye drops or surgery is currently the only approved targeted treatment for glaucoma. Despite these treatments, however, many glaucoma patients continue to experience progressive vision loss, though perhaps more slowly. 

Experts think that neuroinflammation, a significant factor in several neurodegenerative diseases, may be the reason. Pioglitazone is a drug often prescribed to treat high blood sugar caused by type 2 diabetes. Pioglitazone works by helping your body better utilize insulin, and multiple studies have established that the drug also reduces inflammatory responses in patients with type 2 diabetes and coronary artery disease (both of which are risk factors for glaucoma), as well as in those with Alzheimer’s disease and chronic traumatic brain injury.

Based on these outcomes, a group of scientists from China and the U.S. used mouse models to investigate whether or not a low-dose regimen of pioglitazone could protect nerve cells in the eye called retinal ganglion cells (RGCs), and help those cells survive by reducing neuroinflammation.* 

What the researchers did

The damage to, deterioration, and death of RGCs is what causes vision loss in glaucoma patients. These patients would benefit from treatments that directly target and protect RGCs, but such therapies are not yet available. The main challenge of developing such neuroprotective glaucoma treatments is the many factors that contribute to the disease’s development, including:

• Insufficient blood flow to the eye, 
• Immune system-related health issues, 
• Oxidative stress, 
• Metabolic issues, and 
• Genetics.   

Since inflammation can trigger and/or exacerbate the above issues, the study authors evaluated pioglitazone’s ability to remove, or at least alter, that common factor. 

To do that, they artificially induced glaucoma in mice, after which 20 mice were placed on a low-dose regimen of pioglitazone in their drinking water, beginning at the age of 6 months. A second group of 20 control mice were left untreated. 

The treatment group was then divided in an early treatment group and a late treatment group. In the latter group, glaucoma damage was allowed to progress for three months before the pioglitazone treatment was started.

What they found

The researchers found that the mice receiving pioglitazone treatment experienced reduced RGC damage and degeneration. Specifically, they discovered that:

• The optic nerves of the untreated mice showed an average damage score of 2.85, which was significantly worse than the 2.00 damage score of the treated mice. 
• The early treatment group showed some reversal of the damage.
• The late treatment group showed that pioglitazone prevented further decline, and partially reversed vision loss. 

What it means

This study was designed to assess whether or not the neuro-protective effect of pioglitazone seen in other neurodegenerative diseases could also occur in glaucoma. The findings showed that pioglitazone treatment:

• Prevented further loss of vision, 
• Restored visual acuity, and
• Increased retinal function, despite continued IOP elevation.

These effects were demonstrated in mice with both mild and advanced glaucoma, though particularly in the mice with mild cases. It’s still unclear exactly how and why these results occurred. Decreased neuroinflammation is strongly suggested, but further research is needed.

The study authors are encouraged that their findings help target several pathways that pioglitazone can take to help glaucoma patients. 

*Zeng, H., Dumitrescu, A. V., Wadkins, D., Elwood, B., W. et al. (2022, February 9). Biomolecules 12(2): 281. DOI: 10.3390/biom12020281. https://www.mdpi.com/2218-273X/12/2/281/htm