Researchers at Baylor College of Medicine and Okayama University in Japan have developed a promising new eye drop formulation to treat dry eye disease and tested it in mice. The team reports: Research Ophthalmology and Vision Science They found that the treatment significantly reduced typical dry eye features, including inflammation, damage to the ocular surface, and loss of goblet cells, which produce factors that help stabilize tears and lubricate the eye. This finding supports the conduct of human studies to evaluate the safety and effectiveness of this treatment, which could benefit millions of people with dry eye disease.
Dry eye disease is a common condition that causes irritation, redness, and blurred vision. Dry eye disease occurs more often in women as they age. It occurs when the eyes do not produce enough tears, or when environmental conditions such as dryness or wind cause the tears to evaporate quickly. In more severe cases, dry eye can damage the eye surface and cornea, affecting daily activities such as reading and driving. People with this condition tend to have it throughout their lives. ”
Dr. Stephen C. Pragfelder, Corresponding author, James and Margaret Elkins Professor of Ophthalmology, Baylor University
Current treatments include steroid drugs that suppress the immune response that causes eye inflammation. “Unfortunately, long-term use of steroids is not recommended, as they can lead to glaucoma (damage to the optic nerve that can lead to blindness) and cataracts,” Pflugfelder said. “We need improved treatments.”
Previous research has shown that the immune system plays an important role in eye health. Among immune cells, resident macrophages act as guardians. These cells remain in tissues for long periods of time and help maintain normal function by removing debris, reducing inflammation, and supporting tissue repair.
In dry eye disease, this balance is disrupted. Stress triggers the recruitment of other immune cells from the blood, namely circulating monocytes, which promote inflammation. At the same time, helpful resident macrophages become less effective and produce less of the protective molecules they normally produce. Collectively, these changes contribute to corneal damage and loss of specialized goblet cells.
“We hypothesized that increasing the function of protective macrophages could reduce inflammation and improve eye health,” Pflugfelder said. “We began a collaboration with Dr. Hiroki Tsunoda, a research professor at Okayama University who is an expert in generating alternatives to steroids for the treatment of immune-mediated diseases. We were interested in testing his compounds, called rexinoids, in a mouse model of human dry eye.”
The Tsunoda lab had developed a rexinoid called NEt-3IB that strengthens the protective function of resident macrophages. However, NEt-3IB in its original form does not mix well with water, a requirement for eye drops. The Tsunoda team modified the compound to be more soluble in water while retaining its ability to stimulate the protective role of macrophages.
“In this study, we were excited to discover that application of NEt-3IB eye drops shifts resident macrophages into a protective role by suppressing the production of inflammatory compounds and stimulating the production of healing compounds that promote debris clearance and immune balance,” Professor Pflugfelder said. “This treatment also maintained the integrity of the corneal barrier and the number and size of goblet cells during exposure to desiccation stress.”
Importantly, while steroid eye treatments can increase intraocular pressure and can cause glaucoma with long-term use, this study suggested that NEt-3IB caused a much smaller increase in intraocular pressure than the steroid dexamethasone and may be safer with long-term use. Further studies are needed to evaluate the effects of long-term use of NEt-3IB.
Current treatments for dry eye often focus on reducing inflammation, but do not necessarily restore the eye’s natural protective mechanisms. This study suggests that redirecting immune cells to reduce inflammation and strengthen protective functions could improve treatment options for dry eye disease.
First authors Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, and Karen Zheng (all from Baylor College of Medicine) contributed to this study.
This research was supported by the Lions Sight Foundation, the National Institutes of Health (NIH) (grants EY11915, U01 EY034692, CA125123, S10OD018033, S10OD023469, 1S10OD02346901, 2P30ES030285), and an NIH Core Grant. (EY002520), CPRIT Core Facility Support Award (CPRIT-RP180672), P30 Digestive Disease Center Support Grant (NIDDK-DK56338), P30 Cancer Center Support Grant (NCI-CA125123), and unrestricted grants from Blindness Prevention Research, the Hamill Foundation, and the Sid W. Richardson Foundation.
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Baylor College of Medicine
Reference magazines:
Aram, J. others. (2026). Rexinoid NEt-3IB promotes resident macrophage gene expression and attenuates desiccation-induced ocular surface disease. Research ophthalmology and vision science. Doi: 10.1167/iovs.67.4.31. https://iovs.arvojournals.org/article.aspx?articleid=2811721
