In a new preclinical study published in Investigative Ophthalmology & Visual Science, researchers at Baylor College of Medicine, Texas, US, report that a synthetic rexinoid compound, NEt-3IB, reduced ocular surface inflammation and preserved goblet cells in a mouse model of desiccation-induced dry eye disease.
“Rexinoid therapy may prove to be a novel approach to treat dry eye by stimulating endogenous production of homeostatic/anti-inflammatory factors,” the study authors wrote in the paper.
The work centers on tissue-resident macrophages – long-lived immune cells that help maintain ocular surface integrity. Previous research from the same group showed that these cells become depleted or dysfunctional during dry eye, contributing to goblet cell loss and epithelial barrier disruption. The investigators also identified retinoid X receptor alpha (RXRα) signaling as a key regulator of resident macrophage behavior.
To test whether activating this pathway could protect the ocular surface, the team treated mice exposed to desiccating stress with topical NEt-3IB three times daily for five days. NEt-3IB is a water-soluble synthetic rexinoid designed specifically for ocular delivery.
Using single-cell RNA sequencing, the researchers found that NEt-3IB shifted conjunctival macrophages away from an inflammatory phenotype and toward a more homeostatic state.
These immune changes translated into measurable ocular surface benefits. Corneal permeability assays showed significantly less epithelial barrier disruption in treated mice, while conjunctival goblet cell density, cell size, and glycoprotein volume were all preserved compared with vehicle-treated controls.
The effects appeared to be mediated primarily through macrophages rather than epithelial cells themselves. Conditional RXRα deletion in macrophages worsened corneal barrier dysfunction, whereas epithelial RXRα knockout had little effect.
The investigators also compared NEt-3IB with dexamethasone in cultured monocytes stimulated with lipopolysaccharide. While both agents were shown to suppress inflammatory cytokines, only NEt-3IB increased expression of reparative factors such as Igf1 and Il10.
Another potentially important distinction involved intraocular pressure (IOP). While prolonged dexamethasone treatment caused sustained IOP elevation in mice, NEt-3IB produced only transient increases at select time points.
The study authors do caution that these findings remain preliminary. The study used an acute murine dry eye model, and longer-term studies will be needed to determine whether rexinoid therapy is effective in chronic disease or established dry eye. Safety profiling will also be essential before clinical translation.
Still, the work offers a glimpse into a future where dry eye therapies move beyond broad immunosuppression toward targeted immune modulation. Rather than silencing inflammation outright, rexinoids could help to restore the ocular surface’s own capacity for repair.
