Language
English
Publication Date
4-1-2026
Journal
Investigative Ophthalmology & Visual Science
DOI
10.1167/iovs.67.4.31
PMID
41979250
PMCID
PMC13089652
PubMedCentral® Posted Date
4-14-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.
Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled dextran was used to assess corneal barrier, and conjunctival goblet cell parameters were measured in periodic acid-Schiff (PAS)-stained wholemounts.
Results: NEt-3IB significantly stimulated homeostatic, phagocytotic, and anti-inflammatory gene expression and suppressed inflammatory gene signatures in conjunctival monocyte/macrophage cells compared to vehicle (Padj < 0.05). Latent time trajectory analysis and flow cytometry further revealed that NEt-3IB preserved resident macrophage-associated gene and protein expression. Compared to vehicle, corneal labeled dextran uptake was lower (P = 0.001) and conjunctival goblet cell total (P = 0.001) and single-cell (P = 0.01) areas were higher in the NEt-3IB group. The impact of NEt-3IB on differentially expressed genes in cultured monocytes mirrored its effects in vivo. NEt-3IB and dexamethasone suppressed inflammatory mediator expression; however, NEt-3IB enhanced the expression of homeostatic factors, including Igf1 and Il10.
Conclusions: Rexinoid NEt-3IB suppresses inflammatory and stimulates homeostatic gene expression in the monocyte/macrophage lineage and desiccation-induced ocular surface disease. Rexinoid therapy may prove to be a novel approach to treat dry eye by stimulating endogenous production of homeostatic/anti-inflammatory factors.
Keywords
Dry Eye Syndromes, Animals, Macrophages, Conjunctiva, Gene Expression Regulation, Rabbits, Desiccation, Monocytes, Disease Models, Animal, Gene Expression, Humans, Female, Dexamethasone
Published Open-Access
yes
Recommended Citation
Alam, Jehan; Qu, Yangluowa; Shao, Jianming; et al., "Rexinoid NEt-3IB Promotes Resident Macrophage Gene Expression and Mitigates Desiccation-Induced Ocular Surface Disease" (2026). Faculty, Staff and Students Publications. 7400.
https://digitalcommons.library.tmc.edu/baylor_docs/7400