IL-17 Producing Lymphocytes Cause Dry Eye and Corneal Disease With Aging in RXRα Mutant Mouse.

Purpose: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation. Methods: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells. Results: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear volume, corneal barrier disruption, corneal/conjunctival cornification and goblet cell loss, and corneal vascularization, opacification, and ulceration with aging. ScRNA-seq of conjunctival immune cells identified γδ T cells as the predominant IL-17 expressing population in both strains and there is a 4-fold increased percentage of γδ T cells in Pinkie. Compared to WT, IL-17a, and IL-17f significantly increased in Pinkie with conventional T cells and γδ T cells as the major producers. Flow cytometry revealed an increased number of IL-17+ γδ T cells in Pinkie. Tear concentration of the IL-17 inducer IL-23 is significantly higher in Pinkie. 9-cis RA treatment suppresses stimulated IL-17 production by γδ T and stimulatory activity of monocyte supernatant on γδ T cell IL-17 production. Compared to WT bone marrow chimeras, Pinkie chimeras have increased IL-17+ γδ T cells in the conjunctiva after desiccating stress and anti-IL-17 treatment suppresses dry eye induced corneal MMP-9 production/activity and conjunctival goblet cell loss. Conclusion: These findings indicate that RXRα suppresses generation of dry eye disease-inducing IL-17 producing lymphocytes s in the conjunctiva and identifies RXRα as a potential therapeutic target in dry eye.

Evaluation of crystalline lens and intraocular lens tilt using a swept-source optical coherence tomography biometer.

PURPOSE: To evaluate crystalline lens and intraocular lens (IOL) tilt using a swept-source optical coherence tomography (SS-OCT) biometer (IOLMaster 700). SETTING: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. DESIGN: Retrospective case series. METHODS: The study patients were evaluated for 1) repeatability of the crystalline lens tilt measurement, 2) preoperative crystalline lens and postoperative IOL tilt in right eyes, 3) mirror symmetry between right eyes and left eyes, 4) the correlation between preoperative crystalline lens and postoperative IOL tilt, and 5) the correlation between the magnitude of lens tilt and ocular parameters. RESULTS: The study comprised 333 patients. The repeatability was 0.1 degrees for tilt magnitude and 3.0 degrees for tilt direction. Both the crystalline lens and IOL had anterior tilt of the nasal portion with mean tilt magnitudes of 3.7 degrees ± 1.1 (SD) (range 0.4 to 6.9 degrees) for the crystalline lens and 4.9 ± 1.8 degrees (range 1.6 to 10.7 degrees) for the IOL. There was mirror symmetry between right eyes and left eyes. The mean IOL tilt magnitude exceeded crystalline lens tilt by 1.2 ± 1.1 degrees (range -3.2 to 4.0 degrees), and the 2 values were significantly correlated (all P < .01). The magnitude of crystalline lens tilt significantly increased with decreasing axial length and with increasing angle α (all P < .05). CONCLUSIONS: The repeatability of crystalline lens tilt measurements using the SS-OCT biometer was excellent. There was mirror symmetry between the right eyes and left eyes. Preoperative crystalline lens tilt could be used to predict the postoperative IOL tilt. The lens tilt magnitude was greater in short eyes and in eyes with larger angle α.

Suppression of Th1-Mediated Keratoconjunctivitis Sicca by Lifitegrast.

PURPOSE: Increased interferon gamma (IFN-γ) expression in dry eye causes ocular surface epithelial disease termed keratoconjunctivitis sicca (KCS). The purpose of this study was to investigated the effects of the LFA-1 antagonist, lifitegrast, in a mouse desiccating stress (DS) dry eye model that develops KCS similar to Sjögren syndrome. METHODS: Mice were treated with vehicle or lifitegrast twice daily for 5 days and expression of Th1 family genes (IFN-γ, CXCL9, and CXCL11) was evaluated by real-time polymerase chain reaction. Cornea barrier function was assessed by Oregon Green dextran staining and goblet cell number and area were measured. RESULTS: Compared to the vehicle-treated group, the lifitegrast-treated group had significantly lower expression of Th1 family genes, less corneal barrier disruption, and greater conjunctival goblet cell density/area. CONCLUSIONS: These findings indicate that lifitegrast inhibits DS-induced IFN-γ expression and KCS. This suggests that ICAM-LFA-1 signaling is involved with generation of Th1 inflammation in KCS.