Abstract
The goal of this study was to explore the specific signaling pathways related to inflammation in two experimental mouse dry eye (EDE) models. Female C57BL/6 mice housed for 10 days in a controlled desiccative environment were either treated with scopolamine (EDE-1; n = 18) or subjected to extraorbital lacrimal gland excision bilaterally (EDE-2; n = 10). Non-induced mice (n = 20) served as healthy controls. A corneal fluorescein staining (CFS) scoring was used at baseline through to day (D) 10 to evaluate epitheliopathy. At D10, corneas and conjunctivas were collected for multiplexed transcriptomic analysis with the NanoString® mouse inflammatory CodeSet. Both EDE-1 and EDE-2 mice presented a change in corneal integrity, with a significant increase in CFS scores at D10. More gene transcripts were identified in EDE-2 compared with EDE-1 (116 vs. 96, respectively), and only a few were common to both models, 13 for the cornea and 6 for the conjunctiva. The gene functional annotation analysis revealed that the same inflammatory pathways were involved in both models. Comparative profiling of gene expression in the two EDE models leads to the identification of various targets and signaling pathways, which can be extrapolated to and confirmed in human disease.
Highlights
IntroductionDry eye disease (DED) is a multifactorial disease affecting the ocular surface and is defined by the loss of tear film homeostasis, resulting in destabilized tear film and hyperosmolarity, alterations in the corneal and conjunctival epithelia, inflammation, and neurosensory abnormalities [1]
Upon placement in a CER with a desiccative controlled environment, mice treated with scopolamine (EDE-1) or having undergone excision of their extraorbital lacrimal glands (EDE-2) were examined for corneal epitheliopathy via corneal fluorescein staining (CFS) (Figure 1A)
Corneal epitheliopathy increased at D3, reaching 10.26 ± 0.5 and 11.9 ± 0.9 for experimental mouse dry eye (EDE)-1 and EDE-2, respectively, and a stable CFS score was observed for healthy controls at 2.85 ± 0.2
Summary
Dry eye disease (DED) is a multifactorial disease affecting the ocular surface and is defined by the loss of tear film homeostasis, resulting in destabilized tear film and hyperosmolarity, alterations in the corneal and conjunctival epithelia, inflammation, and neurosensory abnormalities [1]. The quality of life of patients with DED symptoms can be significantly degraded [2,3]. Over the past few decades, numerous research studies have described modulation of inflammatory mediators in the tear film or ocular surface tissues, supporting the hypothesis that inflammation is one of the core mechanisms of DED [4,5,6,7,8] (Table 1). Dry Eye Disease (Human) Immune system Cytokines Over the past few decades, numerous research studies have described modulation of inflammatory mediators in the tear film or ocular surface tissues, supporting the hypothesis that inflammation is one of the core mechanisms of DED [4,5,6,7,8] (Table 1). 4.0/).
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