ArticleInvestigative ophthalmology & visual science2022
Early Dry Eye Disease Onset in a NOD.H-2h4 Mouse Model of Sjögren's Syndrome.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Pathophysiology of the gut-eye axis in a Sjögren's disease-like dry eye mouse model: An exploratory evaluation of dietary heat-treated Enterococcus faecalis FK-23.Experimental physiology · 2026Article
- Research progress in animal models of dry eye disease: Types, mechanisms, and application prospects.Animal models and experimental medicine · 2026Review
- Corneal Fluorescein Staining in FDA-Reviewed Dry Eye Registrational Clinical Trials: Evidence of Limited Endpoint Responsiveness.Ophthalmic research · 2026Article
- The Immunobiology of Dry Eye Disease: A Review of the Pathogenesis, Regulation and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Linarine inhibits inflammatory responses in dry eye disease mice by modulating purinergic receptors.Frontiers in immunology · 2024Article
- Therapeutic potential for P2YPurinergic signalling · 2023Review
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
Purpose: To develop a mouse model of human dry eye disease (DED) for investigation of sex differences in autoimmune-associated dry eye pathology. Methods: Ocular surface disease was assessed by quantifying corneal epithelial damage with lissamine green stain in the NOD.H-2h4,IFNγ-/-,CD28-/- (NOD.H-2h4 DKO) mouse model of Sjögren's syndrome (SS). Lacrimal gland function was assessed by tear volume quantification with phenol red thread and lacrimal gland inflammation (i.e., dacryoadenitis) was assessed by quantification of immune cell foci, flow cytometric analysis of immune cell composition, and expression of proinflammatory markers. Results: The NOD.H-2h4 DKO mouse model of SS exhibits greater age-dependent increases in corneal damage than in NOD.H-2h4 parental mice and demonstrates an earlier disease onset in females compared to males. The severity of ocular surface disease correlates with loss of goblet cell density, increased conjunctivitis, and dacryoadenitis that is more pronounced in NOD.H-2h4 DKO than NOD.H-2h4 mice. B cells dominate lacrimal infiltrates in 16-week-old NOD.H-2h4 and NOD.H-2h4 DKO mice, but T helper cells and macrophages are also present. Lacrimal gland expression of proinflammatory genes, including the P2X7 and P2Y2 purinergic receptors, is greater in NOD.H-2h4 DKO than NOD.H-2h4 mice and correlates with dacryoadenitis. Conclusions: Our results demonstrate for the first time that autoimmune dry eye disease occurs in both sexes of NOD.H-2h4 DKO and NOD.H-2h4 mice, with earlier onset in female NOD.H-2h4 DKO mice when compared to males of the same strain. This study demonstrates that both NOD.H-2h4 and NOD.H-2h4 DKO mice are novel models that closely resemble SS-related and sex-dependent DED.
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