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A Chronic Autoimmune Dry Eye Rat Model with Increase in Effector Memory T Cells in Eyeball Tissue
Published on: June 7, 2017
Spontaneous T cell mediated keratoconjunctivitis in Aire-deficient mice.
S Yeh1, C S de Paiva, C S Hwang
1Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA.
The British Journal of Ophthalmology
|May 12, 2009
Summary
Autoimmune Regulator (Aire) gene deficiency in mice causes T cell infiltration and goblet cell loss on the ocular surface, worsening with dry eye conditions. This suggests immune mechanisms drive APECED-related eye disease.
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- Autoimmune polyendocrinopathy-candiasis-ectodermal dystrophy (APECED) causes severe eye disease, including keratoconjunctivitis and vision loss.
- The exact pathogenesis of APECED-related ocular surface disease remains unclear.
- The autoimmune regulator (Aire) gene is central to APECED pathogenesis.
Purpose of the Study:
- To investigate the ocular surface immune environment in a murine model of APECED.
- To assess conjunctival goblet cell density and response to desiccating stress in Aire-deficient mice.
- To elucidate the role of immune-mediated mechanisms in APECED-associated eye conditions.
Main Methods:
- Aire-deficient and wild-type (WT) mice were exposed to desiccating stress and pharmacological tear inhibition.
- Immune cell populations (CD4+, CD8+, CD11b+, CD45+) were quantified in ocular tissues and meibomian glands.
- Conjunctival goblet cell density was measured and compared between groups.
Main Results:
- Aire-deficient mice exhibited significantly higher CD4+ T cell infiltration in the conjunctival epithelium and cornea.
- Increased CD4+, CD8+, and CD11b+ immune cells were found in the peripheral cornea and meibomian glands of Aire-deficient mice.
- Conjunctival goblet cell density was markedly reduced in Aire-deficient mice, both at baseline and under stress.
Conclusions:
- Aire deficiency results in ocular surface inflammation characterized by CD4+ and CD8+ T cell infiltration and goblet cell loss.
- Desiccating stress exacerbates this proinflammatory state in the Aire-deficient ocular environment.
- Immune-mediated pathways are implicated in the severe blepharitis and keratoconjunctivitis observed in the APECED murine model.
