Mooren ulcer: an immunopathologic study

To determine the pattern and distribution of mononuclear cells, adhesion, and co-stimulatory molecules in the conjunctiva of patients with Mooren ulcer.

Conjunctival biopsy specimens were obtained from 6 patients with Mooren ulcer and 6 healthy individuals. Immunohistochemistry was performed on frozen sections of the cryopreserved human conjunctivas using monoclonal antibodies directed against CD1alpha, CD3, CD4, CD8, CD20, CD25, CD57, and CD68 cells; the adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1), very late activation-4 (VLA-4), ICAM-1, and LFA-1; and the co-stimulatory molecules CD28, B7-1, B7-2, and CTLA-4.

Differences in expression on the conjunctival epithelium from patients with Mooren ulcer and normal subjects were noted only for VCAM-1, VLA-4, ICAM-1, and LFA-1. The ratio of CD4+/CD8+ cells in Mooren ulcer specimens was significantly higher (3.5-fold). However, in the substantia propria, Mooren ulcer specimens revealed significantly increased numbers of CD1alpha+, CD3+, CD4+, CD20+, CD28+, B7-1+, B7-2+, and CD68+ cells. The ratios of CD4+/CD8+ cells and B7-2+/antigen-presenting cells in Mooren ulcer specimens were significantly higher (5-fold). All tested adhesion molecules showed significant up-regulation in the patients' conjunctivas. Mooren ulcer vascular endothelial cells prominently expressed E-selectin, VCAM-1, VLA-4, and ICAM-1 compared with normal conjunctiva.

The simultaneous presence of multiple types of inflammatory cells, adhesion, and co-stimulatory molecules in Mooren ulcer conjunctiva suggests that their interaction may contribute to a sustained immune activation as at least part of the pathogenic mechanism of this disorder.