Mutations in Gpnmb and Tryp1 are required for development of spontaneous anterior uveitis in DBA/2J mice with pigmentary glaucoma

Abstract

Abstract: : Purpose: DBA/2J mice spontaneously develop anterior uveitis that is associated with pigment dispersion and eventually glaucoma. We wished to determine whether either or both of the mutant genes in these mice (Tryp1, Gpnmb) is required for breakdown of the blood:aqueous barrier and infiltration of inflammatory cells into the aqueous humor. Methods: AqH was collected from eyes of 6 mo old female DBA/2J, DBA/2J with Gpnmb^wt/wt, and DBA/2J with Tryp1^wt/wt, and analyzed for content of protein and leukocytes. AqH from similarly aged BALB/c mice served as control. Results: Whereas AqH from DBA/2J mice contained high levels of protein (>3 mg/ml) and numerous leukocytes (>90/µl), AqH from mice with either wild–type Gpnmb or Tyrp1 genes displayed protein levels (< 1 mg/ml) and leukocyte counts (< 10/µl) that were only slightly higher than that in AqH of normal BALB/c mice. Conclusion: Anterior uveitis, compromised blood:aqueous barrier, and leukocyte infiltration develop in eyes of DBA/2J mice as a consequence of epistatic interactions between the two unlinked mutant genes Gpnmb and Tyrp1.

Keywords: uveitis–clinical/animal model • immune tolerance/privilege • genetics