title: Effect of Brimonidine on the B Cells, T Cells, and Cytokines of the Ocular Surface and Aqueous Humor in Rat Eyes.
abstract: OBJECTIVE
  One serious ocular side effect associated with the long-term use of topical brimonidine tartrate is anterior uveitis. This study investigated the changes in the levels of several inflammatory cytokines, B cells, and T cells in rat eyes treated with topical brimonidine tartrate.
  
  
  METHODS
  Twenty Sprague-Dawley male rats were divided into 2 groups of 10 rats each. In the brimonidine group, rats were treated with brimonidine 3 times per day for 10 months. The rat cytokine multiplex method was used to determine the levels of cytokines [interleukin (IL)-1α, IL-1β, IL-2, IL-6, tumor necrosis factor alpha (TNF-α)] in the conjunctiva, cornea, aqueous humor, and lens. The cornea and conjunctiva were subjected to immunohistochemical staining using anti-CD20 antibody and anti-CD3 antibody.
  
  
  RESULTS
  The concentrations of IL-1β, IL-2, and IL-6 in the conjunctiva were significantly lower in the brimonidine group (P = 0.033, 0.017, and 0.016, respectively) than in the control group. Compared to the control group, the concentration of IL-2 in the cornea was also significantly lower in the brimonidine group (P = 0.037). However, in the analysis of the cytokines in the aqueous humor, the concentrations of IL-1β and IL-2 were significantly higher in the brimonidine group than in the control group (P = 0.016 and 0.008, respectively). There was no significant difference in CD20-positive B-cell and CD3-positive T-cell infiltration of the conjunctival biopsy specimens between the brimonidine group and the control group. Corneal specimens of both groups also showed no infiltration of CD20-positive B cells and CD3-positive T cells.
  
  
  CONCLUSIONS
  These results suggest that the increase in some inflammatory cytokines in the aqueous humor after the long-term brimonidine treatment may contribute to the pathogenesis of brimonidine-induced uveitis.
authors.affiliation: 1 Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea , Seoul, Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: 2 Department of Pediatrics, College of Medicine, The Catholic University of Korea , Seoul, Korea.
authors.forename: Hyun-Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: 1 Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea , Seoul, Korea.
authors.forename: Young Chun
authors.initials: YC
authors.lastname: Lee
authors.affiliation: 1 Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea , Seoul, Korea.
authors.forename: Su-Young
authors.initials: SY
authors.lastname: Kim
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D000068438:Brimonidine Tartrate / Q000008:administration & dosage / Q000633:toxicity*; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000473:pathology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016207:Cytokines; D000068438:Brimonidine Tartrate