title: In vitro effects of preserved or preservative-free antiglaucoma medications on human complement system.
abstract: OBJECTIVE
  Antiglaucoma drugs have been associated with conjunctival and trabecular inflammatory cell infiltrates. However, the underlying mechanisms are still poorly understood. The aim of this study was to assess the effects of antiglaucoma medications on the complement system, an early mediator of the inflammatory response.
  
  
  METHODS
  Human serum was first treated with a classical or alternative pathway activator (aggregated human IgG or zymosan, respectively) in the presence or the absence of preservative-free or benzalkonium (BAK)-preserved antiglaucoma drugs. CH50 assay was then performed to assess the functional activity of residual complement in treated serum.
  
  
  RESULTS
  In the absence of complement activator, the antiglaucoma drugs tested in this study were all devoid of intrinsic complement-activating potency. Preserved and preservative-free carteolol as well as preserved latanoprost did not worsen or prevent complement activation induced by zymosan or aggregated IgG. Unexpectedly, both preserved and unpreserved timolol and betaxolol significantly counteracted the effects of complement activators. Timolol prevented activation triggered by both IgG and zymosan to the same extent (24% to 29%), despite the presence of BAK in the preserved formulation. Betaxolol was twice as effective at preventing the effect of IgG (34% to 37%) than that of zymosan (14%), regardless of the presence of BAK. However, BAK itself strongly aggravated complement activation by both activators.
  
  
  CONCLUSIONS
  Carteolol, timolol, betaxolol and latanoprost did not activate complement system. On the contrary, the beta-blockers timolol and betaxolol exerted an anti-inflammatory effect by preventing complement activation. The deleterious effect of benzalkonium seems to have been neutralized within the preserved eyedrops through a mechanism that remains to be elucidated. Our study suggests that inflammatory signs in glaucoma patients should not be attributed to complement activation by antiglaucoma drugs.
authors.affiliation: Department of Ophthalmology, Quinze-Vingts National Hospital, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Blondin
authors.forename: Pascale
authors.initials: P
authors.lastname: Hamard
authors.forename: Béatrice
authors.initials: B
authors.lastname: Cholley
authors.forename: Nicole
authors.initials: N
authors.lastname: Haeffner-Cavaillon
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D015784:Betaxolol / Q000494:pharmacology; D002354:Carteolol / Q000494:pharmacology; D003165:Complement System Proteins / Q000187:drug effects*; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D013999:Timolol / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D001548:Benzalkonium Compounds; D011310:Preservatives, Pharmaceutical; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol; D002354:Carteolol; D003165:Complement System Proteins; D015784:Betaxolol