title: In Vivo Effects of Preservative-free and Preserved Prostaglandin Analogs: Mouse Ocular Surface Study.
abstract: OBJECTIVE
  Chronic use of topical hypotensive agents induces several side effects caused by preservatives. The purpose of this study was to evaluate the effects of prostaglandin analogs with varying concentrations of benzalkonium chloride (BAC), preservative-free (PF), and alternative preservatives on mouse corneal tissue.
  
  
  METHODS
  Thirty-five, 8- to 10-week-old female C57BL/6 mice (five mice for each group) were used for this study. To the control group, we applied normal saline, and to each drug-treated group we applied 0.02% BAC, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), travoprost 0.004% (with 0.001% polyquad) or tafluprost 0.0015% with/without 0.001% BAC, once a day (9 p.m.) for 4 weeks. Corneal fluorescein staining was evaluated in all groups. After harvest, the corneal tissues were embedded in paraffin and then Hematoxylin-Eosin stain was performed for histopathological examination. Immunofluorescence staining was done against TNF-α, IL-6, HLA DR, pJNK, and pAkt.
  
  
  RESULTS
  In corneal fluorescein staining, severe punctate epithelial keratitis was seen in the groups of 0.02% BAC, 0.02% BAC containing bimatoprost 0.01% and latanoprost 0.005%. The surface desquamation, irregular surface, loss of cell borders, anisocytosis and stromal shrinkage were observed in the groups of BAC-containing eye drops. Moreover, the groups treated with BAC-containing eye drops have high inflammatory markers, significantly decreased cell viability-related signal, pAkt, and higher apoptosis-inducing signal, pJNK, than the control group. On the other hand, travoprost 0.004% and PF tafluprost 0.0015% have less cellular morphologic changes, lower inflammation, and higher cellular viability than BAC-containing formulations.
  
  
  CONCLUSIONS
  Corneal damage, increased inflammation and apoptosis and low cell viability were observed in BAC-containing groups. PF or alternatively preserved glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, Daegu, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, Daegu, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, Daegu, Korea.
authors.forename: Yeoun-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, Daegu, Korea.
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Developmental Biology Laboratory, Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Se-Hyung
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Developmental Biology Laboratory, Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Jae-Chang
authors.initials: JC
authors.lastname: Jung
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, Daegu, Korea.
authors.forename: Kyoo Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, Daegu, Korea.
authors.forename: Young Jeung
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000818:Animals; D002470:Cell Survival; D003228:Conjunctiva / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D011465:Prostaglandins, Synthetic / Q000008:administration & dosage*
chemical_list: D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D011465:Prostaglandins, Synthetic
keywords: Benzalkonium compounds; Cornea; Pharmaceutical preservatives; Synthetic prostaglandins