title: Effects of Latanoprost and Bimatoprost on the Expression of Molecules Relevant to Ocular Inflow and Outflow Pathways.
abstract: OBJECTIVE
  The intraocular pressure (IOP)-lowering and side effects in response to different prostaglandin F2α analogues can be variable, but, the underlying basis for this difference remains unknown. This study investigated the differential changes of cellular proteins relevant to IOP-lowering effects of latanoprost and bimatoprost.
  
  
  METHODS
  The human T lymphoblast (MOLT-3) cell line and immortalized human trabecular meshwork (iHTM) cells were studied by quantitative PCR and by immunofluorescence after treatment with either latanoprost or bimatoprost. New Zealand white rabbit eyes were treated topically with each agent and, following euthanasia, anterior segment tissues were studied with immunostaining.
  
  
  RESULTS
  In cultured MOLT-3 cells, mRNA expression of both c-fos and matrix metalloproteinase 9 increased significantly in response to each agent. In addition, there was little change in tissue inhibitor of metalloproteinase (TIMP)-3 mRNA, but a significant decrease in TIMP-4. Fibronectin mRNA in MOLT-3 cells was down-regulated with bimatoprost, but was up-regulated with latanoprost. Immunofluorescence analysis of iHTM cells showed that intracellular fibronectin was significantly decreased by bimatoprost, but was increased by latanoprost. Both latanoprost and bimatoprost increased mRNA expression of NF-кB p65 and decreased that of IкBα. Aquaporin-1 mRNA expression was significantly down-regulated by bimatoprost. Immunostaining also revealed a significant decrease of aquaporin-1 in the ciliary epithelium of New Zealand white rabbits after bimatoprost treatment.
  
  
  CONCLUSIONS
  Similarities in protein expression produced by latanoprost and bimatoprost in vitro may be relevant to the mechanism for their IOP-lowering effects in vivo. Differences in fibronectin expression and in aquaporin-1 expression in response to each agent may contribute to variability in the IOP-lowering efficacy in some studies.
authors.affiliation: Department of Biopharmaceutics, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Fen
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Ophthalmology & Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: B'Ann T
authors.initials: BT
authors.lastname: Gabelt
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Cai
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China.
authors.forename: Juanhui
authors.initials: J
authors.lastname: Cao
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology & Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kaufman
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D051398:Aquaporin 1 / Q000235:genetics; D000069580:Bimatoprost / Q000494:pharmacology*; D002460:Cell Line; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D016328:NF-kappa B / Q000235:genetics; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D005353:Fibronectins; D016328:NF-kappa B; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D051398:Aquaporin 1; D000077338:Latanoprost; D000069580:Bimatoprost