title: Pilocarpine-induced dilation of Schlemm's canal and prevention of lumen collapse at elevated intraocular pressures in living mice visualized by OCT.
abstract: OBJECTIVE
  The goal was to assess effects of IOP and pilocarpine-induced ciliary muscle contraction on conventional outflow pathway tissues in living anesthetized mice.
  
  
  METHODS
  Intraocular pressure was controlled by intracameral cannulation of mouse eyes while imaging using spectral-domain optical coherence tomography (SD-OCT). Time-lapse sagittal SD-OCT sections through Schlemm's canal (SC) were acquired while changing IOP stepwise between 10 and 45 mm Hg. After topical application of 1% pilocarpine, the series of IOP steps and imaging were repeated. Effects of pilocarpine on IOP and outflow facility in living mice were verified by rebound tonometry and flow measurements at three different IOPs, respectively. In vivo OCT images were compared with eyes analyzed by standard histology.
  
  
  RESULTS
  In living mice imaged by SD-OCT, the lumen of SC progressively collapsed with increasing IOP, reaching near complete closure at 20 mm Hg. Schlemm's canal collapse was reversible, with the lumen opening within minutes after returning IOP from 45 to 10 mm Hg. Pilocarpine-induced ciliary muscle contraction changed SC lumen area by 131.6% ± 21.0% compared with untreated controls at 10 mm Hg, opened the trabecular meshwork, and prevented complete collapse of the SC lumen at higher pressures. Similar results were observed by standard histology. Pilocarpine increased outflow facility 4-fold (P = 0.02) and lowered IOP (16.46 ± 2.23 vs. 11.08 ± 2.28 mm Hg, P = 0.03).
  
  
  CONCLUSIONS
  Spectral-domain OCT was effective at visualizing changes in SC lumen in living mice. Results with pilocarpine are consistent with the concept that a primary role for the ciliary muscle is to prevent collapse of SC.
authors.affiliation: Department of Ophthalmology, Duke University, Durham, North Carolina, United States.
authors.forename: Guorong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Duke University, Durham, North Carolina, United States Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States.
authors.forename: Sina
authors.initials: S
authors.lastname: Farsiu
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Chiu
authors.affiliation: Department of Ophthalmology, Duke University, Durham, North Carolina, United States.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez
authors.affiliation: Department of Anatomie II, University Erlangen-Nürnberg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Lütjen-Drecoll
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom.
authors.forename: Darryl R
authors.initials: DR
authors.lastname: Overby
authors.affiliation: Department of Ophthalmology, Duke University, Durham, North Carolina, United States Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States.
authors.forename: W Daniel
authors.initials: WD
authors.lastname: Stamer
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002924:Ciliary Body / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009798:Ocular Hypertension / Q000503:physiopathology / Q000517:prevention & control*; D010862:Pilocarpine / Q000494:pharmacology*; D041623:Tomography, Optical Coherence / Q000379:methods*; D014129:Trabecular Meshwork / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D018721:Muscarinic Agonists; D010862:Pilocarpine
keywords: aqueous humor; glaucoma; ocular hypertension; optical coherence tomography; pilocarpine; trabecular meshwork