The use of cyclodialysis to limit exposure to elevated intraocular pressure in rat glaucoma models

Elaine C. Johnson, William O. Cepurna, Lijun Jia, John C. Morrison

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Elevated intraocular pressure (IOP) is the most common risk factor for glaucoma and pressure control is the goal of current clinical glaucoma therapy. Yet, recent clinical studies have documented that, even after therapeutic lowering of IOP, glaucomatous visual field loss can progress in many patients. Experimental elevation of IOP in the rat is commonly used to model human glaucomatous injury. However, there currently is no rodent model for the clinical situation of glaucomatous progression in eyes with apparently controlled IOP. The purpose of this study was to evaluate the ability of surgical cyclodialysis to produce both prolonged, non-injurious reduction of IOP in rat eyes and to stably normalize IOP in eyes with experimental pressure elevation. To perform cyclodialysis, a blunted spatula was fashioned from a hypodermic needle and used to separate a portion of the ciliary body from the sclera, opening a channel into the suprachoroidal space to allow aqueous outflow. Experimental IOP elevation was produced in rats by unilateral injection of hypertonic saline. Cyclodialysis in normal eyes resulted in an average 40 ± 4% reduction in IOP, without marked hypotony. IOP lowering could be sustained for at least 6 months. The risk of retinal or optic nerve injury following a single cyclodialysis procedure was minimal as evidenced by unaltered levels of four injury-responsive retinal mRNAs and by normal optic nerve morphology. Cyclodialysis in eyes with experimental IOP elevation resulted in IOP normalization that was sustained for durations of 7 and 21 days in 88% and 53% of eyes, respectively. In addition, in eyes with the same cumulative dose of elevated IOP prior to the procedure, successful IOP normalization by cyclodialysis resulted in significantly less optic nerve injury than that seen in eyes in which IOP control was ineffective (p = 0.03). These studies show that cyclodialysis provides a simple, non-injurious method to reduce experimentally elevated IOP in rats that can be used to model the clinical situation of eyes previously damaged by pressure. This tool offers new opportunities for identifying and studying the molecular processes associated with glaucomatous progression and for testing potential neuroprotective therapies in a clinically relevant situation.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalExperimental Eye Research
Volume83
Issue number1
DOIs
StatePublished - Jul 1 2006

Keywords

  • animal model
  • cyclodialysis
  • glaucoma
  • glia
  • intraocular pressure
  • optic nerve
  • retinal ganglion cell

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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