Pressure Clamping During Ocular Perfusions Drives Nitric Oxide-Mediated Washout

Ruth A. Kelly, Fiona S. McDonnell, Michael L. De Ieso, Darryl R. Overby, W. Daniel Stamer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

PURPOSE. The aim of this study was to test the hypothesis that nitric oxide (NO) mediates a pressure-dependent, negative feedback loop that maintains conventional outflow homeostasis and thus IOP. If true, holding pressure during ocular perfusions will result in uncontrolled production of NO, hyper-relaxation of the trabecular meshwork, and washout. METHODS. Paired porcine eyes were perfused at constant pressure of 15 mm Hg. After 1 hour acclimatization, one eye was exchanged with N5-[imino(nitroamino)methyl]-Lornithine, methyl ester, monohydrochloride (L-NAME) (50 μm) and the contralateral eye with DBG, and perfused for 3 hours. In a separate group, one eye was exchanged with DETA-NO (100 nM) and the other with DBG and perfused for 30 minutes. Changes in conventional outflow tissue function and morphology were monitored. RESULTS. Control eyes exhibited a washout rate of 15% (P = 0.0026), whereas eyes perfused with L-NAME showed a 10% decrease in outflow facility from baseline over 3 hours (P < 0.01); with nitrite levels in effluent positively correlating with time and facility. Compared with L-NAME–treated eyes, significant morphological changes in control eyes included increased distal vessel size, number of giant vacuoles, and juxtacanalicular tissue separation from the angular aqueous plexi (P < 0.05). For 30-minute perfusions, control eyes showed a washout rate of 11% (P = 0.075), whereas DETA-NO–treated eyes showed an increased washout rate of 33% from baseline (P < 0.005). Compared with control eyes, significant morphological changes in DETA-NO–treated eyes also included increased distal vessel size, number of giant vacuoles and juxtacanalicular tissue separation (P < 0.05). CONCLUSIONS. Uncontrolled NO production is responsible for washout during perfusions of nonhuman eyes where pressure is clamped.

Original languageEnglish (US)
Article number36
JournalInvestigative Ophthalmology and Visual Science
Volume64
Issue number7
DOIs
StatePublished - Jun 2023
Externally publishedYes

Keywords

  • nitric oxide
  • ocular perfusion
  • outflow facility
  • porcine
  • pressure clamping
  • trabecular meshwork
  • washout

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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