Differential Intraocular Pressure Measurements by Tonometry and Direct Cannulation After Treatment with Soluble Adenylyl Cyclase Inhibitors.

TitleDifferential Intraocular Pressure Measurements by Tonometry and Direct Cannulation After Treatment with Soluble Adenylyl Cyclase Inhibitors.
Publication TypeJournal Article
Year of Publication2017
AuthorsGandhi JK, Chowdhury URoy, Manzar Z, Buck J, Levin LR, Fautsch MP, Marmorstein AD
JournalJ Ocul Pharmacol Ther
Volume33
Issue8
Pagination574-581
Date Published2017 10
ISSN1557-7732
KeywordsAcepromazine, Adenylyl Cyclase Inhibitors, Anesthetics, Animals, Anterior Chamber, Catheterization, Ethanol, Female, Humans, Injections, Intraperitoneal, Intraocular Pressure, Ketamine, Mice, Mice, Inbred C57BL, Tomography, Optical Coherence, Tonometry, Ocular, Xylazine
Abstract

PURPOSE: To validate the increase in intraocular pressure (IOP) caused by soluble adenylyl cyclase (sAC) inhibitors and determine reasons behind variation in IOP measurements performed by tonometry.

METHODS: C57BL/6J mice were administered DMSO solubilized sAC inhibitors (KH7 or LRE-1) by intraperitoneal injection. Two hours post-treatment, mice were anesthetized with avertin or ketamine/xylazine/acepromazine (KXA). IOP was measured by a rebound tonometer or direct cannulation of the anterior chamber. Spectral-domain optical coherence tomography was used to measure anterior chamber depth and corneal thickness in live mice. Outflow facility was measured in perfused, enucleated mouse eyes.

RESULTS: Compared with DMSO controls, KH7 treatment caused an increased IOP in avertin- and KXA-anesthetized mice when measured by direct cannulation [avertin: 14.4 ± 2.1 mmHg vs. 11.1 ± 1.0 mmHg (P = 0.003); KXA: 14.4 ± 1.0 mmHg vs. 11.3 ± 0.8 mmHg (P < 0.001)] and tonometry [avertin: 10.8 ± 1.4 mmHg vs. 7.4 ± 0.6 mmHg (P < 0.001); KXA: 11.9 ± 0.9 mmHg vs. 10.3 ± 1.7 mmHg (P = 0.283)]. However, treatment with KH7 in nonanesthetized mice showed a significant decrease in IOP measured by tonometry and compared with DMSO-treated animals [13.1 ± 2.6 mmHg vs. 15.6 ± 0.5 mmHg (P = 0.003)]. Both KH7- and DMSO-treated groups anesthetized with avertin showed increased corneal thickness, whereas KH7-treated mice anesthetized with KXA exhibited a shallower anterior chamber compared with untreated mice. KH7 decreased outflow facility by 85.1% in nonanesthetized, enucleated eyes (P < 0.003).

CONCLUSIONS: Systemically administered DMSO and anesthesia have significant effects on anterior chamber characteristics, resulting in altered IOP readings measured by tonometry. In the presence of DMSO and anesthesia, tonometry IOP readings should be confirmed with direct cannulation.

DOI10.1089/jop.2017.0027
Alternate JournalJ Ocul Pharmacol Ther
PubMed ID28686538
PubMed Central IDPMC5649413
Grant ListR01 EY021153 / EY / NEI NIH HHS / United States
R21 EY025810 / EY / NEI NIH HHS / United States
R01 EY026490 / EY / NEI NIH HHS / United States