ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure in vivo

Uttio Roy Chowdhury, Bradley H. Holman, Michael P Fautsch

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose. To evaluate the expression of ATP-sensitive potassium (KATP) channel subunits and study the effect of KATP channel openers diazoxide and nicorandil on intraocular pressure (IOP) in an in vivo mouse model. Methods. Expression of KATP channel subunits in normal C57BL/6 mouse eyes was studied by immunohistochemistry and confocal microscopy. Wild-type C57BL/6 mice were treated with KATP channel openers diazoxide (n = 10) and nicorandil (n = 10) for 14 days. Similar treatments with diazoxide were performed on Kir6.2(-/-) mice (n = 10). IOP was recorded with a handheld tonometer 1 hour, 4 hours, and 23 hours following daily treatment. Posttreatment histology was examined by light and transmission electron microscopy. Results. The KATP channel subunits SUR2B, Kir6.1, and Kir6.2 were identified in all tissues within mouse eyes. Treatment with diazoxide in wild-type mice decreased IOP by 21.5 6 3.2% with an absolute IOP reduction of 3.9 6 0.6 mm Hg (P = 0.002). Nicorandil also decreased IOP (18.9 6 1.8%) with an absolute IOP reduction of 3.4 6 0.4 mm Hg (P = 0.002). Treatment with diazoxide in Kir6.2(-/-) mice had no effect on IOP. No morphological abnormalities were observed in diazoxide- or nicorandil-treated eyes. Conclusions. KATP channel openers diazoxide and nicorandil are effective regulators of IOP in mouse eyes. Kir6.2 appears to be a major KATP channel subunit through which IOP is lowered following treatment with diazoxide.

Original languageEnglish (US)
Pages (from-to)4892-4899
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number7
DOIs
StatePublished - 2013

Fingerprint

Nicorandil
Diazoxide
KATP Channels
Intraocular Pressure
Inbred C57BL Mouse
Therapeutics
Transmission Electron Microscopy
Confocal Microscopy
Histology
Immunohistochemistry
Light

Keywords

  • Anterior segment
  • Intraocular pressure
  • Potassium channel

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure in vivo. / Chowdhury, Uttio Roy; Holman, Bradley H.; Fautsch, Michael P.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 7, 2013, p. 4892-4899.

Research output: Contribution to journalArticle

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abstract = "Purpose. To evaluate the expression of ATP-sensitive potassium (KATP) channel subunits and study the effect of KATP channel openers diazoxide and nicorandil on intraocular pressure (IOP) in an in vivo mouse model. Methods. Expression of KATP channel subunits in normal C57BL/6 mouse eyes was studied by immunohistochemistry and confocal microscopy. Wild-type C57BL/6 mice were treated with KATP channel openers diazoxide (n = 10) and nicorandil (n = 10) for 14 days. Similar treatments with diazoxide were performed on Kir6.2(-/-) mice (n = 10). IOP was recorded with a handheld tonometer 1 hour, 4 hours, and 23 hours following daily treatment. Posttreatment histology was examined by light and transmission electron microscopy. Results. The KATP channel subunits SUR2B, Kir6.1, and Kir6.2 were identified in all tissues within mouse eyes. Treatment with diazoxide in wild-type mice decreased IOP by 21.5 6 3.2{\%} with an absolute IOP reduction of 3.9 6 0.6 mm Hg (P = 0.002). Nicorandil also decreased IOP (18.9 6 1.8{\%}) with an absolute IOP reduction of 3.4 6 0.4 mm Hg (P = 0.002). Treatment with diazoxide in Kir6.2(-/-) mice had no effect on IOP. No morphological abnormalities were observed in diazoxide- or nicorandil-treated eyes. Conclusions. KATP channel openers diazoxide and nicorandil are effective regulators of IOP in mouse eyes. Kir6.2 appears to be a major KATP channel subunit through which IOP is lowered following treatment with diazoxide.",
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N2 - Purpose. To evaluate the expression of ATP-sensitive potassium (KATP) channel subunits and study the effect of KATP channel openers diazoxide and nicorandil on intraocular pressure (IOP) in an in vivo mouse model. Methods. Expression of KATP channel subunits in normal C57BL/6 mouse eyes was studied by immunohistochemistry and confocal microscopy. Wild-type C57BL/6 mice were treated with KATP channel openers diazoxide (n = 10) and nicorandil (n = 10) for 14 days. Similar treatments with diazoxide were performed on Kir6.2(-/-) mice (n = 10). IOP was recorded with a handheld tonometer 1 hour, 4 hours, and 23 hours following daily treatment. Posttreatment histology was examined by light and transmission electron microscopy. Results. The KATP channel subunits SUR2B, Kir6.1, and Kir6.2 were identified in all tissues within mouse eyes. Treatment with diazoxide in wild-type mice decreased IOP by 21.5 6 3.2% with an absolute IOP reduction of 3.9 6 0.6 mm Hg (P = 0.002). Nicorandil also decreased IOP (18.9 6 1.8%) with an absolute IOP reduction of 3.4 6 0.4 mm Hg (P = 0.002). Treatment with diazoxide in Kir6.2(-/-) mice had no effect on IOP. No morphological abnormalities were observed in diazoxide- or nicorandil-treated eyes. Conclusions. KATP channel openers diazoxide and nicorandil are effective regulators of IOP in mouse eyes. Kir6.2 appears to be a major KATP channel subunit through which IOP is lowered following treatment with diazoxide.

AB - Purpose. To evaluate the expression of ATP-sensitive potassium (KATP) channel subunits and study the effect of KATP channel openers diazoxide and nicorandil on intraocular pressure (IOP) in an in vivo mouse model. Methods. Expression of KATP channel subunits in normal C57BL/6 mouse eyes was studied by immunohistochemistry and confocal microscopy. Wild-type C57BL/6 mice were treated with KATP channel openers diazoxide (n = 10) and nicorandil (n = 10) for 14 days. Similar treatments with diazoxide were performed on Kir6.2(-/-) mice (n = 10). IOP was recorded with a handheld tonometer 1 hour, 4 hours, and 23 hours following daily treatment. Posttreatment histology was examined by light and transmission electron microscopy. Results. The KATP channel subunits SUR2B, Kir6.1, and Kir6.2 were identified in all tissues within mouse eyes. Treatment with diazoxide in wild-type mice decreased IOP by 21.5 6 3.2% with an absolute IOP reduction of 3.9 6 0.6 mm Hg (P = 0.002). Nicorandil also decreased IOP (18.9 6 1.8%) with an absolute IOP reduction of 3.4 6 0.4 mm Hg (P = 0.002). Treatment with diazoxide in Kir6.2(-/-) mice had no effect on IOP. No morphological abnormalities were observed in diazoxide- or nicorandil-treated eyes. Conclusions. KATP channel openers diazoxide and nicorandil are effective regulators of IOP in mouse eyes. Kir6.2 appears to be a major KATP channel subunit through which IOP is lowered following treatment with diazoxide.

KW - Anterior segment

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