A period of controlled elevation of IOP (CEI) produces the specific gene expression responses and focal injury pattern of experimental rat glaucoma

John C. Morrison, William O. Cepurna, Shandiz Tehrani, Tiffany E. Choe, Hari Jayaram, Diana C. Lozano, Brad Fortune, Elaine C. Johnson

Research output: Research - peer-reviewArticle

  • 1 Citations

Abstract

PURPOSE. We determine if several hours of controlled elevation of IOP (CEI) will produce the optic nerve head (ONH) gene expression changes and optic nerve (ON) damage pattern associated with early experimental glaucoma in rats. METHODS. The anterior chambers of anesthetized rats were cannulated and connected to a reservoir to elevate IOP. Physiologic parameters were monitored. Following CEI at various recovery times, ON cross-sections were graded for axonal injury. Anterior ONHs were collected at 0 hours to 10 days following CEI and RNA extracted for quantitative PCR measurement of selected messages. The functional impact of CEI was assessed by electroretinography (ERG). RESULTS. During CEI, mean arterial pressure (99 ± 6 mm Hg) and other physiologic parameters remained stable. An 8-hour CEI at 60 mm Hg produced significant focal axonal degeneration 10 days after exposure, with superior lesions in 83% of ON. Message analysis in CEI ONH demonstrated expression responses previously identified in minimally injured ONH following chronic IOP elevation, as well as their sequential patterns. Anesthesia with cannulation at 20 mm Hg did not alter these message levels. Electroretinographic A-and Bwaves, following a significant reduction at 2 days after CEI, were fully recovered at 2 weeks, while peak scotopic threshold response (pSTR) remained mildly but significantly depressed. CONCLUSIONS. A single CEI reproduces ONH message changes and patterns of ON injury previously observed with chronic IOP elevation. Controlled elevation of IOP can allow detailed determination of ONH cellular and functional responses to an injurious IOP insult and provide a platform for developing future therapeutic interventions.

LanguageEnglish (US)
Pages6700-6711
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number15
DOIs
StatePublished - Dec 1 2016

Fingerprint

Optic Disk
Glaucoma
Gene Expression
Wounds and Injuries
Optic Nerve
Optic Nerve Injuries
Electroretinography
Anterior Chamber
Catheterization
Arterial Pressure
Anesthesia
RNA
Polymerase Chain Reaction
Therapeutics

Keywords

  • Animal models
  • Glaucoma
  • Intraocular pressure
  • Optic nerve head

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

A period of controlled elevation of IOP (CEI) produces the specific gene expression responses and focal injury pattern of experimental rat glaucoma. / Morrison, John C.; Cepurna, William O.; Tehrani, Shandiz; Choe, Tiffany E.; Jayaram, Hari; Lozano, Diana C.; Fortune, Brad; Johnson, Elaine C.

In: Investigative Ophthalmology and Visual Science, Vol. 57, No. 15, 01.12.2016, p. 6700-6711.

Research output: Research - peer-reviewArticle

@article{8934b316efd340868552ec31d29896eb,
title = "A period of controlled elevation of IOP (CEI) produces the specific gene expression responses and focal injury pattern of experimental rat glaucoma",
abstract = "PURPOSE. We determine if several hours of controlled elevation of IOP (CEI) will produce the optic nerve head (ONH) gene expression changes and optic nerve (ON) damage pattern associated with early experimental glaucoma in rats. METHODS. The anterior chambers of anesthetized rats were cannulated and connected to a reservoir to elevate IOP. Physiologic parameters were monitored. Following CEI at various recovery times, ON cross-sections were graded for axonal injury. Anterior ONHs were collected at 0 hours to 10 days following CEI and RNA extracted for quantitative PCR measurement of selected messages. The functional impact of CEI was assessed by electroretinography (ERG). RESULTS. During CEI, mean arterial pressure (99 ± 6 mm Hg) and other physiologic parameters remained stable. An 8-hour CEI at 60 mm Hg produced significant focal axonal degeneration 10 days after exposure, with superior lesions in 83% of ON. Message analysis in CEI ONH demonstrated expression responses previously identified in minimally injured ONH following chronic IOP elevation, as well as their sequential patterns. Anesthesia with cannulation at 20 mm Hg did not alter these message levels. Electroretinographic A-and Bwaves, following a significant reduction at 2 days after CEI, were fully recovered at 2 weeks, while peak scotopic threshold response (pSTR) remained mildly but significantly depressed. CONCLUSIONS. A single CEI reproduces ONH message changes and patterns of ON injury previously observed with chronic IOP elevation. Controlled elevation of IOP can allow detailed determination of ONH cellular and functional responses to an injurious IOP insult and provide a platform for developing future therapeutic interventions.",
keywords = "Animal models, Glaucoma, Intraocular pressure, Optic nerve head",
author = "Morrison, {John C.} and Cepurna, {William O.} and Shandiz Tehrani and Choe, {Tiffany E.} and Hari Jayaram and Lozano, {Diana C.} and Brad Fortune and Johnson, {Elaine C.}",
year = "2016",
month = "12",
doi = "10.1167/iovs.16-20573",
volume = "57",
pages = "6700--6711",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "15",

}

TY - JOUR

T1 - A period of controlled elevation of IOP (CEI) produces the specific gene expression responses and focal injury pattern of experimental rat glaucoma

AU - Morrison,John C.

AU - Cepurna,William O.

AU - Tehrani,Shandiz

AU - Choe,Tiffany E.

AU - Jayaram,Hari

AU - Lozano,Diana C.

AU - Fortune,Brad

AU - Johnson,Elaine C.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - PURPOSE. We determine if several hours of controlled elevation of IOP (CEI) will produce the optic nerve head (ONH) gene expression changes and optic nerve (ON) damage pattern associated with early experimental glaucoma in rats. METHODS. The anterior chambers of anesthetized rats were cannulated and connected to a reservoir to elevate IOP. Physiologic parameters were monitored. Following CEI at various recovery times, ON cross-sections were graded for axonal injury. Anterior ONHs were collected at 0 hours to 10 days following CEI and RNA extracted for quantitative PCR measurement of selected messages. The functional impact of CEI was assessed by electroretinography (ERG). RESULTS. During CEI, mean arterial pressure (99 ± 6 mm Hg) and other physiologic parameters remained stable. An 8-hour CEI at 60 mm Hg produced significant focal axonal degeneration 10 days after exposure, with superior lesions in 83% of ON. Message analysis in CEI ONH demonstrated expression responses previously identified in minimally injured ONH following chronic IOP elevation, as well as their sequential patterns. Anesthesia with cannulation at 20 mm Hg did not alter these message levels. Electroretinographic A-and Bwaves, following a significant reduction at 2 days after CEI, were fully recovered at 2 weeks, while peak scotopic threshold response (pSTR) remained mildly but significantly depressed. CONCLUSIONS. A single CEI reproduces ONH message changes and patterns of ON injury previously observed with chronic IOP elevation. Controlled elevation of IOP can allow detailed determination of ONH cellular and functional responses to an injurious IOP insult and provide a platform for developing future therapeutic interventions.

AB - PURPOSE. We determine if several hours of controlled elevation of IOP (CEI) will produce the optic nerve head (ONH) gene expression changes and optic nerve (ON) damage pattern associated with early experimental glaucoma in rats. METHODS. The anterior chambers of anesthetized rats were cannulated and connected to a reservoir to elevate IOP. Physiologic parameters were monitored. Following CEI at various recovery times, ON cross-sections were graded for axonal injury. Anterior ONHs were collected at 0 hours to 10 days following CEI and RNA extracted for quantitative PCR measurement of selected messages. The functional impact of CEI was assessed by electroretinography (ERG). RESULTS. During CEI, mean arterial pressure (99 ± 6 mm Hg) and other physiologic parameters remained stable. An 8-hour CEI at 60 mm Hg produced significant focal axonal degeneration 10 days after exposure, with superior lesions in 83% of ON. Message analysis in CEI ONH demonstrated expression responses previously identified in minimally injured ONH following chronic IOP elevation, as well as their sequential patterns. Anesthesia with cannulation at 20 mm Hg did not alter these message levels. Electroretinographic A-and Bwaves, following a significant reduction at 2 days after CEI, were fully recovered at 2 weeks, while peak scotopic threshold response (pSTR) remained mildly but significantly depressed. CONCLUSIONS. A single CEI reproduces ONH message changes and patterns of ON injury previously observed with chronic IOP elevation. Controlled elevation of IOP can allow detailed determination of ONH cellular and functional responses to an injurious IOP insult and provide a platform for developing future therapeutic interventions.

KW - Animal models

KW - Glaucoma

KW - Intraocular pressure

KW - Optic nerve head

UR - http://www.scopus.com/inward/record.url?scp=85006371262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006371262&partnerID=8YFLogxK

U2 - 10.1167/iovs.16-20573

DO - 10.1167/iovs.16-20573

M3 - Article

VL - 57

SP - 6700

EP - 6711

JO - Investigative Ophthalmology and Visual Science

T2 - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 15

ER -