Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model

Marta Pazos, Hongli Yang, Stuart K. Gardiner, William O. Cepurna, Elaine Johnson, John Morrison, Claude F. Burgoyne

Research output: Contribution to journalArticle

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Abstract

Purpose: To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Methods: Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Results: Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p <0.0022), and in 7 of 8 EG eyes (p <0.005). In at least 5 EG eyes, significant expansions (p <0.005) in Bruch's membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). Conclusion: In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye.

Original languageEnglish (US)
Pages (from-to)173-186
Number of pages14
JournalExperimental Eye Research
Volume145
DOIs
StatePublished - Apr 1 2016

Fingerprint

Optic Nerve
Glaucoma
Theoretical Models
Optic Disk
Nerve Expansion
Bruch Membrane
Intraocular Pressure
Optic Nerve Diseases
Sclera
Retina
Veins
Perfusion
Injections
Wounds and Injuries

Keywords

  • Glaucoma
  • Neural canal
  • Optic nerve
  • Optic nerve head
  • Proprietary interest category: N
  • Rat
  • Scleral canal

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model. / Pazos, Marta; Yang, Hongli; Gardiner, Stuart K.; Cepurna, William O.; Johnson, Elaine; Morrison, John; Burgoyne, Claude F.

In: Experimental Eye Research, Vol. 145, 01.04.2016, p. 173-186.

Research output: Contribution to journalArticle

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abstract = "Purpose: To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Methods: Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Results: Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p <0.0022), and in 7 of 8 EG eyes (p <0.005). In at least 5 EG eyes, significant expansions (p <0.005) in Bruch's membrane opening (BMO) (range 3-10{\%}), the anterior and posterior scleral canal openings (8-21{\%} and 5-21{\%}, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30{\%} and 8-41{\%}, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). Conclusion: In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye.",
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AU - Yang, Hongli

AU - Gardiner, Stuart K.

AU - Cepurna, William O.

AU - Johnson, Elaine

AU - Morrison, John

AU - Burgoyne, Claude F.

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AB - Purpose: To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Methods: Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Results: Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p <0.0022), and in 7 of 8 EG eyes (p <0.005). In at least 5 EG eyes, significant expansions (p <0.005) in Bruch's membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). Conclusion: In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye.

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