Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model.
To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG).



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.



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).



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.
Hospital de l'Esperança, Parc de Salut Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
Marta
M
Pazos
Devers Eye Institute, Optic Nerve Head Research Laboratory, Legacy Research Institute, Portland, OR, USA.
Hongli
H
Yang
Devers Eye Institute, Discoveries in Sight Research Laboratories, Legacy Research Institute, Portland, OR, USA.
Stuart K
SK
Gardiner
Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA.
William O
WO
Cepurna
Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA.
Elaine C
EC
Johnson
Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA.
John C
JC
Morrison
Devers Eye Institute, Optic Nerve Head Research Laboratory, Legacy Research Institute, Portland, OR, USA. Electronic address: cfburgoyne@deverseye.org.
Claude F
CF
Burgoyne
D000818:Animals; D016570:Bruch Membrane / Q000473:pathology; D004195:Disease Models, Animal; D005901:Glaucoma / Q000209:etiology / Q000473:pathology*; D008297:Male; D054259:Neural Tube / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology*; D051381:Rats; D012462:Saline Solution, Hypertonic; D012590:Sclera / Q000473:pathology*
D012462:Saline Solution, Hypertonic
Glaucoma; Neural canal; Optic nerve; Optic nerve head; Proprietary interest category: N; Rat; Scleral canal