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

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. ONH’s 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<.0022), and in 7 of 8 EG eyes (p<.005). In at least 5 EG eyes, significant expansions (p<.005) in Bruch’s membrane opening (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=.042). Conclusion In the rat ONH, the optic nerve and surrounding Bruch’s membrane opening 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.

Melanopsin-Containing or Non-Melanopsin–Containing Retinal Ganglion Cells Response to Acute Ocular Hypertension With or Without Brain-Derived Neurotrophic Factor Neuroprotection

“…55,[59][60][62][63][64][65] Our ultrasound imaging Doppler studies document that AOH also results in mechanical deformation of the ocular globe, adding to the previous literature showing that IOP elevation results in deformation of the optic nerve head and peripapillary structures. 66 Such deformations may in turn play a significant role in the pathophysiology of RGC axonal damage following chronic [67][68] or acute 69 elevation of the IOP. Thus, AOH may result in a complex severe insult that leads to a (1) direct ischemic injury to the retina because it halts blood flow, (2) pressure-induced retinal damage because the IOP is increased several fold its basal value during a period of 75 minutes, and (3) deformation of the eye that may also affect retinal axons within the retina and at their exit of the eye through the optic nerve head.…”

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

“…Our method for 3D HMRN, delineation (Figure 13) and parameterization (Figures 14–15) of the monkey ONH has been described within a series of previous reports (Burgoyne et al, 2004; Downs et al, 2007; Lockwood et al, 2015; Pazos et al, 2016; Reynaud et al, 2016; Yang et al, 2007a; Yang et al, 2009a; Yang et al, 2007b; Yang et al, 2011b) and is summarized in detail in a recent book chapter (Yang et al, Accepted for publication Nov 2016 Forthcoming 2017). After, sacrifice and 3D reconstruction of a 6 mm trephine that contains the ONH and pp-sclera, 40 radial digital section images (4.5° degrees apart) of the reconstruction are manually delineated (Figure 13) and global values for 19 standard 3D HMRN parameters (Figures 14–15) are quantified as previously described (Downs et al, 2007; Yang et al, 2007a; Yang et al, 2009a; Yang et al, 2007b; Yang et al, 2011b).…”

Biomechanical aspects of axonal damage in glaucoma: A brief review

“…The superior opening contains a vascular plexus that passes through the sclera and partially surrounds the optic nerve. The inferior scleral opening contains the central retinal artery and three long posterior ciliary arteries (Pazos et al, 2015a, b). …”