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M. Pazos, S. Gardiner, J. Reynaud, J. Grimm, W. O. Cepurna, E. C. Johnson, J. C. Morrison, C. F. Burgoyne, H. Yang; Radial Optic Nerve Expansion Within the Expanding Scleral Canal in the Hypertonic Saline Rat Early Experimental Glaucoma (EEG) Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4806.
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© ARVO (1962-2015); The Authors (2016-present)
To 3D reconstruct rat optic nerve heads (ONHs) with varying stages of unilateral EEG so as to provide the first 3D description of normal and EEG ONH anatomy in this species.
Hypertonic saline was unilaterally injected into the episcleral veins of 8 adult rats producing variable levels of chronic IOP elevation. All animals were sacrificed 4 weeks post-injection by perfusion fixation and orbital optic nerve crossections from both eyes of all animals were graded (1 normal, 5 extensive) by 5 masked observers (Morrison, Exp Eye Res, 1997). Three mm-trephined ONH and peripapillary sclera were 3D reconstructed and delineated at 1.5 micron/voxel resolution (Yang, IOVS, 2009). For each ONH, we quantified 80 radii at different angles of anterior scleral opening (ASCO), anterior nerve cross section at the ASCO (ON-ASCO) and posterior cross section at the posterior scleral opening (ON-PSCO). Treatment and quadrant effects were assessed overall and within each rat by ANOVA (P<0.0001 to account for multiple comparisons).
Peak IOP in the EEG eyes ranged from 36 to 45.8 mmHg (mean fellow eye IOP 28.5 mm Hg). EEG eye optic nerve damage grades ranged from 1.22 to 3.28 (about 3-34% axonal loss). All parameters both overall and in a majority of individual rats (6 of 8 EEG eyes), were found to be significantly expanded by treatment (8 -23% ASCO; 21-48% ON-ASCO; and 12-57% ON-PSCO). Overall by quadrant all parameters were significantly expanded. Individually, expansions were larger and more frequent within the superior and temporal quadrants for ASCO and superiorly and inferiorly for ON-ASCO and ON-PSCO. The 2 EEG eyes with the lowest injury grade demonstrated the least change, overall and regionally (temporal in one and superior/inferior in the other). ON-ASCO expansion was significantly correlated to optic nerve damage grading (R2= 0.59, P<0.05).
This study presents the first quantitative 3D histomorphometric analysis of the normal and EEG rat ONH. Our data support previous descriptions of scleral canal expansion in the neuropathy (Chauhan et al, IOVS, 2002 and Guo et al, BJO, 2005) but for the first time describe radial optic nerve expansion within the canal that may precede scleral canal expansion and correlate to optic nerve axon loss. The absence of a robust lamina cribrosa makes the rat model uniquely suited to study non-laminar related neural and connective tissue damage.
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