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WO Cepurna, L Jia, EC Johnson, JC Morrison; Superior Scleral Localization of Rat Optic Nerve Head Responses to Mildly Elevated Intraocular Pressure . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4045.
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Purpose: Light microscopic evaluation of focal optic nerve lesions in rats with elevated intraocular pressure (eIOP) is preferentially localized to the superior nerve. In this study, we use transmission electron microscopy (TEM) to quantify alterations in the optic nerve head (ONH) following exposure to mild eIOP and localize them to specific nerve head regions. Methods: Sustained eIOP was produced in rats by unilateral sclerosis of outflow pathways. After 5 weeks, tissues were perfusion fixed and optic nerve cross sections graded for injury by light microscopy. Three groups of ONH were selected for TEM evaluation: (1) fellows (F), (2) eIOP exposure but with normal optic nerve morphology (eIOP-N) and (3) eIOP with a focal optic nerve lesion (eIOP-L). ONH cross sections were cut at 100 and 250 microns distal to Bruch’s membrane in the unmyelinated region. Sections were randomly placed on 300 mesh grids, systematically photographed and printed at X30,000. Grid squares were used to divide the ONH into inferior, central and superior regions. Among objects counted in the photos were multivesicular inclusions (MVI) of degenerating axonal debris, electron lucent vacuoles and axons. Regional distribution was statistically analyzed using Student’s t-test and ANOVA. Results: In the two eIOP groups, electron lucent vacuoles associated with astrocytic end feet and distal processes were found in both ONH levels, while none were found in the fellow eyes (p<0.0001). Within eIOP ONH regions, vacuoles were more common in the superior 100 µm compared to the superior 250 µm level (p<0.002) and eIOP-N nerve heads at the100 µm level had more vacuoles superiorly than inferiorly (p<0.004). Elevated IOP increased the prevalence of MVI at both ONH levels (p<0.01). eIOP-N nerve heads at the100 µm level also had significantly more MVI in the superior, compared to inferior region (p<0.04). Axon count was significantly decreased by eIOP (p<0.05) at all nerve head levels, and in eIOP-L nerve heads at the100 µm level, there was a significant decrease in axon count the superior, compared to the inferior, region (p<0.04). Conclusion: In the ONH, mild eIOP results in increased astrocytic-associated vacuoles and axonal debris-containing MVI, as well as decreased axon counts at the superior scleral level. This is correlated with the superior localization of focal optic nerve lesions, indicating that the superior, scleral ONH is the initial site of nerve injury with eIOP.
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