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Elaine Johnson, William Cepurna, John Morrison; Radiation Treatment Does Not Protect the Rat Optic Nerve from Elevated Intraocular Pressure (IOP)-Induced Injury. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4010.
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Sublethal irradiation has been shown to powerfully protect the optic nerve from elevated IOP-induced injury in the DBA/2j mouse genetic glaucoma model (Howell et al, PMID 22426214). The purpose of this study is to determine if the same treatment provides neuroprotection in an experimentally-induced glaucoma model in the rat.
At 6 weeks following head-only irradiation (10 Gy), episcleral vein injection of hypertonic saline was used to elevate IOP unilaterally in Brown Norway rats (N=28) as well as in a group of non-irradiated control rats (N=27). IOP was measured three times weekly using a TonoLab tonometer in awake animals. At 5 weeks post-injection, optic nerve cross-sections were graded using an injury scale ranging from 1 (normal) to 5 (>50% axon degeneration). Statistical analyses utilized t-test, linear regression and 2 way ANOVA.
For the radiation and control glaucoma model nerves, the mean (± SEM) injury grades were not significantly different (3.65±0.30 and 3.55±0.32, respectively). This mean injury grade is approximately equivalent to 35% of optic nerve axons in the process of degeneration. Analysis of IOP levels above uninjected fellow eye values showed that mean (radiation: 7.0±1.3 mmHg; control: 5.4±1.2 mm Hg) and peak (radiation:16.9±2.0 mmHg; control: 18.5±2.2 mm Hg) were not different between the two glaucoma model groups. Linear regression analysis of either mean or peak IOP to injury grade revealed no significant difference in the regression lines, although in both cases the best fit was to peak IOP (R2 =0.80 radiation, 0.66 control). 2-way ANOVA of nerves grouped by either mean or peak IOP range did not reveal any significant differences in optic nerve injury grade between radiation and control glaucoma model nerve groups with equivalent IOP exposures. For both mean and peak IOP analyses, radiation treatment had no overall effect on injury grade, while the effect of IOP level was extremely significant (p<0.0001).
In contrast to previous observations in the DBA/2j mouse genetic glaucoma model, head-only irradiation does not protect the optic nerve from injury from chronic experimentally-induced IOP elevation in the rat.
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