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Tzu Lun Huang, Rong-Kung Tsai; Therapeutic window of systemic methylprednisolone in a rat model of anterior ischemic optic neuropathy (rAION). Invest. Ophthalmol. Vis. Sci. 2016;57(12):5089.
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© ARVO (1962-2015); The Authors (2016-present)
Controversy exists regarding the methylprednisolone (MP) treatment for in non-arteritic anterior ischemic optic neuropathy in human (NAION). We tested the hypothesis that systemic MP treatment had significantly neuroprotective effects on RGC survival in immediate treatment after insult using a rat model of ischemic optic neuropathy (rAION).
After rAION induction, the rats were randomly assigned to either the MP-treated group (n =36) or the PBS-treated ischemia-only (n= 12) or sham group (n =12). MP injections were given at immediately (MP-0d, n = 12), 7 days (MP-1W, n =12) or 14 days (MP-2W d, n =12) after rAION. Outcome measurements included density of RGCs with retrograde Fluoro-Gold labeling, flash visual-evoked potentials (FVEP), TUNEL assays of the retinal sections and ED1 staining of the optic nerve. Optic nerve vascular permeability was quantified in the amount of Evan's blue dye extravasation. Statistical analysis was performed with IBM SPSS 19. We used Kruskal-Wallis test and Mann-Whitney U test to evaluate differences between the groups.
At the 4th week post-infarct, MP treatment significantly rescued the RGCs (mm2) in the central retinas (2050 ± 160) and mid-peripheral retinas (1040 ± 240) in 0D-MP compared with other treated groups (all p<0.05, n=6 each group).Functional assessment with fVEP demonstrated that amplitude improvements of P1 (55 ±uV) were significantly found in 0D-MP treated group comparing with other groups (all p<0.05, n=6 each group). TUNEL assays showed a significantly decrease in the number of apoptotic cells in the RGC layers of 0D- MP and 1W-MP treated retinas compared to the PBS-treated group (6.3 ± 1.9 cells/HPF, 9.9 ± 3.0 cells/HPF v,s 14.3± 2.7 positive cells/HPF, p=0.001 and p=0.02, respectively ). ED1 positive cells (/HPF) were significantly decreased in the ONs of the 0D-MP compared to other groups (all p<0.05). Results of vascular permeability showed that re-establishment of BRB and infiltration of external microglia into ON before day 2 post rAION.
Immediately MP treatment may play a role in rescue RGC survival rate and electrophysiologic visual function improvement in a rAION model. The rescue effects may be through the multiple actions on anti-apoptosis of RGCs as well as anti-inflammation in optic nerves.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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