Early Methylprednisolone Treatment Can Stabilize the Blood-Optic Nerve Barrier in a Rat Model of Anterior Ischemic Optic Neuropathy (rAION)

Abstract

Purpose: We investigated whether methylprednisolone (MP) treatment halting retinal ganglion cell (RGC) death and having anti-inflammatory effect over a narrow therapeutic window affects the integrity of the blood-optic nerve barrier (BOB) in a rat model of ischemic optic neuropathy (rAION).

Methods: The optic nerve (ON) vascular permeability was determined by Evans blue extravasation. Changes in the levels of TNF-α and IL-1β cytokines were analyzed using quantitative RT-PCR (qRT-PCR) from day 1 to day 5 post-rAION. Rats were treated with MP starting on days 0, 1, 2, and 7 post-rAION. The survival and apoptosis of the RGCs were determined by fluoroGold labeling and TUNEL assay, and the visual function was assessed with flash visual-evoked potentials (FVEPs) 4 weeks postinfarct. Inflammation of the ON was detected by immunohistochemical staining of ED1.

Results: Macrophage recruitment in the ON was significantly reduced, which was compatible with the reduction in ON vascular permeability, after MP treatment starting on days 0 and 1 postinsult compared to PBS treatment (both, P < 0.05). There was significant reduction in TNF-α and IL-1β expression in MP-treated rats (all, P < 0.05). The survival number and antiapoptotic effect on RGCs, and the P1-N2 FVEP amplitude significantly improved with MP treatment starting on days 0 and 1 (all, P < 0.05).

Conclusions: Early treatment with MP halts RGC death and mitigates macrophage infiltration with decreased expression of proinflammatory cytokines in acute rAION. The very narrow therapeutic window is related to the quick stabilization of the disrupted BOB by early application of MP.