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Steven L. Bernstein, Mary A. Johnson, Neil R. Miller; PGJ2 is Neuroprotective in Primate Nonarteritic Anterior Ischemic Optic Neuropathy (pNAION). Invest. Ophthalmol. Vis. Sci. 2011;52(14):4671.
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We have previously demonstrated that 15 deoxy, Δ12,14 prostaglandin J2 (PGJ2) is neuroprotective in a rodent model of NAION. Analysis of gene expression revealed that the expression level of the parent enzyme, PGD2 synthase, is expressed at roughly equivalent levels in rodents, nonhuman old world primates, and humans, suggesting that relative levels of activity and responsiveness may be similar among species. We now show that this compound is effective in rhesus monkeys in improving recovery from NAION when administered after NAION induction.
We induced NAION in 2 male rhesus monkeys (Maccaca Mullata) using previously published parameters (2.5mg/kg rose Bengal IV, 200mW laser power, 1.06mm spot size, 532nm laser light) to a predicted 50-60% RGC loss. Electrophysiology, fundus photography, OCT, and fluorescein- and ICG-angiography were performed prior to induction and at 1d, 7d, 14d, 21d, 30d, and 40d post-induction. Immediately following unilateral pNAION induction, 50ug of sterile PGJ2 was injected intravitreally. Thirty days later, NAION was induced in the contralateral control eye, which was then injected with sterile vehicle (50ul 20% ETOH in saline). Tissues were analyzed at 40-80 days post-induction by immunohistochemistry and transmission electron microscopy.
Optic nerve edema was present in each pNAION-induced eye, but there was less edema in PGJ2-treated eyes, than in vehicle treated eyes. An afferent pupillary defect was present in the treated eye, which reversed after the fellow eye was treated, suggesting that PGJ2 treatment reduced damage to the ON. VEP and pERG amplitudes were greater in PGJ2-treated eyes than in pNAION-vehicle controls. Fluorescein angiography revealed less overall dye leakage from the PGJ2-treated nerves, with faster resolution of edema. Overall axonal numbers were greater in the ON of PGJ2-treated eyes, than in vehicle-treated eyes.
Intravitreal PGJ2 appears to be effective in reducing the extent of damage after pNAION. PGJ2 works, at least in part, by direct reduction of ON edema, minimizing the edema-associated compartmentation syndrome within the ON that occurs during NAION. This drug appears to be a promising agent for treatment of clinical NAION. Further studies are planned to determine the treatment window for PGJ2 in NAION.
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