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S. L. Bernstein, B. J. Slater, V. Touitou, Y. Guo, M. A. Johnson; Prostaglandin D2 Pathway-Mediated Neuroprotection in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (NAION). Invest. Ophthalmol. Vis. Sci. 2010;51(13):1455.
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The 28K form of Prostaglandin D2 synthase (PGD2S) has been shown to be expressed at high levels in the CNS, and PGD2S activity is expressed at high levels in the human optic nerve (ON), and is evolutionarily conserved at high levels in primates and humans. PGD2S expression changes following rodent ON stroke. We wanted to determine if PGD2S pathway activation is neuroprotective in a rodent model of nonarteritic anterior ischemic optic neuropathy (rAION).
All animal protocols were approved by the UMAB-IACUC. The metabolically active form of the PGD2 metabolite 15 deoxy 12,14 hydroxy prostaglandin J2 (PGJ2) was systemically administered (100ug/kg) to 10 male Sprague Dawley rats, following rAION induction (IV Rose Bengal, 12 sec, 50mW 532nm) in one eye. The other eye was left as a control. An additional group of animals were injected with vehicle only. Animals were allowed to recover, retinal fundi were evaluated 2 days post induction,and animals euthanized 30 days post-induction. Stereological analysis was performed using stereoinvestigator, on flat mounted Brn3a immunostained retinae. Electron microscopy was performed on excised optic nerves of both groups.Electroretinography was performed using appropriate standards and statistical analyses
PGJ2 treatment resulted in a decrease in ON edema at 2 days, compared with vehicle controls. There was a statistically significant ~25% increase in Brn3A (+) RGCs, compared with the vehicle treated control group. There was a similar improvement in the ON appearance of rAION/treated eyes, compared to rAION/vehicle controls. No electroretinographic changes were seen in treated animals.
Systemic PGJ2 treatment is effective in reducing ON edema following rAION, and reduces long term RGC loss. Since high PGD2S levels are evolutionarily conserved between rodent and primate species, enhancement of the PGD2S pathway by exogenous PGJ2 treatment may be appropriate for both primate experimental analysis and ultimately, clinical NAION treatment.
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