April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Pgj2 Neuroprotects In Rodent Naion By Reducing Optic Nerve Edema And Compartment Syndrome
Author Affiliations & Notes
  • James D. Nicholson
    Ophthalmology Research,
    University of Maryland at Baltimore, Baltimore, Maryland
  • Adam C. Puche
    Anatomy & Neurobiology,
    University of Maryland at Baltimore, Baltimore, Maryland
  • Steven L. Bernstein
    Ophthalmology, Univ of Maryland Sch of Medicine, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  James D. Nicholson, None; Adam C. Puche, None; Steven L. Bernstein, None
  • Footnotes
    Support  EY015304, EY019529
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5904. doi:
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      James D. Nicholson, Adam C. Puche, Steven L. Bernstein; Pgj2 Neuroprotects In Rodent Naion By Reducing Optic Nerve Edema And Compartment Syndrome. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5904.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The rodent non-arteritic anterior ischemic optic neuropathy (rAION) model has many features similar to clinical NAION, including optic nerve (ON) edema and reduced optic nerve perfusion, retinal ganglion cell (RGC) loss and ON scarring. We previously reported that prostaglandin J2 (PGJ2) reduces post-rAION ON edema and RGC loss. In order to characterize PGJ2's mechanism of action, we utilized an improved vascular filling method that allows precise quantification of ON patency, sizes, and total volume, enabling determination whether PGJ2 interferes with post-stroke thrombosis or whether it affects edema.

Methods: : rAION was induced in one eye of adult male Sprague-Dawley rats as previously described; the contralateral eye of each animal was used as an individual naive control. One group of animals were treated with PGJ2 i.v. after stroke induction; a second group was treated with vehicle i.v after stroke induction. At 4 h or 1 dy post-induction, rats from each group were euthanized and their vasculature perfused with a gelatin & FITC-BSA mixture which was then fixed in situ. ON's were then sectioned ex vivo and imaged on a Zeiss LSM 510 confocal. Vasculature in tiled optical z-stack head images were quantified using a filament model by Imaris software. Immunohistochemistry was performed using antibodies for laminin and thrombin to demonstrate thrombus and loss of perfusion in collapsed vessels.

Results: : Similar levels of thrombosis were present in both vehicle and PGJ2 treated animals, but minimal ON edema was seen at 4 h in rAION-induced animals treated with either PGJ2 or vehicle. Considerable edema was present at 1 dy in the vehicle treated animals. Concurrently, only small differences in ON head capillary filling were seen, comparing naive vs. vehicle treated stroked eyes at 4 h post-induction. There was no difference between PGJ2 and vehicle treated rAION eyes at this time point. However, 1 dy post-induction, there was severe loss of ON head capillary patency in vehicle-treated animals, but considerably increased ON head capillary perfusion in PGJ2-treated animals.

Conclusions: : Our results suggest that, like human NAION, the majority of rAION pathology is likely due to post-infarct compression of ON capillary vessels by later onset ON edema, producing a compartment syndrome. PGJ2 does not alter early vascular thrombosis levels, but rather works by reducing post-infarct edema relieving the compartment syndrome and improving perfusion.

Keywords: microscopy: light/fluorescence/immunohistochemistry • optic nerve • neuroprotection 

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