Estrogen is not neuroprotective in a rodent model of optic nerve stroke.
OBJECTIVE
Nonarteritic anterior ischemic optic neuropathy (NAION) is an optic nerve (ON) infarct of retinal ganglion cell (RGC) axons, and the most common cause of ON-related sudden vision loss. Estrogen has been previously proposed as a neuroprotective treatment for central nervous system ischemia. We evaluated estrogen's potential in post-ON infarct treatment to reduce neuronal loss following a model of NAION, rodent anterior ischemic optic neuropathy (rAION).


METHODS
We used the rat rAION model, coupled to array and northern analyses, to evaluate estrogen-associated, early post-infarct retinal gene expression changes. rAION was induced in ovariectomized female rats, which were then treated with either estrogen or vehicle. Stereological analysis of post-rAION RGC numbers was performed, using retrograde RGC fill-labeling with fluorogold.


RESULTS
rAION induces an early increase in estrogen expressed transcript-1 (EET-1), but EET-1 expression is not affected by systemic estrogen pretreatment. Post-rAION, there is no significant increase in RGC numbers in estrogen treated animals compared with vehicle-treated controls. Estrogen treatment following stroke does not increase preservation of ON structure, compared with vehicle controls.


CONCLUSIONS
While the rAION-axonal stroke model is a useful adjunct for evaluating potential AION neuroprotective treatments, post-stroke estrogen administration does not appear neuroprotective in this form of central nervous system insult. Similarly, estrogen is likely to be ineffective in improving ON structural integrity following an ischemic infarct.
Bernstein
Steven L
SL
Department of Ophthalmology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. slbernst@umaryland.edu
Mehrabyan
Zara
Z
Guo
Yan
Y
Moianie
Nima
N
D000818:Animals; D002452:Cell Count; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes; D007238:Infarction / Q000209:etiology* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018917:Optic Neuropathy, Ischemic / Q000150:complications*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D004967:Estrogens; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D013266:Stilbamidines