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S.L. Bernstein, A.Z. Murphy, M.A. Johnson; Estrogen is Neuroprotective in a Model of Anterior Ischemic Optic Neuropathy (AION) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5213.
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Purpose: To determine whether estrogen is neuroprotective in reducing the damage seen in the rodent model of AION. We previously demonstrated that AION can be induced in rats (rAION; Bernstein et al, IOVS, 2001) and mice (Goldenberg-Cohen et al, IOVS, 2002). Estrogen is neuroprotective in a number of neural injury models. Initial survey of multiple pharmacologic agents suggests estrogen may also protect RGCs subjected to AION. Accordingly, we wished to quantitate the degree of estrogen-related protection. Methods: Female ovariectomized (OVX) Sprague-Dawley rats (105-120g) were injected with 1mg/kg depo-estradiol 7d prior to, and immediately after, rAION induction (group 1). rAION was induced in one eye, with the contralateral eye left uninduced. An additional group of OVX animals were induced without estrogen, as a control (group 2). A second group of animals (estrogen + and -) were injected post-induction intra-cerebrally, using bilateral pre-tectal fluorogold injections, to analyze RGC retrograde transport through the optic nerve to the retina. Visual evoked potentials (VEPs) were obtained from group 1 and 2 animals 30 days post-induction. Following euthanasia, RGC counts were quantitated from group 1 and 2 animals. Results: Initial analysis of RGC numbers between rAION and uninduced eyes, comparing the treated and untreated animals, suggests that prior estrogen administration may exert a 20% neuroprotective effect in RGC preservation following rAION. VEP and histological analysis of treated and untreated animals suggests that that there may be functional differences in the number of surviving RGCs and axonal preservation in estrogen treated animals, compared to controls. Conclusions: The rAION model is useful in accurately quantitating pharmacological neuroprotective effectiveness in optic nerve ischemia. Animal results suggest that estrogen may be a useful neuroprotective adjunct in human AION treatment. Further experiments must be done to determine whether estrogen is effective post-AION, and optimal dose and timing.
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