Abstract
Purpose: :
AION, an optic nerve stroke, has an incidence of approximately 1:15,000/yr in the U.S and is the leading cause of sudden optic nerve related vision loss in individuals over 50. While estrogen has been shown to have neuroprotective effects in a number of neuronal damage models, its role in AION is unclear. We used a rodent AION model (rAION) to determine if estrogen exerts a neuroprotective effect on male rats.
Methods: :
10 male Wistar rats were subdivided into two treatment groups: estrogen and control. Estrogen animals received 17–Estradiol (10mg/mL in 60% DMSO/PBS) immediately prior to rAION induction. Control animals received 60% DMSO/PBS vehicle. Following IV rose Bengal, rAION was induced in the OD eye (50mW/13 sec exposure/532nM). The OS eye served as the control. 14d post–induction, animals were stereotactically injected with 3 ul–2% fluorogold into each superior colliculus (SC). 14 days post–SC injection, we euthanized and quantitated retrograde–labeled flat–mounted retinal ganglion cells (RGCs). RGC loss (OD vs OS) was determined using a sterological imaging package (Stereoinvestigator Ver 5.0). Data was then analyzed for statistical significance.
Results: :
AION–induced RGC loss was determined for estrogen treated and non–estrogen control animals. Post–rAION RGC–survival was 34.8% for the estrogen treated animals and 30.2% in non–estrogen treated males. Overall RGC numbers in the uninduced eyes were similar for both groups.
Conclusions: :
In addition to estrogen’s effectiveness in female rats, there is likely a neuroprotective effect of estrogen against rAION in male rats. Since estrogen controls expression of over 200 genes, the sexual response discrepancy in neuroprotection levels suggests that there may be a graded sexually dimorphic response of estrogen that increases estrogen’s neuroprotective effects in females.
Keywords: neuroprotection • ischemia • cell survival