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Rachael S. Allen, Timothy W. Olsen, Heather A. Cale, Katherine C. Morrison, Jeffrey H. Boatright, Machelle T. Pardue, Donald G. Stein; Progesterone Treatment In Rodent Anterior Ischemic Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3475.
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Optic nerve stroke, or anterior ischemic optic neuropathy (AION), is the leading cause of sudden vision loss related to optic nerve dysfunction in older adults. No effective treatment currently exists. The neurosteroid progesterone has protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, including reduced inflammation, swelling, and neuronal death; and improved behavioral and functional recovery. The substantial overlap of mechanisms involved in optic nerve stroke and mechanisms modulated by progesterone leads us to hypothesize that progesterone protects against retinal ganglion cell death in optic nerve stroke.
The rodent AION model was used to induce monocular optic nerve stroke, while the contralateral eye served as a control. Rats were treated systemically with vehicle or progesterone at 1, 6, 24, 48, 72, 96, and 120 hours post surgery. Electroretinograms and visual evoked potentials (VEPs) were performed at 3 days post surgery. At 14 days, rats were euthanized, eyes were enucleated, and retinal flat mounts were immuno-labeled with the retinal ganglion cell specific antibody, Brn3a. Retinal ganglion cells were counted using an imaging analysis software.
As measured by VEPs, stroke eyes from vehicle treated animals (n = 8) performed at 68% of the level of their contralateral control eyes. Meanwhile, stroke eyes from progesterone treated animals (n = 7) performed at 95% of the level of their contralateral controls (p = 0.08). These results indicate clinically relevant improvement in visual function. Additionally, stroke retinas from progesterone treated animals (n = 8) had more Brn3a stained retinal ganglion cells than their vehicle treated counterparts (n = 8) (approximately 10,000 more or 15% on average).
Given the current observations along with the growing literature on the neuroprotective effects of progesterone in cerebral stroke and TBI, progesterone may prove to be an effective treatment in the rodent anterior ischemic optic neuropathy model as well.
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