Rachael S Allen1, Timothy W Olsen2, Iqbal Sayeed3, Heather A Cale3, Katherine C Morrison3, Yuliya Oumarbaeva3, Irina Lucaciu3, Jeffrey H Boatright4, Machelle T Pardue4, Donald G Stein3. 1. Emergency Medicine Emory University, Atlanta, Georgia, United States 2Department of Ophthalmology, Emory University, Atlanta, Georgia, United States 3Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Decatur, Georgia, United States. 2. Department of Ophthalmology, Emory University, Atlanta, Georgia, United States. 3. Emergency Medicine Emory University, Atlanta, Georgia, United States. 4. Department of Ophthalmology, Emory University, Atlanta, Georgia, United States 3Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Decatur, Georgia, United States.
Abstract
PURPOSE: To determine whether the neurosteroid progesterone, shown to have protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, is also protective in ocular ischemia animal models. METHODS: Progesterone treatment was tested in two ocular ischemia models in rats: a rodent anterior ischemic optic neuropathy (rAION) model, which induces permanent monocular optic nerve stroke, and the middle cerebral artery occlusion (MCAO) model, which causes transient ischemia in both the retina and brain due to an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. Visual function and retinal histology were assessed to determine whether progesterone attenuated retinal injury in these models. Additionally, behavioral testing and 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining in brains were used to compare progesterone's neuroprotective effects in both retina and brain using the MCAO model. RESULTS: Progesterone treatment showed no effect on visual evoked potential (VEP) reduction and retinal ganglion cell loss in the permanent rAION model. In the transient MCAO model, progesterone treatment reduced (1) electroretinogram (ERG) deficits, (2) MCAO-induced upregulation of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), and (3) retinal ganglion cell loss. As expected, progesterone treatment also had significant protective effects in behavioral tests and a reduction in infarct size in the brain. CONCLUSIONS: Progesterone treatment showed protective effects in the retina following MCAO but not rAION injury, which may result from mechanistic differences with injury type and the therapeutic action of progesterone.
PURPOSE: To determine whether the neurosteroid progesterone, shown to have protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, is also protective in ocular ischemia animal models. METHODS:Progesterone treatment was tested in two ocular ischemia models in rats: a rodent anterior ischemic optic neuropathy (rAION) model, which induces permanent monocular optic nerve stroke, and the middle cerebral artery occlusion (MCAO) model, which causes transient ischemia in both the retina and brain due to an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. Visual function and retinal histology were assessed to determine whether progesterone attenuated retinal injury in these models. Additionally, behavioral testing and 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining in brains were used to compare progesterone's neuroprotective effects in both retina and brain using the MCAO model. RESULTS:Progesterone treatment showed no effect on visual evoked potential (VEP) reduction and retinal ganglion cell loss in the permanent rAION model. In the transient MCAO model, progesterone treatment reduced (1) electroretinogram (ERG) deficits, (2) MCAO-induced upregulation of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), and (3) retinal ganglion cell loss. As expected, progesterone treatment also had significant protective effects in behavioral tests and a reduction in infarct size in the brain. CONCLUSIONS:Progesterone treatment showed protective effects in the retina following MCAO but not rAION injury, which may result from mechanistic differences with injury type and the therapeutic action of progesterone.
Authors: Rachael S Allen; Iqbal Sayeed; Yuliya Oumarbaeva; Katherine C Morrison; Paul H Choi; Machelle T Pardue; Donald G Stein Journal: Restor Neurol Neurosci Date: 2016-11-22 Impact factor: 2.406
Authors: Elena G Sergeeva; Claudia Espinosa-Garcia; Fahim Atif; Machelle T Pardue; Donald G Stein Journal: Exp Neurol Date: 2018-05-02 Impact factor: 5.330
Authors: Rachael S Allen; Cara T Motz; Andrew Feola; Kyle C Chesler; Raza Haider; Sriganesh Ramachandra Rao; Lara A Skelton; Steven J Fliesler; Machelle T Pardue Journal: J Neurotrauma Date: 2018-07-02 Impact factor: 5.269