Progesterone treatment in two rat models of ocular ischemia

Rachael S. Allen, Timothy W. Olsen, Iqbal Sayeed, Heather A. Cale, Katherine C. Morrison, Yuliya Oumarbaeva, Irina Lucaciu, Jeffrey H. Boatright, Machelle T. Pardue, Donald G. Stein

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2880-2891
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number5
DOIs
StatePublished - 2015

Keywords

  • Anterior ischemia optic neuropathy
  • Electroretinogram
  • Middle cerebral artery occlusion
  • Progesterone
  • Retinal ischemia

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Allen, R. S., Olsen, T. W., Sayeed, I., Cale, H. A., Morrison, K. C., Oumarbaeva, Y., Lucaciu, I., Boatright, J. H., Pardue, M. T., & Stein, D. G. (2015). Progesterone treatment in two rat models of ocular ischemia. Investigative Ophthalmology and Visual Science, 56(5), 2880-2891. https://doi.org/10.1167/iovs.14-16070