April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion
Author Affiliations & Notes
  • Rachael S Allen
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Rehab R&D Center of Excellence, Atlanta VA Medical Center, Decatur, GA
  • Iqbal Sayeed
    Emergency Medicine, Emory University School of Med, Atlanta, GA
  • Yuliya Oumarbaeva
    Emergency Medicine, Emory University School of Med, Atlanta, GA
  • Katherine Morrison
    Emergency Medicine, Emory University School of Med, Atlanta, GA
  • Irina Lucaciu
    Emergency Medicine, Emory University School of Med, Atlanta, GA
  • Heather Cale
    Emergency Medicine, Emory University School of Med, Atlanta, GA
  • Paul H Choi
    Emergency Medicine, Emory University School of Med, Atlanta, GA
  • Jeffrey H Boatright
    Ophthalmology, Emory University School of Med, Atlanta, GA
  • Machelle T Pardue
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Rehab R&D Center of Excellence, Atlanta VA Medical Center, Decatur, GA
  • Donald G Stein
    Emergency Medicine, Emory University School of Med, Atlanta, GA
  • Footnotes
    Commercial Relationships Rachael Allen, None; Iqbal Sayeed, None; Yuliya Oumarbaeva, None; Katherine Morrison, None; Irina Lucaciu, None; Heather Cale, None; Paul Choi, None; Jeffrey Boatright, None; Machelle Pardue, None; Donald Stein, BHR Pharma (C), BHR Pharma (F), BHR Pharma (R), Emory University (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1892. doi:
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      Rachael S Allen, Iqbal Sayeed, Yuliya Oumarbaeva, Katherine Morrison, Irina Lucaciu, Heather Cale, Paul H Choi, Jeffrey H Boatright, Machelle T Pardue, Donald G Stein; Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1892.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To determine whether progesterone, which has been shown to reduce inflammation and infarct size in the brain and improve behavioral outcomes after middle cerebral artery occlusion (MCAO), reduces inflammation and improves electroretinogram (ERG) responses in the retina after MCAO.

Methods: MCAO surgery was performed on male Sprague-Dawley rats. Progesterone or vehicle was given systemically at 1, 6, 24, and 48 h post-MCAO. Grip-strength and sticky tape task were performed at 1-day post-MCAO and ERGs assessed at 2 days post-MCAO. Brains and retinas were taken for histology at 3 days post-MCAO. In another set of rats, protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h post-MCAO (n = 5/group).

Results: Following MCAO, vehicle-treated rats showed significant deficits in behavioral tests, while progesterone-treated rats showed significant improvements (71-84% recovery). Vehicle-treated rats also showed significant reductions in ERG amplitude in ipsilateral eyes post-MCAO, while progesterone-treated rats showed a trend for increased ERG amplitudes (23% recovery). Contralateral eyes from vehicle-treated rats also showed significant reductions in ERG amplitude post-MCAO, while contralateral eyes from progesterone-treated rats showed significant increases (64% recovery). After MCAO, vehicle-treated rats exhibited increased levels of pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b and decreased levels of cytosolic NF-κB in both brain and retina. Progesterone treatment in MCAO rats significantly attenuated levels of nuclear NF-κB and IL-6 in both brain and retina, while levels of cytosolic NF-κB showed significant increases. Progesterone treatment significantly attenuated levels of pNF-κB, TNF-α, and CD11b after MCAO in brain, with smaller reductions in retina. After MCAO, progesterone receptor A and B were upregulated in brain and downregulated in retina.

Conclusions: While progesterone treatment reduced inflammation in both brain and retina, protective effects were more dramatic in brain. Progesterone treatment also resulted in greater improvements in brain function-based behavioral tasks than in the retina-based ERG. This differential effect may be due to differences in expression of progesterone receptors in brain and retina after injury.

Keywords: 572 ischemia • 615 neuroprotection • 490 cytokines/chemokines  
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