IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2010;2(2):148-160

Original Article
Retinal proteomic changes under different ischemic conditions – implication of an
epigenetic regulatory mechanism

Cheri Stowell, Lin Wang, Brian Arbogast, Jing-quan Lan, George A. Cioffi, Claude F. Burgoyne, An Zhou

Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, OR; Devers Eye Institute, Portland, OR; 3Oregon
State University, Corvallis, OR, USA.

Received May 25, 2010, accepted June 22, 2010, available online June 30, 2010

Abstract: In retina, an ischemic injury-resistant condition (ischemic tolerance) can be induced by a sub-lethal ischemic treatment
(preconditioning) prior to an otherwise injurious ischemic insult. In this work, we compared retinal proteomic changes under three
different ischemic conditions, as a means to identify the effector mechanisms that underlie retinal ischemic tolerance. Transient retinal
ischemia was induced by elevating the intraocular pressure (IOP) in three groups of adult rats as follows: Group 1, ischemic-
preconditioned, 110 mmHg for 8 minutes followed by 48 hours reperfusion; Group 2, ischemic-injured, 110 mmHg for 60 minutes
followed by 24 hours reperfusion; Group 3, ischemic-tolerant, preconditioning treatment followed by another 60 minutes of 110 mmHg
and 24 hours reperfusion. Protein quantities in each of the afore-mentioned retinal ischemic conditions, as determined by quantitative
mass spectrometry, were compared with that of the contralateral control eyes (sham-treated). As a result, a total of 328 proteins were
identified and quantified; among them, 30-60% of proteins showed a change in abundance under one or more retinal ischemic
conditions. In particular, in ischemic-tolerant retinas, histone proteins H2B, H3 and H4 demonstrated an increase in abundance,
whereas histone H2A showed a decrease in abundance. Further immunohistochemical analyses confirmed the results of proteomic
analyses, and detected an up regulation of tri-methylated histone H3, mono-ubiquitinated histone H2A and Polycomb group protein
RING2. Together, these results suggest a role of epigenetic regulation in the induction of retinal ischemic tolerance that involves
histone and polycomb proteins.(IJPPP1005002).

Key words: Neuroprotection, ischemia, epigenetics, proteomics, retina, high intraocular pressure

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Address all correspondence to:
An Zhou, PhD
Robert S. Dow Neurobiology Laboratories
Legacy Clinic Research and Technology Center
1225 N.E. Second Avenue
Portland, OR 97232, USA.
Tel: (503) 413-5410, Fax: (503) 413-5465
E-mail:
azhou@downeurobiology.org