HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Goldenberg-Cohen, N. Articles by Bernstein, S. L. Search for Related Content PubMed PubMed Citation Articles by Goldenberg-Cohen, N. Articles by Bernstein, S. L.

Oligodendrocyte Dysfunction after Induction of Experimental Anterior Optic Nerve Ischemia

¹From the Wilmer Ophthalmological Institute and the ⁵Departments of Otolaryngology, ⁷Neurology, and ⁸Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; and the ³Departments of Ophthalmology, ⁴Anatomy and Neurobiology, and ⁹Genetics, University of Maryland School of Medicine, Baltimore, Maryland. ²Present affiliation: Department of Ophthalmology, Schneider Children’s Medical Center, Petah-Tikva, Israel, and Sackler School of Medicine, Tel Aviv, Israel; and Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel.

PURPOSE. The early response and survival of oligodendrocytes after axonal stroke and their potential contribution to neuronal survival in vivo have not been adequately addressed. The purpose of this study was to investigate the changes occurring in the retina and optic nerve (ON) in anterior ischemic optic neuropathy (AION), using a c-fos transgenic mouse model.

METHODS. A new mouse model of AION (rodent AION) was developed to evaluate the in vivo stress response of oligodendrocytes and retinal ganglion cells (RGCs) in a transgenic mouse strain, using the immediate early stress-response gene c-fos, RT-QPCR technology, immunohistochemistry, and electron microscopy. Confocal microscopy was used with cell-specific antibodies to characterize the timing of cells responding to rAION. The TUNEL assay detected cells undergoing apoptosis. Ultrastructural changes were analyzed by electron microscopy.

RESULTS. In rAION, oligodendrocytes rapidly respond in vivo to ischemic ON damage, with c-fos activation as an early detectable event. Early evidence of progressive oligodendrocyte stress, is followed by demyelination, wallerian degeneration of the ON, and oligodendrocyte and RGC death far from the primary lesion.

CONCLUSIONS. After rAION induction oligodendrocytes, as well as RGCs, undergo progressive stress, with dysfunction and apoptosis. The findings lead to a proposal that progressive retrograde oligodendrocyte stress, away from the primary lesion, is an important factor after ischemic optic neuropathy. Postinduction demyelination must be addressed for effective neuroprotection of ischemic and hypoxic white matter.

This article has been cited by other articles:

				B. J. Slater, Z. Mehrabian, Y. Guo, A. Hunter, and S. L. Bernstein Rodent Anterior Ischemic Optic Neuropathy (rAION) Induces Regional Retinal Ganglion Cell Apoptosis with a Unique Temporal Pattern Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3671 - 3676. [Abstract] [Full Text] [PDF]

				C. S. Chen, M. A. Johnson, R. A. Flower, B. J. Slater, N. R. Miller, and S. L. Bernstein A Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 2985 - 2992. [Abstract] [Full Text] [PDF]

				S. L. Bernstein, Y. Guo, B. J. Slater, A. Puche, and S. E. Kelman Neuron Stress and Loss Following Rodent Anterior Ischemic Optic Neuropathy in Double-Reporter Transgenic Mice Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2304 - 2310. [Abstract] [Full Text] [PDF]