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(Investigative Ophthalmology and Visual Science. 2006;47:3853-3859.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0231
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Evoked Expression of the Glutamate Transporter GLT-1c in Retinal Ganglion Cells in Human Glaucoma and in a Rat Model

Robert K. P. Sullivan,1 Elizabeth WoldeMussie,2 Lauren Macnab,1 Guadalupe Ruiz,2 and David V. Pow1

1From the Department of Anatomy, School of Biomedical Sciences, University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales, Australia; and the 2Department of Biological Sciences, Allergan Inc., Irvine, California.

PURPOSE. Glaucoma is a common disease of the eye, a key characteristic consequence of which is the death of retinal ganglion cells. The cause of this loss is unknown, though glutamate-mediated toxicity has been implicated. Glutamate transporters are key regulators of glutamate; therefore, the purpose of the study was to determine whether unusual excitation is associated with unusual expression of one or more transporters.

METHODS. The expression of a splice variant of the glutamate transporter GLT-1 (EAAT2) was examined in normal and glaucomatous retinas from humans and rats.

RESULTS. In normal eyes of humans and rats, GLT-1c was expressed only in photoreceptors. In glaucoma, there was additional robust expression of GLT-1c in retinal ganglion cells, including occasional displaced ganglion cells. Conversely, cells such as displaced amacrine cells and amacrine cells were unlabeled.

CONCLUSIONS. The induction of GLT-1c expression by retinal ganglion cells supports the notion that an anomaly or anomalies in glutamate homeostasis may be evident in glaucoma and that such anomalies selectively influence retinal ganglion cells. By analogy to in vitro experiments in which elevated glutamate levels induce expression of glutamate transporters, the authors hypothesize that expression of GLT-1c may represent an attempt by retinal ganglion cells to protect themselves against elevated levels of glutamate. Such anomalies in glutamate levels cannot be restricted to the ganglion cell layer, as this would not have affected displaced ganglion cells. GLT-1c may be a useful indicator of the extent of stress of the retinal ganglion cells and thus a tool for examining outcomes of potential therapeutic and experimental interventions.




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W. Fan, X. Li, and N. G. F. Cooper
CaMKII{alpha}B Mediates a Survival Response in Retinal Ganglion Cells Subjected to a Glutamate Stimulus
Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3854 - 3863.
[Abstract] [Full Text] [PDF]


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