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Abstract #3382 Published in IGR 4-2
Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat
Martin KRG; Levkovitch Verbin H; Valenta D; Baumrind L; Pease ME; Quigley HAInvestigative Ophthalmology and Visual Science 2002; 43: 2236-2243
PURPOSE: High levels of glutamate can be toxic to retinal ganglion cells. Effective buffering of extracellular glutamate by retinal glutamate transporters is therefore important. This study was conducted to investigate whether glutamate transporter changes occur with two models of optic nerve injury in the rat. METHODS: Glaucoma was induced in one eye of 35 adult Wistar rats by translimbal diode laser treatment to the trabecular meshwork. Twenty-five more rats underwent unilateral optic nerve transection. Two glutamate transporters, GLAST (EAAT-1) and GLT-1 (EAAT-2), were studied by immunohistochemistry and quantitative Western blot analysis. Treated and control eyes were compared three days and one, four, and six weeks after injury. Optic nerve damage was assessed semiquantitatively in epoxy-embedded optic nerve cross sections. RESULTS: Trabecular laser treatment resulted in moderate intraocular pressure (IOP) elevation in all animals. After one to six weeks of experimental glaucoma, all treated eyes had significant optic nerve damage. Glutamate transporter changes were not detected by immunohistochemistry. Western blot analysis demonstrated significantly reduced GLT-1 in glaucomatous eyes compared with control eyes at three days (29.3% ± 6.7%, p = 0.01), one week (55.5% ± 13.6%, p = 0.02), four weeks (27.2% ± 10.1%, p = 0.05), and six weeks (38.1% ± 7.9%, p = 0.01; mean reduction ± SEM, paired t tests, n = 5 animals per group, four duplicate Western blot analyses per eye). The magnitude of the reduction in GLT-1 correlated significantly with mean IOP in the glaucomatous eye (r2 = 0.31, p = 0.01, linear regression). GLAST was significantly reduced (33.8% ± 8.1%, mean ± SEM) after four weeks of elevated IOP (p = 0.01, paired t test, n = 5 animals per group). In contrast to glaucoma, optic nerve transection resulted in an increase in GLT-1 compared with the control eye (p = 0.01, paired t test, n = 15 animals). There was no significant change in GLAST after transection. CONCLUSIONS: GLT-1 and GLAST were significantly reduced in an experimental rat glaucoma model, a response that was not found after optic nerve transection. Reductions in GLT-1 and GLAST may increase the potential for glutamate-induced injury to RGC in glaucoma.
Dr. K.R.G. Martin, Glaucoma Research Laboratory, Wilmer Eye Institute, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
5 Experimental glaucoma; animal models
