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D.J. Holcombe, G.A. Gole, S.D. Grozdanic, N.L. Barnett; Perturbed Retinal Glutamate Transport in a Mouse Model of Chronic Ocular Hypertension . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3786.
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Purpose: To investigate whether the expression or activity of retinal glutamate transporters are affected in a laser–induced mouse model of experimental glaucoma. The role of glutamate neurotoxicity in glaucomatous optic neuropathy is controversial. However, glutamate receptor antagonists have been shown to offer limited neuroprotection in animal models of glaucoma, supporting the notion that elevated extracellular glutamate levels may contribute to the pathogenesis of glaucoma. Methods: Indocyanine green (100 µl 10 mg/ml) was injected into the lateral tail veins of anaesthetised C57/BL6J mice. Ocular hypertension was induced by focal laser to the episcleral veins using an 810nm diode laser. Intraocular pressure (IOP) was measured with a Tonopen every 7 days. Twenty–one days after laser surgery, 0.5 µl of the non–endogenous glutamate analogue D–aspartate was injected into the vitreous (final concentration 50 µM) for 90 minutes. Glutamate transport activity was assessed by immunohistochemical localisation of D–aspartate. Fluorescence immunohistochemistry was used to assess the expression of the transporter proteins and of glial fibrillary acidic protein (GFAP). Results: Laser treated eyes had a moderate increase in IOP to 20.1±1.9 mmHg (n=10) compared with 11.6±1.0 mmHg (n=12) for non–treated control eyes. Elevated IOP induced a marked increase in Müller cell GFAP expression. Moreover, a significant change in glutamate transporter activity was evident. A slight reduction of D–aspartate uptake by Müller cells was seen. In addition, there was an appearance of D–aspartate immunoreactivity in ganglion cells. No major change in transporter expression was apparent following chronic ocular hypertension. Conclusions: These results suggest that glutamate transport mechanisms are perturbed by chronic ocular hypertension, which may contribute to the death of retinal ganglion cells in glaucomatous neuropathy.
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