Purchase this article with an account.
P. Bu, E.B. Stubbs, Jr, J.I. Perlman; Attenuated Retinal Function in GLAST Knockout Mice Occurs Independently of Neurotransmitter Distribution . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5313.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Clearance of extracellular glutamate by the selective amino acid transporter GLAST is essential for retinal function. GLAST knockout mice, compared to age–matched wild type controls, reproducibly demonstrate reduced scotopic electroretinographic (ERG) responses. In this study, relative changes in retinal neurotransmitter distribution in association with altered retinal function in GLAST knockout mice were assessed. Methods: Scotopic ERG a–wave and b–wave responses were quantitated from dark–adapted eight–week old GLAST knockout mice (n=5) and age–matched C57BL/6J control mice (n=5) by a single flash stimulus presented in order of increasing luminance. The distribution of the excitotoxic retinal neurotransmitter glutamate, the inhibitory neurotransmitter gamma amino butyric acid (GABA), and glutamine were determined by immunohistochemistry with silver intensification. Results:Scotopic ERG a–wave amplitudes of dark–adapted GLAST knockout mice were significantly attenuated (p<0.03) compared with ERG a–wave responses from wild type control mice (GLAST (–/–): 293 ± 35 µV vs. C57BL/6J: 446 ± 122 µV). Scotopic ERG b–wave amplitudes of GLAST knockout mice were similarly reduced (507 ± 56 µV compared to 777 ± 210 µV for wild type; p< 0.03). The overall morphology of the retina from GLAST knockout mice was not measurably different from wild type control retina. The neurotransmitter distribution of retinal glutamate, glutamine or GABA was similarly unaffected by the loss of the GLAST transporter. Conclusions: In this study, we confirm diminished scotopic ERG responses in GLAST knockout mice compared to wild type controls. Altered retinal function in mice lacking the GLAST amino acid transporter appears to occur by a mechanism that is independent of changes in retinal glutamate, glutamine or GABA distribution.
This PDF is available to Subscribers Only