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Ralph Jensen; Blocking mGluR1 receptors but not GABAA receptors increases light responsiveness of retinal ganglion cells in a rat model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2013;54(15):667.
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© ARVO (1962-2015); The Authors (2016-present)
Transmitter release from the axon terminals of retinal bipolar cells is modulated by GABA acting on GABAA and GABAC receptors. Recently I reported (Exp. Eye Res. 2012) that the GABAC receptor antagonist TPMPA increases both light sensitivity and maximum peak response of most retinal ganglion cells (RGCs) in the P23H rat. Here, I examined whether a similar effect could occur with a GABAA receptor antagonist or a metabotropic glutamate receptor type 1 (mGluR1) antagonist, which is thought to inhibit GABA release onto bipolar cells.
Extracellular recordings were made from P23H rat RGCs in the isolated retina. The responses (spike activity) of these cells to flashes of light were recorded and intensity-response curves were constructed. Receptor antagonists were bath applied.
The mGluR1 antagonist JNJ16259685 (0.5 µM) increased light sensitivity of all ON-center RGCs (n = 20) examined and 7 of 9 OFF-center RGCs examined. For ON-center cells, light sensitivity increased on average by 0.58 log unit. For OFF-center cells, light sensitivity increased on average by 0.12 log unit. JNJ16259685 increased the maximum peak response of 13 of the 20 ON-center RGCs to a high intensity light stimulus. On average (n = 20) the maximum peak response increased by 7%. For OFF-center cells (n = 9), JNJ16259685 had no statistically significant on the maximum peak response. JNJ16259685 also had no statistically significant effect on the dynamic operating range of either ON-center or OFF-center RGCs. The effect of the GABAA receptor antagonist SR95531 (5 µM) on the light responsiveness of 9 ON-center RGCs was examined. On average SR95531 decreased the maximum peak response of the RGCs by 18%. No statistically significant effect was found on either the light sensitivity or dynamic operating range of the RGCs.
The mGluR1 antagonist JNJ16259685 increases light responsiveness of most P23H rat RGCs. The greatest effect was on ON-center RGCs, similar to that found previously with the GABAC receptor antagonist TPMPA.
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