Primate Retinal Signaling Pathways: Suppressing<scp>on</scp>-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-<i>NYX</i>Genetic Night Blindness

Khan, Naheed W.; Kondo, Mineo; Hiriyanna, K. T.; Jamison, Jeffrey Adam; Bush, Ronald A.; Sieving, Paul A.

doi:10.1152/jn.00365.2004

Cited by 59 publications

(74 citation statements)

References 82 publications

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“…Briefly, the amplitudes of the LN components, particularly the LN-off and the LN-add components, were decreased in patients who also displayed perimetric changes. The amplitudes and implicit times of the different on-and off-components agree well with those described in previous studies using square wave stimuli (Simpson & Viswanathan, 2007;Viswanathan et al, 2000) and sawtooth stimuli (Alexander et al, 2001(Alexander et al, , 2003Barnes et al, 2002;Khan et al, 2005;Rodrigues et al, 2010) but also to those elicited by long flashes (Shinoda et al, 2001;Sieving, 1993;Sustar et al, 2006). In three studies (Rodrigues et al, 2010;Simpson & Viswanathan, 2007;Viswanathan et al, 2000), the asymmetries were explicitly investigated in a similar manner as in the present study.…”

Section: Discussionsupporting

confidence: 90%

“…This is in qualitative agreement with responses shown by Alexander et al (2001) and Khan et al (2005). Single retinal ganglion cell responses showed an optimal temporal frequency at about 20 Hz to these stimuli (Kremers et al, 1993), indicating that there is no direct relationship between single ganglion cell data and the LNs.…”

Section: The Effects Of Contrast Temporal Frequency and Stimulus Wavsupporting

confidence: 91%

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Human photopic ON- and OFF-ERG responses elicited by square wave and sawtooth stimuli.

Pangeni

Kremers

2013

Psychology & Neuroscience

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In this study, the on-and off-responses elicited by luminance square wave and sawtooth stimuli at different temporal frequencies and contrasts are described quantitatively. Adding on-and off-responses reveals response asymmetries. Full-field stimuli were produced using a Ganzfeld bowl with arrays of light-emitting diodes (LEDs) as light sources. ERG responses were recorded from six normal subjects. The amplitudes and implicit times of components of the on-and off-responses and the additions were analyzed. The amplitudes of the on-, off-and addition components elicited by square wave stimuli did not depend on temporal frequency with the exception of the late negative components, which decreased with increasing temporal frequency up to 4 Hz. The amplitudes of all components elicited by sawtooth stimuli, except the P-on, decreased with increasing temporal frequency. The amplitude of all components elicited by square wave and sawtooth stimuli were positively correlated with stimulus contrast. The implicit times of the on-components to square wave stimuli and all response components to sawtooth stimuli decreased with increasing temporal frequency. Contrast had an effect on the implicit times of the N-on, P-on, P-off and P-add components elicited by square wave stimuli and the N-on, P-on, P-add and LN-on components elicited by sawtooth stimuli. The asymmetries between on-and off-responses can possibly be used to reveal inner retinal contributions and may therefore be interesting in detecting glaucomatous changes.

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Section: Discussionsupporting

confidence: 90%

Section: The Effects Of Contrast Temporal Frequency and Stimulus Wavsupporting

confidence: 91%

Human photopic ON- and OFF-ERG responses elicited by square wave and sawtooth stimuli.

Pangeni

Kremers

2013

Psychology & Neuroscience

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“…Some of the clinical findings in our patients, including the normal to moderately subnormal visual acuity, the severely reduced ERG b-waves in response to brief flashes, and the defect in ERG ON responses, parallel those found in patients with the complete form of X-linked night blindness caused by NYX mutations (41,55,56). However, two of our patients with GRM6 mutations had greater reductions of a-wave amplitudes than are typically seen in the complete form of X-linked night blindness (18); further investigations of additional cases are necessary to determine whether this finding would clinically distinguish patients with GRM6 vs. NYX mutations.…”

Section: Discussionsupporting

confidence: 77%

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

Dryja

McGee²,

Berson³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

222

175

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We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20͞15 to 20͞40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform. bipolar cell ͉ glutamate receptor ͉ retina

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“…Miyake et al, 1887;Pesch et al, 2000). Blockade of transmission between photoreceptors and DBCs by a glutamate analogue the binds to mGlur6 receptors, APB (L-2-amino-4-phosphonobutyric acid), similarly results in no ERG b-wave under photopic and scotopic conditions in the macaque retina, a retina very similar to that of humans (Khan et al, 2005;Knapp & Schiller, 1984;Sieving et al, 1994), and in the retina of normal mice (Kang Derwent et al, 2007;Sharma et al, 2005), In contrast, blockade of transmission from photoreceptors to HBCs using an iontotropic glutamate receptor antagonist in macaques and mice results in a reduced photopic ERG a-wave and in macaques, elimination of the d-wave (Maeda et al, 2003;Sharma et al, 2005;Sieving et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Shirato

Maeda

Miura

et al. 2008

Experimental Eye Research

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The purpose of this study was to determine the contributions of postreceptoral neurons to the lightadapted ERG of the Nob mouse, a model for complete-type congenital stationary night blindness (CSNB1) that lacks a b-wave from depolarizing bipolar cells. Ganzfeld ERGs were recorded from anesthetized adult control mice, control mice injected intravitreally with L-2-amino-4-phosphonobutyric acid (Control APB mice) to remove On pathway activity, and Nob mice. ERGs also were recorded after PDA (cis-2, 3-piperidine-dicarboxylic acid, 3-5 mM) was injected to block transmission to hyperpolarizing (Off) bipolar and horizontal cells, and all 3rd order neurons. Stimuli were brief (< 4 ms, 0.4 -2.5 log sc td s) and long (200 ms, 2.5 -4.6 log sc td) LED flashes (λmax = 513 nm, on a rod suppressing background (2.6 log sc td). Sinusoidal modulation of the LEDs (mean, 2.6 log sc td; contrast, 100%; 3 to 36 Hz) was used to study flicker ERGs.Brief-flash ERGs of Nob mice presented as long-lasting negative waves with a positive-going intrusion that started about 50 ms after the flash and peaked around 120 ms. Control APB mice had similar responses, and in both cases, PDA removed the positive-going intrusion. For long flashes, PDA removed a small, slow "d-wave" after light offset. With sinusoidal stimulation, the fundamental (F1) amplitude of control mice ERG peaked at 8 Hz (~70 μV). For Nob mice the peak was ~20 μV at 6 Hz before PDA and ~10 μV at 3 Hz or lower after PDA. F1 responses were present up to 21 Hz in control and Nob eyes and 15 Hz in Nob eyes after PDA. Between 3 and 6 Hz, F1 phase was 170°-210° more delayed in Nob than control mice; phase was hardly altered by PDA. With vector analysis, a substantial postreceptoral input to the Nob flicker ERG was revealed. In control mice, the second harmonic (F2) response showed peaks of ~10 μV at 3 Hz and 13 Hz. Nob mice showed almost no F2. In summary, in this study it was found that in Nob mice, postreceptoral neurons from the Off pathway make a positive-going contribution to the light-adapted flash ERG, and contribute substantially to sinusoidal flicker ERG.

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Primate Retinal Signaling Pathways: Suppressingon-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYXGenetic Night Blindness

Abstract: . Sieving. Primate retinal signaling pathways: suppressing ON-pathway activity in monkey with glutamate analogues mimics human CSNB1-NYX genetic night blindness.

Cited by 59 publications

References 82 publications

Human photopic ON- and OFF-ERG responses elicited by square wave and sawtooth stimuli.

Human photopic ON- and OFF-ERG responses elicited by square wave and sawtooth stimuli.

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

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