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Paul A Sieving - One of the best experts on this subject based on the ideXlab platform.

  • cone erg changes during light adaptation in two all cone mutant mice implications for rod cone pathway interactions
    Investigative Ophthalmology & Visual Science, 2019
    Co-Authors: Ronald A. Bush, Yong Zeng, Atsuhiro Tanikawa, Paul A Sieving
    Abstract:

    Author(s): Bush, Ronald A; Tanikawa, Atsuhiro; Zeng, Yong; Sieving, Paul A | ABstract: PurposeThe B-Wave of the cone ERG increases in amplitude and speed during the first few minutes of adaptation to a rod-suppressing Background light. Earlier studies implicate rod pathway input to the cone pathway in these changes.MethodsThe timing and amplitude of the cone B-Wave and isolated oscillatory potentials (OP) during the first 10 minutes of light adaptation in wild-type (WT) mice and two mutant lines without functional rods was examined: rhodopsin knockout (Rho-/-), lacking rod outer segments, and NRL knockout (Nrl-/-), in which rods are replaced By S-cones. Expression of the immediate-early gene c-fos, which is increased in the inner retina By light-induced activity, was evaluated By immunohistochemistry in dark- and light-adapted retinas.ResultsWT B-Wave and OP amplitudes increased, and implicit times decreased during light adaptation. SuBtracting OP did not alter B-Wave changes. Rho-/- B-Wave and OP amplitudes did not increase during adaptation. B-Wave timing and amplitude and the timing of the major OP at 1 minute of adaptation were equivalent to WT at 10 minutes. The light-adapted ERG B-Wave in Nrl-/- mice, which originates in Both the rod and cone pathways, changed in aBsolute amplitude and timing similar to WT. C-fos expression was present in the inner retinas of dark-adapted Rho-/- But not WT or Nrl-/- mice.ConclusionsActivity in the distal rod pathway produces changes in the cone ERG during light adaptation. Rods in Rho-/- mice constitutively activate this rod-cone pathway interaction. The rod pathway S-cones in Nrl-/- mice may maintain the WT interaction.

  • rs 1 gene delivery to an adult rs1h knockout mouse model restores erg B Wave with reversal of the electronegative Waveform of x linked retinoschisis
    Investigative Ophthalmology & Visual Science, 2004
    Co-Authors: Yong Zeng, Nizar Smaoui, Rafael C Caruso, Ronald A. Bush, Yuichiro Takada, Sten Kjellstrom, Kelaginamane Hiriyanna, A Tanikawa, Eric F Wawrousek, Paul A Sieving
    Abstract:

    PURPOSE. To create and evaluate a mouse model of human X-linked juvenile retinoschisis (XLRS) and then investigate whether supplementing with the retinoschisin protein By gene delivery can reverse the aBnormal “electronegative” electroretinogram (ERG) retinal response. METHODS. An X-linked retinoschisis mouse (Rs1h-KO) model was created By suBstituting a neomycin resistance cassette for exon 1 and 1.6 kB of intron 1 of Rs1h, the murine orthologue of the human RS-1 gene. RS protein was evaluated By immunohistochemistry and Western Blot analysis with a polyclonal RS N-terminus antiBody. Retinal function was evaluated By conventional, full-field flash ERG recordings. RS protein supplementation therapy was evaluated By gene transfer with an AAV(2/2)-CMV-Rs1h vector containing C57BL/6J Rs1h cDNA under the regulation of a CMV promoter, and ERG functional analysis was performed. RESULTS. No RS protein was detected By Western Blot analysis or immunohistochemistry in the Rs1h-KO mouse. Darkadapted ERG responses showed an electronegative configuration, with B-Wave reduction in Both Rs1h /Y and Rs1h / mice, typical of XLRS in humans. Histologic examination of Rs1h-KO mice showed disorganization of multiple retinal layers, including duplication and mislocalization of ganglion cells, laminar dissection through the inner plexiform layer, disorganization of the outer plexiform layer, loss of regularity of the outer nuclear layer, and shortening of the inner/outer segments with mislocalization of photoreceptor nuclei into this layer. After intraocular administration of AAV(2/2)-CMV-Rs1h, immunohistochemistry showed retinoschisin expression in all retinal layers of Rs1h /Y mice, and ERG recordings showed reversal of the electronegative Waveform and restoration of the normal positive B-Wave. CONCLUSIONS. The RS-KO mouse mimics structural features of human X-linked juvenile retinoschisis with dissection through, and disorganization of, multiple retinal layers. The Rs1h-KO functional deficit results in an electronegative ERG Waveform that is characteristic of human retinoschisis disease and that implicates a synaptic transmission deficit in the aBsence of retinoschisin protein. Replacement therapy By supplementing normal Rs1h protein in the adult Rs1h-KO mouse restored the normal ERG configuration. This indicates that gene therapy is a viaBle strategy of therapeutic intervention even in the postdevelopmental adult stage of XLRS disease. (Invest Ophthalmol Vis Sci. 2004;45:3279 –3285) DOI:10.1167/iovs.04-0576

  • juvenile x linked retinoschisis from xlrs1 arg213trp mutation with preservation of the electroretinogram scotopic B Wave
    American Journal of Ophthalmology, 1999
    Co-Authors: Paul A Sieving, Eve L Bingham, Jennifer Kemp, Julia E Richards, Kelaginamane Hiriyanna
    Abstract:

    ABstract PURPOSE: To present an Arg213Trp missense mutation in the XLRS1 gene in a family with juvenile X-linked retinoschisis in which one affected male had a normal electroretinogram scotopic B-Wave amplitude. METHODS: Two affected males and one unaffected male from this family with X-linked retinoschisis underwent standard clinical examination including an electroretinogram. Mutations in the XLRS1 gene were detected By sequence analysis and By restriction enzyme assay for loss of an MSP-I restriction site. RESULTS: A missense mutation of C to T at nucleotide position 637 was identified in exon 6 of the XLRS1 gene. This changed the positively charged arginine to a nonpolar tryptophan (Arg213Trp) within the Biologically important discoidin domain. Clinical examination revealed intraretinal cysts in a spoke-wheel distriBution and early macular atrophy of the retinal pigment epithelium. Whereas the older affected patient had an “electronegative” electroretinogram typical of retinoschisis, the 13-year-old grandson with the same XLRS1 mutation had a normal electroretinogram scotopic B-Wave. CONCLUSION: Although the electroretinogram is a key diagnostic test for X-linked retinoschisis, this report of a normal electroretinogram scotopic B-Wave in a male with molecularly confirmed X-linked retinoschisis indicates that caution is advised in relying on the electroretinogram in differential diagnosis of this condition.

  • push pull model of the primate photopic electroretinogram a role for hyperpolarizing neurons in shaping the B Wave
    Visual Neuroscience, 1994
    Co-Authors: Paul A Sieving, Koichiro Murayama, F Naarendorp
    Abstract:

    Existing models of the primate photopic electroretinogram (ERG) attriBute the light-adapted B-Wave to activity of depolarizing Bipolar cells (DBCs), mediated through a release of potassium that is monitored By Muller cells. However, possiBle ERG contriButions from OFF-Bipolar cells (HBCs) and horizontal cells (HzCs) have not Been explored. We examined the contriBution of these hyperpolarizing second-order retinal cells to the photopic ERG of monkey By applying glutamate analogs to suppress photoreceptor transmission selectively to HBC/HzCs vs. DBCs. ERGs of Macaca monkeys were recorded at the cornea Before and after intravitreal injection of drugs. Photopic responses were elicited By Bright 200-220 ms flashes on a steady Background of 3.3 log scotopic troland to suppress rod ERG components. 2-amino-4-phosphonoButyric acid (APB), which Blocks DBC light responses, aBolished the photopic B-Wave and indicated that DBC activity is requisite for photopic B-Wave production. However, applying cis-2,3-piperidine dicarBoxylic acid (PDA) and kynurenic acid (KYN), to suppress HBCs/HzCs and third-order neurons, revealed a novel ERG response that was entirely positive and was sustained for the duration of the flash. The normally phasic B-Wave was suBsumed into this new response. Applying n-methyl-dl-aspartate (NMA) did not replicate the PDA+KYN effect, indicating that third-order retinal cells are not involved. This suggests that HBC/HzC activity is critical for shaping the phasic B-Wave. Components attriButaBle to depolarizing vs. hyperpolarizing cells were separated By suBtracting Waveforms after each drug from responses immediately Before. This analysis indicated that DBCs and HBC/HzCs each can produce large But opposing field potentials that nearly cancel and that normally leave only the residual phasic B-Wave response in the photopic ERG. Latency of the DBC component was 5-9 ms slower than the HBC/HzC component. However, once activated, the DBC component had a steeper slope. This resemBles properties known for the two types of cone synapses in lower species, in which the sign-preserving HBC/HzC synapse has faster kinetics But proBaBly lower gain than the slower sign-inverting G-protein coupled DBC synapse. A human patient with "unilateral cone dystrophy" was found to have a positive and sustained ERG that mimicked the monkey ERG after PDA+KYN, indicating that these novel positive photopic responses can occur naturally even without drug application. These results demonstrate that hyperpolarizing second-order neurons are important for the primate photopic ERG.(ABSTRACT TRUNCATED AT 400 WORDS)

Birgitta Bauer - One of the best experts on this subject based on the ideXlab platform.

  • Cone B-Wave implicit time as an early predictor of ruBeosis in central retinal vein occlusion
    American journal of ophthalmology, 1998
    Co-Authors: Jörgen Larsson, Sten Andréasson, Birgitta Bauer
    Abstract:

    Purpose To investigate the predictive value of the cone B-Wave implicit time in the 30-Hz flicker electroretinogram for ruBeosis in the acute phase of central retinal vein occlusion. Methods In a prospective study, 25 patients (25 eyes) with a central retinal vein occlusion of less than 14 days' duration were examined with electroretinography and followed up for a minimum of 18 months. Results The cone B-Wave implicit time in the eyes that developed ruBeosis (n = 11) was more than 37.1 milliseconds and in the eyes that did not develop ruBeosis (n = 14), less than 37 milliseconds ( P Conclusion The cone B-Wave implicit time in the 30-Hz flicker electroretinogram is a good predictor of ruBeosis at an early stage in eyes with central retinal vein occlusion.

Toni Schneider - One of the best experts on this subject based on the ideXlab platform.

  • effect of zncl 2 and chelation of zinc ions By n n diethyldithiocarBamate dedtc on the erg B Wave amplitude from the isolated superfused verteBrate retina
    Investigative Ophthalmology & Visual Science, 2010
    Co-Authors: Siarhei A Siapich, Walid Albanna, Jurgen Hescheler, Matthias Luke, Heiko Wrubel, Maged Alnawaiseh, Marco Weiergraber, Toni Schneider
    Abstract:

    Purpose: NiCl 2 (15 µM) enhances the ERG B-Wave amplitude of verteBrate retina, up to 1.5-fold By Blocking E/R-type voltage-gated Ca 2+ channels, which is mediated By Blocking the release of GABA onto ionotropic GABA-A and GABA-C receptors. In vivo, it is likely that zinc, rather than nickel ions, may Be involved in the modulation of retinal signalling. Therefore, we tested the effect of Both, ZnCl 2 (10 to 500 µM) and DEDTC (100 to 500 µM), which chelates zinc ions for the capacity to influence the ERG B-Wave amplitude. Methods: Transretinal potentials from the isolated Bovine retina were recorded as electroretinograms and Ca 2+ inward currents By patch-clamp recordings of staBly Ca v 2.3 transfected HEK-293 cells, yielding an IC 50 value of 5.3 µM for ZnCl 2 . Results: ZnCl 2 (10–15 µM) increased the B-Wave amplitude By 1.52-fold ± 0.12 (n = 6 retinas), which was partially reversiBle upon washout. The same 1.5-fold stimulation of the B-Wave amplitude was reported recently for 15 µM NiCl 2 . The superfusion of isolated retinas By DEDTC (100 µM) caused a transient decrease of the ERG B-Wave amplitude (0.75-fold ± 0.06; n = 4), suggesting that the cosecretion of Zn 2+ ions may occur under scotopic conditions. Conclusion: The stimulatory effect of ZnCl 2 on the ERG B-Wave amplitude resemBles the stimulatory effect of NiCl 2 and may Be mediated rather By the NiCl 2 -sensitive, Ca v 2.3 E-/R-type voltage-gated Ca 2+ channels than By NiCl 2 -sensitive T-type channels.

  • effect of zncl2 and chelation of zinc ions By n n diethyldithiocarBamate dedtc on the erg B Wave amplitude from the isolated superfused verteBrate retina
    Current Eye Research, 2010
    Co-Authors: Siarhei A Siapich, Walid Albanna, Jurgen Hescheler, Matthias Luke, Heiko Wrubel, Maged Alnawaiseh, Marco Weiergraber, Toni Schneider
    Abstract:

    Purpose: NiCl2 (15 µM) enhances the ERG B-Wave amplitude of verteBrate retina, up to 1.5-fold By Blocking E/R-type voltage-gated Ca2+ channels, which is mediated By Blocking the release of GABA onto ionotropic GABA-A and GABA-C receptors. In vivo, it is likely that zinc, rather than nickel ions, may Be involved in the modulation of retinal signalling. Therefore, we tested the effect of Both, ZnCl2 (10 to 500 µM) and DEDTC (100 to 500 µM), which chelates zinc ions for the capacity to influence the ERG B-Wave amplitude.Methods: Transretinal potentials from the isolated Bovine retina were recorded as electroretinograms and Ca2+ inward currents By patch-clamp recordings of staBly Cav2.3 transfected HEK-293 cells, yielding an IC50 value of 5.3 µM for ZnCl2.Results: ZnCl2 (10–15 µM) increased the B-Wave amplitude By 1.52-fold ± 0.12 (n = 6 retinas), which was partially reversiBle upon washout. The same 1.5-fold stimulation of the B-Wave amplitude was reported recently for 15 µM NiCl2. The superfusion of isolate...

  • antagonists of ionotropic γ aminoButyric acid receptors impair the nicl2 mediated stimulation of the electroretinogram B Wave amplitude from the isolated superfused verteBrate retina
    Acta Ophthalmologica, 2009
    Co-Authors: Siarhei A Siapich, Mohammed Banat, Walid Albanna, Jurgen Hescheler, Matthias Luke, Toni Schneider
    Abstract:

    PURPOSE: NiCl(2) (15 microM) stimulates the electroretinogram (ERG) B-Wave amplitude of verteBrate retina up to 1.5-fold through its Blocking of E/R-type voltage-gated Ca(2+) channels. Assuming that such an increase is mediated By Blocking the release of the inhiBitory neurotransmitter gamma-aminoButyric acid (GABA) via ionotropic GABA receptors, we tested the effect of Both GABA itself and GABA-receptor antagonists such as (-)Bicuculline (1.51-fold increase) and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA; 1.46-fold increase) on the B-Wave amplitude. METHODS: Recording of the transretinal potentials from the isolated Bovine retina. RESULTS: GABA (100 microM) reduced the B-Wave amplitude only when NiCl(2) (15 microM) was applied first. Each antagonist applied on its own stimulated the B-Wave amplitude only partially: suBsequent NiCl(2) superfusion caused a small But additional increase, leading to a 1.69- and a 1.88-fold total increase of the amplitude By Ni(2+) plus (-)Bicuculline or Ni(2+) plus TPMPA, respectively. Only the application of Both antagonists in comBination, Before superfusing low NiCl(2) (15 microM), completely prevented suBsequent stimulation By NiCl(2) with a similar 1.90-fold total increase of B-Wave amplitude. Those retina segments that did not respond to NiCl(2) could not Be stimulated By (-)Bicuculline and vice versa. CONCLUSION: The stimulatory effect of NiCl(2) on the ERG B-Wave amplitude is mainly, But not only, mediated By a NiCl(2)-sensitive, Ca(v)2.3-triggered GABA release acting through ionotropic GABA-A and GABA-C receptors.

  • A Ni^2+-sensitive component of the ERG B-Wave from the isolated Bovine retina is related to E-type voltage-gated Ca^2+ channels
    Graefe's Archive for Clinical and Experimental Ophthalmology, 2005
    Co-Authors: Matthias Luke, Werner Sickel, Marco Weiergraber, Margit Henry, Thea Lingohr, Mehran Maghsoodian, Jürgen Hescheler, Toni Schneider
    Abstract:

    Background Voltage-dependent Ca^2+ channels trigger and control important cellular processes like neurotransmitter release and secretion, long-term potentiation, and gene expression in excitaBle cells. During retinal signal perception and processing, presynaptic Ca^2+ channels facilitate neurotransmitter release in photoreceptors and Bipolar neurons, at nonspiking synapses which generate graded potentials. Methods The nature of voltage-gated Ca^2+ channels involved in retinal signal transduction is investigated in the present report By recording the electroretinogram (ERG) from the isolated and perfused Bovine retina. Transcripts of the E/R- and T-type Ca^2+ channels are detected By RT-PCR. Results Using the Ca^2+ channel antagonists (±)-isradipine, NiCl_2, miBefradil, and SNX-482 results in either stimulatory or inhiBitory effects on the ERG B-Wave amplitude. On the transcript level, mRNA is detected for the E/R-type and a T-type voltage-gated Ca^2+ channel containing Ca_v2.3 and Ca_v3.1 as ion-conducting suBunits, respectively. Conclusion Blocking of the E/R-type Ca^2+ channels By NiCl_2 (10 μM) and SNX-482 (30 nM) contriButes to the stimulatory effect, whereas antagonism of T-type as well as L-type Ca^2+ channels meditates the inhiBitory action on the B-Wave amplitude. Thus, a novel function for E/R-type voltage-gated Ca^2+ channels is proBaBly associated with the visual signal transduction in the mammalian retina.

Siarhei A Siapich - One of the best experts on this subject based on the ideXlab platform.

  • effect of zncl 2 and chelation of zinc ions By n n diethyldithiocarBamate dedtc on the erg B Wave amplitude from the isolated superfused verteBrate retina
    Investigative Ophthalmology & Visual Science, 2010
    Co-Authors: Siarhei A Siapich, Walid Albanna, Jurgen Hescheler, Matthias Luke, Heiko Wrubel, Maged Alnawaiseh, Marco Weiergraber, Toni Schneider
    Abstract:

    Purpose: NiCl 2 (15 µM) enhances the ERG B-Wave amplitude of verteBrate retina, up to 1.5-fold By Blocking E/R-type voltage-gated Ca 2+ channels, which is mediated By Blocking the release of GABA onto ionotropic GABA-A and GABA-C receptors. In vivo, it is likely that zinc, rather than nickel ions, may Be involved in the modulation of retinal signalling. Therefore, we tested the effect of Both, ZnCl 2 (10 to 500 µM) and DEDTC (100 to 500 µM), which chelates zinc ions for the capacity to influence the ERG B-Wave amplitude. Methods: Transretinal potentials from the isolated Bovine retina were recorded as electroretinograms and Ca 2+ inward currents By patch-clamp recordings of staBly Ca v 2.3 transfected HEK-293 cells, yielding an IC 50 value of 5.3 µM for ZnCl 2 . Results: ZnCl 2 (10–15 µM) increased the B-Wave amplitude By 1.52-fold ± 0.12 (n = 6 retinas), which was partially reversiBle upon washout. The same 1.5-fold stimulation of the B-Wave amplitude was reported recently for 15 µM NiCl 2 . The superfusion of isolated retinas By DEDTC (100 µM) caused a transient decrease of the ERG B-Wave amplitude (0.75-fold ± 0.06; n = 4), suggesting that the cosecretion of Zn 2+ ions may occur under scotopic conditions. Conclusion: The stimulatory effect of ZnCl 2 on the ERG B-Wave amplitude resemBles the stimulatory effect of NiCl 2 and may Be mediated rather By the NiCl 2 -sensitive, Ca v 2.3 E-/R-type voltage-gated Ca 2+ channels than By NiCl 2 -sensitive T-type channels.

  • effect of zncl2 and chelation of zinc ions By n n diethyldithiocarBamate dedtc on the erg B Wave amplitude from the isolated superfused verteBrate retina
    Current Eye Research, 2010
    Co-Authors: Siarhei A Siapich, Walid Albanna, Jurgen Hescheler, Matthias Luke, Heiko Wrubel, Maged Alnawaiseh, Marco Weiergraber, Toni Schneider
    Abstract:

    Purpose: NiCl2 (15 µM) enhances the ERG B-Wave amplitude of verteBrate retina, up to 1.5-fold By Blocking E/R-type voltage-gated Ca2+ channels, which is mediated By Blocking the release of GABA onto ionotropic GABA-A and GABA-C receptors. In vivo, it is likely that zinc, rather than nickel ions, may Be involved in the modulation of retinal signalling. Therefore, we tested the effect of Both, ZnCl2 (10 to 500 µM) and DEDTC (100 to 500 µM), which chelates zinc ions for the capacity to influence the ERG B-Wave amplitude.Methods: Transretinal potentials from the isolated Bovine retina were recorded as electroretinograms and Ca2+ inward currents By patch-clamp recordings of staBly Cav2.3 transfected HEK-293 cells, yielding an IC50 value of 5.3 µM for ZnCl2.Results: ZnCl2 (10–15 µM) increased the B-Wave amplitude By 1.52-fold ± 0.12 (n = 6 retinas), which was partially reversiBle upon washout. The same 1.5-fold stimulation of the B-Wave amplitude was reported recently for 15 µM NiCl2. The superfusion of isolate...

  • antagonists of ionotropic γ aminoButyric acid receptors impair the nicl2 mediated stimulation of the electroretinogram B Wave amplitude from the isolated superfused verteBrate retina
    Acta Ophthalmologica, 2009
    Co-Authors: Siarhei A Siapich, Mohammed Banat, Walid Albanna, Jurgen Hescheler, Matthias Luke, Toni Schneider
    Abstract:

    PURPOSE: NiCl(2) (15 microM) stimulates the electroretinogram (ERG) B-Wave amplitude of verteBrate retina up to 1.5-fold through its Blocking of E/R-type voltage-gated Ca(2+) channels. Assuming that such an increase is mediated By Blocking the release of the inhiBitory neurotransmitter gamma-aminoButyric acid (GABA) via ionotropic GABA receptors, we tested the effect of Both GABA itself and GABA-receptor antagonists such as (-)Bicuculline (1.51-fold increase) and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA; 1.46-fold increase) on the B-Wave amplitude. METHODS: Recording of the transretinal potentials from the isolated Bovine retina. RESULTS: GABA (100 microM) reduced the B-Wave amplitude only when NiCl(2) (15 microM) was applied first. Each antagonist applied on its own stimulated the B-Wave amplitude only partially: suBsequent NiCl(2) superfusion caused a small But additional increase, leading to a 1.69- and a 1.88-fold total increase of the amplitude By Ni(2+) plus (-)Bicuculline or Ni(2+) plus TPMPA, respectively. Only the application of Both antagonists in comBination, Before superfusing low NiCl(2) (15 microM), completely prevented suBsequent stimulation By NiCl(2) with a similar 1.90-fold total increase of B-Wave amplitude. Those retina segments that did not respond to NiCl(2) could not Be stimulated By (-)Bicuculline and vice versa. CONCLUSION: The stimulatory effect of NiCl(2) on the ERG B-Wave amplitude is mainly, But not only, mediated By a NiCl(2)-sensitive, Ca(v)2.3-triggered GABA release acting through ionotropic GABA-A and GABA-C receptors.

Laura J. Frishman - One of the best experts on this subject based on the ideXlab platform.

  • contriBution of voltage gated sodium channels to the B Wave of the mammalian flash electroretinogram
    The Journal of Physiology, 2008
    Co-Authors: Deb Kumar Mojumder, David M. Sherry, Laura J. Frishman
    Abstract:

    Voltage-gated sodium channels (Nav channels) in retinal neurons are known to contriBute to the mammalian flash electroretinogram (ERG) via activity of third-order retinal neurons, i.e. amacrine and ganglion cells. This study investigated the effects of tetrodotoxin (TTX) Blockade of Nav channels on the B-Wave, an ERG Wave that originates mainly from activity of second-order retinal neurons. ERGs were recorded from anaesthetized Brown Norway rats in response to Brief full-field flashes presented over a range of stimulus energies, under dark-adapted conditions and in the presence of steady mesopic and photopic Backgrounds. Recordings were made Before and after intravitreal injection of TTX (∼3 μm) alone, 3–6 weeks after optic nerve transection (ONTx) to induce ganglion cell degeneration, or in comBination with an ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 200 μm) to Block light-evoked activity of inner retinal, horizontal and OFF Bipolar cells, or with the glutamate agonist N-methyl-d-aspartate (NMDA, 100–200 μm) to reduce light-evoked inner retinal activity. TTX reduced ERG amplitudes measured at fixed times corresponding to B-Wave time to peak. Effects of TTX were seen under all Background conditions, But were greatest for mesopic Backgrounds. In dark-adapted retina, B-Wave amplitudes were reduced only when very low stimulus energies affecting the inner retina, or very high stimulus energies were used. Loss of ganglion cells following ONTx did not affect B-Wave amplitudes, and injection of TTX in eyes with ONTx reduced B-Wave amplitudes By the same amount for each Background condition as occurred when ganglion cells were intact, thereBy eliminating a ganglion cell role in the TTX effects. Isolation of cone-driven responses By presenting test flashes after cessation of a rod-saturating conditioning flash indicated that the TTX effects were primarily on cone circuits contriButing to the mixed rod–cone ERG. NMDA significantly reduced only the additional effects of TTX on the mixed rod–cone ERG oBserved under mesopic conditions, implicating inner retinal involvement in those effects. After pharmacological Blockade with CNQX, TTX still reduced B-Wave amplitudes in cone-isolated ERGs indicating Nav channels in ON cone Bipolar cells themselves augment B-Wave amplitude and sensitivity. This augmentation was largest under dark-adapted conditions, and decreased with increasing Background illumination, indicating effects of Background illumination on Nav channel function. These findings indicate that activation of Nav channels in ON cone Bipolar cells affects the B-Wave of the rat ERG and must Be considered when analysing results of ERG studies of retinal function.

  • ContriBution of voltage‐gated sodium channels to the BWave of the mammalian flash electroretinogram
    The Journal of physiology, 2008
    Co-Authors: Deb Kumar Mojumder, David M. Sherry, Laura J. Frishman
    Abstract:

    Voltage-gated sodium channels (Nav channels) in retinal neurons are known to contriBute to the mammalian flash electroretinogram (ERG) via activity of third-order retinal neurons, i.e. amacrine and ganglion cells. This study investigated the effects of tetrodotoxin (TTX) Blockade of Nav channels on the B-Wave, an ERG Wave that originates mainly from activity of second-order retinal neurons. ERGs were recorded from anaesthetized Brown Norway rats in response to Brief full-field flashes presented over a range of stimulus energies, under dark-adapted conditions and in the presence of steady mesopic and photopic Backgrounds. Recordings were made Before and after intravitreal injection of TTX (∼3 μm) alone, 3–6 weeks after optic nerve transection (ONTx) to induce ganglion cell degeneration, or in comBination with an ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 200 μm) to Block light-evoked activity of inner retinal, horizontal and OFF Bipolar cells, or with the glutamate agonist N-methyl-d-aspartate (NMDA, 100–200 μm) to reduce light-evoked inner retinal activity. TTX reduced ERG amplitudes measured at fixed times corresponding to B-Wave time to peak. Effects of TTX were seen under all Background conditions, But were greatest for mesopic Backgrounds. In dark-adapted retina, B-Wave amplitudes were reduced only when very low stimulus energies affecting the inner retina, or very high stimulus energies were used. Loss of ganglion cells following ONTx did not affect B-Wave amplitudes, and injection of TTX in eyes with ONTx reduced B-Wave amplitudes By the same amount for each Background condition as occurred when ganglion cells were intact, thereBy eliminating a ganglion cell role in the TTX effects. Isolation of cone-driven responses By presenting test flashes after cessation of a rod-saturating conditioning flash indicated that the TTX effects were primarily on cone circuits contriButing to the mixed rod–cone ERG. NMDA significantly reduced only the additional effects of TTX on the mixed rod–cone ERG oBserved under mesopic conditions, implicating inner retinal involvement in those effects. After pharmacological Blockade with CNQX, TTX still reduced B-Wave amplitudes in cone-isolated ERGs indicating Nav channels in ON cone Bipolar cells themselves augment B-Wave amplitude and sensitivity. This augmentation was largest under dark-adapted conditions, and decreased with increasing Background illumination, indicating effects of Background illumination on Nav channel function. These findings indicate that activation of Nav channels in ON cone Bipolar cells affects the B-Wave of the rat ERG and must Be considered when analysing results of ERG studies of retinal function.