Dynamic random noise shrinks the twinkling aftereffect induced by artificial scotomas

AbstractPhysiological alterations in cortical neurons are induced during adaptation to an artificial scotoma, a small homogeneous patch within a dynamic random noise or patterned background. When the dynamic noise is replaced by an equiluminant gray background, a twinkling aftereffect can be seen in the location of the artificial scotoma. Following binocular adaptation, we discovered that the perceived size of the twinkling aftereffect was dramatically smaller than the inducing artificial scotoma. Dichoptic adaptation induced shrinkage in the twinkling aftereffect that was similar to that found after binocular adaptation, suggesting that the twinkling aftereffect and its shrinkage both have cortical origins. We speculate that this perceptual shrinkage may reflect the interaction between two cortical mechanisms: a twinkling aftereffect mechanism that spreads throughout the artificial scotoma, and a filling-in mechanism that has a greater influence at the edges of the artificial scotoma and spreads inwards

Chapter 6 Negative components of the electroretinogram from proximal retina and photoreceptor

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29553/1/0000641.pd

Peroxisomal alanine : glyoxylate aminotransferase (AGT1) is a photorespiratory enzyme with multiple substrates in Arabidopsis thaliana

At least two glyoxylate aminotransferases are hypothesized to participate in the steps of photorespiration located in peroxisomes. Until recently, however, genes encoding these enzymes had not been identified. We describe the isolation and characterization of an alanine : glyoxylate aminotransferase ( AGT1 , formerly AGT ) cDNA from Arabidopsis thaliana . Southern blot analysis confirmed that Arabidopsis AGT1 is encoded by a single gene. Homologs of this class IV aminotransferase are also known in other plants, animals, and methylotrophic bacteria, suggesting an ancient evolutionary origin of this enzyme. AGT1 transcripts were present in all tissues of Arabidopsis , but were most abundant in green, leafy tissues. Purified, recombinant Arabidopsis AGT1 expressed in Escherichia coli catalyzed three transamination reactions using the following amino donor : acceptor combinations: alanine : glyoxylate, serine : glyoxylate, and serine : pyruvate. AGT1 had the highest specific activity with the serine : glyoxylate transamination, and apparent K m measurements indicate that this is the preferred in vivo reaction. In vitro import experiments and subcellular fractionations localized AGT1 to peroxisomes. Sequence analysis of the photorespiratory sat mutants revealed a single nucleotide substitution in the AGT1 gene from these plants. This transition mutation is predicted to result in a proline-to-leucine substitution at residue 251 of AGT1. When this mutation was engineered into the recombinant AGT1 protein, enzymatic activity using all three donor : acceptor pairs was abolished. We conclude that Arabidopsis AGT1 is a peroxisomal photorespiratory enzyme that catalyzes transamination reactions with multiple substrates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73264/1/j.1365-313x.2001.00961.x.pd

ISCEV Standard for full-field clinical electroretinography (2022 update).

The full-field electroretinogram (ERG) is a mass electrophysiological response to diffuse flashes of light and is used widely to assess generalized retinal function. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical ERG testing. Minimum protocols for basic ERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis, monitoring and inter-laboratory comparisons, while also responding to evolving clinical practices and technology. The main changes in this updated ISCEV Standard for clinical ERGs include specifying that ERGs may meet the Standard without mydriasis, providing stimuli adequately compensate for non-dilated pupils. There is more detail about analysis of dark-adapted oscillatory potentials (OPs) and the document format has been updated and supplementary content reduced. There is a more detailed review of the origins of the major ERG components. Several tests previously tabulated as additional ERG protocols are now cited as published ISCEV extended protocols. A non-standard abbreviated ERG protocol is described, for use when patient age, compliance or other circumstances preclude ISCEV Standard ERG testing

Immunotoxin-Induced Ablation of the Intrinsically Photosensitive Retinal Ganglion Cells in Rhesus Monkeys

Purpose: Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin, and are primarily involved in non-image forming functions, such as the pupillary light reflex and circadian rhythm entrainment. The goal of this study was to develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys.Methods: An immunotoxin for the macaque melanopsin gene (OPN4), consisting of a saporin-conjugated antibody directed at the N-terminus, was prepared in solutions of 0.316, 1, 3.16, 10, and 50 μg in vehicle, and delivered intravitreally to the right eye of six rhesus monkeys, respectively. Left eyes were injected with vehicle only. The pupillary light reflex (PLR), the ipRGC-driven post illumination pupil response (PIPR), and electroretinograms (ERGs) were recorded before and after injection. For pupil measurements, 1 and 5 s pulses of light were presented to the dilated right eye while the left pupil was imaged. Stimulation included 651 nm (133 cd/m2), and 4 intensities of 456 nm (16–500 cd/m2) light. Maximum pupil constriction and the 6 s PIPR were calculated. Retinal imaging was performed with optical coherence tomography (OCT), and eyes underwent OPN4 immunohistochemistry to evaluate immunotoxin specificity and ipRGC loss.Results: Before injection, animals showed robust pupil responses to 1 and 5 s blue light. After injection, baseline pupil size increased 12 ± 17%, maximum pupil constriction decreased, and the PIPR, a marker of ipRGC activity, was eliminated in all but the lowest immunotoxin concentration. For the highest concentrations, some inflammation and structural changes were observed with OCT, while eyes injected with lower concentrations appeared normal. ERG responses showed better preserved retinal function with lower concentrations. Immunohistochemistry showed 80–100% ipRGC elimination with the higher doses being more effective; however this could be partly due to inflammation that occurred at the higher concentrations.Conclusion: Findings demonstrated that the OPN4 macaque immunotoxin was specific for ipRGCs, and induced a graded reduction in the PLR, as well as, in ipRGC-driven pupil response with concentration. Further investigation of the effects of ipRGC ablation on ocular and systemic circadian rhythms and the pupil in rhesus monkeys will provide a better understanding of the role of ipRGCs in primates

The uniform field and pattern ERG in macaques with experimental glaucoma: removal of spiking activity. Invest Ophthalmol Vis Sci.

PURPOSE. To determine whether the uniform field and pattern ERGs that are reduced in macaque eyes with experimental glaucoma have the same inner-retinal origins. METHODS. ERGs were recorded from 14 anesthetized adult macaques using DTL electrodes. Six monkeys had laser-induced experimental glaucoma, and two others received intravitreal injections of tetrodotoxin (TTX, 6 M) to block spiking activity of inner-retinal neurons. The remaining 6 animals were normal. Uniform fields and grating patterns (0.1-3 cpd) were square-wave modulated at 1.7 Hz (transient) and 8 Hz (steady state). The test field (42°ϫ 32°) had a mean luminance of 44 cd/m 2 and a contrast of 10% to 82%. RESULTS. In normal eyes transient ERGs to uniform fields contained photopic negative responses (PhNR) after the b-wave and after the d-wave. Transient pattern electroretinograms (PERGs) at each contrast reversal showed positive (P 50 ) potentials followed by negative (N 95 ) potentials of time course similar to that of the PhNR. The PhNR and N 95 were greatly reduced or eliminated by experimental glaucoma and by TTX. Summing responses to luminance increments and decrements of the uniform field could simulate the PERG to low spatial frequency stimuli. Further, the PERG responses to high spatial frequencies were similar to the simulation in shape but slightly delayed in time. Experimental glaucoma and TTX had similar effects on the N 95 of the simulated PERG as to those on the actual PERG. However, P 50 was more reduced by experimental glaucoma than by TTX, indicating a nonspiking contribution to P 50 . For the steady state condition, the uniform field ERG, the simulated PERG, and the actual PERG all were affected by experimental glaucoma and TTX, indicating that they contained contributions from the spiking activity of ganglion cells. 1,2 Glaucoma is a disease characterized by progressive degeneration of the optic nerve and loss of retinal ganglion cells. CONCLUSIONS. 3-5 Findings from clinical studies have differed on which components of the PERG are maximally affected by glaucoma (for reviews see Refs. 6 and 7) and how well those changes correlate with the other clinical findings in glaucoma (e.g., Refs. 8 -14). However, some recent studies The macaque model of laser-induced experimental glaucoma has been used widely to study structural damage and functional losses resulting from elevation of intraocular pressure

Effect of Experimental Glaucoma in Primates on Oscillatory Potentials of the Slow-Sequence mfERG

PURPOSE. To determine the effect of experimental glaucoma in macaque monkeys on oscillatory potentials (OPs) in the slowsequence multifocal electroretinogram (mfERG). METHODS. Photopic slow-sequence mfERGs were recorded from anesthetized adult macaque monkeys and normal human subjects. The stimulus consisted of 103 equal-sized hexagons within 17°of the fovea. The m-sequence was slowed, with 14 blank frames, ϳ200 ms, interleaved between flashes for monkeys and 7 blank frames, ϳ100 ms, for humans, to produce waveforms similar to the photopic full-field flash ERG. Recordings were made under control conditions (24 monkey eyes, 7 human) and after laser-induced experimental glaucoma in monkeys (n ϭ 8). A Fourier fast transform [FFT] was used to determine the frequency ranges of the major OPs. OP amplitudes were quantified by using root mean square (RMS) for two-frequency bands in five horizontal and four vertical locations. Visual field defects were assessed using behavioral static perimetry. Full-field photopic flash ERGs also were recorded. RESULTS. OPs in two distinct frequency bands were discriminated in the monkey mfERG: fast OPs, with a peak frequency of 143 Ϯ 20 Hz, and slow OPs, with a peak at 77 Ϯ 8 Hz. There were similar findings in humans and with the flash ERG in monkeys. The fast OP RMS in monkey control eyes was significantly larger in temporal than nasal retina (P Ͻ 0.01) and in superior versus inferior retina (P Ͻ 0.05) as reported previously. The slow OP RMS was largest in the foveal region. Experimental glaucoma reduced fast OP RMS in all locations studied, even when visual field defects were moderate (MD ϭ Ϫ5 to Ϫ10 dB; P Ͻ 0.05), whereas the slow OP RMS was reduced significantly primarily in the foveal region when field defects were severe (MD Ͻ Ϫ10 dB; P Ͻ 0.05). The fast OP RMS showed a moderate correlation with local visual field sensitivity and with local ganglion cell density (calculated from visual field sensitivity). For the slow OPs the correlation was much poorer. Consistent with previous studies, the photopic negative response (PhNR) amplitude was significantly reduced when the visual sensitivity was minimally affected. CONCLUSIONS. OPs in the ERG of primates fall in two frequency bands: fast OPs with a peak frequency around 143 Hz and slow OPs, with a peak frequency around 77 Hz. The fast OPs, which rely more on the integrity of retinal ganglion cells and their axons than do the slow OPs, have potential 1 The death of retinal ganglion cells in POAG is reflected by increased cupping of the optic disc, loss of nerve fiber layer and functional visual field defects. 2 Perimetry has been considered to be the gold standard in the diagnosis of glaucoma. However, a disadvantage of standard perimetry is that the first visual field defects appear only after a significant proportion (ϳ25%-40%) of ganglion cells and nerve fibers have died. 3-5 Therefore, more sensitive tests that can detect early retinal ganglion cell changes in glaucoma would be useful. One technique that objectively measures retinal function is the electroretinogram (ERG). The ERG is a useful tool for noninvasive assessment of function in normal and diseased retinas. In recent years, several studies in patients with glaucoma and in primate models of glaucoma have shown that the photopic ERG has components that are sensitive to glaucomatous optic neuropathy. These components include the negative potential at 95 ms of the transient pattern (p)ERG, known as the N95 6 -8 ; the photopic negative response (PhNR) of the photopic full-field flash ERG 9 -12 ; and the oscillatory potentials Although these components of the ERG are sensitive to glaucomatous damage, they reflect activity of the whole or large regions of the retina, and do not provide information about regional ganglion cell defects. In contrast, the results of perimetry indicate the regional nature of damage to the ganglion cells and their axons. A test that measures responses from different retinal locations might be more sensitive to early changes in the retinal ganglion cell responses that occur locally and would be lost in averaging of ERG responses over the entire retina. The multifocal ERG (mfERG) technique developed by Sutter has made it possible to obtain a topographic representation of the retinal functio

The effect of eccentricity on the contrast response function of multifocal visual evoked potentials (mfVEPs)

MfVEPs were recorded with a 22 deg radius, 60-sector pattern reversal dartboard stimulus (VERIS) at 6 contrast levels (10, 25, 35, 50, 75, 95%). Contrast response functions (CRFs) based on response amplitudes were adequately described by a simple hyperbolic function. The effect of reducing contrast on the amplitude was most apparent in the central 1 deg radius, which had a C50 (contrast at 50% of the maximum response) in excess of 50%, compared to values for C50 in more eccentric regions that were 30% or lower. Mean latency increased 6 (± 0.7 SE) ms from the highest to the lowest contrast tested, and did not vary sgnificantly with eccentricity