Panx1b Modulates the Luminance Response and Direction of Locomotion in the Zebrafish

Pannexin1 (Panx1) can form ATP-permeable channels that play roles in the physiology of the visual system. In the zebrafish two ohnologs of Panx1, Panx1a and Panx1b, have unique and shared channel properties and tissue expression patterns. Panx1a channels are located in horizontal cells of the outer retina and modulate light decrement detection through an ATP/pH-dependent mechanisms and adenosine/dopamine signaling. Here, we decipher how the strategic localization of Panx1b channels in the inner retina and ganglion cell layer modulates visually evoked motor behavior. We describe a panx1b knockout model generated by TALEN technology. The RNA-seq analysis of 6 days post-fertilization larvae is confirmed by real-time PCR and paired with testing of locomotion behaviors by visual motor and optomotor response tests. We show that the loss of Panx1b channels disrupts the retinal response to an abrupt loss of illumination and it decreases the larval ability to follow leftward direction of locomotion in low light conditions. We concluded that the loss of Panx1b channels compromises the final output of luminance as well as motion detection. The Panx1b protein also emerges as a modulator of the circadian clock system. The disruption of the circadian clock system in mutants suggests that Panx1b could participate in non-image forming processes in the inner retina.

Panx1b modulates the luminance response and direction of motion in the zebrafish

Pannexin1 (Panx1) can form ATP-permeable integral membrane channels that play roles in the physiology of the visual system. Two independent gene copies of Panx1, panx1a and panx1b, have been identified in the zebrafish with unique and shared properties and tissue expression patterns. Panx1a channels, located in horizontal cells of the outer retina, modulate light decrement detection through an ATP/pH-dependent mechanisms and adenosine/dopamine signaling. Here, we decipher how the strategic localization of Panx1b channels in the inner retina and ganglion cell layer modulates visually evoked motor behavior. We describe a panx1b knockout model generated by TALEN technology. The RNA-seq analysis of 6 days post-fertilization larvae is confirmed by Real-Time PCR and paired with testing of visual-motor behaviors. The Panx1b protein emerges as a modulator of the circadian clock system. The loss of panx1b also disrupts the retinal response to the abrupt loss of illumination and decreases the larval ability to follow leftward direction of motion in the dark. The evidence suggests that in the retina Panx1b contributes to the OFF pathways function, like Panx1a, though through different signaling mechanisms. In this process, the loss of Panx1b channels compromises the final output of luminance as well as direction of motion detector RGCs. In addition, the disruption of the circadian clock system in mutants suggests that Panx1b could participate in non-image forming processes in the inner retina.

Postoperative Multimodal Analysis in Successful Gas Displacement of a Submacular Hemorrhage

In this report, we describe a case of timely gas vitrectomy to displace a moderate submacular hemorrhage from the submacular space without tPA, release vitreoretinal traction along the borders of a posterior retinal tear, and analyze postoperative multimodal imaging findings in a 34-year-old male patient whose right eye was injured by a stone. The patient underwent a successful nontissue plasminogen activator gas vitrectomy 3 days after the accident. A multimodal evaluation with spectral-domain optical coherence tomography (SD-OCT), 10-2 and 30-2 campimetry, microperimetry, multifocal electroretinography (mfERG), and visual evoked potentials was performed 6 months after the accident. The multimodal imaging tests yielded abnormal foveal SD-OCT patterns, with a fibrous sealed tear in the retinal pigment epithelium. Campimetry showed low levels of retinal sensitivity; microperimetry and mfERG revealed a subnormal retinal response and a reduction in the N1 and P1 wave amplitudes. The visual evoked potential responses were normal. Multidisciplinary examination at 6 months postoperatively revealed a structurally and functionally abnormal macula. The retina remained attached. Our functional findings indicate that submacular hemorrhage should be treated in a timely manner to minimize photoreceptor damage.

Absence of Excess Intra-Individual Variability in Retinal Function in People With Schizophrenia

People with schizophrenia exhibit increased intra-individual variability in both behavioral and neural signatures of cognition. Examination of intra-individual variability may uncover a unique functionally relevant aspect of impairment that is not captured by typical between-group comparisons of mean or median values. We and others have observed that retinal activity measured using electroretinography (ERG) is significantly reduced in people with schizophrenia; however, it is currently unclear whether greater intra-individual variability in the retinal response can also be observed. To investigate this, we examined intra-individual variability from 25 individuals with schizophrenia and 24 healthy controls under two fERG conditions: (1) a light-adapted condition in which schizophrenia patients demonstrated reduced amplitudes; and (2) a dark-adapted condition in which the groups did not differ in amplitudes. Intraclass correlation coefficients (ICC) were generated to measure intra-individual variability for each subject, reflecting the consistency of activation values (in μv) across all sampling points (at a 2 kHz sampling rate) within all trials within a condition. Contrary to our predictions, results indicated that the schizophrenia and healthy control groups did not differ in intra-individual variability in fERG responses in either the light- or dark-adapted conditions. This finding remained consistent when variability was calculated as the standard deviation (SD) and coefficient of variation (CV) of maximum positive and negative microvolt values within the a- and b-wave time windows. This suggests that although elevated variability in schizophrenia may be observed at perceptual and cognitive levels of processing, it is not present in the earliest stages of sensory processing in vision.

Retinal Response of Low Myopes during Orthokeratology Treatment

The aim of this study was to evaluate the changes in retinal activity during orthokeratology (OK) treatment in 20 myopic eyes. Pattern electroretinography (PERG) and visual evoked potential (VEP) were assessed with the RETI-port/scan21 (Roland Consult, Wiesbaden, Germany). Measurements were taken at baseline (BL) and 1 night (1N), 15 nights (15N), 30 nights (30N), and 60 nights (60N) of OK lens wear. Repeated measures analysis of variance (ANOVA) and the Friedman test were used. Twenty eyes (23.20 ± 3.46 years, 70% female) with visual acuity ≤ 0.00 logMAR in post-treatment showed that despite a slight increase in retinal and cortical response amplitude, observed with both PERG and VEP, respectively, immediately after the initial treatment, these differences found were not statistically significant during the 60 days of OK treatment, despite a statistically significant increase in N95 response with PERG. This shows that retinal and cortical visual-related electrical activity is maintained or slightly increased during OK treatment.

Decoding network-mediated retinal response to electrical stimulation: implications for fidelity of prosthetic vision

ObjectivePatients with the photovoltaic subretinal implant PRIMA demonstrated letter acuity by ~0.1 logMAR worse than the sampling limit for 100μm pixels (1.3 logMAR) and performed slower than healthy subjects, which exceeded the sampling limit at equivalently pixelated images by ~0.2 logMAR. To explore the underlying differences between the natural and prosthetic vision, we compare the fidelity of the retinal response to visual and subretinal electrical stimulation through single-cell modeling and ensemble decoding.ApproachResponses of the retinal ganglion cells (RGC) to optical or electrical (1mm diameter arrays, 75μm pixels) white noise stimulation in healthy and degenerate rat retinas were recorded via MEA. Each RGC was fit with linear-non-linear (LN) and convolutional neural network (CNN) models. To characterize RGC noise level, we compared statistics of the spike-triggered average (STA) in RGCs responding to electrical or visual stimulation of healthy and degenerate retinas. At the population level, we constructed a linear decoder to determine the certainty with which the ensemble of RGCs can support the N-way discrimination tasks.Main resultsAlthough LN and CNN models can match the natural visual responses pretty well (correlation ~0.6), they fit significantly worse to spike timings elicited by electrical stimulation of the healthy retina (correlation ~0.15). In the degenerate retina, response to electrical stimulation is equally bad. The signal-to-noise ratio of electrical STAs in degenerate retinas matched that of the natural responses when 78±6.5% of the spikes were replaced with random timing. However, the noise in RGC responses contributed minimally to errors in the ensemble decoding. The determining factor in accuracy of decoding was the number of responding cells. To compensate for fewer responding cells under electrical stimulation than in natural vision, larger number of presentations of the same stimulus are required to deliver sufficient information for image decoding.SignificanceSlower than natural pattern identification by patients with the PRIMA implant may be explained by the lower number of electrically activated cells than in natural vision, which is compensated by a larger number of the stimulus presentations.