Potassium Channel and NKCC Cotransporter Involvement in Ocular Refractive Control Mechanisms

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba2+ and 10−5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba2+ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia

Different Temporal Structure for Form versus Surface Cortical Color Systems – Evidence from Chromatic Non-Linear VEP

Physiological studies of color processing have typically measured responses to spatially varying chromatic stimuli such as gratings, while psychophysical studies of color include color naming, color and light, as well as spatial and temporal chromatic sensitivities. This raises the question of whether we have one or several cortical color processing systems. Here we show from non-linear analysis of human visual evoked potentials (VEP) the presence of distinct and independent temporal signatures for form and surface color processing. Surface color stimuli produced most power in the second order Wiener kernel, indicative of a slowly recovering neural system, while chromatic form stimulation produced most power in the first order kernel (showing rapid recovery). We find end-spectral saturation-dependent signals, easily separable from achromatic signals for surface color stimuli. However physiological responses to form color stimuli, though varying somewhat with saturation, showed similar waveform components. Lastly, the spectral dependence of surface and form color VEP was different, with the surface color responses almost vanishing with yellow-grey isoluminant stimulation whereas the form color VEP shows robust recordable signals across all hues. Thus, surface and form colored stimuli engage different neural systems within cortex, pointing to the need to establish their relative contributions under the diverse chromatic stimulus conditions used in the literature

A Close Eye on the Eagle-Eyed Visual Acuity Hypothesis of Autism

Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD

Temporal whole field sawtooth flicker without a spatial component elicits a myopic shift following optical defocus irrespective of waveform direction in chicks.

Purpose: Myopia (short-sightedness) is the commonest visual disorder and greatest risk factor for sight threatening secondary pathologies. Myopia and hyperopia can be induced in animal models by rearing with optical lens defocus of opposite sign. The degree of refractive compensation to lens-induced defocus in chicks has been shown to be modified by directionally drifting sawtooth spatio-temporal luminance diamond plaids, with Fast-ON sawtooth spatio-temporal luminance profiles inhibiting the myopic shift in response to negative lenses, and Fast-OFF profiles inhibiting the hyperopic shift in response to positive lenses. What is unknown is whether similar sign-of-defocus dependent results produced by spatio-temporal modulation of sawtooth patterns could be achieved by rearing chicks under whole field low temporal frequency sawtooth luminance profiles at 1 or 4 Hz without a spatial component, or whether such stimuli would indiscriminately elicit a myopic shift such as that previously shown with symmetrical (or near-symmetrical) low frequency flicker across a range of species. Methods: Hatchling chicks (n = 166) were reared from days five to nine under one of three defocus conditions (No Lens, +10D lens, or -10D lens) and five light conditions (No Flicker, 1 Hz Fast-ON/Slow-OFF sawtooth flicker, 4 Hz Fast-ON/Slow-OFF sawtooth flicker, 1 Hz Fast-OFF/Slow-ON sawtooth flicker, or 4Hz Fast-OFF/Slow-ON sawtooth flicker). The sawtooth flicker was produced by light emitting diodes (white LEDs, 1.2 -183 Lux), and had no measurable dark phase. Biometrics (refraction and ocular axial dimensions) were measured on day nine. Results: Both 1 Hz and 4 Hz Fast-ON and Fast-OFF sawtooth flicker induced an increase in vitreous chamber depth that was greater in the presence of negative compared to positive lens defocus. Both sawtooth profiles at both temporal frequencies inhibited the hyperopic shift in response to +10D lenses, whilst full myopic compensation (or over-compensation) in response to -10D lenses was observed. Conclusions: Whole field low temporal frequency Fast-ON and Fast-OFF sawtooth flicker induces a generalized myopic shift, similar to that previously shown for symmetrical sine-wave and square-wave flicker. Our findings highlight that temporal modulation of retinal ON/OFF pathways per se (without a spatial component) is insufficient to produce strong sign-of-defocus dependent effect

Young children : YC ; the journal of the National Association for the Education of Young Children

The goal of this study was to investigate the effect of optical defocus and spatial contrast on refractive development and, in particular,on anterior chamber growth. Ninety chicks were raised from day 4-10 post-hatching wearing monocular lenses (+/-10 Dor 0 D), in an environment with either high, low or no spatial contrast patterns: 30%, 6% or 0% contrast, respectively. At day 10, the chicks' refractive state and ocular components were assessed using retinoscopy and A-scan ultrasonography. Ocular defocus resulted in sign-dependent significant differences in refractive error, axial length and vitreous chamber depth. Lens wear also led to significant spatial contrast dependent changes in anterior chamber depth. Varying ambient spatial contrast in the chick's environment did not inhibit emmetropization processes; however, anterior chamber growth was particularly susceptible to changes in spatial contrast

Effects of optical defocus and spatial contrast on anterior chamber depth in chicks.

The goal of this study was to investigate the effect of optical defocus and spatial contrast on refractive development and, in particular,on anterior chamber growth. Ninety chicks were raised from day 4-10 post-hatching wearing monocular lenses (+/-10 Dor 0 D), in an environment with either high, low or no spatial contrast patterns: 30%, 6% or 0% contrast, respectively. At day 10, the chicks' refractive state and ocular components were assessed using retinoscopy and A-scan ultrasonography. Ocular defocus resulted in sign-dependent significant differences in refractive error, axial length and vitreous chamber depth. Lens wear also led to significant spatial contrast dependent changes in anterior chamber depth. Varying ambient spatial contrast in the chick's environment did not inhibit emmetropization processes; however, anterior chamber growth was particularly susceptible to changes in spatial contrast

The application of quantitative analysis-parameters to detect and quantify the lung emphysema with HR-CT data

Das Ziel der vorliegenden HR-CT Untersuchung war die Detektion und Quantifizierung des Lungenemphysems mithilfe der computerbasierten Analyseparameter Emphysemindex, fraktale Dimension, Lungenvolumen und Lungendichte. In diese Studie gingen die HR-CT-Daten von 51 COPD Patienten und 23 gesunden Probanden ein. Mit Hilfe einer semiautomatischen Software wurden die HR-CT Bildserien segmentiert und analysiert. Für die fraktalen Dimensionen wurden anhand verschiedener Schwellenwerte fünf Analysebereiche festgelegt und mit der Masse-Radius Methode berechnet. Der Grenzwert für den Emphysemindex wurde bei -950 HE festgelegt. Die Ergebnisse zeigen hoch signifikante Korrelationen zwischen den einzelnen Parametern, insbesondere wenn die Gruppe der COPD Patienten separat betrachtet wird. Für die fraktale Dimension erreicht der Schwellenwertbereich von Th [-1000, -900] HE die höchsten Korrelationen. Darüber hinaus können signifikante Unterschiede zwischen den COPD Patienten und den gesunden Probanden für den Emphysemindex, das Lungenvolumen und die Lungendichte gefunden werden. Für das Anfangsstadium der COPD GOLD I resultierten keine signifikanten Ergebnisse. Die Berechnungen für die fraktale Dimension ergaben durchweg keine signifikanten Ergebnisse. Eine differenzierte Betrachtung zeigte, dass der Emphysemindex einen großen Überschneidungsbereich zwischen beiden Gruppen aufweist. Gesunde Probanden und COPD Patienten verfügen über einen Empyhsemindex von bis zu 12,3 %; dieser Bereich scheint somit noch physiologisch zu sein. In einer neuen Gruppeneinteilung wurde der Emphysemindex von 12,3 % als Grenzwert verwendet und anschließend erneut auf Unterschiede hinsichtlich der fraktalen Dimension untersucht. Es resultieren hoch signifikante Ergebnisse. Die Analyseparamter Emphysemindex, Lungenvolumen und -dichte sind geeignet um zwischen COPD Patienten und gesunden Probanden zu differenzieren. Schwierigkeiten bestehen in der reliablen Detektion milder Emphysem- Erscheinungsformen. Die neue Gruppeneinteilung führte auch bei der fraktalen Dimension zu signifikanten Ergebnissen, sodass auch dieser Parameter das Lun- genemphysem erfolgreich zu quantifizieren scheint.The purpose of this HR-CT study was the detection and quantification of pulmonary emphysema with computer-based parameters such as emphysema index, fractal dimension, lung volume and lung density. In this restrospective study, the HR-CT images of 51 COPD Patients and 23 healthy subjects were segmented and analyzed by a semi-automatically operating software. For the fractal dimensions five areas of analysis where defined based on different thresholds. They were calculated with the mass-radius-method. A cut-off threshold of -950 Hounsfield Units was used for the emphysema index. The results show highly significant correlations between the different parameters, especially when COPD patients were considered separately. For the fractal dimen- sion the highest correlation was achieved with a threshold of [-1000, -900] HU. In addition, significant differences were found between COPD patients and healthy subjects regarding emphysema index, lung volume and lung density. No significant results were found for the initial stage of COPD GOLD I. The calculation of the fractal dimension showed no significant results. A detailed analysis displayed a big overlap for the emphysema index between both groups. The emphysema index of the healthy subjects and COPD patients ranged up to 12,3 %;; thus this range can be considered physiological. Within a new group classification the emphysema index of 12,3 % was used as threshold and subsequently analyzed on differences in the fractal dimension. The results were of great significant. The parameters emphysema index, lung volume, and lung density are appropriate to distinguish between COPD patients and healthy subjects. Difficulties occur in the reliable detection of mild emphysema manifestations. The new group classification also led to significant results in the fractal dimension. On this account it seems to be a successful parameter to quantify pulmonary emphysema

The effects of modality dominance and accuracy on motor reaction times to unimodal and bimodal stimuli

Purpose: Despite limited understanding of the underlying neural mechanisms involved in merging various sensory inputs and, in turn, the construction of a unified representation of the environment, it would appear that multisensory stimuli have a facilitating effect on information processing. It was the aim of this study to investigate multisensory processing using patterns of motor reaction times (MRTs) on a simple discrimination task as a means of categorizing groups of individuals. Method: Twenty-six adults were presented with temporally and spatially coincident unimodal (auditory or visual) and bimodal (auditory and visual) stimuli (100 ms duration), consisting of blue flashes as invalid (Vi) and red flashes as target (Vt) stimuli, and 500 Hz tones as invalid (Ai) and 600 Hz tones as target (At) stimuli. Overall, eight stimulus conditions were used: Ai, Vi, AiVi, At, Vt, AiVt, AtVi, and AtVt. Participants were required to press a button immediately in response to target stimuli: MRTs and response accuracy were recorded. Participants were subdivided into groups of visual dominant [Vis-Dom (n=16)] where MRT for Vt < At and auditory dominant [Aud-Dom, n=10] where MRT for At < Vt. Results: Both Vis-Dom and Aud-Dom groups showed similar levels of facilitation for duel target bimodal stimuli (AtVt), i.e., MRTs were approximately 60 ms faster compared to unimodal stimuli and single target bimodal stimuli. Furthermore, MRTs to single target bimodal stimuli mirrored MRTs to unimodal stimuli, i.e., Vis-Dom and Aud-Dom participants' MRT were faster to AiVt and AtVi stimuli, respectively. An increase in speed, for all stimulus conditions, was also associated with high response accuracy. Conclusion: MRTs are partly dependent on an individual's dominant modality and performance accuracy. Nevertheless, maximum facilitation is achieved with duel target bimodal stimuli

Low frequency temporal modulation of light promotes a myopic shift in refractive compensation to all spectacle lenses.

Emmetropization, the process by which ocular growth of young animals adapts to ensure focussed retinal images, can be disrupted by high frequency flicker, causing a hypermetropic shift. Emmetropization can also be disrupted differentially, in a sign dependent manner, by pharmacological alteration of the balance of activation of the ON and OFF retinal sub-systems in normal light or by rearing in an environment with a moving spatiotemporally varied diamond pattern (yielding local sawtooth illumination on the retina). Thus the aim of this experiment was to determine whether low frequency temporal modulation alone was sufficient to cause defocus sign-dependent interference with compensation. Chicks were reared for 6 or 7 days with monocular +/-10 D, 0 D, or No Lenses in a 12h light/dark cycle. Luminance of the environment was temporally modulated during the light cycle with a non-square wave profile pulse of 250 msec duration, with the illumination fluctuating between 1.5 and 180 lux at 1 Hz, 2 Hz, 4 Hz or with no flicker (0 Hz-180 lux). Final refractive state and ocular dimensions, measured using retinoscopy and A-scan ultrasonography, demonstrated that in the absence of temporal luminance modulation (0 Hz), chicks compensated to induced defocus in the expected sign-dependent manner. However, under 1, 2 and 4 Hz flickering light conditions, there was an overall myopic offset of approximately 6D across lens groups with refractive compensation to positive lenses more strongly inhibited. This myopic offset was reflected by increases in the depth of both vitreous and anterior chambers. However, luminance modulation had no effect on refraction or ocular parameters in the No Lens conditions. This is a hitherto unreported strong interaction between lens wear and low frequency temporally modulated light, with the refractive compensation mechanism being overridden by a generalized myopic shift

The effects of modality dominance and accuracy on motor reaction times to unimodal and bimodal stimuli

Purpose: Despite limited understanding of the underlying neural mechanisms involved in merging various sensory inputs and, in turn, the construction of a unified representation of the environment, it would appear that multisensory stimuli have a facilitating effect on information processing. It was the aim of this study to investigate multisensory processing using patterns of motor reaction times (MRTs) on a simple discrimination task as a means of categorizing groups of individuals. Method: Twenty-six adults were presented with temporally and spatially coincident unimodal (auditory or visual) and bimodal (auditory and visual) stimuli (100 ms duration), consisting of blue flashes as invalid (Vi) and red flashes as target (Vt) stimuli, and 500 Hz tones as invalid (Ai) and 600 Hz tones as target (At) stimuli. Overall, eight stimulus conditions were used: Ai, Vi, AiVi, At, Vt, AiVt, AtVi, and AtVt. Participants were required to press a button immediately in response to target stimuli: MRTs and response accuracy were recorded. Participants were subdivided into groups of visual dominant [Vis-Dom (n=16)] where MRT for Vt &lt; At and auditory dominant [Aud-Dom, n=10] where MRT for At &lt; Vt. Results: Both Vis-Dom and Aud-Dom groups showed similar levels of facilitation for duel target bimodal stimuli (AtVt), i.e., MRTs were approximately 60 ms faster compared to unimodal stimuli and single target bimodal stimuli. Furthermore, MRTs to single target bimodal stimuli mirrored MRTs to unimodal stimuli, i.e., Vis-Dom and Aud-Dom participants' MRT were faster to AiVt and AtVi stimuli, respectively. An increase in speed, for all stimulus conditions, was also associated with high response accuracy. Conclusion: MRTs are partly dependent on an individual's dominant modality and performance accuracy. Nevertheless, maximum facilitation is achieved with duel target bimodal stimuli