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The effects of adaptation to visual stimuli on the velocity of subsequent ocular following responses.

We examined the effect of prior adaptation to moving and flickering stimuli on the velocity of subsequent ocular following responses in man. Experiments consisted of two phases: an adaptation phase in which moving or flickering stimuli were presented while the eyes fixated a small spot and a test phase in which ocular following responses were free to occur. The effects resulting from prior adaptation were characterized by determining the mean initial eye velocities in the period 200-500 ms after the onset of the test stimulus. It was found that 8 s of prior exposure to a grating pattern moving at between 1.5 and 4 cycles.s-1 significantly reduced initial eye velocities in all subjects. Prior exposure to a flickering stimulus (temporal frequency 3.2 cycles.s-1) also attenuated the velocities of initial eye movements, but to a far lesser extent. These results suggest that a motion-dependent and a weaker flicker-dependent process have an adaptive influence on the generation of ocular following responses. Initial eye velocities were measured as a function of the contrast of the prior adapting gratings. The velocities were found to decrease with increasing adapting contrast. The reductions in eye velocity were well described by a decaying exponential function. The motion-dependent adaptive effect showed significant inter-ocular transfer and had the same temporal tuning when transferred (i.e. optimum adaptation at between 1.5 and 4 cycles.s-1). The flicker-dependent effect did not show inter-ocular transfer. There is a distinct similarity between the adaptive process that causes attenuation of ocular following velocities and the adaptive mechanism that induces perceptual motion after-effects. This similarity is discussed.

Acceleration↗

Phospholipase D from photoreceptor rod outer segments is a downstream effector of RhoA: evidence of a light-dependent mechanism.

Photoreceptor cells contain rod outer segments (ROS) which are specialized light-sensitive organelles. The biological function of ROS is to generate a photoresponse, which occurs via the classic transducin-mediated pathway. Moreover, ROS undergo light-regulated membrane turnover and protein translocation whose mechanisms have not been fully elucidated to date. Phospholipase D (PLD) is a key enzyme involved in lipid signal transduction and membrane trafficking. We have previously reported that PLD activity is present in purified ROS (Salvador, G.A., Giusto, N.M., 1998. Characterization of phospholipase D activity in bovine photoreceptor membranes. Lipids 33, 853-860). We now demonstrate that ROS PLD activity is enhanced by phosphatidylinositol bisphosphate (PIP2) and cytosolic factors in a GTP dependent-manner. Western blot analysis demonstrates the presence of PLD1 isoform in purified ROS. In ROS obtained from dark-adapted retinas (DROS), PIP2-dependent PLD activity was higher than that observed in ROS obtained from light-adapted retinas (LROS). In addition, experiments carried out in the presence of C3 toxin inhibited PLD activity from DROS whereas pertussis toxin did not affect the enzyme activity. Western blot analysis demonstrates the presence of RhoA, a PLD upstream-regulator. Moreover, RhoA levels were higher in DROS with respect to those in LROS. The present study reports evidence of the involvement of the small G-protein, RhoA, in ROS PLD regulation. Our data strongly suggest that RhoA regulates ROS PLD activity under a light-dependent mechanism.

Adaptation, Ocular↗

Amblyopia and suppression in binocular cortical neurones of strabismic cat.

The neural mechanism of strabismic amblyopia was investigated by recording the spatio-temporal properties of striate cortical neurones of cats raised with a surgically induced esotropia. Multiple pseudo-random flashed or phase-alternating stimuli were used, and through cross-correlation, the Wiener kernels were extracted. This analysis has shown that in neurones which retain binocularity to adulthood, two different neural mechanisms of adaptation to ocular misalignment exist. Some of these neurones become amblyopic, such that the non-deviating eye dominates the response for high spatial frequencies while the strabismic eye dominates at low spatial frequencies. Other neurones adapt through active suppression of the monocular response to stimulation of the strabismic eye when the non-deviating eye is simultaneously stimulated.

Amblyopia↗

Adaptive changes of the vestibulo-ocular reflex in flatfish are achieved by reorganization of central nervous pathways.

Flatfish provide a natural model for the study of adaptive changes in the vestibulo-ocular reflex system. During metamorphosis their vestibular and oculomotor coordinate systems undergo a 90 degree relative displacement. As a result, during swimming movements different types of compensatory eye movements are produced before and after metamorphosis by the same vestibular stimulation. Intracellular staining of central nervous connections in the flatfish with horseradish peroxidase revealed that in postmetamorphic fish secondary horizontal semicircular canal neurons contact vertical eye muscle motoneuron pools on both sides of the brain via pathways that are absent in all other vertebrates studied.

Adaptation, Physiological↗

Clinical method for measuring adaptation of tonic accommodation and vergence accommodation.

Previous work indicates that tonic adapters of accommodation and vergence have indirect effects on accommodative vergence and vergence accommodation and that these crosslink responses interact with one another to produce clear and single vision. Clinical measurements of tonic accommodation, tonic vergence, vergence accommodation (CA/C ratio), and accommodative vergence (AC/A ratio) are therefore of value in determining possible binocular vision abnormalities. Currently, clinical methods are only available for measuring the tonic vergence (phoria) and the AC/A ratio. We have determined a fast and accurate method for evaluating both tonic accommodation (accommodative phoria) and vergence accommodation (CA/C ratio). In both procedures, the loop of accommodation was opened with a 0.2 cpd difference of Gaussian (DOG) target. This target was found to be incapable of stimulating any reflex accommodation, yet it is localized in space and can easily stimulate binocular fixation. Our results indicate that opening the loop of accommodation with a pinhole Maxwellian view or with a 0.2 cpd DOG produces similar response values for tonic accommodative aftereffects and vergence accommodation responses. The decay rate of tonic accommodative aftereffects as well as changes in the resting focus of accommodation caused by vergence accommodation (CA/C) can be measured clinically using dynamic retinoscopy in combination with the DOG target. Clinical values of the CA/C ratio obtained with these techniques were highly correlated (r = 0.92) with laboratory measures obtained with an objective infrared optometer and eye trac monitor.

Accommodation, Ocular↗

Phosducin and PP33 are in vivo targets of PKA and type 1 or 2A phosphatases, regulators of cell elongation in teleost rod inner-outer segments.

Teleost rod photoreceptors elongate in the light and shorten in darkness. We are investigating the role of cAMP-dependent protein kinase (PKA), phosphatases and target phosphoproteins in the regulation of photoreceptor cell shape. Preparations of rod fragments, consisting of the motile inner segment with attached photosensory outer segment (RIS-ROS), undergo light-stimulated elongation in culture. The PKA-selective inhibitor, H89, enhanced RIS-ROS elongation in both light and darkness, suggesting that elongation is associated with dephosphorylation of PKA substrates. Okadaic acid and calyculin A, inhibitors of type 1 and 2A phosphatases, blocked light-dependent and light-independent elongation with relative potencies suggesting that elongation requires dephosphorylation by type 1 phosphatase in light and type 2A phosphatase in darkness. To identify targets of PKA and phosphatases, RIS-ROS were isolated from retinas prelabeled with 32P-orthophosphate, and then incubated in the presence of kinase inhibitors or phosphatase inhibitors. Two phosphoproteins, PP33 and PP35, were phosphorylated by PKA and dephosphorylated by type 1 or 2A phosphatases in light- and dark-cultured RIS-ROS. PP35 (but not PP33) was immunoprecipitated by an antibody to phosducin, a PKA-regulated modulator of phototransduction (Lee et al., 1992); PP35 was also phosphorylated in vitro by a Ca2+ calmodulin-activated kinase. PP33 further differed from PP35 in its phosphopeptide maps and phosphorylation by PKC. We conclude that RIS-ROS elongation is correlated with the dephosphorylation of PKA substrates by type 1 or 2A phosphatases. Candidate mediator proteins include PP35, a fish phosducin homolog, and PP33, a newly described photoreceptor phosphoprotein.

Adaptation, Ocular↗

Circadian regulation of hydroxyindole-O-methyltransferase mRNA levels in rat pineal and retina.

Hydroxyindole-O-methyltransferase (HIOMT, EC 2.1.1.4) catalyzes the methylation of acetylserotonin to complete the synthesis of melatonin in the pineal and retina. A complete 1728 nucleotide cDNA encoding rat pineal HIOMT was isolated, characterized, and used to evaluate day/night levels of HIOMT mRNA. As previously reported for HIOMT enzyme activity, HIOMT mRNA levels were also greater in the pineal than in the retina. Northern blot analysis and in situ hybridization were useful for detection of HIOMT mRNA in the pineal but not the retina, whereas the reverse transcriptase-polymerase chain reaction or RNase protection assay revealed transcripts for HIOMT both in the pineal and retina. Investigating HIOMT mRNA levels in rat pineal and retina at 6 time-points throughout a 24 h period revealed higher levels of HIOMT message during darkness. The daily fluctuation in HIOMT mRNA persisted in constant darkness, verifying an endogenous circadian rhythm both in the pineal and retina. In mammalian pineals, sympathetic innervation, synthesizing norepinephrine that activates beta (beta) adrenergic receptors, entrain several circadian bodily functions through the synthesis and release of melatonin. A single injection of the beta-adrenergic agonist, isoproterenol, induced a dramatic increase of HIOMT mRNA levels in the light-adapted pineal, in vivo. Moreover, a single injection of the beta-adrenergic antagonist, propranolol, prevented the nocturnal increase of pineal HIOMT mRNA. Using a combination of methods, it has been shown that the level of HIOMT mRNA fluctuates daily in both the pineal gland and retina. This day/night rhythm can be modulated either by beta receptor agonists or antagonists when applied appropriately during the circadian cycle, suggesting that the mRNA changes in HIOMT may be controlled at the transcriptional level.

Acetylserotonin O-Methyltransferase↗

BCM network develops orientation selectivity and ocular dominance in natural scene environment.

A two-eye visual environment is used in training a network of BCM neurons. We study the effect of misalignment between the synaptic density functions from the two eyes, on the formation of orientation selectivity and ocular dominance in a lateral inhibition network. The visual environment we use is composed of natural images. We show that for the BCM rule a natural image environment with binocular cortical misalignment is sufficient for producing networks with orientation-selective cells and ocular dominance columns. This work is an extension of our previous single cell misalignment model Shouval et al., 1996.

Adaptation, Ocular↗

The S-cone electroretinogram: a comparison of techniques, normative data and age-related variation.

The blue sensitive mechanism in human colour vision is highly susceptible to damage in ocular disease. There is a need for objective methods to assess this and several methods of recording the blue cone (S-cone) electroretinogram (ERG) have been described. We therefore compared a silent substitution technique (SST) and a selective adaptation technique (SAT) using a novel combination of optical filters, on 24 normal subjects. The age-related variation in the S-cone ERG was also investigated in a further 73 normal subjects. S-cone ERGs elicited by SAT were of higher amplitude, (p < 0.001) with smaller coefficients of variation than those elicited with SST. The SST method has already been shown to be highly sensitive in primary open angle glaucoma and, unlike SAT, has no significant age related variation. However, the results of this study suggest that the new, SAT method may prove to be more convenient and effective in clinical practice, provided that age norms are applied.

Adaptation, Ocular↗

Strabismus.

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Accommodation, Ocular↗

Neuronal events correlated with long-term adaptation of the horizontal vestibulo-ocular reflex in the primate flocculus.

The activity of flocculus Purkinje cells was examined in Japanese monkeys during sustained vestibular-visual stimulation which caused adaptation of the horizontal vestibulo-ocular reflex (H-VOR). In the floccular area related to the H-VOR by microstimulation. Purkinje cells consistently changed their simple spike responsiveness to head rotation in parallel with the adaptive H-VOR gain change. Similar changes occurred even after the H-VOR had been extinguished by lesioning of the vestibular nuclei. The complex spike discharge, on the other hand, modulated during vestibular-visual stimulation with a reciprocal pattern to the adaptive changes in the simple spike discharge. These results support the hypothesis that the flocculus adaptively modifies the H-VOR through their simple spike activity under the influence of visual climbing fiber signals.

Adaptation, Physiological↗

Smooth pursuit rather than visual signals mediate short-term adaptation of the cervico-ocular reflex in humans.

Cervical stimulation in the horizontal plane induces small and variable eye movements in normal human adults [cervico-ocular reflex (COR)]. In patients with bilateral vestibular loss, the slow COR component increases in amplitude and is thought to contribute to gaze stabilization during head movements, as it is directed opposite to head-on-trunk excursions. The procedures underlying COR slow phase gain enhancement in the compensatory direction remain unclear. We studied the horizontal COR during passive trunk oscillations of +/-16 degrees under the stationary head at 0.1 Hz in ten normal subjects, aged 24-30 years, before and immediately after the application of an adaptation procedure engaging various combinations of sinusoidal neck-proprioceptive, pursuit and retinal slip signals. The duration of this adaptation period was 40 min. A significant gain increase and phase modulation in the compensatory direction were observed in four out of eight subjects after exposing them to neck-proprioceptive stimulation, while pursuing a spot moving in-phase with their trunk. In contrast, staring at the rotating optokinetic pattern or fixating at a stationary spot, while being subjected to combined cervical and optokinetic stimulation, failed to result in any significant modification of the subjects' COR gain and phase. Conceivably, the contribution of the pursuit system was greatly reduced in the paradigm using optokinetic stimulation, while full engagement of retinal slip signals, in the absence of any pursuit contribution, was obtained in the latter adaptation paradigm. These results indicate that motor responses of target tracking rather than simply sensory signals of retinal slip may represent the 'error signal' modifying the COR in humans.

Adaptation, Physiological↗

[Meridian photopic and mesopic color perimetry in normal, young and presbyopic subjects].

The authors report their results of static color perimetry performed with the Harms perimeter. Photopic testing was performed among 10 young normal subjects and then with 10 presbyopes with otherwise unremarkable ocular examinations. Mesopic testing was done with 9 young subjects. Three thresholds of perception were stated: achromatic, minimally colored, and chromatic. Using photopic testing, red perception was far more sensitive in central vision, and the inverse was found in peripheral vision. Tritanomaly exists in the fovea, and at 15 degrees nasal to the fovea, the 3 color curves cross. In presbyopia, age is responsible for decreased sensation of red and green compared to white, and, all color perception disappears beyond the blind spot. The decrease in sensitivity for blue is even more significant realising a foveal tritanopia. At a lower luminance level, mesopic testing revealed an achromatic threshold for green and blue with central lowering of sensitivity. Deductions are made concerning the anatomo-physiologic mechanisms involved.

Adaptation, Ocular↗

Adaptations and deficits in the vestibulo-ocular reflex after sixth nerve palsy.

PURPOSE: The effects of paralytic strabismus on the vestibulo-ocular reflex (VOR) have not been systematically investigated in humans. The purpose of this study was to analyze the VOR in patients with unilateral peripheral sixth nerve palsy. METHODS: Twenty-one patients with unilateral peripheral sixth nerve palsy (6 severe, 7 moderate, 8 mild) and 15 normal subjects were studied. Subjects made sinusoidal +/-10 degrees head-on-body rotations in yaw and pitch at approximately 0.5 and 2 Hz, and in roll at approximately 0.5, 1, and 2 Hz. Eye movement recordings were obtained using magnetic scleral search coils in each eye in darkness and during monocular viewing in light. Static torsional VOR gains, defined as change in torsional eye position divided by change in head position during sustained head roll, were also measured. RESULTS: In all patients, horizontal VOR gains in darkness were decreased in the paretic eye in both abduction and adduction, but remained normal in the nonparetic eye in both directions. In light, horizontal visually enhanced VOR (VVOR) gains were normal in both eyes in moderate and mild palsy. In severe palsy, horizontal VVOR gains remained low in the paretic eye during viewing with either eye, whereas those in the nonparetic eye were higher than normal when the paretic eye viewed. Vertical VOR and VVOR were normal, but dynamic and static torsional VOR and VVOR gains were reduced in both eyes in all patients. CONCLUSIONS: In darkness, horizontal VOR gains were reduced during abduction of the paretic eye in all patients, as anticipated in sixth nerve palsy. Gains were also reduced during adduction of the paretic eye, suggesting that innervation to the medial rectus has changed. After severe palsy, vision did not increase abducting or adducting horizontal VVOR gains to normal in the paretic eye, but caused secondary increase in VVOR gains to values above unity in the nonparetic eye, when the paretic eye fixated. In mild and moderate palsy, vision enhanced the VOR in the paretic eye but caused no change in the nonparetic eye, suggesting a monocular readjustment of innervation selectively to the paretic eye. Vertical VOR and VVOR gains were normal, indicating that the lateral rectus did not have significant vertical actions through the excursions that we tested (+/-10 degrees ). Reduced torsional VOR gains in the paretic eye can be explained by the esotropia in sixth nerve palsy. Torsional VOR gain normally varies with vergence. We attribute the reduced torsional gains in the paretic eye to the mechanism that normally lowers it during convergence. The low torsional gains in the nonparetic eye may be an adaptation to reduce torsional disparity between the two eyes.

Abducens Nerve Diseases↗

The tau mutation shortens the period of rhythmic photoreceptor outer segment disk shedding in the hamster.

The outer segments of vertebrate retinal photoreceptors undergo periodic shedding of membrane from their distal tips. This circadian rhythm of disk shedding persists with a period of about 24 h in the absence of external time cues. A circadian oscillator controlling photoreceptor disk shedding may exist in the eye, but in addition, the circadian clock in the hypothalamic suprachiasmatic nucleus (SCN) may also influence ocular rhythms including that of disk shedding. The tau mutation directly affects the SCN, and shortens the period of locomotor activity from 24 h in wild-type hamsters to 20 h in homozygous mutants. Here we show that homozygous tau-mutant hamsters in a 20-h light/dark cycle exhibit a 20-h oscillation in the rate of disk shedding, with peak phagosome numbers in the retinal pigmented epithelium occurring just after light onset. The numbers of phagosomes are significantly elevated from mid-dark levels prior to light onset, indicating that the disk shedding cycle anticipates dawn. Under conditions of constant darkness, the disk shedding rhythm in tau-mutant hamsters persists with a period of approximately 20 h. These results indicate that a rhythm of retinal photoreceptor outer segment disk shedding exists in the hamster eye, and that the period of this rhythm is shortened by the tau mutation.

Adaptation, Ocular↗

Role of impression cytology during hypovitaminosis A.

AIMS: Evaluation of the morphological damage to the ocular surface of patients operated for biliopancreatic diversion for pathological obesity and the correlation of impression cytology with vitamin A plasma levels, adaptometry, and other general variables. METHODS: 48 patients (15 males, 33 females, age range 21-73) and 34 normal subjects were examined with fluorescein and rose bengal, a plasma dose of vitamin A, and adaptometry. The results of the various tests were subdivided into three levels (0 = normal, 1 = moderately altered, 2 = seriously altered). The impression cytology and adaptometry results were correlated with vitamin A levels and other patient data (age, nutritional condition, time since operation, percentage weight loss). All the examinations were repeated after intramuscular therapy with vitamin A. RESULTS: Corneoconjunctival alterations visible with fluorescein and rose bengal staining were present in 67.7% of cases, impression cytology alterations in 93.7%, adaptometric alterations in 82.2%; vitamin A plasma levels were below normal in 95.8% of cases. After the therapy with vitamin A a significant reduction was found for every examination. The correlation between impression cytology and adaptometry and vitamin A plasma levels and between corneoconjunctival alterations and vitamin A plasma levels was significant. There was no significant correlation between impression cytology and nutritional condition, age time since operation, and percentage weight loss. CONCLUSION: These results show impression cytology is a specific indicator for hypovitaminosis A because it is not influenced by other factors related to the general condition of the patient. Many patients with hypovitaminosis A not demonstrating ocular symptoms of changes visible with fluorescein and rose bengal showed alterations with impression cytology.

Adaptation, Ocular↗

Throwing accuracy during prism adaptation: male advantage for throwing accuracy is independent of prism adaptation rate.

Previous studies have found that men are more accurate at throwing an object at a target than are women, independent of experience. However, these studies' results are based on average scores from multiple trials. As such, it is unknown whether the male advantage results from superior throwing accuracy or from a superior ability to calibrate subsequent throws. This study examined whether men can calibrate repeated throws more quickly and accurately than women, 25 men and 30 women were required to throw velcro-covered balls at a carpet-covered target, both with and without 10-diopter prism lenses. Participants had multiple trials in both conditions. Analyses examined whether there was a sex difference in the rate of adaptation to the prism lenses (as indicated by calibration of subsequent throws), instead of simply averaging all throwing accuracy scores and looking for an overall sex difference. Men threw the balls significantly more accurately than women, both with and without the prism lenses. However, there was no significant sex difference found on the rate of prism adaptation, as measured by improvement across the trials, i.e., calibration. Although men were more accurate at throwing balls overall, there was no sex difference in calibration of subsequent throws in adapting to the prism lenses, therefore indicating that the male advantage in throwing accuracy does not result from superior ability to calibrate subsequent throws but rather from superior throwing accuracy overall.

Accommodation, Ocular↗