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Determination of the intra- and interlaboratory reproducibility of the low volume eye test and its statistical relationship to the Draize eye test.

The reproducibility of toxicologic test methods, including alternative tests, is a key scientific and regulatory concern. In the present work, historic rabbit eye irritation data were used to determine the intra- and interlaboratory reproducibility of the low volume eye test (LVET). The standard Draize eye irritation test was used as the basis for comparison. The LVET and Draize tests had similar degrees of intra- and interlaboratory reproducibility as determined by examination of their coefficients of variation, although the variability in LVET results was directionally lower. Results from 70 parallel Draize and LVET tests indicated a strong positive association between results from the two tests, for corneal, iridial, conjunctival, and maximum average scores (MAS). Correlation coefficients were 0.60, 0.73, 0.69, and 0.73, respectively (P </= 0.0001). The linear relationship between LVET and Draize MAS values was examined by regression analysis and found to follow the relationship LVET MAS = 0.522 (Draize MAS). Thus, the LVET is at least as reproducible as the Draize test and gives responses that are (linearly) correlated to the Draize. The previous findings that the LVET is more predictive of human eye responses than the Draize test lends additional support for its use as a refined alternative to the Draize test.

Alcohols↗

Frontal eye field lesions impair predictive and visually-guided pursuit eye movements.

The study initially explored the frontal eye field's (FEF) control of predictive eye movements, i.e., eye movements driven by previous rather than current sensory signals. Five monkeys were trained to pursue horizontal target motion, including sinusoidal targets and "random-walk" targets which sometimes deviated from a sine motion. Some subjects also tracked other target trajectories and optokinetic motion. FEF ablations or cold lesions impaired predictive pursuit, but also degraded visually guided foveal pursuit of all targets. Unilateral lesions impaired pursuit of targets moving in both horizontal orbital fields and in both directions of movement. Saccadic estimates of target motion were generally accurate. The slow-phase velocity of optokinetic pursuit (collected after 54 s of OKN) also appeared normal. Pursuit recovered over 1-3 weeks after surgery but the deficits were then reinstated by removal of FEF in the other hemisphere. Thereafter, a slight deficit persisted for up to 10 weeks of observation in two subjects. The pattern of symptoms suggests that FEF lies subsequent to parietal area MST and prior to the pontine nuclei in controlling pursuit eye movements.

Animals↗

Dust exposure, eye redness, eye cytology and mucous membrane irritation in a tobacco industry.

In a study of 75 workers employed in a tobacco factory producing cheroots we measured cellular contents of tear fluid, redness of eyes, discomfort, total (0-5.7 mg/m3) and respirable dust in the breathing zone and total ambient dust by stationary sampling (0.08-1.0 mg/m3). A matched group of 50 office workers in a telephone company (total ambient dust concentration between 0.08-0.13 mg/m3) was similarly examined as referents. We found a difference between the two companies with regard to cell counts, with tobacco workers having the largest numbers except for lymphocytes. Among tobacco workers we furthermore found that the number of cuboidal and columnar epithelial cells increased during the day. The increase of cuboidal cells, however, occurred mainly in a small group of tobacco workers exposed to the highest concentrations of tobacco dust (mean = 1.26 mg/m3). No difference in the sensation of eye irritation was found between companies, but increased irritation in the morning was associated with increased exposure to total dust during the workshift among tobacco workers. A dose-dependent difference in photographically measured eye redness was found among the tobacco workers. It could not be explained by differences in tobacco smoking, sex, age, sleeping habits or use of glasses. Irritation of lips and upper airways as reported by questionnaire were more common in tobacco workers than in referents. In conclusion the tobacco workers, more often than the referents, had complaints and objective changes in the mucous membranes of the eyes. These may be related to tobacco dust exposure.

Adult↗

Concurrence of mouthing movement and rapid eye movement/non-rapid eye movement phases with advance in gestation of the human fetus.

To evaluate whether mouthing movement in the human fetus is related to advance in gestational age and whether such movement is concurrent with rapid eye movement or non-rapid eye movement phases, 26 fetuses from 28 to 41 weeks' gestation were observed for 60 continuous minutes with real-time ultrasonography. It was evident that regular mouthing movement every 300 to 600 msec concurred with the non-rapid eye movement period, from 35 weeks' gestation to term. Random mouthing movements that occurred at a wide range of intervals from 300 msec to approximately 525 seconds were observed predominantly during the rapid eye movement period and were unrelated to advance in gestational age. These observations were discussed in relation to biologic implications.

Eye Movements↗

Saccades induced by stimulation of the frontal eye fields: interaction with voluntary and reflexive eye movements.

Saccadic eye movements were evoked in alert monkeys by electrical stimulation of the frontal eye fields (FEF). The interaction of FEF movements with voluntary saccades, pursuit, and vestibular nystagmus (VN) was examined. An FEF saccade in one direction could be evoked as little as 10 msec after the onset of a natural rapid movement (saccade, fast phase of VN) in the opposite direction. Thus, refractory periods between similar eye movements are directionally specific. The frequency of evoked FEF saccades following natural slow movements (pursuit, slow phase of VN) in either direction was reduced as though saccade thresholds were elevated. The FEF appears capable of modulating any ongoing eye movement.

Animals↗

Eye movement control during reading: I. The location of initial eye fixations on words.

Sixty-six college students read two chapters from a contemporary novel while their eye movements were monitored. The eye movement data were analyzed to identify factors that influence the location of a reader's initial eye fixation on a word. When the data were partitioned according to the location of the prior fixation (i.e. launch site), the distribution of fixation locations on the word (i.e. landing site distribution) was highly constrained, normal in shape, and not influenced by word length. The locations of initial fixations on words can be accounted for on the basis of five principles of perceptuo-oculomotor control: a word-object has a specific functional target location, a saccadic range error occurs that produces a systematic deviation of landing sites from the functional target location, the saccadic range error is reduced somewhat for saccades that follow longer eye fixations, there exists perceptuo-oculomotor variability that is a second, nonsystematic source of variation in landing sites, and the perceptuo-oculomotor variability increases with distance of the launch site from the target.

Eye Movements↗

Contribution of eye muscle proprioception to velocity-response characteristics of eye movements: involvement of the cerebellar flocculus.

The vestibulo-ocular reflex (VOR) and optokinetic nystagmus (OKN) were examined in alert pigmented rabbits following interruption of proprioceptive afferents from the extraocular muscles in one eye by surgical section of the ophthalmic branch of the trigeminal nerve (V1 nerve). Deficits were mainly produced in movement dynamics of the ipsilateral eye including reduction of (1) the VOR gain at a high frequency of head rotation, (2) the OKN gain and (3) the velocity of quick eye movements in the OKN. In some of the rabbits examined, the cerebellar flocculus was lesioned by local injection of kainic acid before severance of the V1 nerve. No significant additional reductions of VOR or OKN gains were produced by V1 nerve section in the flocculus-lesioned rabbits. These results suggest that proprioceptive signals from eye muscles act to improve VOR and OKN dynamics through the neuronal mechanisms involving the cerebellar flocculus.

Animals↗

Pigeon's eyes converge during feeding: evidence for frontal binocular fixation in a lateral-eyed bird.

Pigeons' head-in-space and eye-in-head positions were simultaneously recorded (EOG) in video during feeding. A linear correlation was found between the experimentally measured eye convergence (sum of both EOGs ) and grain parallax (calculated from interocular and eye-to-grain distances). This graded convergence of the eyes on approaching a target is considered evidence of frontal binocular fixation. Since such convergence prevails when the animal is forced to rely on frontal monocular or on lateral vision, a central mechanism controlling frontal fixation in the pigeon must be presupposed .

Animals↗

Regulation of hydrogen peroxide in eye humors. Effect of 3-amino-1H-1,2,4-triazole on catalase and glutathione peroxidase of rabbit eye.

Activities of catalase (H2O2: H2O2 oxidoreductase, EC 1.11.1.6) and GSH peroxidase (GSH: H202 oxidoreductase, EC 1.11.1.9) have been measured in iris, ciliary body, retina, corneal epithelium, corneal endothelium, lens capsule-epithelium and decapsulated lens. 3-Amino-1H-1,2,4-triazole is a specific inhibitor of catalase and a potent cataractogenic agent. We observed marked inhibition of catalase activity in these tissues 1--6 h after the administration of a single intravenous dose of 1 g 3-aminotriazole per kg body weight in rabbit. This was associated with a 2--3-fold increase in the H2O2 concentrations of aqueous humor and vitreous humor. The increased peroxide concentrations were restored to the physiological levels as the catalase activity of eye tissues gradually returned to normal with time after injection. Under the conditions, GSH peroxidase activity of the afore-mentioned eye tissues was unaltered, GSH and protein sulfhydryl of lens were not changed, and ascorbic acid of aqueous humor and vitreous humor was not significantly altered. Based on these findings our conclusion is that catalase of eye tissues regulates the endogenous H2O2 in eye humors to the physiological level. We speculate that H2O2 may be the triggering factor in cataract induced by 3-aminotriazole.

Amitrole↗

Immunolocalization of heat shock proteins in the retina of normal monkey eyes and monkey eyes with laser-induced glaucoma.

PURPOSE: To examine the expression and localization of heat shock proteins (HSPs) in the retinas of normal and experimentally induced primate glaucoma eyes. These proteins are known to be produced in response to a variety of stresses. METHODS: Experimental glaucoma was induced in the right eyes of three adult monkeys by repeated applications of argon laser to the chamber angle. Immunostaining with a panel of antibodies against HSP 90, 70, 60, 47, and 27 was performed on retinal sections prepared from the normal and glaucomatous monkey eyes. RESULTS: The intensity of immunostaining for HSP 90, 60, and 27 was greatly enhanced in the retinas of glaucomatous eyes. Prominent reactivity was observed in the inner retinal layers, especially in the ganglion cell and nerve fiber layers. The staining intensity for HSP 70 was also moderately increased, while immunoreactivity against HSP 47 remained almost unchanged in glaucomatous retinas. Immunostaining against glial fibrillary acidic protein was increased and the immunolabeling pattern appeared to be identical with that of HSP 90 in glaucoma retinas. CONCLUSIONS: The level of HSP 90, 70, 60, and 27 in primate retinas was increased in experimentally induced ocular hypertension. The differences in expression pattern suggest that each HSP may have its unique role in responding to damage or injury related to intraocular pressure elevation.

Animals↗

The cyclopean eye in vision: the new and old data continue to hit you right between the eyes.

We argue against recent claims by Erkelens and van Ee (Vision Res., in press) and by Erkelens (Vision Res. 40 (2000) 2411) that "the concept of the cyclopean eye is em leader always irrelevant as far as vision is concerned" (p. 1157) [corrected] and that "perceived direction during monocular viewing is based on the signals of the viewing eye only" (p. 2411), respectively. In Experiment 1, we presented a pair of small lights on a visual axis and measured the absolute visual direction of the near light with reference to different parts of the face. The near light appeared in front of the bridge of the nose or very near it, contrary to what was expected from Erkelens and van Ee's claim that monocular stimuli are seen in their correct locations. In Experiment 2, we replicated Erkelens' experiments with measurements of phoria and analyses of eye movements. The results confirmed his finding that the cyclopean illusion occurred rarely in the monocular condition, but our phoria and eye movement data provided the basis for a very different interpretation. Our data show that the oculomotor signal in his particular monocular condition was considerably weaker than in his binocular condition; therefore, the rarity of the monocular cyclopean illusion is not surprising. Moreover, since both claims above are based on an over-generalization of the results of Erkelens' study, neither claim is persuasive.

Adult↗

Comparison of the morphologic changes after selective laser trabeculoplasty and argon laser trabeculoplasty in human eye bank eyes.

OBJECTIVE: To compare the histopathologic changes in the human trabecular meshwork (TM) after argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) with a Q-switched, frequency-doubled, neodymium:yttrium-aluminum-garnet laser. DESIGN: Human "in vitro" experimental study. TISSUE AND CONTROLS: Eight human autopsy eyes were obtained within 18 hours of death from persons aged 71 to 78 years. METHODS: The anterior segment of autopsy eyes was isolated, and one half of each trabecular meshwork underwent SLT and the other half ALT. Specimens were evaluated with scanning and transmission electron microscopy. MAIN OUTCOME MEASURES: Structural changes in the TM were detected by scanning electron microscopy, and cellular or intracellular changes were seen with transmission electron microscopy. RESULTS: Evaluation of the TM after ALT revealed crater formation in the uveal meshwork at the junction of the pigmented and nonpigmented TM. Coagulative damage was evident at the base and along the edge of craters, with disruption of the collagen beams, fibrinous exudate, lysis of endothelial cells, and nuclear and cytoplasmic debris. Evaluation of the TM after SLT revealed no evidence of coagulative damage or disruption of the corneoscleral or uveal trabecular beam structure. Minimal evidence of mechanical damage was present after SLT, and the only ultrastructural evidence of laser tissue interaction was cracking of intracytoplasmic pigment granules and disruption of trabecular endothelial cells. CONCLUSIONS: SLT applied "in vitro" to the TM of human eye bank eyes seemed to cause no coagulative damage and less structural damage to the human TM when compared with ALT and, therefore, may be a safer and more repeatable procedure.

Aged↗

A novel Eyes Absent 2 protein is expressed in the human eye.

The Drosophila eyes absent (eya) gene has a role in regulating cell death and/or differentiation and is expressed throughout development. We evaluated the transcripts and proteins encoded by one of the human homologues of Drosophila eya coined Eyes Absent 2 (EYA2). Interestingly, EYA2 was expressed in several neuroblastoma cell lines as four distinct transcripts having alternative 5'-ends, whereas only one EYA2 transcript was expressed in the normal human eye. Due to different translation start sites on the four unique transcripts, two isoforms of EYA2 protein (one previously identified and one novel) could be generated in neuroblastoma cells, but the sole EYA2 transcript expressed in the eye can only encode the novel isoform. Immunoblot analyses suggest that EYA2 may also be post-translationally modified. Finally, the alternative EYA2 transcripts have dissimilar numbers of upstream open reading frames in their 5'-untranslated regions. Therefore, in addition to encoding alternative isoforms of EYA2, regulation of EYA2 expression appears to involve both transcriptional and translational components.

5' Untranslated Regions↗

Air bubble endothelial damage during phacoemulsification in human eye bank eyes: the protective effects of Healon and Viscoat.

Following insertion of either Healon (sodium hyaluronate) or Viscoat (sodium chondroitin sulfate-sodium hyaluronate) into the anterior chamber of human eye bank eyes, a controlled amount of small air bubbles was introduced into the anterior chamber during phacoemulsification. After vital staining, damage to endothelial cells in the central cornea was quantified. Endothelial damage averaged 4.5% in eyes in which no viscoelastic was used (positive control), whereas damage was only 0.4% (P less than .001) in eyes in which a viscoelastic was inserted but no air bubbles were introduced (negative control). Endothelial damage in test specimens using air plus Healon averaged 4.9%. Damage in test specimens using air plus Viscoat averaged 0.3% (P less than .02). As demonstrated by scanning electron microscopy, many areas in the positive controls and in the Healon test specimens were damaged too extensively to quantitate accurately by the method we used. Thus, Viscoat may prevent or lessen damage to the corneal endothelium by small air bubbles during phacoemulsification.

Air↗

Not just pretty eyes: Drosophila eye-colour mutations and lysosomal delivery.

Analysis of Drosophila eye-colour mutations has made seminal contributions to the fields of genetics and biochemistry. Recent findings suggest that a subset of eye-colour genes is crucial for vesicular transport of proteins to pigment granules, specialized lysosomes of eye-pigment cells. Thus, classical work describing more than 85 eye-colour mutations and their genetic interactions offers a remarkable, untapped resource for the genetic analysis of protein delivery to lysosomes.

Animals↗

Topography of supplementary eye field afferents to frontal eye field in macaque: implications for mapping between saccade coordinate systems.

Two discrete areas in frontal cortex are involved in generating saccadic eye movements--the frontal eye field (FEF) and the supplementary eye field (SEF). Whereas FEF represents saccades in a topographic retinotopic map, recent evidence indicates that saccades may be represented craniotopically in SEF. To further investigate the relationship between these areas, the topographic organization of afferents to FEF from SEF in Macaca mulatta was examined by placing injections of distinct retrograde tracers into different parts of FEF that represented saccades of different amplitudes. Central FEF (lateral area 8A), which represents saccades of intermediate amplitudes, received afferents from a larger portion of SEF than did lateral FEF (area 45), which represents shorter saccades, or medial FEF (medial area 8A), which represents the longest saccades in addition to pinna movements. Moreover, in every case the zone in SEF that innervated lateral FEF (area 45) also projected to medial FEF (area 8A). In one case, a zone in rostral SEF projected to both lateral area 8A from which eye movements were evoked by microstimulation as well as medial area 8A from which pinna movements were elicited by microstimulation. This pattern of afferent convergence and divergence from SEF onto the retinotopic saccade map in FEF is indicative of some sort of map transformation between SEF and FEF. Such a transformation would be necessary to interconnect a topographic craniotopic saccade representation in SEF with a topographic retinotopic saccade representation in FEF.

Afferent Pathways↗

[The language of the eye. Expressive functions of the eye].

The eye is an effective and frequently used means of communication. Innate ocular signals express basic feelings and are identical all over the world. Acquired signals depend on cultural status, intelligence, and education. Eye diseases and orbital anomalies can provide misleading impressions, because they can be confused with true eye signals or because they can trigger innate reaction mechanisms. Surgically, the eye can often be improved as an emittor of signals; the message, however, has to be composed by the patient.

Emotions↗

Eye position and eye velocity integrators reside in separate brainstem nuclei.

Two types of central nervous system integrators are critical for oculomotor performance. The first integrates velocity commands to create position signals that hold fixation of the eye. The second stores relative velocity of the head and visual surround to stabilize gaze both during and after the occurrence of continuous self and world motion. We have used recordings from single neurons to establish that the "position" and "velocity" integrators for horizontal eye movement occupy adjacent, but nonoverlapping, locations in the goldfish medulla. Lidocaine inactivation of each integrator results in the eye movement deficits expected if horizontal eye position and velocity signals are processed separately. These observations also indicate that each brainstem compartment generates and stores these signals. Consequently, each integrator exhibits functional autonomy. Therefore, we propose that the intrinsic electrophysiological properties of the constituent neurons in each brainstem subnucleus may be sufficient for producing integrator rhythmicity.

Animals↗