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Method to protect rabbit eyes and reduce potential stress from eye irritation or injury associated with exposure to vapors and particulates in inhalation studies.

Many pharmaceuticals are administered to children and adults as sprays provided in nebulizers or metered-dose inhalers. Stress associated with possible eye irritation and injury attributable to exposure to vapors and particulates during the required safety testing procedures of such medicines is a potential confounding factor in these studies. Reducing stress and the potential changes associated with stress is particularly important in safety studies involving pregnant animals because maternal stress has been known to be associated with adverse outcomes for the offspring. Training and acclimating rabbits to wearing modified pediatric swim goggles during exposure to vapors and aerosol particles provides a simple, inexpensive method to reduce or eliminate potential stress from eye irritation.

Administration, Inhalation↗

Analysis of IL-6 levels in human vitreous fluid obtained from uveitis patients, patients with proliferative intraocular disorders and eye bank eyes.

Several studies suggest a role for IL-6 in the pathogenesis of uveitis. Earlier we have shown that aqueous humour obtained from patients with uveitis contained raised levels of IL-6. In the study described here we investigated the IL-6 levels in vitreous fluid samples obtained from 75 uveitis patients with different uveitis entities. Vitreous samples from 14 patients with proliferative intraocular disorders (PID) and 29 eye bank eyes were used as controls. All the samples were tested in the IL-6 B9 bioassay as well as in a sensitive ELISA for IL-6. Raised IL-6 levels were detected in the vitreous fluid of uveitis patients as well as patients with PID, implicating IL-6 as a common inflammatory mediator. The highest mean level of IL-6 was found in the vitreous fluid of patients with acute retinal necrosis. The mean IL-6 levels measured by the ELISA were higher compared to the levels measured by the B9 bioassay. This may be caused by the presence of B9 bioassay inhibitory factors in the vitreous fluid of these patients.

Biological Assay↗

A histological study of the eye lesions in 12 leprosy patients with tuberculoid lesion in 4 eyes.

The histological reactions in 12 eyes of 12 leprosy patients were studied (5 BT, 1 BB, 1 BL and 5 LL). Granuloma lesions composed of epithelioid cells, Langerhans giant cells, macrophages and lymphocytes were found in various intraocular tissues, e.g. cornea, sclera, iris, ciliary body or retina in 4 patients (1 BT and 3 LL). Of the 3 LL patients, according to the records, 2 were cured and in the other patient the outcome of the treatment was not mentioned. In view of the finding of the granulomatous lesions in the clinically cured patients and tuberculoid granuloma in the intraocular tissues in the LL patients, could there be some peculiarities in the intraocular sites? Or perhaps the tuberculoid reaction is just a manifestation of an upgrading reaction? More examinations on human leprosy eye specimens will be needed to answer these questions.

Adult↗

An eye for an eye. A simplified model for teaching.

We developed an easily constructed, inexpensive eye model that consists of a Styrofoam head carved out to house a slide holder, a wide-angle, clinical photographic fundus slide, a plastic face, and an anatomically correct eye. The model can be used by students and residents to learn direct and indirect ophthalmoscopy, fundus photography, and laser photocoagulation. This model gives students and residents a realistic learning experience without inconveniencing or endangering patients.

Eye↗

Microvasculature of the avian eye: studies on the eye of the duckling with microcorrosion casting, scanning electron microscopy, and stereology.

The microvasculature of the eye of the duckling was studied with microcorrosion casting, scanning electron microscopy, and stereology. Most blood to the eyeball first passes through the arterial ophthalmic rete mirabile, a complex of small arteries which intermixes with a similar complex of veins (venous ophthalmic rete mirabile) at the ventrotemporal angle of the eye. The present study reveals the ultrastructural anatomy and the compact, three-dimensional arrangement of vessels in this rete, which had been shown by previous investigators to function as a countercurrent heat exchanger. Vessels from this rete include the supraorbital and infraorbital arteries, which supply the eyeball anteriorly, and the ophthalmotemporal artery, which supplies the eyeball posteriorly. The internal ophthalmic and ethmoidal arteries, branches of the cerebral carotid artery, anastomose with the ophthalmotemporal artery posteriorly. Blood is distributed to the eyeball anteriorly by two ring arteries: the iridial ring artery, which circumscribes the iris and which receives blood from the long ciliary and infraorbital arteries; and the more peripheral, ciliary ring artery, which receives blood mostly from the infraorbital and ethmoidal arteries. Within the iris is a dense, freely anastomosing bed of capillaries which extends to the edge of the pupil and then loops back beneath the ciliary body. The vasculature of the ciliary body consists of radially arranged plates of anastomosing capillaries of irregular bore which mimic the contours of that organ, but permit changes in pupil diameter. The present study demonstrates the three-dimensional anatomy of the very dense capillary net of the choriocapillaris deep to the retina and the capillary mass of the pecten, and thus supports the finding of earlier investigators that nutrients diffusing from these structures nourish the avascular retina. The pecten consists of a pleated sheet of freely anastomosing capillaries which protrudes into the vitreous body from near the optic nerve. The choriocapillaris and the pecten are supplied by branches of the ophthalmotemporal artery: the former by numerous short posterior ciliary arteries, the latter by two or three arteries which further divide into one or two smaller vessels for each of its folds. Veins of the choroid layer at the periphery of the anterior surface of the eyeball, and to some extent on its lateral walls, are revealed by the corrosion-casting technique as unusual, flattened vessels of large caliber which lie in closely spaced parallel arrays. The large surface area thus created may function in heat dissipation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Visual defects in the uninjured eye of patients with unilateral eye injury.

We have examined the electroretinographic responses, the psychophysically determined course of dark adaptation and/or the scotopic and photopic (static) perimetric profile of the uninjured eyes of 11 patients with unilateral intraocular foreign bodies. Most of the patients showed subnormal ERG amplitudes over a range of light intensities, and subnormal light sensitivity in isolated retinal areas. The data suggest that eyes not directly injured by a unilateral traumatic ocular episode may show visual defects.

Adolescent↗

Eye movement disorders after frontal eye field lesions in humans.

Eye movements were recorded electro-oculographically in three patients with a small ischemic lesion affecting the left frontal eye field (FEF) and in 12 control subjects. Reflexive visually guided saccades (gap and overlap tasks), antisaccades, predictive saccades, memory-guided saccades, smooth pursuit and optokinetic nystagmus (OKN) were studied in the three patients. Staircase saccades and double step saccades were also studied in one of the three patients. For both leftward and rightward saccades, latency in the overlap task (but not in the gap task) and that of correct antisaccades and of memory-guided saccades was significantly increased, compared with the results of controls. There was a significant decrease in the amplitude gain of all rightward saccades programmed using retinotopic coordinates (gap and overlap tasks, predictive and memory-guided saccades), whereas the amplitude gain of corresponding leftward saccades was preserved. Such an asymmetry between leftward and rightward saccades was significant. In the staircase paradigm as well as for the first saccade in the double step paradigm (with the use of retinotopic coordinates in both cases), the amplitude gain of rightward saccades was also significantly lower than that of leftward saccades. Moreover, in the double step paradigm, the amplitude gain of the first rightward saccade was significantly lower than that of the second rightward saccade (programmed using extraretinal signals), which was preserved. The percentage of errors in the antisaccade task did not differ significantly from that of normal subjects. In the predictive saccade paradigm, the percentage of predictive rightward saccades was significantly decreased. The left smooth pursuit gain for all tested velocities, the right smooth pursuit gain for higher velocities, and the left OKN gain were significantly decreased. The results show, for the first time in humans, that the FEF plays an important role in (1) the disengagement from central fixation, (2) the control of contralateral saccades programmed using retinotopic coordinates, (3) saccade prediction and (4) the control of smooth pursuit and OKN, mainly ipsilaterally. In contrast, the left FEF did not appear to be crucial for the control of the only type of saccades programmed using extraretinal signals studied here.

Brain↗

The dominant Drop eye mutations of Drosophila melanogaster define two loci implicated in normal eye development.

The three existing dominant gain-of-function Drop alleles, Dr1, DrMio and DrWe, previously assumed to define a single locus, severely disrupt eye development. Genetic analysis of ethylmethanesulphonate (EMS) and irradiation-induced revertants revealed that the Drop mutations define two loci: the Drop locus, which is defined by the Dr1 and DrMio mutants, and a separate locus defined by the DrWe mutation, which has been renamed Wedge. The majority of the Dr1 and DrMio revertants are embryonic lethal in trans, mutant embryos exhibiting trachea that fail to join the Filzkörper, thus revealing a role for the Drop gene in embryogenesis. Clonal analysis of lethal revertant alleles suggests a role for both genes in eye development. In the Drop homozygous mutant clones, the outer photoreceptor cells R1-R6 develop aberrantly. Wedge, however, is not required by the developing photoreceptor cells but its absence does disrupt normal ommatidial alignment. Although the Drop and nearby string loci were shown to be genetically distinct, both Dr1 and DrMio were found to interact in trans with lesions at the string locus, causing loss and derangement of bristles and loss of neuromuscular coordination.

Alleles↗

Altered secretion of kidney lysosomal enzymes in the mouse pigment mutants ruby-eye, ruby-eye-2-J, and maroon.

Melanosomes and lysosomes share structural and biosynthetic properties. Three mouse pigment mutants, ruby-eye, ruby-eye-2-J, and maroon, have abnormally high concentrations of kidney lysosomal enzymes. concentrations of kidney nonlysosomal enzymes and of liver and serum lysosomal enzymes are normal. By light microscopy the mutants have normal kidney lysosome morphology. It does not appear that the mutant genes cause an increased rate of production of lysosomes since the increased kidney beta-glucuronidase concentration is not accompanied by a corresponding increase in rate of synthesis. The common defect in all mutants is a decreased rate of secretion of lysosomal enzymes from kidney into urine. Eight mouse pigment mutants are not known which affect both melanosome and lysosome function. They should serve as useful models for the study of the biogenesis, structure, and processing of these and other subcellular organelles.

Animals↗

Three-dimensional vestibular eye and head reflexes of the chameleon: characteristics of gain and phase and effects of eye position on orientation of ocular rotation axes during stimulation in yaw direction.

We investigated gaze-stabilizing reflexes in the chameleon using the three-dimensional search-coil technique. Animals were rotated sinusoidally around an earth-vertical axis under head-fixed and head-free conditions, in the dark and in the light. Gain, phase and the influence of eye position on vestibulo-ocular reflex rotation axes were studied. During head-restrained stimulation in the dark, vestibulo-ocular reflex gaze gains were low (0.1-0.3) and phase lead decreased with increasing frequencies (from 100 degrees at 0.04 Hz to < 30 degrees at 1 Hz). Gaze gains were larger during stimulation in the light (0.1-0.8) with a smaller phase lead (< 30 degrees) and were close to unity during the head-free conditions (around 0.6 in the dark, around 0.8 in the light) with small phase leads. These results confirm earlier findings that chameleons have a low vestibulo-ocular reflex gain during head-fixed conditions and stimulation in the dark and higher gains during head-free stimulation in the light. Vestibulo-ocular reflex eye rotation axes were roughly aligned with the head's rotation axis and did not systematically tilt when the animals were looking eccentrically, up- or downward (as predicted by Listing's Law). Therefore, vestibulo-ocular reflex responses in the chameleon follow a strategy, which optimally stabilizes the entire retinal images, a result previously found in non-human primates.

Adaptation, Physiological↗

Geometric optics of trilobite eyes: a theoretical study of the shape of the aspherical interface in the cornea of schizochroal eyes of phacopid trilobites.

A general method is given to determine theoretically the shape of the aspherical interface that eliminates spherical aberration in an optionally shaped thick lens. The theory is applied to trilobite eyes. On the basis of the geometric optical method presented, the refractive indices and focal length of the original corneal lenses of trilobites can be determined. The shape of the aspherical interface in the cornea of some phacopid trilobites with schizochroal eyes is investigated. The theoretical aspherical interfaces agree well with the real ones.

Animals↗

Early unilateral eye removal produces a regional gradient in soma sizes in the uncrossed projection from the remaining eye.

Early unilateral eye removal reduces natural cell death within the population of ipsilaterally projecting ganglion cells in the remaining eye. Here it is shown that there is a gradient in the soma sizes of cells which survive as a consequence of this manipulation. The additional ipsilateral projection from the far temporal retina arises mainly from cells with medium-to-large somas. Those located on the nasal side of the optic disk have small somas, while those located between the optic disk and the naso-temporal division arise from predominantly small cells whose soma sizes are intermediate between those which are located in the more nasal and more temporal regions.

Animals↗

New endoscopic technique to analyze various modern specialized intraocular lenses in research eyes and human eyes obtained postmortem.

PURPOSE: To describe a new modification of the Miyake-Apple posterior video photographic technique and its 2 variations. We have developed a new endoscopic technique that is especially amenable for observation of modern specialized intraocular lenses (IOLs). DESIGN: Laboratory study. PARTICIPANT: Three cadaver eyes obtained postmortem. METHODS: Human eyes obtained postmortem were prepared according to our modified preparation technique used for analyses of whole globes. An intraocular endoscope was utilized to demonstrate all aspects of the interior of an experimentally implanted IOL, with specialized reference to anterior segment structures, obtaining posterior, oblique, and side view images. MAIN OUTCOME MEASURES: Different interior dynamic views of the anterior segment structures before and after implantation of an IOL. RESULTS: High-magnification images of different intraocular structures both before and after device insertion as well as the device itself were obtained. Oblique and side view images from different locations were also available and informative. These images helped to create a 3-dimensional view of these objects and their relations to the surrounding structures. CONCLUSION: The combination of the intraocular endoscope with the closed-system technique is a useful addition to our 3 previously described techniques: (1) the original Miyake-Apple posterior video/photograph technique and the (2) closed system and (3) side/oblique view (keyhole technique) modifications.

Anterior Eye Segment↗

Reconstituted human corneal epithelium: a new alternative to the Draize eye test for the assessment of the eye irritation potential of chemicals and cosmetic products.

The aim of this study was to evaluate the interest of a new three-dimensional epithelial model cultivated from human corneal cells to replace animal testing in the assessment of eye tolerance. To this end, 65 formulated cosmetic products and 36 chemicals were tested by means of this in vitro model using a simplified toxicokinetic approach. The chemicals were selected from the ECETOC data bank and the EC/HO International validation study list. Very satisfactory results were obtained in terms of concordance with the Draize test data for the formulated cosmetic products. Moreover, the response of the corneal model appeared predictive of human ocular response clinically observed by ophthalmologists. The in vitro scores for the chemicals tested strongly correlated with their respective scores in vivo. For all the compounds tested, the response of the corneal model to irritants was similar regardless of their chemical structure, suggesting a good robustness of the prediction model proposed. We concluded that this new three-dimensional epithelial model, developed from human corneal cells, could be promising for the prediction of eye irritation induced by chemicals and complex formulated products, and that these two types of materials should be tested using a similar protocol. A simple shortening of the exposure period was required for the chemicals assumed to be more aggressively irritant to the epithelial tissues than the cosmetic formulae.

Animal Testing Alternatives↗

Use of microbubble ultrasound contrast agent to demonstrate the iris valve effect in human eye bank eyes.

PURPOSE: To demonstrate that the interface between the normal iris and the lens surface functions as a flap valve. METHOD: Microbubble ultrasound contrast agent was injected into the anterior and posterior chambers of human eye bank eyes and the distribution of contrast imaged with high-frequency ultrasound. RESULTS: Contrast agent did not enter the posterior chamber when injected into the anterior chamber, but contrast agent injected into the posterior chamber easily flowed into the anterior chamber. CONCLUSIONS: The iris-lens interface normally functions as a flap valve, preventing retrograde flow from the anterior to the posterior chamber. A temporary increase in anterior chamber pressure thus results in iris concavity in pigmentary dispersion syndrome.

Adult↗

The organization of rapid eye movement activity during rapid eye movement sleep is impaired in the elderly.

Rapid eye movement activity (REMA) during rapid eye movement activity (REM) sleep was studied in eight elderly subjects and six young adults as a control group. Beyond global quantitative features (REMA density), we evaluated the organizational aspects of REMA, that is its occurrence in burst mode, still largely unknown in the aged. REMA density in the elderly is not significantly different than that of young adults. By contrast, the duration of REMA bursts is reduced in the elderly, as well as the 'burst state-to-burst-state' probability, i.e. the probability for successive inter-REMA time intervals to be part of the same REMA burst. These results show that global aspects of the quantitative features of REMA are preserved in the elderly, whereas their organizational aspects are impaired. These data are consistent with the hypothesis that aging is associated with a difficulty in maintaining physiological processes over time.

Adult↗