In vitro induction and transplantation of eye during early Xenopus development

A vertebrate eye was induced via a series of coordinated inductive interactions. Here, we describe a novel in vitro system to induce eye formation at high frequency using Xenopus early gastrulae. The eye formed in vitro is morphologically similar to the normal eye. When the in vitro eye was transplanted into a stage-33 tadpole, the optic nerve was seen extending from the grafted eye to the tectum of the host brain and the in vitro eye graft was retained after metamorphosis. In addition, we transplanted the eye formed in vitro into a tadpole with both eyes removed. The resultant juvenile frogs could perceive brightness using the grafted eye and thereby control their skin color, suggesting that the eye formed in vitro could function normally.     

Biomechanical modeling of eye trauma for different orbit anthropometries

In military, automotive, and sporting safety, there is concern over eye protection and the effects of facial anthropometry differences on risk of eye injury. The objective of this study is to investigate differences in orbital geometry and analyze their effect on eye impact injury. Clinical measurements of the orbital aperture, brow protrusion angle, eye protrusion, and the eye location within the orbit were used to develop a matrix of simulations. A finite element (FE) model of the orbit was developed from a computed tomography (CT) scan of an average male and transformed to model 27 different anthropometries. Impacts were modeled using an eye model incorporating lagrangian-eulerian fluid flow for the eye, representing a full eye for evaluation of omnidirectional impact and interaction with the orbit. Computational simulations of a Little League (CD25) baseball impact at 30.1m/s were conducted to assess the effect of orbit anthropometry on eye injury metrics. Parameters measured include stress and strain in the corneoscleral shell, internal dynamic eye pressure, and contact forces between the orbit, eye, and baseball. The location of peak stresses and strains was also assessed. Main effects and interaction effects identified in the statistical analysis illustrate the complex relationship between the anthropometric variation and eye response. The results of the study showed that the eye is more protected from impact with smaller orbital apertures, more brow protrusion, and less eye protrusion, provided that the orbital aperture is large enough to deter contact of the eye with the orbit.     

Disconjugated binocular eye movements at onset of multiple sleep latency test in childhood narcolepsy

In four of six subjects with narcolepsy, multiple sleep latency tests-examined disconjugated binocular eye movements were observed in the very beginning of multiple sleep latency test recordings. The eye movements appeared before disappearance of alpha and decrease of chin electromyography. All subjects with disconjugated eye movements had also rapid eye movement sleep without atonia and symptoms of rapid eye movement behavior disorder in their past history. Three of them (all children) had post-vaccination narcolepsy. It is not known whether such eye movements are seen in most narcoleptic subjects or whether they are more common in autoimmune/inflammatory narcolepsy with involvement of the structures that coordinate eye movements.

     

Kinematics of Visually-Guided Eye Movements

One of the hallmarks of an eye movement that follows Listing’s law is the half-angle rule that says that the angular velocity of the eye tilts by half the angle of eccentricity of the line of sight relative to primary eye position. Since all visually-guided eye movements in the regime of far viewing follow Listing’s law (with the head still and upright), the question about its origin is of considerable importance. Here, we provide theoretical and experimental evidence that Listing’s law results from a unique motor strategy that allows minimizing ocular torsion while smoothly tracking objects of interest along any path in visual space. The strategy consists in compounding conventional ocular rotations in meridian planes, that is in horizontal, vertical and oblique directions (which are all torsion-free) with small linear displacements of the eye in the frontal plane. Such compound rotation-displacements of the eye can explain the kinematic paradox that the fixation point may rotate in one plane while the eye rotates in other planes. Its unique signature is the half-angle law in the position domain, which means that the rotation plane of the eye tilts by half-the angle of gaze eccentricity. We show that this law does not readily generalize to the velocity domain of visually-guided eye movements because the angular eye velocity is the sum of two terms, one associated with rotations in meridian planes and one associated with displacements of the eye in the frontal plane. While the first term does not depend on eye position the second term does depend on eye position. We show that compounded rotation - displacements perfectly predict the average smooth kinematics of the eye during steady- state pursuit in both the position and velocity domain.     

Eyeless collaborates with Hedgehog and Decapentaplegic signaling in Drosophila eye induction

eyeless (ey) is a key regulator of the eye development pathway in Drosophila. Ectopic expression of ey can induce the expression of several eye-specification genes (eya, so, and dac) and induce eye formation in multiple locations on the body. However, ey does not induce eye formation everywhere where it is ectopically expressed, suggesting that EY needs to collaborate with additional factors for eye induction. We examined ectopic eye induction by EY in the wing disc and found that eye induction was spatially restricted to the posterior compartment and the anterior-posterior (A/P) compartmental border, suggesting a requirement for both HH and DPP signaling. Although EY in the anterior compartment induced dpp and dac, these were not sufficient for eye induction. Coexpression experiments show that EY needs to collaborate with high level of HH and DPP to induce ectopic eye formation. Ectopic eye formation also requires the activation of an eye-specific enhancer of the endogenous hh gene.     

The "practical mathematics" of recording three-dimensional eye position using scleral coils.

The "gold standard" for recording the three-dimensional rotation of the eye involves placing two coils of wire, embedded in a soft plastic ring, on the sclera of the eye, then placing the subject inside a set of orthogonal oscillating magnetic fields, and using the currents induced in the eye coils to deduce the position of the coil, and hence of the eye, in space. Eye movements are actually eye rotations, which can be described mathematically by a special class of matrices, rotation matrices, or, alternatively, by a rotation vector related to the axis of the rotation. This article deals with the mathematical tools needed to implement the signal processing from such a multifield, dual-coil system and compute the precise rotational movement of the eye. One reason for making such careful measurements is to study an interesting constraint on eye movements, called Listing's law, which expresses ocular torsion, or rotation of the eye about its line of sight, in terms of the direction of gaze. Techniques for experimentally quantitating these constraints are also presented. Following a treatment of the "ideal" case, with coils and eye in perfect alignment, the additional techniques for dealing with various departures from ideality that are almost always encountered experimentally are examined. A final section deals with developing a validation protocol for eye movement analysis techniques using mechanical and computer simulations of eye movements.     

PP2A:B56epsilon is required for eye induction and eye field separation

Eye induction and eye field separation are the earliest events during vertebrate eye development. Both of these processes occur much earlier than the formation of optic vesicles. The insulin-like growth factor (IGF) pathway appears to be essential for eye induction, yet it remains unclear how IGF downstream pathways are involved in eye induction. As a consequence of eye induction, a single eye anlage is specified in the anterior neural plate. Subsequently, this single eye anlage is divided into two symmetric eye fields in response to Sonic Hedgehog (Shh) secreted from the prechordal mesoderm. Here, we report that B56epsilon regulatory subunit of protein phosphatase 2A (PP2A) is involved in Xenopus eye induction and subsequent eye field separation. We provide evidence that B56epsilon is required for the IGF/PI3K/Akt pathway and that interfering with the PI3K/Akt pathway inhibits eye induction. In addition, we show that B56epsilon regulates the Hedgehog (Hh) pathway during eye field separation. Thus, B56epsilon is involved in multiple signaling pathways and plays critical roles during early development.     

Selenium Compound Protects Corneal Epithelium against Oxidative Stress

The ocular surface is strongly affected by oxidative stress, and anti-oxidative systems are maintained in corneal epithelial cells and tear fluid. Dry eye is recognized as an oxidative stress-induced disease. Selenium compound eye drops are expected to be a candidate for the treatment of dry eye. We estimated the efficacy of several selenium compounds in the treatment of dry eye using a dry eye rat model. All of the studied selenium compounds were uptaken into corneal epithelial cells in vitro. However, when the selenium compounds were administered as eye drops in the dry eye rat model, most of the selenium compounds did not show effectiveness except for Se-lactoferrin. Se-lactoferrin is a lactoferrin that we prepared that binds selenium instead of iron. Se-lactoferrin eye drops suppressed the up-regulated expression of heme oxygenase-1, cyclooxygenase-2, matrix metallopeptidase-9, and interleukin-6 and also suppressed 8-OHdG production in the cornea induced by surgical removal of the lacrimal glands. Compared with Se-lactoferrin, apolactoferrin eye drops weakly improved dry eye in high dose. The effect of Se-lactoferrin eye drops on dry eye is possibly due to the effect of selenium and also the effect of apolactoferrin. Se-lactoferrin is a candidate for the treatment of dry eye via regulation of oxidative stress in the corneal epithelium.     

Why do birds sleep with one eye open? Light exposure of the chick embryo as a determinant of monocular sleep.

Together with some aquatic mammals, birds exhibit a unique behavioral and electrophysiological state called "unihemispheric sleep," in which one cerebral hemisphere is awake and the other is sleeping. Slow-wave sleep in one hemisphere is associated with closure of the contralateral eye, while the eye contralateral to the awake hemisphere is open; closure of both eyes, in contrast, is associated with bihemispheric slow-wave sleep or with REM sleep. During the last few days of incubation, the chick's embryo is turned in the egg so that it occludes its left eye, whereas light entering through the shell can stimulate the right eye. Here we show that in the first two days after hatching, chicks coming from eggs incubated in the light prevalently slept with their right eye open, whereas those coming from eggs incubated in the dark prevalently slept with their left eye open. Thus, asymmetric light stimulation in the embryo can modulate the left-right direction of eye opening during post-hatching monocular sleep.     

Cellular and ultrastructural features of the regenerating adult eye in the marine gastropod llyanassa obsoleta

Light and electron microscopic techniques were used to study the cellular and ultrastructural components of the regenerating adult eye of the marine prosobranch gastropod Ilyanassa obsoleta. Behavioral tests were used to determine return of vision in animals with generated eyes. As early as 3 days after removal of the adult eye, the regenerating eye primordium appeared as a pigmented mass of cells that invaginated from the surface epithelium in the area of the wound. Twelve days after eye removal, the regenerating eye was very similar to the postmetamorphic juvenile eye and to the adult eye: It contained a retinal layer, as well as an extracellular lens, cornea, connective tissue capsule, and forming optic nerve; vision had returned. Growth of the eye and its components was linear; size ratios established among forming eye components were maintained during growth. The events of eye regeneration appear to recapitulate embryonic eye formation. The sequence of invagination, pigmentation, and lens, optic nerve, and retinal pattern formation are similar.     

Viral infection of the lungs through the eye

Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.     

Application of 3-Dimensional Printing Technology to Construct an Eye Model for Fundus Viewing Study

Objective

To construct a life-sized eye model using the three-dimensional (3D) printing technology for fundus viewing study of the viewing system.

Methods

We devised our schematic model eye based on Navarro''s eye and redesigned some parameters because of the change of the corneal material and the implantation of intraocular lenses (IOLs). Optical performance of our schematic model eye was compared with Navarro''s schematic eye and other two reported physical model eyes using the ZEMAX optical design software. With computer aided design (CAD) software, we designed the 3D digital model of the main structure of the physical model eye, which was used for three-dimensional (3D) printing. Together with the main printed structure, polymethyl methacrylate(PMMA) aspherical cornea, variable iris, and IOLs were assembled to a physical eye model. Angle scale bars were glued from posterior to periphery of the retina. Then we fabricated other three physical models with different states of ammetropia. Optical parameters of these physical eye models were measured to verify the 3D printing accuracy.

Results

In on-axis calculations, our schematic model eye possessed similar size of spot diagram compared with Navarro''s and Bakaraju''s model eye, much smaller than Arianpour''s model eye. Moreover, the spherical aberration of our schematic eye was much less than other three model eyes. While in off- axis simulation, it possessed a bit higher coma and similar astigmatism, field curvature and distortion. The MTF curves showed that all the model eyes diminished in resolution with increasing field of view, and the diminished tendency of resolution of our physical eye model was similar to the Navarro''s eye. The measured parameters of our eye models with different status of ametropia were in line with the theoretical value.

Conclusions

The schematic eye model we designed can well simulate the optical performance of the human eye, and the fabricated physical one can be used as a tool in fundus range viewing research.     

The effects of simulating a realistic eye model on the eye dose of an adult male undergoing head computed tomography

In head computed tomography, radiation upon the eye lens (as an organ with high radiosensitivity) may cause lenticular opacity and cataracts. Therefore, quantitative dose assessment due to exposure of the eye lens and surrounding tissue is a matter of concern. For this purpose, an accurate eye model with realistic geometry and shape, in which different eye substructures are considered, is needed. To calculate the absorbed radiation dose of visual organs during head computed tomography scans, in this study, an existing sophisticated eye model was inserted at the related location in the head of the reference adult male phantom recommended by the International Commission on Radiological Protection (ICRP). Then absorbed doses and distributions of energy deposition in different parts of this eye model were calculated and compared with those based on a previous simple eye model. All calculations were done using the Monte Carlo code MCNP4C for tube voltages of 80, 100, 120 and 140 kVp. In spite of the similarity of total dose to the eye lens for both eye models, the dose delivered to the sensitive zone, which plays an important role in the induction of cataracts, was on average 3% higher for the sophisticated model as compared to the simple model. By increasing the tube voltage, differences between the total dose to the eye lens between the two phantoms decrease to 1%. Due to this level of agreement, use of the sophisticated eye model for patient dosimetry is not necessary. However, it still helps for an estimation of doses received by different eye substructures separately.     

Eye movements of flatfish for the changes of gravity (II)

In this study, we analysed the eye movements of flatfish for body tilting and compared with that of goldfish. The fish was fixed on the tilting table controlled by computer. The eye movements for body tilting along the different body axis were video-recorded. The vertical and torsional eye rotations were analysed frame by frame. In normal flatfish, vertical eye movement of left eye to leftward tilting was larger than that to rightward tilting. For head up or head down tilting, clear vertical eye movements were observed. On the other hand, torsional eye movements showed similar characteristics as goldfish. These results suggested that sacculus and lagena were important for otolith-ocular eye movements in flatfish.     

After-effects and the integration of patterns of neural activity within a channel

Prolonged inspection of an adapting simulus changes the appearance of a subsequent test stimulus. There are five distinct viewing conditions under which such 'after-effects' may be generated. There are MON-MON (inspect with one eye, same eye), BIN-BIN (inspect with both eyes, test both eyes), BIN-MON (inspect with both eyes, test only one eye), MON-BIN (inspect with one eye, test with both) and TRANSFER (inpect with one eye, test with the other eye). A model based upon the assumption of the linearly additive effects of adaptation generated in 'dominance classes' or cortical units that are driven either by one eye, or the other eye, or by either or both eyes together, is described. This model generates predictions concerning the expected ralative magnitudes of after-effects generated under the five viewing modes described above, and experiments are described that confirm these predictions. The model can be extended to gaenerate predictions about other experimental conditions. A more complex version of the model is consistent with electrophysiologically derived estimates of the proportion of cortical units in each dominance class.     

Drosophila nemo promotes eye specification directed by the retinal determination gene network

Drosophila nemo (nmo) is the founding member of the Nemo-like kinase (Nlk) family of serine-threonine kinases. Previous work has characterized nmo's role in planar cell polarity during ommatidial patterning. Here we examine an earlier role for nmo in eye formation through interactions with the retinal determination gene network (RDGN). nmo is dynamically expressed in second and third instar eye imaginal discs, suggesting additional roles in patterning of the eyes, ocelli, and antennae. We utilized genetic approaches to investigate Nmo's role in determining eye fate. nmo genetically interacts with the retinal determination factors Eyeless (Ey), Eyes Absent (Eya), and Dachshund (Dac). Loss of nmo rescues ey and eya mutant phenotypes, and heterozygosity for eya modifies the nmo eye phenotype. Reducing nmo also rescues small-eye defects induced by misexpression of ey and eya in early eye development. nmo can potentiate RDGN-mediated eye formation in ectopic eye induction assays. Moreover, elevated Nmo alone can respecify presumptive head cells to an eye fate by inducing ectopic expression of dac and eya. Together, our genetic analyses reveal that nmo promotes normal and ectopic eye development directed by the RDGN.     

New determinations of the eye rotation center and criteria for the formation of its membrane in terms of the floating eye model and experimental support of the latter

It is well known that the eye is a phylogenetically stabilized body with rotation properties. The eye has an elastic cover and is filled with uniform fluid. According to the theory of covers and other concepts on the configuration of turning fluid mass we concluded that the eyeball has an elliptic configuration. Classification of the eyeball is here presented with simultaneous studies of the principles of the eye situation. The parallelism between the state and different types of heterophory and orthophory was studied. To determine normal configuration it is necessary to have in mind some principles of achieving advisable correct situation of the eye in orbit. We determined the centre of the eye rotation and showed that it is impossible to situate it out of the geometrical centre of the eyeball. It was pointed out that for adequate perception the rotation centre must be situated on the visual axis. Using the well known theory of floating we experimentally determined that the centre of the eye rotation lies on the level of the floating eye, just on the point of cross of the visual line with the optical axis. It was shown experimentally on the basis of recording the eye movements in the process of eyelid closing that weakening of the eye movements is of gravitational pattern and proceeds under the action of stability forces, which directly indicates the floating state of the eye. For the first time using the model of the floating eye it was possible to show the formation of extraeye vacuum by straining the back wall. This effect can be obtained without any difficulty, if the face is turned down. The role of negative pressure in the formation of the eye ametropy, as well as new conclusions and prognostications about this new model are discussed.     

Mosaic: a position-effect variegation eye-color mutant in the mosquito Anopheles gambiae

The Mosaic (Mos) mutation, isolated in the F1 of 60Co-irradiated mosquitoes, confers variegated eye color to third and fourth instar larvae, pupae, and adults of the mosquito Anopheles gambiae. Mos is recessive in wild pink eye (p+) individuals, but is dominant and confers areas of wild-type pigment in mutant pink eye backgrounds. Mos is located 14.4 cM from pink eye on the X chromosome and is associated with a duplication of division 2B euchromatin that has been inserted into division 6 heterochromatin. Various combinations of Mos, pink eye alleles, and the autosomal mutation red eye were produced. In all cases, the darker pigmented regions of the eye in Mos individuals show the phenotypic interactions expected if the phenotype of those regions is due to expression of a p+ allele. Expression of Mos is suppressed by rearing larvae at 32 degrees C relative to 22 degrees C. All of these characteristics are consistent with Mos being a duplicated wild copy of the pink eye gene undergoing position-effect variegation.