Role In Eye Research Articles

Understanding Selective Refusal of Eye Donation

Corneal transplantation is the most common form of organ transplantation performed globally. However, of all organs, eyes have the highest rate of refusal of donation. This study explored the reasons why individuals decide whether or not to donate corneas. Twenty-one individuals were interviewed who had made a donation decision (13 refused corneal donation and eight consented). Analysis was performed using Grounded Theory. Refusal of corneal donation was related to concerns about disfigurement and the role of eyes in memory and communication. The request for donation therefore raised concerns about a potential adverse change in the ongoing relationship with the deceased, even in death. For those who refused donation, these concerns overshadowed awareness of need or benefit of transplantation. Adjusting the donation message to be more congruent with the real, lived experience of corneal donation may to some extent "prepare" individuals when the donation question is raised.

The Relative Role of Eyes, Eyebrows, and Eye Region in Face Recognition

The Relative Role of Eyes, Eyebrows, and Eye Region in Face Recognition

Visual rehabilitation with keratoprosthesis after tenonplasty as the primary globe-saving procedure for severe ocular chemical injuries

To analyze the outcome (functional and anatomic) of eyes that underwent tenonplasty as the primary globe-saving procedure in severe ocular chemical injuries (grade V-VI Dua's classification). The records of patients who underwent tenonplasty for associated scleral ischemia in severe chemical burns in our institute between October 2005 and June 2011 were analyzed retrospectively. Out of 31 eyes that underwent tenonplasty, 21 belonged to grade V and VI of Dua's classification with diffuse scleral ischemia for which a four-quadrant tenonplasty was performed and only these 21 eyes were included for further analysis. The time to presentation following chemical injury, the need for revision surgeries, the time to complete epithelization, the procedures performed for ocular surface reconstruction and for visual rehabilitation and their outcome, both functional and anatomic, were analyzed. Of the 21 eyes of 13 patients, four were unilateral and nine were bilateral cases of chemical injury. The mean time to presentation following chemical injury was 14.61days. Tenonplasty with amniotic membrane transplantation (AMT) was performed as the primary surgery. Revision tenonplasty was required in six eyes (seven procedures), the mean time to complete epithelization of the ocular surface was 5.4±4.03months. Of the 21 eyes, three lost perception of light following phthisis, evisceration for corneal infection, and uncontrolled glaucoma. Eighteen of 21 eyes were salvaged anatomically, of which ten eyes of 13 patients underwent surgery for visual rehabilitation. Among the unilateral cases, two eyes underwent ex vivo limbal stem cell transplant (LSCT) with or without keratoplasty for further visual rehabilitation. Among the patients with bilateral burns, visual rehabilitative procedure was performed in only one eye. Modified osteo-odonto-keratoprosthesis (MOOKP) was performed in five eyes, Boston type 1 keratoprosthesis in two eyes, and penetrating keratoplasty with keratolimbal allograft with systemic immunosuppression in one eye. One patient with bilateral injury is awaiting Boston keratoprosthesis type 1 for one eye. Of these eight eyes (bilateral injuries), all achieved a BCVA of 20/200 or better over a mean follow-up period of 27.37±14.5months following visual rehabilitative procedure. Tenonplasty has a globe-saving role in eyes with severe chemical injuries with associated scleral ischemia, by accelerating the healing process. Further on, these eyes can undergo visual rehabilitative procedures and our results highlight the feasibility of achieving a good functional outcome following anatomical stability. The role of tenonplasty to salvage the eye in the initial management of chemical injury, the need for multiple surgeries, close follow-up, and monitoring of intraocular pressure prior to and after procedures for visual rehabilitation cannot be underemphasized.

The role of episcleral venous pressure in glaucoma associated with Sturge-Weber syndrome

To evaluate the role of episcleral venous pressure (EVP) in the pathogenesis of glaucoma associated with Sturge-Weber syndrome (SWS). EVPs were determined prospectively using an episcleral venomanometer in 22 eyes of 11 patients aged 8-18 years with SWS with or without glaucoma. Pressure measurements in the glaucomatous eyes of patients with SWS were compared to those of patients with facial port wine marks but no glaucoma and to the contralateral uninvolved eye in both groups. EVP in eyes with glaucoma (mean, 20.9 mm Hg) was significantly higher (P < 0.01) than EVP in contralateral uninvolved eyes (mean, 9.6 mm Hg). In patients with unilateral port wine mark and no glaucoma, EVP was normal for ipsilateral and contralateral eyes (mean, 8.6 mm Hg and 9.6 mm Hg, respectively). Our data support the hypothesis that elevated EVP plays an important role in eyes with SWS glaucoma.

Lack of the ventral anterior homeodomain transcription factor VAX1 leads to induction of a second pituitary

The pituitary gland is an endocrine organ that is developmentally derived from a fold in the oral ectoderm and a juxtaposed fold in the neural ectoderm. Here, we show that the absence of Vax1, a homeodomain transcription factor known for its role in eye and optic chiasm development, causes the rostral oral ectoderm to form an ectopic fold that eventually develops into a separate second pituitary with all the pituitary cell types and neuronal fibers characteristic of the normal pituitary. The induction of the second pituitary is associated with a localized ectopic expression of Fgf10, a gene encoding a growth factor known to recruit oral ectodermal cells into the pituitary. Interestingly, there are rare cases of pituitary duplications in humans that are also associated with optic nerve dysplasia, suggesting that VAX1 might be involved in the pathogenesis of this disorder.

Cloning, localization, and functional expression of the electrogenic Na+ bicarbonate cotransporter (NBCe1) from zebrafish

Mutations in the electrogenic Na+/nHCO3- cotransporter (NBCe1, SLC4A4) cause severe proximal renal tubular acidosis, glaucoma, and cataracts in humans, indicating NBCe1 has a critical role in acid-base homeostasis and ocular fluid transport. To better understand the homeostatic roles and protein ontogeny of NBCe1, we have cloned, localized, and downregulated NBCe1 expression in zebrafish, and examined its transport characteristics when expressed in Xenopus oocytes. Zebrafish NBCe1 (zNBCe1) is 80% identical to published mammalian NBCe1 cDNAs. Like other fish NBCe1 clones, zebrafish NBCe1 is most similar to the pancreatic form of mammalian NBC (Slc4a4-B) but appears to be the dominant isoform found in zebrafish. In situ hybridization of embryos demonstrated mRNA expression in kidney pronephros and eye by 24 h postfertilization (hpf) and gill and brain by 120 hpf. Immunohistochemical labeling demonstrated expression in adult zebrafish eye and gill. Morpholino knockdown studies demonstrated roles in eye and brain development and caused edema, indicating altered fluid and electrolyte balance. With the use of microelectrodes to measure membrane potential (Vm), voltage clamp (VC), intracellular pH (pH(i)), or intracellular Na+ activity (aNa(i)), we examined the function of zNBCe1 expressed in Xenopus oocytes. Zebrafish NBCe1 shared transport properties with mammalian NBCe1s, demonstrating electrogenic Na+ and HCO3- transport as well as similar drug sensitivity, including inhibition by 4,4'-diiso-thiocyano-2,2'-disulfonic acid stilbene and tenidap. These data indicate that NBCe1 in zebrafish shares many characteristics with mammalian NBCe1, including tissue distribution, importance in systemic water and electrolyte balance, and electrogenic transport of Na+ and HCO3-. Thus zebrafish promise to be useful model system for studies of NBCe1 physiology.

What do infants see in faces? ERP evidence of different roles of eyes and mouth for face perception in 9-month-old infants.

The study examined whether face-specific perceptual brain mechanisms in 9-month-old infants are differentially sensitive to changes in individual facial features (eyes vs. mouth) and whether sensitivity to such changes is related to infants' social and communicative skills. Infants viewed photographs of a smiling unfamiliar female face. On 30% of the trials, either the eyes or the mouth of that face were replaced by corresponding parts from a different female. Visual event-related potentials (ERPs) were recorded to examine face-sensitive brain responses. Results revealed that increased competence in expressive communication and interpersonal relationships was associated with a more mature response to faces, as reflected in a larger occipito-temporal N290 with shorter latency. Both eye and mouth changes were detected, though infants derived different information from these features. Eye changes had a greater impact on the face perception mechanisms and were not correlated with social or communication development, whereas mouth changes had a minimal impact on face processing but were associated with levels of language and communication understanding.

Signaling pathways in innate immunity

AbstractInflammation has a key role in the pathogenesis of AMD. This lecture will review the recent progress in understanding the different host‐defence mechanisms against pathogens and self‐based danger signals involved in the activation of innate immunity. The innate defence system utilizes pattern recognition receptors (PRR) to respond to a variety of pathogen‐associated (PAMP) and danger‐associated (DAMP) molecular structures. Along with the well‐known complement and scavenger receptor systems, Toll‐like receptors (TLR) and NOD‐like receptors (NLR) have also a crucial part in host‐defence and these receptor systems can be activated both by PAMPs and DAMPs. Pattern recognition receptors are located either in cell surface, such as TLR2 and TLR4, or in intracellular locations, e.g. TLR3, TLR9 and all NLRs. PRRs show some specificity to ligands and also in downstream they activate different signaling pathways, most common of which are NF‐kB and IRF‐dependent pathways inducing inflammatory responses. Retinal pigment epithelial cells (RPE) have an important role in eye host‐defence, both at apical and basolateral surfaces. Most of the TLRs are expressed in RPE cells, especially TLR3 and TLR4, and they can participate in photoreceptor outer segment recognition. TLR3 can also suppress angiogenesis. The functions of NLRs, e.g. those forming inflammasomes, are still unknown, although the danger‐type of activation signals, such as oxidative stress and potassium efflux, are present in retinal pigment epithelium. It seems that the activation of innate immunity system via DAMPs and PRRs may have a central role in the pathogenesis of AMD.

The role of eye and head movements in detecting information about fly balls.

The authors attempted to identify perceptual mechanisms that pick up information for initiating a run to catch fly balls and for judging their landing locations. Fly balls have been shown to be tracked with the eyes and head (R. R. D. Oudejans, C. F. Michaels, F. C. Bakker, & K. Davids, 1999). This raised the question of whether constraining eye and head movements of experienced baseball players by having them wear eye-movement-preventing goggles (eye movements would lead to losing sight of the ball) or a head-movement-preventing neck brace, or both, would limit their capacity (a) to start running in the correct direction and (b) to make correct judgments about the balls' landing locations. Restrictions had minimal effects on response accuracy, but response latency was affected. The goggles increased latency of both running and judging. Moreover, the neck brace decreased judgment time, particularly for difficult balls, suggesting that head stability is important for making judgments. High performance levels suggested that the perceptual system was flexible; that is, different parts of the system can perform the same function. The implications of these findings for perceptual mechanisms are discussed.

Diagnostic Value of GDx Polarimetry in a Taiwan Chinese Population

To study the diagnostic ability of scanning laser polarimetry with variable corneal compensation (GDx VCC) for early glaucomatous (EG) eyes and glaucoma-suspect (GS) eyes in a Taiwan Chinese population. This prospective cross-sectional study included 82 EG eyes (mean deviation, MD: -3.32 +/- 2.20 dB), 45 GS eyes (MD: -2.43 +/- 2.16 dB), and 62 normal eyes. Retinal nerve fiber layer thickness of each subject was measured using GDx VCC and Humphrey Field Analyzer visual field testing. Measured GDx VCC parameters were compared among groups. The area under the receiver operating characteristic (AROC) curve of each parameter was used to differentiate normal from EG eyes or GS eyes. The correlation between MD and each parameter was also evaluated. For both normal versus EG and normal versus GS, the largest AROC values were for nerve fiber indicator, superior average thickness, and inferior average thickness. There was no significant correlation between MD and GDx-VCC-measured parameters either in EG or GS eyes. GDx VCC shows only moderate ability to distinguish normal eyes from eyes with early glaucoma. However, its diagnostic role in eyes with suspicious discs and normal visual fields is uncertain at this moment in the Taiwan Chinese population. Further studies are needed to address this issue.

Basal and 3,3′,4,4′,5-pentachlorobiphenyl-induced expression of cytochrome P450 1A, 1B and 1C genes in zebrafish

The cytochrome P4501C ( CYP1C) gene subfamily was recently discovered in fish, and zebrafish ( Danio rerio) CYP1C1 transcript has been cloned. Here we cloned the paralogous CYP1C2, showing that the amino acid sequence is 78% identical to CYP1C1, and examined gene structure and expression of CYP1A, CYP1B1, CYP1C1, and CYP1C2. Xenobiotic response elements were observed upstream of the coding regions in all four genes. Zebrafish adults and embryos were exposed (24 h) to 100 nM 3,3′,4,4′,5-polychlorinated biphenyl (PCB126) or 20 ppm acetone and subsequently held in clean water for 24 h (adults) or 48 h (embryos). All adult organs examined (eye, gill, heart, liver, kidney, brain, gut, and gonads) and embryos showed basal expression of the four genes. CYP1A was most strongly expressed in liver, whereas CYP1B1, CYP1C1, and CYP1C2 were most strongly expressed in heart and eye. CYP1B1 and the CYP1C genes showed an expression pattern similar to one another and to mammalian CYP1B1. In embryos CYP1C1 and CYP1C2 tended to have a higher basal expression than CYP1A and CYP1B1. PCB126 induced CYP1A in all organs, and CYP1B1 and CYP1C1 in all organs except gonads, or gonads and brain, respectively. CYP1C2 induction was significant only in the liver. However, in embryos all four genes were induced strongly by PCB126. The results are consistent with CYP1C1 and CYP1C2, as well as CYP1A and CYP1B1, being regulated by the aryl hydrocarbon receptor. While CYP1A may have a protective role against AHR agonists in liver and gut, CYP1B1, CYP1C1, and CYP1C2 may also play endogenous roles in eye and heart and possibly other organs, as well as during development.

Conserved elements in Pax6 intron 7 involved in (auto)regulation and alternative transcription

Pax6 is a transcription factor with an essential role in eye, central nervous system, and pancreas development. Its expression pattern is restricted to these specific domains within the developing embryo. Here four conserved elements are identified in Pax6 intron 7, showing a high level of sequence conservation between human, mouse, pufferfish, and zebrafish. Three of these are shown to act as cis-regulatory elements, directing expression of a reporter gene to distinct subsets of the Pax6 expression domain. CE1 regulates gene expression in late eye development, CE2 drives expression in the diencephalon and in the developing heart tube where Pax6 is not normally expressed, while CE3 directs expression in rhombencephalon. CE2 is shown to be autoregulated in the diencephalon, responding to absence of Pax6. We identify a highly conserved Pax6 recognition site and demonstrate its ability to bind Pax6 specifically. CE1 is embedded in a CpG island, and we identify a novel Pax6 transcript which initiates from this region. Functional analysis of evolutionary conserved sequences pinpoints novel cis-acting elements that govern the regulation of the complex spatio-temporal and quantitative expression of Pax6.

Multiple levels of representation of reaching in the parieto-frontal network.

In daily life, hand and eye movements occur in different contexts. Hand movements can be made to a visual target shortly after its presentation, or after a longer delay; alternatively, they can be made to a memorized target location. In both instances, the hand can move in a visually structured scene under normal illumination, which allows visual monitoring of its trajectory, or in darkness. Across these conditions, movement can be directed to points in space already foveated, or to extrafoveal ones, thus requiring different forms of eye-hand coordination. The ability to adapt to these different contexts by providing successful answers to their demands probably resides in the high degree of flexibility of the operations that govern cognitive visuomotor behavior. The neurophysiological substrates of these processes include, among others, the context-dependent nature of neural activity, and a transitory, or task-dependent, affiliation of neurons to the assemblies underlying different forms of sensorimotor behavior. Moreover, the ability to make independent or combined eye and hand movements in the appropriate order and time sequence must reside in a process that encodes retinal-, eye- and hand-related inputs in a spatially congruent fashion. This process, in fact, requires exact knowledge of where the eye and the hand are at any given time, although we have no or little conscious experience of where they stay at any instant. How this information is reflected in the activity of cortical neurons remains a central question to understanding the mechanisms underlying the planning of eye-hand movement in the cerebral cortex. In the last 10 years, psychophysical analyses in humans, as well as neurophysiological studies in monkeys, have provided new insights on the mechanisms of different forms of oculo-manual actions. These studies have also offered preliminary hints as to the cortical substrates of eye-hand coordination. In this review, we will highlight some of the results obtained as well as some of the questions raised, focusing on the role of eye- and hand-tuning signals in cortical neural activity. This choice rests on the crucial role this information exerts in the specification of movement, and coordinate transformation.

Pax6 in the sepiolid squid Euprymna scolopes: evidence for a role in eye, sensory organ and brain development

The cloning of a Pax6 orthologue from the sepiolid squid Euprymna scolopes and its developmental expression pattern are described. The data are consistent with the presence of a single gene encoding a protein with highly conserved DNA-binding paired and homeodomains. A detailed expression analysis by in situ hybridization and immunodetection revealed Pax6 mRNA and protein with predominantly nuclear localization in the developing eye, olfactory organ, brain lobes (optic lobe, olfactory lobe, peduncle lobe, superior frontal lobe and dorsal basal lobe), arms and mantle, suggestive of a role in eye, brain, and sensory organ development.

Role of eye, head, and shoulder geometry in the planning of accurate arm movements.

Eye-hand coordination requires the brain to integrate visual information with the continuous changes in eye, head, and arm positions. This is a geometrically complex process because the eyes, head, and shoulder have different centers of rotation. As a result, head rotation causes the eye to translate with respect to the shoulder. The present study examines the consequences of this geometry for planning accurate arm movements in a pointing task with the head at different orientations. When asked to point at an object, subjects oriented their arm to position the fingertip on the line running from the target to the viewing eye. But this eye-target line shifts when the eyes translate with each new head orientation, thereby requiring a new arm pointing direction. We confirmed that subjects do realign their fingertip with the eye-target line during closed-loop pointing across various horizontal head orientations when gaze is on target. More importantly, subjects also showed this head-position-dependent pattern of pointing responses for the same paradigm performed in complete darkness. However, when gaze was not on target, compensation for these translations in the rotational centers partially broke down. As a result, subjects tended to overshoot the target direction relative to current gaze; perhaps explaining previously reported errors in aiming the arm to retinally peripheral targets. These results suggest that knowledge of head position signals and the resulting relative displacements in the centers of rotation of the eye and shoulder are incorporated using open-loop mechanisms for eye-hand coordination, but these translations are best calibrated for foveated, gaze-on-target movements.

The effects of eye and limb movements on working memory

Three experiments examined the role of eye and limb movements in the maintenance of information in spatial working memory. In Experiment 1, reflexive saccades interfered with memory span for spatial locations but did not interfere with memory span for letters. In Experiment 2, three different types of eye movements (reflexive saccades, pro-saccades, and anti-saccades) interfered with working memory to the same extent. In all three cases, spatial working memory was much more affected than verbal working memory. The results of these two experiments suggest that eye movements interfere with spatial working memory primarily by disrupting processes localised in the visuospatial sketchpad. In Experiment 3, limb movements performed while maintaining fixation produced as much interference with spatial working memory as reflexive saccades. These results suggest that the interference produced by eye movements is not the result of their visual consequences. Rather, all spatially directed movements appear to have similar effects on visuospatial working memory.

Molecular Cloning and Characterization of ChM1L, a Novel Membrane Molecule Similar to Chondromodulin-I

Chondromodulin-I (ChM-I) is a cartilage-specific glycoprotein that stimulates the growth of chondrocytes and inhibits the tube formation of endothelial cells. In the present study, we identified a novel ChM-I like molecule, designated ChM1L. Cloning of full length cDNAs of human, mouse, and rat ChM1L revealed that ChM1L encodes 317 amino acids novel type II transmembrane protein. ChM1L protein was expressed on the cell surface as N-glycosylated and non-N-glycosylated protein with molecular mass of 45 and 40 kDa, respectively. In adult mouse tissues, ChM1L mRNA was highly expressed in eye, skeletal muscle, and whole rib. The temporal pattern of ChM1L mRNA was examined using whole embryo at day 10 to 19 of gestation. After day 11, ChM1L mRNA was detected and its level was progressively elevated in association with development of mouse embryo. These data suggest that ChM1L is a novel membrane molecule which is similar to ChM-I that plays a regulatory role in eye, skeletal muscle, and development of embryo.

Pax-6 is required for thalamocortical pathway formation in fetal rats.

Pax-6, a transcription regulatory factor, has been demonstrated to play important roles in eye, nose, and brain development by analyzing mice, rats, and humans with a Pax-6 gene mutation. We examined the role of Pax-6 with special attention to the formation of efferent and afferent pathways of the cerebral cortex by using the rat Small eye (rSey2), which has a mutation in the Pax-6 gene. In rSey2/rSey2 fetuses, cortical efferent axons develop with normal trajectory, at least within the cortical anlage, when examined with immunohistochemistry of the neuronal cell adhesion molecule TAG-1 and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) labeling from the cortical surface. A remarkable disorder was found in the trajectory of dorsal thalamic axons by immunostaining of the neurofilament and the neural cell adhesion molecule L1 and DiI labeling from the dorsal thalamus. In normal rat fetuses, dorsal thalamic axons curved laterally in the ventral thalamus without invading a Pax-6-immunoreactive cell cluster in the ventral part of the ventral thalamus. These axons then coursed up to the cortical anlage, passing just dorsal to another Pax-6-immunoreactive cell cluster in the amygdaloid region. In contrast, in rSey2/rSey2 fetuses, dorsal thalamic axons extended downward to converge in the ventrolateral corner of the ventral thalamus and fanned out in the amygdaloid region without reaching the cortical anlage. These results suggest that Pax-6-expressing cell clusters along the thalamocortical pathway (ventral part of the ventral thalamus and amygdala) are responsible for the determination of the axonal pathfinding of the thalamocortical pathway.

Expression of the Vax family homeobox genes suggests multiple roles in eye development.

Homeobox gene products are thought to regulate target genes involved in the regional specification of tissues and organs. Several genes play roles in eye development. We isolated two new mouse homeobox genes, Vax1 and Vax2, expressed in retina primordium. The two genes share the same gene organization, consisting of three exons with predicted amino acid sequences identical in the homeodomain but diversified in other regions. At 9. 5 days post coitum, both Vax genes were expressed in optic vesicles. At 11.5-14.5 dpc, Vax1 became restricted to the optic stalk, while Vax2 was expressed in the ventral half of the neural retina. Mapping of Vax2 between D6Mit3 and D6Mit8 on chromosome 6 indicated a possible linkage with Emx1. The expression patterns of Vax genes suggest separate and specific involvement in eye development. Vax1 may contribute to differentiation of the neuroretina, pigmented epithelium and optic stalk, while Vax2 could function in the establishment of the dorso-ventral axis of the retina and the visual system. The chromosomal location of Vax2 suggests that Vax2-Emx1 and Vax1-Emx2 arose by chromosome duplication of the same ancestral gene.

Roles of eyes, leg proprioceptors and statocysts in the compensatory eye movements of freely walking land crabs (Cardisoma guanhumi)

The compound eyes, the canal organs of the statocysts and proprioceptors in the legs all generate compensatory eye movements in the horizontal plane in the land crab Cardisoma guanhumi. Frequency analyses of the compensatory eye reflexes elicited by each of these inputs show that visual (V) and proprioceptive (P) reflexes respond best below 0.1 Hz, while statocyst (S) reflexes only achieve a high gain above this frequency. They thus increase the range of frequencies over which compensation can occur. Eye and body movements were recorded in an arena under all possible combinations of crabs seeing or blind (V+ or V-), with or without statocysts (S+ or S-) and freely walking or passively transported on a trolley (P+ or P-). Intact crabs (V+S+P+) show good stabilisation of the eyes in space, the only movements with respect to external coordinates being saccadic resetting movements (fast phases of nystagmus). The eyes thus compensate well for body turns, but are unaffected by translatory movements of the body and turns that are not accompanied by a change in the orientation of the long axis of the body in space. In the absence of any one sense, compensation for rotation is significantly impaired, whether measured by the increase in the width of the histograms of changes in the angular positions of the eyes in space ( capdelta &phgr; E), by the mean angular velocity of the eyes (slope of regression line, mE) with respect to the angular velocity of the body (mB) or by response gain plotted against angular acceleration of body turn (a). The absence of two senses reduces the crab's ability to compensate still further, with the statocyst-only condition (V-S+P-) being little better than the condition when all three senses are absent (V-S-P-).Such multisensory control of eye compensation for body rotation is discussed both in terms of making use of every available cue for reducing retinal slip and in making available the information content of the optic flow field.