Open Eyelid Research Articles

The effect of eyelid constriction on perceptions of mating strategy: Beware of the squinty-eyed guy!

Facial features and expressions influence perceptions of attractiveness, personality, behavioral tendencies, and relationship preferences. We manipulated eyelid openness in facial images of two men. Consistent with our predictions, open eyelid images were associated more so with behaviors consistent with long-term mating strategies and lowered eyelid images were associated more so with behaviors consistent with short-term mating strategies. Participants generally rated the men depicted in the open eyelid images as more attractive; however, the difference between images decreased as the prospective relationship length decreased. Participants’ preferences matched their expectations for the people in the images, for example, mate-guarding concerns were stronger for the lowered eyelid images. Our results suggest that eyelid openness serves as a heuristic in evaluating an individual’s mating intentions. Understandably, we did not find effects seen for manipulations of structural characteristics such as facial masculinity and symmetry, which are thought to be indicators of genetic quality.

The Frequencies of Spontaneous and Cortisone-treated Open Eyelid and the Relationship with Cleft Palate between A/WySn and C3H/He Mice

The Frequencies of Spontaneous and Cortisone-treated Open Eyelid and the Relationship with Cleft Palate between A/WySn and C3H/He Mice

ROCK‐I and ROCK‐II cooperatively regulate closure of eyelid and ventral body wall in mouse embryo

Rho-associated kinase (ROCK) is a serine/threonine kinase working in the Rho signaling to actin cytoskeleton. We previously reported that loss of ROCK-I results in the eyelid open at birth (EOB) and omphalocele phenotype in mice, while loss of ROCK-II results in placental dysfunction leading to intrauterine growth retardation and fetal death. Here, we report that after backcross to the C57BL/6 N genetic background, ROCK-II knockout (KO) neonates are born also with open eyelid and umbilical hernia, a phenotype similar to that of ROCK-I KO mice. ROCK-II KO embryos show impaired extension of the eyelid epithelial sheet with disorganized actin bundles in the leading edge of the sheet. These results suggest that ROCK-I and ROCK-II cooperatively regulates the assembly of actin bundles essential for closure of the eyelid and ventral body wall in mouse embryos. Consistently, ROCK-I(+/-)ROCK-II(+/-) double heterozygous mice also show the EOB and omphalocele phenotype.

Vitamin E decreases valproic acid induced neural tube defects in mice

The present study was undertaken to investigate the effect of vitamin E on valproic acid (VPA) induced teratogenesis. Pregnant Balb mice were divided into six groups of 10-11 animals each. The mice in group 1 served as control and were injected with saline subcutaneously on day 8 of gestation, whereas, animals in group 2 received a single injection of VPA (700 mg/kg (s.c.)). Groups 3 and 4 received an oral administration of vitamin E in the doses of 250 and 500 mg/kg, respectively, 1 h before VPA injection. Group 5 and 6 were given vitamin E only, in the same doses as group 3 and 4. On day 18 of gestation, the mice were killed by cervical dislocation. Embryotoxicity was assessed by counting the number of implants, live and dead fetuses, resorptions, crown rump length and fetal body weight. The fetuses were observed for malformations including neural tube defects (excencephaly), open eye lid and micrognathae. VPA administration resulted in a significant reduction of the average live fetuses/litter, fetal weight and crown rump length and a significant increase in malformations (excencephaly, open eye lid and micrognathae). Concomitant administration of vitamin E significantly attenuated VPA induced decrease in the fetal weight, crown rump length and malformations.

Development of a Device for Measuring the Motion of Eyelids and Eyeballs in Domestic Animals

Eyelid and eyeball movements are important aspects in determining the awareness level of a resting domestic animal. We have developed an apparatus for measuring the movement of eyelids and eyeballs of domestic animals. The apparatus consists of a charge-coupled device (CCD) camera that is placed in the eyelid region of a head mask. The device emits an infrared light from a diode as a light source. Two types of apparatus have been developed. One uses a wire system, and the other uses a measurable telemetry system in an unrestricted state. The weight of the device with the wire system is about 50g, and the device with the telemetry system weighs about 880g. The operating time of the telemetry system is 24h or more when nickel-hydrogen is used as the power supply. In an experiment using the wire system with a calf, the movements of the eyelid and eyeball could be divided into four categories: fully open eyelid movement, half-closed eyelid movement, fully closed eyelid movement, and eyeball movement. Results of the measurement experiment showed that the time during which the calf's eyelids were half-closed or fully closed while lying down was longest from midnight to 7: 00 a. m. Furthermore, the eyelids were half-closed or fully closed even during rumination. During the daytime, there were long periods when the animal's eyelids were fully open and eyeball movement was very active. In an experiment with a horse, we used the telemetry system device to measure eyelid and eyeball movements for 24h continuously without any discomfort for the animal.

Pantothenic acid decreases valproic acid‐induced neural tube defects in mice (I)

The effect of the administration of pantothenic acid (PTA) on valproic acid (VPA)-induced teratogenesis was examined in ICR mice. VPA (300, 400, and 500 mg/kg, s.c.) or PTA (3 x 10, 3 x 100, and 3 x 300 mg/kg, i.p.) was injected on day 8.5 of gestation (plug day = day 0.5). Exencephaly was induced dose dependently by single injections of VPA. Three administrations of PTA alone at any dose levels showed neither embryocidal nor teratogenic effects. In combined treatment experiments, PTA (3 x 300 mg/kg) was injected 1 hr before, immediately before, and 1 hr after VPA administration. PTA significantly reduced VPA-induced exencephaly, while none of the other external malformations such as open eyelid or skeletal malformations such as fused, absent, or bifurcated ribs and fused thoracic vertebrae and fused sternebrae were reduced. The results suggest that PTA reduces the incidence of neural tube defect induced by VPA in mice.

Phenytoin teratogenicity and midgestational pharmacokinetics in mice

Mice of the A/J and C57BL/6J (C57) strains were dosed with phenytoin (PHT) every 48 hr throughout pregnancy by gastric intubation to test the hypothesis that maternal plasma PHT concentration may be the significant factor in determining PHT reproductive and developmental toxicity. Serial serum samples were obtained from each mouse from gestation day (GD) 10-GD 12 for determination of individual dam PHT pharmacokinetics. Maximum PHT concentration and PHT AUC (area under-the-time-concentration curve) were regressed to laparotomy and fetal evaluation endpoints to determine whether significant association existed. Although serum PHT concentrations exceeded levels associated with teratogenicity (greater than 10 micrograms/ml), few major malformations were induced in either strain. However, in the A/J strain, there was a significant increased incidence of hydrocephaly and open eyelid. Regression of pharmacokinetic parameters with embryo and maternal endpoints indicated significant associations between gestational weight gain and maximum concentration measured (Cmax) or AUC in both strains. This association was also found for fetal weight in the C57 strain. In the A/J strain, the induction of decreased ossification of the sternebrae was also associated with maternal PHT concentration; however, linear regression of hydrocephaly and open eyelid to PHT concentration was not statistically significant. These results suggest that maternal plasma PHT concentration may be a quantifiable determinant of certain aspects of PHT developmental toxicity in the mouse.

Species and Strain Differences in Teratogenic Effects of Biotin Deficiency in Rodents

The teratogenicity of maternal biotin deficiency of mice, rats and Syrian hamsters was compared. Biotin deficiency during pregnancy caused severe malformations and growth retardation in mouse fetuses. The malformations were mainly cleft palate, micrognathia, micromelia and open eyelid. The ICR and C57BL strains of mice were more susceptible than the A/Jax strain to biotin deficiency. In rats, no malformations were seen in the fetuses from biotin-deficient dams. In hamsters, embryonic lethality was very high in biotin-deficient dams, and teratogenicity of biotin deficiency was rather equivocal. The results of measurements of the maternal and fetal biotin content suggest that a possible underlying mechanism is a difference in the efficiency of the mother-to-fetus transport of biotin among these species.

X-ray- and chemically induced germ-line mutation causing phenotypical anomalies in mice

A large and significant increase of phenotypical anomalies was observed in the progeny of ICR parent mice treated before mating with X-rays, urethane, 7,12-dimethylbenz[ a]anthracene, ethylnitrosourea (ENU), and 4-nitroquinoline 1-oxide, but the increase was not significant with furylfuramide. Major types of induced anomalies were cleft palate, dwarf, open eyelid, tail anomalies, and exencephalus. Dwarf, open eyelid and tail anomalies were predominant types of viable anomalies and were inherited as if they were dominant mutations with varying expressivity or penetrance. Incidence of prenatal anomalies increased with treated doses of X-rays, urethane, or ENU for both spermatozoa and spermatogonia. Spermatogonia were less sensitive to X-rays and urethane than spermatozoa, while ENU induced a very high incidence of prenatal anomalies by the spermatogonial treatment. In contrast to the previous works with X-rays, there was a clear, almost linear increase of anomalies in the dose range from 0 to 216 rad after spermatogonial exposure. For treatment of oocytes, there was also a clear increase with doses of X-rays and urethane. Doubling doses of X-rays for prenatal anomalies were 12 rad for spermatozoa, 27 rad for spermatogonia, and 19 rad for mature oocytes. These values are similar to those for ordinary mouse mutations. However, the mean rate of prenatal anomalies per rad (1.2 × 10 −4, 6.6 × 10 −5 and 9.1 × 10 −5 for spermatozoa, spermatogonia and mature oocytes, respectively) and that for 1 μg/g of ENU (3.4 × 10 −4 for spermatogonia) were 4–40 times higher than that of ordinary mutation in mice, because overall phenotypical abnormalities were scored in this study. Information obtained from the work on phenotypical anomalies is valuable to assess gentic risk of radiation and chemicals, because a majority of human genetic diseases show this kind of irregular and uncertain inheritance and most of the induced anomalies are similar to those found in humans.

Trisomy 16 in the mouse fetus associated with generalized edema and cardiovascular and urinary tract anomalies.

Murine trisomy (Ts) 16 occurs in the fetal and neonatal progeny of males doubly heterozygous for the Robertsonian metacentric chromosomes Rb(16.17)7Bnr/Rb(9.16)9Rma and "all acrocentric" females. The developmental aspects of this trisomy were studied between day 12 of gestation and birth. So far, postnatal survival longer than a few hours after birth has not been observed. The frequency of Ts 16 among all implants decreased from more than 20% on day 14 to values between 4% and 7% shortly before term. Main features of Ts 16 are moderate general hypoplasia, slight developmental retardation, and cardiovascular anomalies. These latter were found in 96% of the trisomies, the great majority belonging to the transposition type, i.e., riding aorta, double outlet right ventricle (DORV) and transposition of the great arteries (TGA). Association with common atrio ventricular (AV)-canal was frequent. Other anomalies as "open eyelid", hydronephrosis, and hydroureter seem to be attributable to the effects of retardation. Generalized transient edema was frequent in the later gestational stages of Ts 16. Severe cardiovascular malformation is possible one of the factors responsible for late fetal or neonatal death in some cases. Another factor probably contributing to Ts 16 fetal mortality is insufficiency of placental function due to hypoplasia of the fetal vasculature of this organ. The teratological study of Ts 16 demands interest since evidence has been forwarded to consider this trisomy as an animal model of human trisomy 21.

The natural elimination of sporadically malformed mouse embryos.

Female A/JKt mice greater than or equal to 250 days old had litters with significantly larger fetal resorption rates and offspring with significantly smaller frequencies of sporadic malformations [cleft lip +/- palate (CLP) and open eyelid (OL)] than females < 250 days old. The OL frequency was reduced in litters with resorption as well as in those without, and thus was apparently associated with advanced maternal age per se; whereas the CLP frequency was reduced only in litters with resorption. It seems therefore that the frequency of CLP was reduced in the offspring of older females by preferential elimination and that of OL by another means, perhaps failure to express a tendency.

Polydactyly Nagoya, Pdn: A new mutant gene in the mouse.

A new hereditary polydactyly (gene symbol Pdn) was found in the course of breeding JCL : ICR mice. The genetic analysis indicated that the polydactyly was an autosomal dominant trait. The homozygotes died within two days after birth. The homozygous fetuses or newborn had 1-3 extra-digits both in te fore- and hindlimbs on the preaxial side. They occasionally showed exencephaly, cleft palate, open eyelid, short tibia and fibula or deformed sternum. The heterozygotes had one extra-digit preaxial side. They occasionally showed exencephaly, heterozygotes had one extra-digit preaxially in the hindlimb and an enlarged first digit on the forelimb which often showed bifurcated distal phalanx. A tab on the postaxial side of the forelimb was found in all homozygotes and in some heterozygotes.

Teratogenic effects of nickel chloride on embryonic mice and its transfer to embryonic mice.

Administration of nickel chloride to the pregnant mice on the seventh to eleventh day of their gestational period, resulted in significant embryotoxic effects in terms of an increased resorption rate, a decreased fetal weight, delay in skeletal ossification and high incidence of malformation. Among the cases of fetal malformation, the following malformations were observed to occur at a higher rate of incidence: acephalia, exencephaly, cerebral hernia, open eyelid, cleft palate, micromelia, ankylosis of the extremity, club foot and skeletal anomalies. Most skeletal anomalies were in the form of vertebral and/or rib fusions and were found mostly at thoracic and lumbar levels. The concentration of nickel retained in embryonic tissues was 800 times higher in the exposed compared to control groups and indicated that increased tissue levels of nickel chloride had a toxic influence on the developing embryo.

Sex, side, and severity in spontaneous malformations of fetal A/JKt mice, and their associations with each other and with fetal weight

Cleft lip and palate (CLP) and open eyelid (OL) occur spontaneously in rather high frequencies in A/JKt mice, but vary greatly in their degree, laterality, and sex distribution. CLP occurs significantly more often in females, and OL even more often in males, than in the opposite sex. The female preponderence for CLP was largely if not entirely due to the increased rate of occurrence of left and incomplete forms of the defect, and to the excess in females heavier than the female median weight; whereas the male preponderance for OL could not be explained by any clear or major disparities of these sorts. CLP and OL occurred together more often than expected in individuals, but not in litters. There was no relation between the rate of defects in successive litters of the same female; nor was a relation detected between extent and severity of defect.

Prenatal epidemiology of spontaneous cleft lip and palate, open eyelid, and embryonic death in A/J mice.

Nongenetic bases of variability in the frequencies of spontaneous cleft lip and palate (CLP), open eyelid (OL), and fetal resorption were searched for in A/J mouse litters of prenatal ages 17-21 days post-VP and parities 1-7. The malformation rates did not decrease with advancing fetal age, and hence prenatal elimination does not account for the lower rates seen in newborns. Multivariate analysis indicated that the frequencies of CLP and resorption were inversely related to maternal age and directly related to litter size, and that the frequency of OL was related, directly, only to litter size; but that none were associated with maternal weight, parity, and several other variables. Regarding uterine location, the frequency of CLP was higher at the ovarian and cervical sites, OL higher at the cervical site, and resorption lower at the ovarian site, than elesewhere. CLP was significantly commoner in females, and OL commoner in males; also, since the percentage of males increased with parity, the frequency of CLP in males relative to that in females decreased with parity, and that of OL increased. Malformed offspring weighed less than normal ones; and the sex with the lower frequency of CLP or OL had the greater weight reduction. The results are discussed in relation to the frequency of malformations in human fetuses and newborns.

Effects of litter size and maternal and temporal factors on the frequency of spontaneous cleft lip and open eyelid in newborn A-J mice.

Study of the etiology of congenital malformations in human beings has been particularly intense in the last 20 years. These abnormalities, which until recently were considered rare and of interest only to pathologists and embryologists, are being studied more now for at least two reasons. First, they are a leading cause of prenatal loss and of morbidity and mortality in children. Second, they present challenges to epidemiologists, geneticists, developmentalists, and evolutionists who seek answers to the perplexities they pose. The many recent family and population surveys of congenital malformations have had important results. The mathematical models' constructed to describe the genetic contribution to the basis of some relatively common congenital malformations are useful. Also, environmental factors are recognized more than ever as significant.2 Animals are used to supplement the data and insights that are provided by observation of human beings. Experimentally induced malformations have yielded much information about structural and chemical pathogenesis and other aspects of human anomalies, but not about etiology. Study of spontaneous malformations may provide information about etiology. The A/J mouse strain is prone to a number of different spontaneous congenital malformations that range in frequency from less than 1% to nearly 20% of the offspring. Like all long inbred strains, it is homozygous at all or nearly all gene loci, and is well-suited to study of the gene-environment interactions that result in deformity of some of its genetically identical members. In this paper, discussion will center on whether the frequencies of the two commonest malformations in this strain were associated with several environmental (nongenetic) variables.

The teratogenic response of mouse embryos to 5-bromodeoxyuridine.

AbstractPregnant ICR mice were administered single intraperitoneal injections of 300, 400, or 500 mg/kg of the thymidine analogue 5‐bromodeoxyuridine during the period of major organogenesis (days 7–11, Witschi stages 12–25). All dosages were teratogenic. The spectrum of malformations present on day 18 followed a definite stage‐dependency. Exencephaly with associated micrognathia and open eyelid were produced only by treatment during the time the anterior neuropore is open (days 7 and 8) with a peak on day 7. Polydactyly was produced by treatment on days 7 through 10 with a peak on day 9; while cleft palate occurred after treatment on days 9 through 11 with a peak on day 10. Experiments with 3H‐BUDR demonstrated that label appeared in the DNA of embryos and maternal liver at a time when the embryo is susceptible to the teratogenic action of BUDR.

Sporadic congenital malformations of newborn inbred mice.

AbstractA retrospective study was made of sporadic congenital malformations in newborn mice of nine inbred strains maintained in this laboratory. Young of seven of the strains had externally observable anomalies. In four the frequency was 0.1–0.5% and the defects formed no obvious pattern. In another it was about 4% and consisted mostly of preaxial polydactyly of the forefoot.In the remaining two the frequency was greater and some of the malformations appeared to constitute particular syndromes. In the C57BL/6JKt strain the overall frequency of malformed offspring was 10.1% and the abnormalities included eye defects, polydactyly, and otocephaly. Those of the eye (microphthalmia and anophthalmia) were commonest and affected females and right eyes much more often than males and left ones. In the A/JKt strain the total frequency of malformed offspring was 10.4% and the abnormalities included cleft lip with or without cleft palate, open eyelid, and polydactyly. Cleft lip was commonest and did not show a sex or side preference.The use of inbred strains to investigate the etiology of sporadic congenital malformations of probable multifactorial origin is to be encouraged.

Development of an open eyelid mutant in Mus musculus

1. 1. The development and histology of the eye is described for an inherited condition designated as slit lids in which the eyelids are either thin or open at birth. 2. 2. Almost invariably the lens was the first portion of the eye affected. The primary defect was an abnormal degree of vacuolization and its earliest appearance was at 14–15 days of gestation. 3. 3. At later ages, usually after birth, corneas and retinas also showed defects and the lens defects frequently increased in severity. Lenses were extruded in some animals; corneas were thickened, opaque and covered by scabs; neural retinas were folded and rosetted. 4. 4. Comparison with two other mutants with open eyelids at birth indicated differences in order and age of appearance of the various eye effects and some differences in histology. 5. 5. It is suggested that the lens defect in mice with slit lids may trigger the syndrome by affecting the vitreous humor and hence intraocular pressure.