PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Eye Abnormalities”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed1998

Response of the timeless protein to light correlates with behavioral entrainment and suggests a nonvisual pathway for circadian photoreception.

The period (per) and timeless (tim) genes are required for circadian behavioral rhythms in Drosophila. The current model for how these rhythms entrain to light is based upon the light induced decrease in timeless protein (TIM) levels. We show here that the TIM response to light correlates with the effect of light on the behavioral rhythm. To identify components of the entrainment pathway, we also assayed the TIM response in flies with mutant visual systems. Flies that lacked eyes displayed a normal response in lateral neurons. The TIM response to a light pulse was attenuated in flies that were mutant for the transient receptor potential (trp) and trp-like (trpl) genes, which are required for calcium conductance in the visual transduction cascade. The reduced TIM response was accompanied by a reduced phase shift in the behavioral rhythm, but neither response was completely eliminated, and the trpl;trp flies entrain to light-dark cycles, suggesting that these genes perturb some aspect of circadian entrainment when mutated but are not essential for it. The TIM response was also unaffected in ninaE flies that lack the rhodopsin protein (rh1). These results support the hypothesis that circadian entrainment does not rely on the visual system and likely involves a dedicated pathway for photoreception.

Animals↗
PubMed2001

The circadian clock of fruit flies is blind after elimination of all known photoreceptors.

Circadian rhythms are entrained by light to follow the daily solar cycle. We show that Drosophila uses at least three light input pathways for this entrainment: (1) cryptochrome, acting in the pacemaker cells themselves, (2) the compound eyes, and (3) extraocular photoreception, possibly involving an internal structure known as the Hofbauer-Buchner eyelet, which is located underneath the compound eye and projects to the pacemaker center in the brain. Although influencing the circadian system in different ways, each input pathway appears capable of entraining circadian rhythms at the molecular and behavioral level. This entrainment is completely abolished in glass(60j) cry(b) double mutants, which lack all known external and internal eye structures in addition to being devoid of cryptochrome.

Animals↗
PubMed2001

Misexpression of Xsiah-2 induces a small eye phenotype in Xenopus.

Recent data demonstrate a structural and functional conservation of factors crucial for the development of the insect and the vertebrate eye. We isolated Xenopus siah-2, a protein with 67% identity to Drosophila sina (seven in absentia) and 85% identity to the mouse and human siah-2 proteins. Sina is required in Drosophila for the R7 photoreceptor cell formation during eye development, because it down regulates proteins that inhibit R7 differentiation via the ubiquitin/proteasome pathway. Nothing is known about the developmental function of the siah protein in vertebrates. We show that in Xenopus siah-2 is expressed maternally and is later restricted to the brain, spinal cord and the developing and mature eye. To demonstrate that the vertebrate factor participates in the process of eye formation we over expressed Xsiah-2 during Xenopus development and observed the formation of a small eye phenotype. The vertebrate counterpart of a C-terminal loss of function sina mutant, that causes a deficiency of the R7 photoreceptor cells in Drosophila, induces in Xenopus also smaller eyes. The small eyes are characterized by a reduced size of the lens, the retina and the pigmented epithelium. As this phenotype has been also described for flies expressing sina ectopically, the data demonstrate the functional and structural conservation of Xsiah-2 and sina in metazoan eye development.

3T3 Cells↗
PubMed1997

Inactivation of the zebrafish homologue of Chx10 by antisense oligonucleotides causes eye malformations similar to the ocular retardation phenotype.

We report the cloning of a zebrafish paired-type homeobox gene, Alx, closely related to the murine Chx10 and the gold fish Vsx-I homeodomain proteins. Alx is first expressed at about 12 h post-fertilization (hpf) when optic vesicles appear. Its expression is restricted to the early retinal neuroepithelium, whereas no signal can be detected in the optic placode. Later, Alx expression follows the differentiation of the neural retina. Inhibition experiments with antisense oligonucleotides resulted in specific eye malformations which are reminiscent of the phenotype of ocular retardation (or) mice, caused by a spontaneous Chx10 mutation. The expression of other developmentally relevant genes such as pax(zf-a), pax(zf-b) and krx-20 was not affected in the antisense treated embryos.

Amino Acid Sequence↗
PubMed1998

Zebrafish contains two pax6 genes involved in eye development.

The Pax6 genes of both vertebrates and invertebrates are expressed in the developing eye and in the central nervous system. These genes encode transcription factors with two DNA-binding domains, an N-terminal paired domain and a homeodomain separated by a flexible linker region. Ectopic eye structures are obtained upon targeted expression of Drosophila, squid, ascidian or mouse Pax6 genes in various imaginal disc primordia of Drosophila. We have previously cloned a Pax6 cDNA from zebrafish. Here we report the cloning of a novel Pax6 homolog from zebrafish denoted Pax6.2. The coding sequences of the two genes show 82% identity whereas the deduced amino acid sequences are 95% identical with complete conservation of the paired- and homeodomains. The embryonic expression patterns of Pax6.1 and Pax6.2 reveal both overlapping and discrete expression domains suggesting a division of labor between these two very similar gene products during development of brain and eye structures. Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. Both Pax6.1 and Pax6.2 are able to induce ectopic eyes in Drosophila, while Pax2 is not, suggesting that eye induction is not a general feature of Pax family genes but a distinct characteristic of Pax6 and its direct homologs. Attempts to detect Pax6. 2 homologs in chick, mice or humans proved unsuccessful suggesting that this gene either was lost during evolution of higher vertebrates or, more likely, arose as part of a larger scale duplication of chromosome segments occurring in the zebrafish lineage.

Amino Acid Sequence↗
PubMed1997

[Antineoplastic chemotherapy and Wernicke's encephalopathy].

BACKGROUND: Wernicke's encephalopathy is usually seen in alcoholic adults. It is rare in childhood and usually discovered in a context of several pathological events. We report here a typical case of a teenager. CASE REPORT: A 15-year-old girl with acute leukemia was given chemotherapy that resulted in profound aplasia and serious infection. She exhibited abnormal eye movements, ataxia, lethargy, enuresis and amnesia. MR examination showed T2-weighted images with increased signal in the thalami (pulvinar) and periaqueducal region. The symptoms improved dramatically with thiamine therapy. Omission of the usual vitamin supplementation between the courses of chemotherapy was responsible for this encephalopathy. CONCLUSION: Thiamine deficiency can lead to death or amnesia. Rapid efficacy of vitamin supplementation helps diagnosis and prevents sequelae.

Adolescent↗
PubMed2003

Ccd1, a novel protein with a DIX domain, is a positive regulator in the Wnt signaling during zebrafish neural patterning.

Wnt signaling plays a crucial role in directing cell differentiation, polarity, and growth. In the canonical pathway, Wnt receptors activate Dishevelled (Dvl), which then blocks the degradation of a key signal transducer, beta-catenin, leading to the nuclear accumulation of beta-catenin and induction of Wnt target genes through TCF/LEF family transcription factors. Here we identified a novel zebrafish gene encoding Ccd1, which possesses a DIX (Dishevelled-Axin) domain. DIX domains are essential for the signal transduction of two major Wnt downstream mediators, Dvl and Axin. Ccd1 formed homomeric and heteromeric complexes with Dvl and Axin and activated TCF-dependent transcription in vitro. In addition, overexpression of ccd1 in zebrafish embryos led to a reduction in the size of the eyes and forebrain (posteriorization), as seen with wnt8 overexpression, whereas a dominant-negative ccd1 (DN-ccd1) caused the opposite phenotype. Furthermore, the Wnt activation phenotype induced by ccd1 was inhibited by the expression of axin1 or DN-ccd1, and the wnt8 overexpression phenotype was rescued by DN-ccd1, suggesting that Ccd1 functions downstream of the Wnt receptor and upstream of Axin. These results indicate that Ccd1 is a novel positive regulator in this Wnt signaling pathway during zebrafish neural patterning.

Amino Acid Sequence↗
PubMed1998

Ocular malformations and developmental genes.

New insights into the pathogenesis of ocular malformations came with the discovery of transcription factors that determine the fate of cells in the developing eye. Several malformations have been matched to individual developmental genes that share conserved DNA sequences such as the homeobox. These disease/gene matches include the oculorenal syndrome and PAX2; aniridia and PAX6; Rieger syndrome and RIEG1/PITX2; cyclopia and Sonic hedgehog; cone-rod dystrophy, Leber's congenital amaurosis and CRX; and recessive septooptic dysplasia and HESX1. Gene mapping and mutation analysis have allowed a more accurate and meaningful classification of genetically heterogeneous diseases such as the anterior segment dysgenesis syndromes. This paper reviews current information on the genetics of ocular malformations.

Eye Abnormalities↗
PubMed2004

Norrin and frizzled; a new vein for the eye.

The Wnt signaling network is arguably one of the most complex molecular modules by which cells communicate. Though we become accustomed to novel components, the discovery of an unexpected Wnt receptor ligand, Norrin, is surprising even to the connoisseur.

Animals↗
PubMed1991

Intraparenchymal and intraventricular hemorrhage without mass effect in traumatic coma.

A group of 57-head injured patients showing computerized tomographic (CT) findings compatible with "diffuse brain injury" or of the so called "diffuse axonal injury" is analyzed. Thirty-four patients showed intraparenchymal hemorrhage in the CT scan study, 8 intraventricular hemorrhage and 15 patients had both intraparenchymal and intraventricular hemorrhage. Forty percent (23/57) of those with these findings had associated intracranial focal lesions. The deep nuclei are the most common location of intraparenchymal hemorrhage. Signs of brain stem hemorrhage were seen in 9 patients. Forty-nine percent of patients in this series had a good outcome. Old age (greater than 60), abnormal motor response, abnormal eye signs, associated with focal lesions, and evidence of brain stem hemorrhage are reliable prognostic parameters for a grave outcome.

Adolescent↗
PubMedDate not supplied

Mouse models of ocular diseases.

The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to discover genetically determined eye variations and disorders. In this paper, we list and describe mouse models for ocular research available from Mouse Eye Mutant Resource at The Jackson Laboratory. While screening mouse strains and stocks at The Jackson Laboratory (TJL) for genetic mouse models of human ocular disorders, we have identified numerous spontaneous or naturally occurring mutants. We characterized these mutants using serial indirect ophthalmoscopy, fundus photography, electroretinography (ERG) and histology, and performed genetic analysis including linkage studies and gene identification. Utilizing ophthalmoscopy, electroretinography, and histology, to date we have discovered 109 new disorders affecting all aspects of the eye including the lid, cornea, iris, lens, and retina, resulting in corneal disorders, glaucoma, cataracts, and retinal degenerations. The number of known serious or disabling eye diseases in humans is large and affects millions of people each year. Yet research on these diseases frequently is limited by the obvious restrictions on studying pathophysiologic processes in the human eye. Likewise, many human ocular diseases are genetic in origin, but appropriate families often are not readily available for genetic studies. Mouse models of inherited ocular disease provide powerful tools for rapid genetic analysis, characterization, and gene identification. Because of the great similarity among mammalian genomes, these findings in mice have direct relevance to the homologous human conditions.

Animals↗
PubMed2001

Outcome of tyrosinaemia type III.

Tyrosinaemia type III is a rare disorder caused by a deficiency of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the catabolic pathway of tyrosine. The majority of the nine previously reported patients have presented with neurological symptoms after the neonatal period, while others detected by neonatal screening have been asymptomatic. All have had normal liver and renal function and none has skin or eye abnormalities. A further four patients with tyrosinaemia type III are described. It is not clear whether a strict low tyrosine diet alters the natural history of tyrosinaemia type III, although there remains a suspicion that treatment may be important, at least in infancy.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed2002

An expanded nystagmus acuity function: intra- and intersubject prediction of best-corrected visual acuity.

The Nystagmus Acuity Function (NAF) provides an objective measurement of the foveation characteristics of nystagmus waveforms and an assessment of potential visual acuity for subjects with congenital (CN) or latent/manifest latent (LMLN) nystagmus. It is based on the subjects' ability to maintain fixation within a physiologically based 'foveation window' of +/- 0.5 degrees and +/- 4.0 degrees/s. However, some subjects are incapable of controlling fixation well enough to remain within this window with duration sufficient for good foveation. To obtain a measure of the CN waveforms of these individuals, we are proposing an eXpanded Nystagmus Acuity Function (NAFX) that relaxes either the position limit, the velocity limit, or both. Data used in this study comes from 11 human subjects with CN (10 idiopathic and 1 with achiasma) and a Belgian sheepdog with achiasma. Visual acuity was tested with a standard Snellen chart and eye movements recorded with infrared oculography or scleral search coil. For the NAFX to be useful, it must not only be applicable for subjects who cannot maintain fixation within the standard limits of the NAF, but also must yield results equivalent to those obtained with the NAF when testing subjects who are capable of maintaining good fixation control. For the latter subjects, the amount of time when position and velocity fell within the expanded limits was measured, the standard deviations of the position and velocity during these times were calculated, and a tau-surface for the exponential function was generated to guarantee the equivalence between the NAF and the NAFX. We developed an automated NAFX equivalent to the original NAF. We demonstrated that equivalence in 10 subjects and the use of the NAFX on two additional (1 human and 1 canine) subjects who were incapable of maintaining fixation within the standard position and velocity limits. We demonstrated the effects of surgery and related the results to visual acuity. We found the results to be comparable to those seen when applying the NAF to subjects who had good fixation control. The NAFX can be determined for CN and LMLN subjects with poor control of fixation by extending the standard NAF position and/or velocity limits for foveation. The resulting function can be used along with the longest foveation domain (derived from the NAFX to measure breadth of a high-NAFX region) to identify the gaze or convergence angles with the best waveform and to predict the best-possible visual acuity that could be achieved with the reduction of their nystagmus.

Algorithms↗
PubMed2002

General utility of the chicken betaB1-crystallin promoter to drive protein expression in lens fiber cells of transgenic mice.

Transgenic mouse technology has been very valuable for the study of lens fiber cells since they can not be propagated in cell culture. The targeting of transgenes to the lens has traditionally been done with the alphaA-crystallin promoter. However, while lens-specific, transgenic lines made with the alphaA-crystallin promoter express the transgene at levels 100-300-fold lower than endogenous alphaA-crystallin. Here we propose an alternative, the chicken betaB1-crystallin promoter (-432/+30). Transgenic mice made with this promoter have successfully expressed CAT, d/n m-calpain, Weel, and betaB2-crystallin mRNA at levels comparable to the endogenous betaB1-crystallin gene and no eye abnormalities such as cataracts, have resulted. All of the transgenic lines made with the chicken betaB1-crystallin promoter have expressed the transgene in the lens fiber cells, and the best lines express at levels close to endogenous betaB1-crystallin. While RNA expression is very high, only moderate protein expression has been achieved, implying that the high protein expression of the crystallins is partially controlled at the level of translation. Thus, the chicken betaB1-crystallin promoter directs high level RNA expression to lens fiber cells, which may be especially useful for the expression of ribozyme and anti-sense RNAs in addition to ectopic proteins.

Animals↗
PubMed1995

The geographical epidemiology of ocular diseases: some principles and methods.

With the increasing availability of geographically referenced data in health research the time is ripe to review the use of particular geographical and spatial analysis techniques in ophthalmic research. Analysis of the geographical distribution of ocular diseases, particularly in Britain, has not had a high profile, but there are certain diseases, such as congenital eye malformations in children, where such analysis methods are particularly appropriate. We review the data requirements and then a variety of analytical techniques, some of which partition geographical space into areal units (such as counties or electoral wards), others of which treat space as continuous. We conclude with some comments on software that is available for such analyses.

Data Collection↗
PubMed1985

Cerebral atrophy and hypoperfusion improve during treatment of Wernicke-Korsakoff syndrome.

Nineteen patients with sudden onset of impaired recent memory, cerebellar ataxia, peripheral neuropathy, and other signs of Wernicke-Korsakoff syndrome (WKS) were treated and examined prospectively for 3 months. Serial studies included histories, neurological examinations, cognitive capacity screening examinations (CCSE), computed tomography (CT) scans, and measurements of regional CBF. Patients were detoxified and withdrawn from sedatives before CBF measurements were examined. Treatment included alcohol withdrawal, nutritious diet, and 300 mg thiamine daily. Before treatment CCSE scores and blood flow values of both white and gray matter were reduced, particularly within both temporoparietal regions. After treatment of compliant patients (n = 10), white and gray matter blood flow increased concurrently with improved CCSE scores. Abnormal eye signs, ataxia, peripheral neuropathy, and performance of activities of daily living also improved. Cerebral atrophy and ventricular enlargement measured by CT decreased. Early recognition and treatment of WKS in compliant patients permit rapid reversals of cognitive and neurological impairments associated with increased blood flow of gray and white matter and improvements of brain atrophy measured by CT scanning.

Adult↗
PubMed1997

Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome).

Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1 or Jaeken syndrome) is the prototype of a class of genetic multisystem disorders characterized by defective glycosylation of glycoconjugates. It is mostly a severe disorder which presents neonatally. There is a severe encephalopathy with axial hypotonia, abnormal eye movements and pronounced psychomotor retardation, as well as a peripheral neuropathy, cerebellar hypoplasia and retinitis pigmentosa. The patients show a peculiar distribution of subcutaneous fat, nipple retraction and hypogonadism. There is a 20% lethality in the first years of life due to severe infections, liver insufficiency or cardiomyopathy. CDG1 shows an autosomal recessive mode of inheritance and has been mapped to chromosome 16p. Most patients show a deficiency of phosphomannomutase (PMM)8, an enzyme necessary for the synthesis of GDP-mannose. We have cloned the PMM1 gene, which is on chromosome 22q13 (ref.9). We now report the identification of a second human PMM gene, PMM2, which is located on 16p13 and which encodes a protein with 66% identity to PMM1. We found eleven different missense mutations in PMM2 in 16 CDG1 patients from different geographical origins and with a documented phosphomannomutase deficiency. Our results give conclusive support to the biochemical finding that the phosphomannomutase deficiency is the basis for CDG1.

Amino Acid Sequence↗