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Biomedical subjects

J Zwaan

Publications and source records attributed to J Zwaan.

At least 37 records · Page 2Linked to original sources

Detection of ascorbic acid in the eye of the early chicken embryo by silver staining.

Ascorbate is found in high concentrations in the aqueous, lens and retina of a variety of animal species. Several functions have been proposed for this, including a vital role in aqueous secretion. We investigated the possible presence of ascorbate in the early embryonic chicken eye as a marker for the differentiation of the ciliary epithelium. Embryonic chicken eyes were processed for histochemical demonstration of ascorbate by silver staining. A strongly positive reaction was found in the interstitial matrix between the lens rudiment and the optic vesicle of the 2-day chicken embryo. By 3 days, with lens and optic cup separating from each other, the silver grains were concentrated in the vitreous cavity, primarily in a band-like configuration between the lens equator and the rim of the optic cup, which is the presumptive ciliary epithelium. A weaker reaction was seen in the lens vesicle and primitive neural retina. During the second and third day of incubation the optic vesicle is just beginning to expand. The appearance of ascorbic acid in the newly formed vitreous cavity at this time may indicate its importance in the biosynthesis of the matrix that is filling the expanding optic vesicle.

Animals↗

Comparison of ascorbic acid levels in the eye and remainder of the chicken embryo during development.

Ascorbic acid was not detectable in egg white and egg yolk of fertilized eggs prior to incubation. It was demonstrated in the embryo at 5 days of incubation and its content in the eyes and other parts of the embryo increased with the embryo's age. Ascorbic acid of the eyes rose rapidly after day 6 during maximal eye growth and reached a peak by days 10-14 when the expansion of the eyes began to level off. Ascorbic acid content of the eyes decreased thereafter, while ascorbic acid in the head and the body tissues continued to rise up to the time of hatching. Whether this rapid increase of ascorbic acid concurrent with the increase of eye diameter indicates a role for ascorbic acid in the growth of the embryonic eye remains to be determined.

Animals↗

Accumulation and distribution of sulfated materials in the maturing mouse lens capsule.

Lenses of late gestational and postnatal normal-eyed mice were tested for accumulated sulfated materials by using Spicer's high-iron-diamine staining method and also for newly incorporated sulfate autoradiographically following administration of 35SO4 either in vivo or in isolated and organ-cultured lenses. Accumulated and newly incorporated sulfate was observed in all lenses for each age group tested. Discrete regional differences were seen in histochemical staining patterns for sulfate on the lens capsule in specimens of all ages, and distinct laminar zonations were seen in the various regions of the capsule in older specimens. Typically, the anterior and equatorial regions of the capsule demonstrated three histochemically distinct laminar zones while the posterior capsule usually demonstrated two laminar zones. Autoradiographic results indicated that sulfate was indeed being incorporated into these regions, and in the same general pattern as seen with histochemistry. The materials were largely insensitive to testicular hyaluronidase but were preferentially sensitive to nitrous acid digestion, indicating the presence of capsular heparan sulfates. Autoradiographic results from organ-cultured lenses indicated that this tissue itself is a primary source of these materials.

Aging↗

Abnormal accumulation of sulphated materials in lens tissue of mice with the aphakia mutation.

Sulphated materials were tested for in the eyes of late gestational and postnatal normal mice and mice with the aphakia mutation using Spicer's high iron diamine staining method. Qualitative identification of these materials was attempted with bovine testicular hyaluronidase and nitrous acid digestion methods. The grossly abnormal morphology of the aphakia lens made it necessary to confirm identification of lens-derived tissue by testing for lens crystallins using standard immunohistological methods. As seen in normal mouse lens maturation, accumulated inter- and intracellular sulphated materials were observed in aphakia lens tissue from just before birth through juvenile maturation. Large cyst-like structures consisting of lens-derived tissue were commonly seen in the eyes of young postnatal mutant mice. Sulphated materials formed basal lamina-like structures on many of these lens-derived units, but a well-defined lens capsule never formed. Abnormal fibrillar structures rich in sulphated materials were seen in the intraocular cavity in many older mutant specimens, most of which were largely resistant to both digestion methods. These results indicate that the potential to elaborate sulphated materials qualitatively similar to those seen in normal mouse lens maturation is present in the aphakia mutant, although the mode of accumulation is grossly disturbed.

Animals↗

Ocular abnormalities in mucolipidosis IV.

Systemic findings in a 23-year-old white man with mucolipidosis type IV included early delayed psychomotor development, mental retardation, and mild facial dysplasia. There was urinary excretion of chondroitin sulfate. Ophthalmologic examination showed corneal haze, pigmentary retinopathy, and severe optic atrophy. Light microscopy showed massively engorged superficial and intermediate epithelial cells of both the cornea and the conjunctiva. By transmission electron microscopy these contained fine granular material consistent with acid mucopolysaccharide and concentric lamellar bodies presumably representing phospholipids. This storage phenomenon was also found in macrophages, plasma cells, ciliary epithelial cells, Schwann cells, retinal ganglion cells, and vascular endothelial cells. Light microscopy also disclosed early cataract formation, marked outer retinal degeneration, and optic atrophy.

Adult↗

Localization of keratin in the cells of the cornea in aphakia and normal mouse embryos.

Abnormal lens morphogenesis in the aphakia mutant in the mouse often results in a club-shaped elongated 'lens' that remains attached to the surface epithelium by a persistent connecting stalk, which is partially solid and partially cystic. Usually, the cells are continuous with the surface epithelium of the cornea and also with the cuboidal cells lining the corneal inner surface. Immunofluorescence with keratin antiserum not only gave positive reactions with the corneal epithelial cells, but also with many cells of the lens stalk, including its cysts, and with islands of cells on the inside of the cornea. These keratin-containing 'endothelial' cells may be the product of metaplasia of the endothelium into epithelium-like cells. Alternatively, they may also be the result of abnormal migration of epithelial cells into the eye or of abnormal differentiation of neural crest cells.

Animals↗

Development of acuity and stereopsis in infants with esotropia.

Visual acuity and stereopsis of 19 esotropic infants and toddlers, 36 normal infants and 7 children with refractive anomalies were measured during the first three years of life using newly developed preferential looking procedures. Children with infantile esotropia corrected with prisms equal in size to the deviation show some degree of binocularity up to at least 21/2 years, as measured by a polaroid bar stereogram procedure with a 1800 seconds of arc disparity. A few children, who did not receive any therapeutic intervention, failed this test during the first and second year. However, all older subjects (over 6 years of age) with a history of infantile esotropia failed the test.

Adolescent↗

Melanin macroglobules as a cellular marker of neurofibromatosis: a quantitative study.

To investigate the usefulness of melanin macroglobules (MMG) as a cellular marker for neurofibromatosis, their density was quantified in biopsies of café-au-lait spots (macules) (CALM) from 22 patients with von Recklinghausen's neurofibromatosis, 6 patients with bilateral acoustic neurofibromatosis, and 19 controls. The density of MMG was significantly higher in biopsies of the CALM of patients with von Recklinghausen's neurofibromatosis than in patients with bilateral acoustic neurofibromatosis (p less than .01) or controls (p less than .0008). The mode of acquisition of von Recklinghausen's neurofibromatosis (inherited vs new mutation) was not related to the density of MMG. On light microscopy, 14/22 (64%) patients with von Recklinghausen's neurofibromatosis had 11 or more MMG per 5 high-power fields. In contrast, none of the other two groups had more than 10 MMG per 5 high-power fields.

Adolescent↗

Histochemical analysis of extracellular matrix material during embryonic mouse lens morphogenesis in an aphakic strain of mice.

Extracellular matrix material (ECM) present during early lens morphogenesis was analyzed histochemically in normal CFW mice and mutant strain aphakia by the Alcian blue 8GX, pH 2.5, Alcian blue 8GX, pH 2.5/periodic acid-Schiff combined, high-iron diamine, and van Gieson methods. At lens placode formation, the optic vesicle basal lamina in both strains was higher in sulfated glycosaminoglycan content than was the ectodermal basal lamina. In the aphakia strain, ECM components were observed intercellularly in the presumptive neural retina and lens rudiment of some specimens. This observation was peculiar to the aphakia strain. At the lens cup stage (10.5 days), the interface ECM became less uniformly dense in the CFW strain, resulting in the formation of a fibrillar structure in the widening interspace area. In contrast, the interface ECM in the mutant strain stained solidly and continuously for acidic materials, particularly sulfated glycosaminoglycans, for a full 2 days longer than in the normal strain. The optic cup and lens rudiment remained closely apposed and intercellular ECM components were observed in these tissues in most mutant specimens throughout these stages. The exact mechanism resulting in these intercellular deposits is unknown, although it is possible that they are either pulled along on the cell surface away from the interface ECM during cell shape changes related to the cell cycle or that they are secreted abnormally due to some disturbed cellular polarity. It is unclear at this time if these abnormalities of the ECM in the aphakia strain play a role in the pathogenesis of the multiple eye anomalies, or if they are a secondary effect of the gene mutation.

Animals↗

The appearance of alpha, beta and gamma crystallins in an anophthalmic strain of mice.

A certain percentage of congenitally anophthalmic mouse embryos have the ability to generate small lens vesicles that have previously been shown to produce alpha crystallin at 13-day gestation. Further immunohistological analysis of 13- and 15-day-gestation anophthalmia embryos indicates that beta crystallin is present in those 13-day embryos which have lens vesicles with lens-fiber formation. Also, 15-day embryos with lenses demonstrating fiber elongation can produce both beta and gamma crystallins. The conclusion is drawn that the genetic potential to produce at least three characteristic biochemical markers of normal lens differentiation is present in the anophthalmia mutant. The spatial distribution patterns of the crystallins in normal and anophthalmia embryos were similar. However, there appeared to be a transposition in the temporal appearance of beta and gamma crystallins in the anophthalmia mutant. Optic cups and associated lenses in 15-day anophthalmia specimens were much smaller than those in controls. The optic and lens rudiments in these anophthalmia embryos were fairly proportional in size, which indicates that some degree of allometric growth compensation had occurred during the course of development. This ability for differential growth compensation in the mouse eye appears to be restricted to the predifferentiative stages of eye formation.

Animals↗

Cell replication and terminal differentiation in the embryonic chicken lens: normal and forced initiation of lens fibre formation.

The relation between cell replication and lens fibre formation was studied in normal 5-day chicken embryos and in embryos in which the lens was reversed. After this microsurgery the epithelial cells were facing the retina and were forced to start fibre differentiation. Embryos were treated with [3H]thymidine followed by autoradiography or with Colcemid to induce metaphase arrest. About half of the control epithelial cells were actively replicating (in contrast, in the earliest stages of lens formation all cells are multiplying). Half of the non-dividing population was accounted for by the annual pad cells. The other half, probably in a resting phase (GO) of the cell cycle, was perhaps slightly more common in the central epithelium. This suggests that a germinative zone may be forming in the lens epithelium as early as 5 days of embryonic life. Normal epithelium had a cell cycle time of about 11 h, with S-phase, M, G1 and G2 lasting 5.5, 0.5, 2, and 3 h. After reversal the labelling index remained at control levels for about 4 h and then dropped to zero at 9 h. Similarly, the mitotic index gradually decreased to zero in 15. It appears that reversal forces the epithelial cells to cease replication when they reach G1. Cells already in GO may form fibres without first going through DNA synthesis. The very sharp boundary between dividing and non-dividing cells at the border of the optic cup suggests that the retina may regulate the irreversible cessation of cell replication associated with lens fibre differentiation.

Animals↗

Eye findings in patients with phenylketonuria.

Untreated phenylketonuria (PKU) is characterized by excretion of phenylpyruvic acid in the urine and mental retardation. Reported eye abnormalities include photophobia (probably due to the albinoid iris), cataracts, and corneal opacities. Eleven patients in an institutionalized population of approximately 1,000 mentally retarded patients had PKU. Cataracts were found in six patients. One patient had bilateral phthisis bulbi and one patient had monocular phthisis. No corneal opacities were found otherwise. All patients with cataracts were middle-aged or had a history of severe self-induced trauma or treatment with high dosages of thioridazine hydrochloride. Albinism is associated with anomalous chiasmal routing of optic fibers and abnormal, extraocular motility. The ocular hypopigmentation of patients with PKU did not have the same results; all seeing patients were orthophoric. Although eye abnormalities are common in PKU except for hypopigmentation, none can be considered a direct effect of the inborn error of metabolism.

Adult↗

The appearance of alpha-crystallin in relation to cell cycle phase in the embryonic mouse lens.

Specific protein synthesis in the embryonic mouse lens was studied by immunofluorescence with antisera to adult mouse lens or crystallin fractions. Positive reactions were first detected in a few cells of the lens cup 18-24 hr after contact between optic vesicle and presumptive lens ectoderm had been established. During formation of the lens vesicle a rapidly increasing fraction of cells produced crystallins. At the time of detachment of the vesicle from the surface all cells of its posterior wall showed immunofluorescence. After fiber elongation became distinct cells of the anterior epithelium began to fluoresce and shortly afterwards the entire rudiment produced crystallins. The early reactions were due entirely to the presence of alpha-crystallin. Reactions were restricted to the lens. Thus, in the mouse as in other species crystallins were detectable by immunofluorescence in vivo only after lens morphogenesis was well underway and only in the lens rudiment itself. Cells first synthesizing crystallins always had an elongated shape and their nuclei were in a basal position. A few hours later mitotic cells displayed fluorescence. Taking into account earlier found relations between cell morphology and cell cycle phase, this indicates that alpha-crystallin is first demonstrable in the S-or early G-2 phase of the cell cycle, and that the start of its synthesis does not preclude continued cell replication. It is interesting that the cellular location, cell cycle phase, and developmental stage, in which crystallins first appear, are comparable in mouse and chick embryo. Yet, entirely different proteins are involved: alpha-crystallin in the first, delta-crystallin in the latter. Implications of this for our understanding of lens induction are discussed.

Animals↗

Crystallin synthesis in the lens rudiment of a strain of mice with congenital anophthalmia.

Immunofluorescence with anti-crystallin antisera was done on the eye rudiments of mouse embryos of a congenitally anophthalmic strain. In a few of the embryos a lens vesicle formed, which, although much smaller than in controls and delayed in development, appeared morphologically normal. alpha-Crystallin could be identified in the cells of the rudiments. In addition the cells looked cytologically similar to those of the normal lens vesicle; they were elongated and the nuclei displayed interkinetic nuclear migration. Therefore, the surface ectoderm of the anophthalmia mouse can differentiate into a lens vesicle that appears biochemically and cytologically normal. This indicates that the optic vesicle in this mutant is capable of inducing a lens, while the surface ectoderm can respond to the stimulus in a normal fashion.

Animals↗

Psychophysical assessment of visual acuity in infants with visual disorders.

The measurement of visual acuity is an essential part of the eye examination of adults, but is rarely attempted in infants being examined for presumed or known eye disease. We have used a preferential looking technique to test visual acuity of infants attending a hospital eye clinic. Serial measurements of acuity of infants attending a hospital eye clinic. Serial measurements of acuity in infants with certain eye diseases can provide examples of the effects of visual deprivation on the developing human visual system. Amongst 14 cases of monocular visual form deprivation in early life, there were 9 infants who had monocular occlusion as therapy for esotropia; 3 infants who had unilateral opacities of the ocular media; and 2 infants who had unilateral eyelid closure from infection or burns. Despite differences in exact mode of deprivation, the effects on visual acuity were similar. There was a reduction of visual acuity in the deprived eye and a simultaneous increase in acuity of the non-deprived eye. These effects of monocular deprivation were not permanent. Recovery occurred with reverse deprivation or by simple cessation of the deprivation. Of 10 children with binocular visual form deprivation, there were 5 who had bilateral congenital cataracts and 5 who had bilateral uncorrected high refractive errors. Infants with cataract surgery before 2 months of age showed normal early development of visual acuity. A 4-6 month delay before treatment resulted in reduced acuity, but recovery subsequently occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Nanophthalmos with uveal effusion: clinical and embryologic considerations.

Three brothers were found to have nanophthalmos as evidenced by marked hyperopia, decreased global axial length, and shallow anterior chambers. The thickness of the lens, measured with A-scan ultrasound biometry in two cases, was much greater than normal. Choroidal thickening with shallow retinal detachments without breaks was found in those patients. Fluorescein angioscopy demonstrated leaks beneath the serous retinal detachments in one. The spontaneous presence of choroidal effusions and retinal detachments in nanophthalmic patients has been reported only rarely. The present findings emphasize that careful examination of the posterior segment should be done prior to anterior segment surgery in these patients to alert the surgeon to the possibility of serious intra- and post-operative choroidal effusions and retinal detachments. An attempt is made to explain some of the clinical findings in nanophthalmos by extrapolating from results obtained on experimental animals. It is postulated that the increased lens size in nanophthalmos may be due to the abnormal accumulation of a factor influencing lens fiber differentiation. The overall small size of the eye may be the result of the formation of a smaller than usual optic vesicle anlage.

Aged↗

Malorientation of mitotic figures in the early lens rudiment of aphakia mouse embryos.

In early embryonic epithelia most cell divisions are oriented with their cleavage furrows perpendicular to the free surface of the tissue. This results in the generation of two daughter cells, which are equivalent with regard to their apical surface. Mitotic figures, in which the long axis through the centers of the chromosome plates (chromatin masses) is perpendicular to the surface, are seen only occasionally. The lens placode and early lens cup of mouse embryos homozygous for the gene aphakia show significantly greater numbers of maloriented mitoses than normal control lenses. The axis connecting the centers of the chromosomal plates is frequently perpendicular or oblique to the surface. This may result in the production of daughter cells, which are unequal as far as their position at the tissue surface is concerned. Later, the lumen of the mutant lens vesicle fills up with cells, which are apparently released from the lens epithelium. Further development of the lens and the eye is grossly disturbed. The release of these cells may be a consequence of the malorientation of their divisions, or both may be the result of a defect in the spatial organization of the lens tissue, possibly due to abnormal cellular adhesion.

Animals↗