Photoreceptor morphogenesis in the human retina: A scanning electron microscopic study

There are a number of scanning electron microscopic (SEM) studies on retinal photoreceptors of vertebrates. However, most of these are concerned with the adult retina, and only a very few deal with developing photoreceptors. In man, SEM studies have not been carried out on photoreceptor morphogenesis during fetal or postnatal stages. Hence, the present study was undertaken to examine the sequential morphological changes in developing photoreceptors during different gestational ages in the human retina. Retinas of human fetuses of gestational ages of 10–25 weeks and from autopsy of a 5-month-old infant were processed for SEM. The observations show some new information on the morphogenesis of photoreceptors. At 10–11 weeks, the outer and inner neuroblastic zones are well developed and separated from each other by the layer of Chievitz. By 15–16 weeks, the photoreceptor precursors appear as spherical inner segments on the scleral surface of the outer neuroblastic zone. Cilia develop as small protrusions from the apical ends of the inner segments. Photoreceptor inner segments become arranged in mosaic pattern by 18–19 weeks. In the mosaic, large cone inner segments (putative blue cones) stand out prominently from the remaining small cone inner segments (prospective red/ green cones). The rod inner segments are identifiable and show cilia. Between 19–20 and 24–25 weeks, the cone inner segments elongate and change in shape from spherical to oval. At 24–25 weeks, the outer segments develop from the distal ends of rod cilia. At this period, the inner segments of rods and cones are interconnected by protoplasmic projections. Although the precursors of both rods and cones appear to be in a similar state of development at 14–15 weeks gestation, the rods undergo morphological maturation earlier than do the cones. Photoreceptor development in the anterior retina lags behind that of the posterior retina by about 10 weeks. At 5 months after birth, the posterior retina possesses fully developed photoreceptors that are comparable to those of the adult. However, the photoreceptors in the ora serrata resemble those in the posterior retina of 24–25 weeks gestation. Anat. Rec. 252:133–139, 1998. © 1998 Wiley-Liss, Inc.     

Enzyme-histochemical visualization of lymphatic capillaries in the mouse tongue: light and electron microscopic study

The distinction between lymphatic capillaries and blood capillaries in the mouse tongue was studied enzyme-histochemically by light and electron microscopy. The lymphatic walls are characterized by a strong 5'-nucleotidase (5'-Nase) activity, whereas those of the blood capillaries reveal a significantly lower or no activity. The alkaline phosphatase (ALPase) activity, on the other hand, is markedly higher in the blood capillaries than in the lymphatic capillaries. The specific reaction of 5'-Nase activity in the lymphatic capillaries is obtained by simultaneous inhibition of ALPase on incubation in a medium (Wachstein and Meisel, 1957) with L-tetramisole for 5'-Nase histochemistry. The distribution and intensity of 5'-Nase activity in the lymphatic capillaries can be adequately visualized by comparison with serial cryostat sections for histochemical detection under light and backscattered imaging scanning electron microscopes. The reaction products of the 5'-Nase activity are localized on the outer surface of the cell membrane of the lymphatic endothelial cells, whereas those in the blood capillaries reveal a weak or no reaction. The present results demonstrates satisfactory isolated visualizations of 5'-Nase activity in the lymphatic capillaries and of ALPase activity in the blood capillaries.     

A light and electron microscopic study of mannosidosis

The present work investigated the light and electron microscopic changes in hypertrophied gingiva in a patient with mannosidosis. The biopsy specimens studied covered a period of 20 months; biopsy specimens were taken before and after a therapeutic trial with oral and local zinc sulfate. The intensity of the disease was progressive, in spite of the zinc, and was characterized by marked hyperplasia of the epithelium and severe inflammation of the stroma. Many of the cells in the inflammatory infiltrate, as well as cells indigenous to the gingiva, showed a striking vacuolation of their cytoplasm. Histiocytes were most numerous and also were most heavily vacuolated, but fibroblasts, endothelial cells, plasma cells, and epithelial cells also manifested the vacuolar change. In the histiocytes, the vacuoles occupied most of the cytoplasm, ranged widely in size, and were contiguous, molded, and intercommunicating. The vacuoles were bound by a single membrane and were filled predominantly by a finely granular material of medium density but also by varying amounts of coarser, darker granules, fragmented membranes, myelin-like figures, lipid droplets, and small vesicles. The vacuoles were interpreted as being consistent with secondary lysosomes that contained excessively stored substrate, similar to what has been observed in the mucopolysaccharidoses, in which the vacuoles have also been demonstrated histochemically and cytochemically to contain acid phosphatase, a known lysosomal marker.     

The thyroid in the spontaneously hypertensive rat: A light and electron microscopic study

The present study was undertaken to seek ultrastructural changes in the thyroid gland of the spontaneously hypertensive rat which would contribute to the understanding of previously reported abnormalities in thyroid function. Light and electron microscopic observations and measurements of plasma T3 and systolic blood pressure were recorded from a colony of Wistar-Kyoto rats (WKY) and of spontaneously hypertensive rats (SHR). The systolic blood pressure of SHR was significantly higher than that of WKY but the plasma T3 levels of the two groups did not differ significantly. After administration of propylthiouracil (PTU), serum T3 levels and systolic pressure of both groups decreased. The size of the thyroid follicles in SHR was highly variable throughout the gland, and the colloid contained unevenly dense areas and cell debris. The follicular cells contained slightly dilated rough surfaced endoplasmic reticulum (ER) and numerous pleomorphic bodies of uneven density. After treatment with PTU, the vessels between the follicles of SHR did not become as dilated as those in WKY but the fine structure of follicular cells in SHR was similar to that of WKY and was characteristic of the typical thyroid response to PTU administration. We suggest that the thyroid in SHR does not respond adequately to the elevated TSH levels reported to be present in these animals, although it can respond to the highly elevated TSH levels which occur with PTU administration. This impairment most probably involves defects in synthesis and/or secretion of thyroid hormones in response to TSH stimulation.     

In utero development and maturation of the retina of a non-primate mammal: A light and electron microscopic study of the guinea pig

Summary A light and electron microscopic examination of retinogenesis in the fetal guinea pig has revealed an early development of synapses and photoreceptor cells. Differentiation of the neural retina begins around day 23 of gestation. By 34 days the retina reaches its maximum thickness. It differentiates an inner plexiform layer in which vesicle-containing processes and primitive synapses are evident. Synaptic ribbons are found in processes of this layer by 43–45 days of gestation. An outer plexiform layer develops within the neuroblast layer at 40 days of gestation; from its first appearance the outer plexiform layer contains synapses complete with synaptic ribbons. Receptor terminals of the , paranuclear and type are present well before birth. Photoreceptor cells form inner segments by 40 days; the formation of outer segments is indicated by 45 days but not widespread until 49 days. The retina appears mature by day 51–57. It is clear that the primate is not unique in the early differentiation of its retinal synapses relative to the time of maturation of its photoreceptor cells. The potential functional capacities of precocious retinae, and the mechanisms of synapse development are discussed.Supported by Grants from the Medical Research Council.     

Citrinin nephrotoxicity in rats: A light and electron microscopic study

Citrinin, a myocotoxin produced by Penicillium citrinum, causes hepatic and renal damage. This study describes light and electron microscopic changes in rat kidneys at intervals of 24, 48, 72, and 96 hr following administration of 50 mg/kg citrinin. Twenty-four hours after treatment, the most prominent change was cytoplasmic vacuolization of epithelial cells of proximal convoluted tubules. This vacuolar change involved clusters of proximal convolutions. Such focal changes were distributed throughout the cortex. Other components of the cortex and medulla appeared relatively normal morphologically; distal tubular damage was not observed. At 48 hr following administration of citrinin, multifocal areas of necrotic proximal convoluted tubules were observed. Extensive mineral deposits were present in the necrotic areas. Intact proximal and distal tubules were observed between the necrotic areas, and components of the medulla were not appreciably altered. At 72 hr, various degrees of regeneration of proximal tubular epithelial cells were noted in areas of necrosis in the cortex. Ninety-six hours following citrinin administration, tubular regeneration was still prominent and, in some cases, kidneys appeared completely normal morphologically.     

A light and electron microscopic study on the embryonic development of the rat carotid body

The embryonic development of the rat carotid body was studied with electron microscopy. In the 11 mm embryo a cell aggregation consisting of undifferentiated cells and unmyelinated nerve fibers appears on the anterior wall of the third branchial artery. Granule-containing cells appear in the 12 mm embryo and continue to increase in number as the cellular aggregation increases in size and becomes separated from the wall of the third branchial artery. Synapse formation and the appearance of fenestrated capillaries occur almost simultaneously at the 17 mm stage. There are two types of synapses, one with membrane densification and vesicles clustered inside the nerve endings, the other with dense material and vesicles inside the granule-containing cells. At the 20 mm stage the undifferentiated cells send enveloping cytoplasmic processes toward adjacent granule-containing cells and the carotid body anlage displays rudimentary lobules.     

Esthesioneuroblastoma: a light and electron microscopic study

The electron microscopic features of an olfactory esthesioneuroblastoma are described. The tumor cells had well developed neuritic processes containing neurotubules and neurofibrils. In addition, neurosecretory granules, similar to those seen in adrenal neuroblastomas, were present in the main cell body as well as in the neuritic processes. The neurites were also well demonstrated by light microscopic examination when stained by the Palmgren silver method. The importance of demonstration of these processes in establishing a firm diagnosis is stressed. Electron microscopic demonstration of neurites and secretory granules in a nasal tumor is diagnostic of an esthesioneuroblastoma.     

Non-pyramidal hippocampal projection neurons: A light and electron microscopic study

Summary Following injections of horseradish peroxidase conjugated with wheat germ agglutinin into the medial nucleus accumbens of the rat, a large number of projecting pyramidal neurons in the hippocampus were retrogradely labelled. In addition to this major projection, a few retrogradely labelled cells were tentatively identified at the light microscopic level as non-pyramidal neurons. These presumptive non-pyramidal neurons were found in all hippocampal layers, although they were mainly outside the stratum pyramidale, in the stratum oriens. Ultrastructurally, in serial sections, the non-pyramidal nature of 20 of these neurons was confirmed by their characteristic features such as deeply indented nuclei, occasional intranuclear inclusions, and symmetric and asymmetric synaptic contacts with their somata. Possible-transmitters used by these neurons are discussed.     

A light and electron microscopic study on pulpal nerve fibers in the lower incisor of the mouse.

Light and electron microscopic studies were made on pulpal nerve fibers in mouse lower incisors, typical continuously growing teeth. Serial sections, from the apex of the odontogenic sheath to the incisal edge of the apical foramen, were examined by light microscopy to identify myelinated fibers passing through the apical foramen. The fine structure of the pulpal nerves was examined by electron microscopy at three sites: 1) the level at the incisal edge of the apical foramen; 2) a level 5 mm incisal from the apex of the odontogenic sheath; and 3) the level where the incisor comes out of the alveolar bone. No myelinated fibers were found passing through the apical foramen; they were also lacking at the three levels of the pulp. At level 2, unmyelinated axons were seen in close contact with smooth muscle fibers of arterioles. At level 3, nerve fibers were difficult to distinguish from processes of fibroblasts and odontoblasts. Degenerating axons were present in Schwann cells, and fine unmyelinated axons running through the odontoblast cell layer were seen. Various types of unmyelinated axons were observed in the apical region (level 1). These axons were classified into 6 types on the basis of their fine structures: Type I, bundles of unmyelinated axons completely or partly ensheathed by Schwann cell cytoplasm (mature type); Type II, bundles of unmyelinated axons in a space formed by a Schwann cell membrane (regenerating type); Type III, bundles of unmyelinated axons ensheathed not by a Schwann cell, but merely by a basal lamina (regenerating type); Type IV, single axons in direct contact with the basal lamina (regenerating or terminal type); Type V, naked, electron-dense axons with many vesicles and mitochondria (growth cone-like type); and Type VI, electron opaque axons, due to loss of axonal organellae (degenerating type). The significance of these structures is discussed in relation to the continuous growth of the rodent incisor.     

Giant cell carcinoma of the lung: A light and electron microscopic study

Three cases of giant cell carcinoma of lung and six other lung carcinomas with large atypical cell formation were studied by both light and electron microscopy. Giant cell carcinomas showed unique light and electron microscopic features, whereas large atypical cells from other lung carcinomas usually retained some ultrastructural characteristics of their cellular origin. The giant cell carcinoma is characterized by abundant mitochondria, a concentric whorl of tonofilament-like fibrils, and aggregates of several pairs of centrioles. The “phagocytic activity” of the giant cell carcinoma is more likely attributable to the so-called tumor cell-tumor cell or leukocyte-tumor cell emperipolesis. Giant cell carcinoma of lung may originate from a primitive multipotential cell in the distal bronchiole or be associated with a squamous, glandular, or clear cell pattern. Whether in pure or mixed form, this tumor should still be considered a specific entity because of its unique light and electron microscopic features and the fulminant clinical course it follows despite rare reported exceptions.     

Tyrosine hydroxylase-immunoreactive neurons of the hypothalamus: A light and electron microscopic study

The localization and morphology of neurons, processes, and neuronal groups in the rat hypothalamus containing tyrosine hydroxylase-like immunoreactivity were studied using an antiserum to bovine tyrosine hydroxylase. This antiserum was thoroughly characterized by precipitation of enzyme activity, immunoblotting, and precipitation of cell-free translation products; a single molecular weight band was recognized by the antiserum. Absorption of the antiserum with purified tyrosine hydroxylase abolished immunocytochemical staining, while addition of bovine dopamine β-hydroxylase had no effect on immunostaining.Immunoreactive cells were found throughout the hypothalamus. Significant numbers of cells were found in the arcuate, periventricular, dorsomedial hypothalamus/zona incerta, posterior hypothalamic regions (A11–A14), and paraventricular nucleus, as previously described, and in addition, in the preoptic area, adjacent to the anterior commissure, medial and lateral to the suprachiasmatic nucleus, dorsal to and in the supraoptic nucleus, at the lateral borders of the ventromedial nucleus, and in the dorsal and ventral lateral hypothalamus. None of the immunoreactive cell groups are totally separated from adjacent cell groups. Dendritic overlap occurs between any two adjacent groups.From cell counts of 30 μm coronal sections, we estimate the hypothalamus has about 12,000 cells based on raw counts, or 8000 immunoreactive cells after correction for possible split cells. Mean soma size varied considerably from one immunoreactive group to another. Cells in the caudal part of the dorsomedial hypothalamus/zona incerta region were the largest, with a mean diameter of 25 μm, while cells in the anterior commissural and posterior hypothalamic group were among the smallest, with mean diameters of 10 μm. The largest immunoreactive cells in the hypothalamus had volumes in excess of ten times greater than the smallest immunoreactive cells.Tyrosine hydroxylase immunoreactivity was found in dendrites in every region of the hypothalamus, sometimes extending hundreds of micrometers from the perikaryon of origin. Although adjacent cell groups were not distinctly separated, the dendritic arbors of the different cell groups differed greatly. Dendritic and somatic appendages were found on some cells, particularly in the paraventricular nucleus. Immunoreactive dendritic arbors were particularly large in cells seen on horizontal sections through the caudal dorsomedial hypothalamic group and through the anterior hypothalamus. Only slight dendritic trees were observed in the rostral dorsomedial hypothalamus/zona incerta region, and in the pericommissural group.Immunoreactive axons, containing dopamine, norepinephrine or epinephrine, were found in every area of the hypothalamus. Axon morphology, size, density and terminals varied from region to region. Axons of hypothalamic origin arose from both immunoreactive somata and primary dendrites. A large number of non-synapsing immunoreactive axons were found in the median eminence, and many were also found throughout the hypothalamus. Retrograde transport of substances injected in the neurohypophysis labeled cells in the most rostral part of the arcuate nucleus and periventricular area; some labeled cells also showed tyrosine hydroxylase immunoreactivity. Many of the immunoreactive boutons contained primarily clear vesicles, while others contained both clear and large dense-core vesicles. Immunoreactive axons made synaptic contact with unlabeled dendrites.     

The ciliary ganglion of the cat: a light and electron microscopic study

The ciliary ganglia of eight healthy adult cats were studied by light and electron microscopy. The ganglion, measuring about 2 mm in length, was consistently found to be attached to the branch from the oculomotor nerve supplying the inferior oblique muscle. The number of neurons varied from 2773 to 3794 after applying Abercrombie's correction. The mean of average somal diameter of the neurons was 36.5 m (SD = 5.0 m) and the mean of somal cross-sectional area was 904.2 m² (SD = 262.8 m²). The mean of average nuclear diameter was 13.9 urn (SD = 1.8 m) and the mean of nuclear cross-sectional area was 142.2 m² (SD = 37.1 m²). The mean of the aspect ratios of the soma and nucleus were 1.2 (SD = 0.1) and 1.1 (SD = 0.1) respectively. The frequency distributions of these parameters were all unimodal. Under the light microscope, the Nissl granules in the neurons were prominent and were distributed peripherally, perinuclearly or randomly in the cytoplasm. Under the electron microscope, the rough endoplasmic reticulum showed a similar pattern of distribution in the cytoplasm. In some neurons, glycogen-like granules were present; these were either distributed randomly throughout the cell, or aligned in single rows in relation to sub-surface cisterns and between the cisterns of smooth and rough endoplasmic reticulum. Most of the dendrites were short protrusions from the cell body; some contained glycogen-like granules. Occasionally, the dendritic protrusions were electron-dense. All the synapses encountered were axodendritic. In most axon terminals, the synaptic vesicles were spherical and measured 30–50 nm in diameter; in some, they were flattened, measuring 50 nm by 20 nm. Some axon terminals containing either spherical or flattened synaptic vesicles also contained large dense-cored vesicles that measured 80–100 nm, while their dense core measured 40–60 nm.     

Retroperitoneal leiomyosarcoma: a light and electron microscopic study

Retroperitoneal leiomyosarcoma arising in a spermatic blood vessel is described. In addition to typical leiomyosarcoma, areas of atypical histiocyte-like cells and storiform pattern bearing a close resemblance to malignant fibrous histiocytoma, were seen. Ultrastructurally, cells with features of smooth muscle, partially differentiated cells with marginal densities and basal lamina and histiocyte-like giant cells were present. Phagocytosis of inflammatory cells by tumour cells with marginal densities and an investment of basal lamina was observed. It is suggested that the precursor cell in this lesion was a primitive mesenchymal cell showing varying degrees of smooth muscle differentiation and giant cell formation.