Fine structure of the retinal pigment epithelium in the Port Jackson shark (Heterodontus phillipi)

The structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been studied by light and electron microscopy in the Port Jackson shark (Heterodontus phillipi). In this elasmobranch the RPE consists of a single layer of low cuboidal cells which show basal (scleral) infoldings and apical (vitreal) processes that enclose photoreceptor outer segments. Laterally these epithelial cells are joined by a series of apically located tight junctions. The RPE cells display a large vesicular nucleus, abundant smooth endoplasmic reticulum as well as numerous polysomes and mitochondria. Phagosomes are present, rough endoplasmic reticulum is scarce and myeloid bodies were not observed. Melanosomes are absent over the choroidally located tapetum lucidum, but are not abundant even in extratapetal areas. This paucity of melanosomes probably makes retinomotor movements unimportant. Bruch's membrane or complexus basalis is a pentalaminate structure. The endothelium of the choriocapillaris is thin but minimally fenestrated.     

Fine structure of the retinal pigment epithelium in the Port Jackson shark (Heterodontus phillipi)

The structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been studied by light and electron microscopy in the Port Jackson shark (Heterodontus phillipi). In this elasmobranch the RPE consists of a single layer of low cuboidal cells which show basal (scleral) infoldings and apical (vitreal) processes that enclose photoreceptor outer segments. Laterally these epithelial cells are joined by a series of apically located tight junctions. The RPE cells display a large vesicular nucleus, abundant smooth endoplasmic reticulum as well as numerous polysomes and mitochondria. Phagosomes are present, rough endoplasmic reticulum is scarce and myeloid bodies were not observed. Melanosomes are absent over the choroidally located tapetum lucidum, but are not abundant even in extratapetal areas. This paucity of melanosomes probably makes retinomotor movements unimportant. Bruch's membrane or complexus basalis is a pentalaminate structure. The endothelium of the choriocapillaris is thin but minimally fenestrated.     

Formation and progression of sub-retinal pigment epithelium deposits in Efemp1 mutation knock-in mice: a model for the early pathogenic course of macular degeneration

Malattia leventinese (ML) is a dominantly inherited macular degenerative disease characterized by the presence of sub-retinal pigment epithelium (RPE) deposits. With the exception of an earlier age of onset, ML patients exhibit symptoms and histopathology compatible with the diagnosis of age-related macular degeneration (AMD), the most common cause of incurable blindness. ML is caused by a mutation (R345W) in the gene EFEMP1 which encodes fibulin-3, a protein of unknown function. We generated a knock-in mouse carrying the disease-associated mutation in the murine Efemp1 gene. Small, isolated sub-RPE deposits developed as early as 4 months of age in both heterozygous and homozygous knock-in mice. Over time these deposits increased in size and number eventually becoming continuous sheets. In older mice membranous debris was observed within the deposits and within Bruch's membrane, and was accompanied by general RPE and choroidal abnormalities including degeneration, vacuolation, loss or disruption of the RPE basal infoldings, choroidal atrophy, and focal thickening of and invasion of cellular processes into Bruch's membrane. Fibulin-3 was found to accumulate in the sub-RPE deposits. Thus, the Efemp1 knock-in mice reconstitute the most important histopathologic symptoms of both ML and AMD. We conclude that these mice are a valuable tool for studying the primary pathogenic course of basal deposits associated with macular degeneration and for testing prevention and treatment strategies for this class of diseases.     

Retinal epithelial fine structure in the brush-tailed possum (Trichosurus vulpecula)

As part of a comparative morphological study, the fine structure of the retinal pigment epithelium (RPE), the choriocapillaris and Bruch's membrane (complexus basalis) has been studied by electron microscopy in the brush-tailed possum (Trichosurus vulpecula), an Australian marsupial. In this species, the RPE consists of a single layer of squamous cells which show numerous shallow basal (scleral) infoldings as well as extensive apical (vitreal) processes enclosing rod outer segments. The epithelial cells are joined laterally by prominent, apically-located tight junctions. Internally smooth endoplasmic reticulum is the most abundant cell organelle with only small amounts of rough endoplasmic reticulum present. Basally-located mitochondria and apically-located melanosomes are abundant while polysomes and the occasional Golgi zone are also noted. The epithelial cell nucleus is large and vesicular. Bruch's membrane shows the typical pentalaminate structure noted for mammalian species. The choriocapillaris is a single layer of anastomosing capillaries which are heavily fenestrated facing the retinal epithelium.     

Morphological changes induced by prolonged darkness in the retinal pigment epithelium of the turtle (Pseudemys scripta elegans)

The retinal pigment epithelium of Vertebrates was shown to be sensitive to cyclic oscillations of light and darkness. The morphological changes induced by prolonged darkness on the retinal epithelial cells of the freshwater turtle were studied, with particular regard to their localization and to their reversibility if animals are recovered under cyclic light. The eyes were processed for light and electron microscopy and a morphological and morphometric analysis was performed on the specimens. After 7 days of prolonged darkness, the vitreal extremity of some epithelial cells was partially detached; on the basal zone the infoldings were missing and vesicles and tubules, often arranged in rows, were observed. After 30 days of prolonged darkness, partial or complete double layers of epithelial cells were present: the superficial layer was connected, by means of the apical fringes, to the photoreceptors, whilst the deepest layer showed vesicles and tubules on its basal zone. After 7 days of recovery to L:D = 12:12, no cyclic activity was demonstrated and only occasional double layers of cells were present; on the basal surface isolated basal infoldings were present where two adjacent cells were joined together. It could be concluded that the detachment of the apical part of some cells, rapidly covered by the lateral sliding of the adjacent cells, and the substitution of the basal infoldings with vesicles and tubules could represent the morphological response of the retinal epithelium to the functional changes induced by prolonged darkness.     

Ultrastructure of the main excretory duct epithelia of the rat parotid and submandibular glands with a review of the literature

The fine structure of the main excretory duct (MED) epithelia of the rat parotid and submandibular glands was investigated by scanning and transmission electron microscopy. The structure of these two MED epithelia was compared. Five principal cell types were observed in the MED epithelium of the parotid gland--cuboidal, basal, light (types I and II), dark, and tuft cells. The cuboidal cells, which were stratified in two or three layers, were the most numerous. Basal cells were situated adjacent to the basal lamina of the epithelium. The type I light cells had well-developed basal plasma membrane infoldings. The type II light cells had poorly developed basal plasma membrane infoldings. The dark and tuft cells resembled those of the MED epithelium of the rat submandibular gland. Four principal cell types were observed in the MED epithelium of the submandibular gland--light cells (types I and II), dark, tuft, and basal cells. The two types of light cells were the most numerous. Dark cells with regular and dense microvilli were relatively narrow in shape and had complicated basal plasma membrane infoldings. There were numerous vesicles or channel-like vesicles in their apical cytoplasm. Tuft cells were characterized by prominent microvilli, many vesicles of various sizes in the apical cytoplasm, and no basal infoldings. Peroxisomes were present in the MED epithelia of the rat parotid and submandibular glands, especially in light and cuboidal cells.     

Spatial cues for the enhancement of retinal pigment epithelial cell function in potential transplants

Retinal pigment epithelial (RPE) cellular morphology and function are vital to the health of the retina. In age-related macular degeneration, RPE dysfunction and changes in Bruch's membrane occur. Thus, a potential cure is a dual-layer biomimetic transplant consisting of a layer of healthy RPE cells cultured on a support membrane. In this study, we investigated human anterior lens capsule as a replacement for Bruch's membrane and also explored different seeding methods as ways of inducing the desired cellular morphology and function. Using in vitro assays, we demonstrated that RPE cells cultured on lens capsule exhibited epithelial characteristics, such as the presence of actin belts and the formation of tight junctions in the monolayer. Bovine photoreceptor outer segments were also incubated with the RPE cells in order to quantify the binding and ingestion activity of the RPE cells. With these assays, we determined that cells seeded by centrifugation appeared to possess the most epithelial-like morphology, with the shortest overall length and the smallest elongation. They also exhibited enhanced metabolic activity, with a 1.5-fold increase over conventional gravity seeding. Thus, the spatial cues provided by centrifugation may assist cells in assuming native RPE function. Therefore, a dual-layer transplant, with RPE cells organized by centrifugation onto lens capsule, appears promising in achieving native retinal function.     

A comparative study of thin-layer cross-sectional anatomic morphology and CT images of the basal cistern and its application in acute craniocerebral traumas

Aim  To compare the cross-sectional morphologic features of successive thin-layers and CT images of the basal cistern and its application in the diagnosis and management of acute craniocerebral traumas. Materials and methods  Successive thin-layer cross-sectional images of the basal cistern were retrieved from the second Chinese visible human (CVH) data set and observed. A total of 40 healthy volunteers were subjected to 64-slice spiral CT scan of the head, and CT images of the basal cistern were compared with CVH images. A total of 413 patients with acute craniocerebral traumas were subjected to 64-slice spiral CT scan of the head, CT image changes of the basal cistern were observed. Results  Thin-layer cross-sectional images retrieved from the CVH data set clearly displayed the sectional anatomic morphology, morphologic change pattern and important adjacent structures of the basal cistern. The quadrigeminal cistern was pateriform or sellaeform; the suprasellar cistern was hexagonal or pentagonal star-shaped; the ambient cistern encircled both sides of the brainstem like an arc band. CT images of the quadrigeminal and ambient cisterns were similar with their CVH images; however, the morphology of the suprasellar cistern changed substantially. In 413 patients with acute craniocerebral traumas, the basal cistern may be normal, or presented with narrowing, obliteration, shift, hematocele, and pneumatosis. Narrowing or obliteration of the basal cistern occurred mostly at the side of dominant intracranial lesions, and frequently occurred in patients with diffuse axonal injury or combination of SDH + CONT + ICH. Conclusions  Thin-layer cross-sectional images of the basal cistern retrieved from the CVH data set correspond satisfactorily to CT images of the basal cistern. Comparison of the two types of images can provide a sectional anatomic basis for the image identification of acute craniocerebral traumas. A careful observation on the initial CT images of the basal cistern for anatomic morphologic changes will help diagnose acute craniocerebral traumas early, improve the management, and appropriately predict the prognosis of the condition.     

The allantois of the North American opossum (Didelphis virginiana) with preliminary observations on the yolk sac endoderm and trophectoderm

During the middle of prenatal day 10, the opossum allantois forms as a ventral outgrowth of the hindgut. By day 11 it appears as a large, fluid filled sac and by the middle of day 12 (just prior to birth) it reaches its maximal development. The simple squamous epithelium lining the allantois consists of only one cell type that often contains numerous filaments in the apical cytoplasm. At the luminal surface, the apices of the cells are united by junctional complexes and desmosomes are present between adjacent cells. The luminal surface is irregular, whereas laterally and basally the cell membranes show few if any infoldings. Mitotic figures and presumptive degenerating cells occasionally occur in the allantoic epithelium which rests on a delicate basal lamina. The allantois is covered by a simple squamous mesothelium that lacks a distinct basal lamina. Between the two epithelial sheets lie mesenchymal cells, collagen fibers, and blood vessels. No specializations of cell membranes were noted in either of the epithelial layers. The yolk sac endoderm consists of a single layer of squamous cells whose cytoplasm contains scattered profiles of rough endoplasmic reticulum and mitochondria. Extensive lateral and basal infoldings of the plasmalemma were not observed in these endodermal cells. The morphology of the trophectodermal (trophoblastic) cells indicates a cell type that is active in the transport of materials. Since the endodermal cells that line the allantois lack morphological features that would suggest the presence of mechanisms for transport or exchange, and because they remain relatively unchanged throughout pregnancy, it is thought that the allantois functions primarily in the storage of urinary wastes during prenatal life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uptake of exogenous substances and marked infoldings of the fluorescent granular pericyte in cerebral fine vessels

Exogenous substances such as trypan blue and horseradish peroxidase administered intraventricularly are taken up by granular pericytes in cerebral fine vessels. These cells are provided with elongated and complicated infoldings. Pinocytotic vesicles occur often along the infoldings, and ends of infoldings are swollen and assume vesicular shapes. The specific morphology of the granular perithelial cells is considered to favor a removal of metabolic wates in cerebral tissue.     

Can the apparent adaptation of dopamine neurons’ mismatch sensitivities be reconciled with their computation of reward prediction errors?

According to modern reinforcement learning theories, midbrain dopamine (DA) neurons are part of an adaptive system within which learned expectations filter reward-related signals to enable computation of reward prediction errors (RPEs). Recent electrophysiological data on DA neuron responses to probabilistic reward schedules inspired the idea that DA neurons might be adapting their mismatch sensitivities to reflect variances of expected rewards. Taken literally as a mathematical hypothesis, this idea contradicts reinforcement learning theory, and most computational models of basal ganglia learning. Here, we report a qualitative mathematical derivation of the implications of a generic class of circuit models for learning to compute RPEs. This analysis and concordant circuit simulations, both of which predict DA neuron responses on probabilistic schedules, support a reinterpretation of the electrophysiological data that is fully compatible with the examined class of RPE models. This reinterpretation implies a novel and readily testable prediction.     

基底前脑巢蛋白免疫阳性神经元研究现状及展望

目的阐述基底前脑nestin免疫阳性神经元的研究现状,为后续研究提供依据。方法对近年发表的有关基底前脑nestin免疫阳性神经元的文献进行分析和综述。结果在人和大鼠的基底前脑存在着一群能表达nestin的成熟神经元,这群神经元是区别于胆碱能神经元和γ-氨基丁酸能神经元的独立的神经元。其形态和分布与胆碱能神经元相似,向海马、大脑皮质及丘脑投射,与学习记忆及神经元的可塑性有关。结论基底前脑nestin免疫阳性神经元的化学属性、纤维联系及电生理特征等有待于进一步研究。这些研究将有助于我们了解成熟神经元表达nestin的功能意义,并为相关疾病的诊治提供新的视角。     

Ocular toxoplasmosis: the role of retinal pigment epithelium migration in infection

Our aim was to study the migration of retinal pigmented epithelium (RPE) into the retinal layer during infection of C57BL/6 mice with Toxoplasma gondii. Eyes from infected and non-infected animals were analyzed on the 60th day of infection by light and transmission electron microscopy. Non-infected eyes showed a normal morphology. In contrast, we observed free parasites in the retinal vasculature, the presence of mononuclear inflammatory infiltrate (MNII) and parasites in the vasculature of choroids in infected eyes. No inflammatory infiltrate was observed; RPE cells were identified near the MNII in nuclear and plexiforme layers. RPE cells were also found on the ganglion cell layer and in the outer segments of the photoreceptor. The morphology showed that RPE cells caused a discontinuity in the nuclear and plexiforme layers. Clusters of parasites were found surrounded by RPE cells and MNII in the inner plexiforme layers. Ultrastructural analysis showed that RPE cells migrated through the epithelium into the inner retinal layers. We did not observe Toxoplasma cysts in many eyes in which pathological changes were detected. Only 8.3% of the animals had Toxoplasma cysts in the inner nuclear layer in the absence of inflammatory cells. The migration of RPE cells can be triggered by a disruption of the RPE monolayer or injury to the neural retina, as in the case of toxoplasmosis.     

Retinal pigment epithelial fine structure in the velvet cichlid (Astronotus ocellatus)

Summary The morphology of the retinal pigment epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) have been studied by light and electron microscopy in the velvet cichlid (Astronotus ocellatus). The RPE is composed of a single layer of large columnar cells. The basal (scleral) border of these cells is minimally infolded, whereas the apical (vitreal) surface displays numerous pigment-laden processes which in light-adaptation surround both rod and cone outer segments. Laterally the RPE cells are joined by a series of basally located tight junctions. Wandering phagocytes are a constant feature within this epithelial membrane. The RPE cells display a large, vesicular nucleus, numerous mitochondria, much smooth endoplasmic reticulum, polysomes, myeloid bodies, phagosomes and melanosomes. Rough endoplasmic reticulum is relatively scarce within these cells. Although only light-adapted specimens were examined, it is thought that the melanosomes are capable of extensive retinomotor movement. The endothelium of the choriocapillaris facing Bruch's membrane is typically very thin but shows few fenestrations. Bruch's membrane is typical of other teleost species in that it is composed of only three layers.     

成年大鼠基底前脑存在一个Nestin免疫阳性神经元簇

目的　观察Nestin免疫活性在成年大鼠基底前脑中的表达和分布 ,并探讨其与胆碱能神经元之间的关系。方法　采用免疫组化方法对成年大鼠基底前脑的切片进行nestin免疫组化染色及其与ChAT ,NADPH d双标染色。结果　在成年大鼠基底前脑的隔斜角带复合体有一个连续的nestin免疫阳性细胞带 ,胞体较大 ,梭形或多极形 ,有 2～ 4个突起。双标染色显示 ,Nestin阳性神经元与ChAT ,NADPH d阳性神经元间杂分布 ,大多数不呈交叉反应 ,只有少数 ,约 10 %呈双标染色。结论　成年大鼠基底前脑存在一个有别于胆碱能神经元的nestin免疫阳性神经元簇 ,其化学属性和生物学意义有待进一步研究。     

Interstitial Capillary in Normal and in Transplanted Kidneys: An Ultrastructural Study

Knowledge about the normal structure and pathology of interstitial capillary is limited. Splitting and multilayering of the basal membrane (BM), as a marker of chronic rejection, has been published in association with transplant glomerulopathy. The authors investigated the ultrastructural features of the interstitial capillary basal membrane in normal (15 biopsies) and in transplanted kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8 biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6 patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8 patients). All biopsies were fixed in 1%OsO 4, embedded in Epon, and examined by electron microscope. Measurements of the interstitial capillary BM were made. The BM of interstitial capillary of intact kidney was a homogenous continuous structure, 88 nm in width on average. Thickening with diffuse multilayering of BM was most intensive in patients with transplant glomerulopathy, and much less intensive in patients with acute tubulointerstitial rejection and in patients with recurrent or de novo glomerulonephritis. These findings may provide the first information about the morphology of the normal basal lamina of interstitial capillary and support the diagnostic value of interstitial capillary changes in chronic rejection.     

大蒜素对人皮肤基底细胞癌A431细胞的放疗增敏作用研究

目的 探讨大蒜素(Allicin)是否能增加人皮肤基底细胞癌A431细胞的放疗敏感性及其作用机制.方法 MTT法检测Allicin对A431细胞的生长抑制率,筛选出半数抑制浓度(IC50);将细胞分为对照组、照射组(IR组)、Allicin组和IR+Allicin组.采用流式细胞仪检细胞自噬水平.结果 MTT结果显示大蒜素作用A431细胞24、48、72 h后IC50分别为35.47、18.64、6.56 mmol/L(F =22.54、18.94和21.63,P＜0.05).和对照组相比,Allicin组和Allicin+ IR组A431细胞的自噬水平均增加(F=30.15、28.36,P＜0.05),以Allicin+ IR组升高最显著.结论 Allicin通过上调人皮肤基底细胞癌A431细胞的自噬水平来增加其放疗敏感性.     

Polarized Vascular Endothelial Growth Factor Secretion by Human Retinal Pigment Epithelium and Localization of Vascular Endothelial Growth Factor Receptors on the Inner Choriocapillaris : Evidence for a Trophic Paracrine Relation

The retinal pigment epithelium (RPE) maintains the choriocapillaris (CC) in the normal eye and is involved in the pathogenesis of choroidal neovascularization in age-related macular degeneration. Vascular endothelial growth factor-A (VEGF) is produced by differentiated human RPE cells in vitro and in vivo and may be involved in paracrine signaling between the RPE and the CC. We investigated whether there is a polarized secretion of VEGF by RPE cells in vitro. Also, the localization of VEGF receptors in the human retina was investigated. We observed that highly differentiated human RPE cells, cultured on transwell filters in normoxic conditions, produced two- to sevenfold more VEGF toward their basolateral side as compared to the apical side. In hypoxic conditions, VEGF-A secretion increased to the basal side only, resulting in a three- to 10-fold higher basolateral secretion. By immunohistochemistry in 30 human eyes and in two cynomolgus monkey eyes, KDR (VEGFR-2) and flt-4 (VEGFR-3) were preferentially localized at the side of the CC endothelium facing the RPE cell layer, whereas flt-1 (VEGFR-1) was found on the inner CC and on other choroidal vessels. Our results indicate that RPE secretes VEGF toward its basal side where its receptor KDR is located on the adjacent CC endothelium, suggesting a role of VEGF in a paracrine relation, possibly in cooperation with flt-4 and its ligand. This can explain the known trophic function of the RPE in the maintenance of the CC and its fenestrated permeable phenotype and points to a role for VEGF in normal eye functioning. Up-regulated basolateral VEGF secretion by RPE in hypoxia or loss of polarity of VEGF production may play a role in the pathogenesis of choroidal neovascularization.     

The fine structure of compensatory growth in the rat kidney after unilateral nephrectomy

The structural changes in the nephrons of the rat kidney during compensatory growth were observed for 96 hours following unilateral nephrectomy. Hypertrophy of tubular epithelial cells involves dilation of the cisternae of rough endoplasmic reticulum, proliferation of Golgi membranes and agranular reticulum, and increase in number of cytoplasmic ribosomes. The appearance of absorption droplets and microtubules, that are polarized along the cell axis, coincides with maximal hypertrophy of proximal tubule cells. Premitotic dedifferentiation of these cells involves flattening of the basal infoldings of the plasmalemma, decrease in number and disorientation of mitochondria, loss of apical compartments, and the reduction in number of microvilli. Cilia appear on the apical borders of some cells. Bundles of 30–50 Å filaments occupy the cytoplasm at the base of proximal tubule cells. In distal tubule cells that are undergoing mitosis, numerous mitochondria remain intimately associated with infoldings of the basal plasmalemma. This persistence of the differentiated basal region prevents complete cell division, and binucleate and multinucleate cells arise as a result of failure of cytoplasmic cleavage after normal karyokinesis. During mitosis, the chromosomes and apical vesicles are restricted to organelle-free masses of cytoplasm that project into the lumen. In collecting tubules, both intercalated and lining cells undergo mitosis during compensatory growth. By 72 hours, a less differentiated cell type, that is active mitotically, appears in the cortical portion of collecting tubules. The number of binucleate epithelial cells increases in the compensating kidney tubules. Unilateral nephrectomy also induces distinct alterations in the fine structure of the glomerulus and the papilla of the contralateral organ.