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Sample records for developing rat retina

  1. Expression of nitric oxide synthase during the development of RCS rat retinas.

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    Sharma, R K; Warfvinge, K; Ehinger, B

    2001-01-01

    Nitric oxide (NO) has been reported to be both neurodestructive and neuroprotective in the central nervous system and could possibly play an important role in neurodegenerative disorders. On the assumption that NO synthesis may influence degenerative processes in the retina, we have examined the development and distribution of nitric-oxide-synthase(NOS)-immunoreactive cells in developing Royal College of Surgeons (RCS) rat retinas, which is an animal model for retinal degeneration. An antibody against constitutive neuronal NOS was used for immunocytochemistry on RCS rat retinas from postnatal (PN) days 3, 7, 10, 14, 35, 70 and 281 and compared with that in the normal rats of PN days 3, 7, 10, 14, 54 and adults. Immunoreactive cells were not seen in PN 3 retinas but were distinctly seen in the PN 7 retina along with a plexus in the inner plexiform layer. In both groups (normal and RCS rats) a distinct sublayering of the plexus in the inner plexiform layer could be seen at PN 10, which became more distinct at PN 14. The immunoreactive cells were detected also in the oldest retina examined, which was PN 281 in the case of RCS rats. In both groups, certain amacrine cells, certain bipolar cells and certain horizontal cells were found to be immunoreactive. In conclusion, the developmental timetable of the NOS immunoreactivity was identical in the normal and the RCS rat retinas. The NOS-immunoreactive cells persisted in the RCS retinas even when the retina had degenerated extensively. Abnormalities with the inducible isoforms of NOS cannot be ruled out from this study. We conclude that the chronological and qualitative development of the constitutive neuronal NOS immunoreactivity is normal in RCS rat retinas. Copyright 2001 S. Karger AG, Basel

  2. Bcl-2 expression during the development and degeneration of RCS rat retinae.

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    Sharma, R K

    2001-12-14

    In various hereditary retinal degenerations, including that in Royal College of Surgeons (RCS) rats, the photoreceptors ultimately die by apoptosis. Bcl-2 is one of the genes, which regulates apoptosis and is thought to promote survival of cells. This study has investigated the developmental expression of Bcl-2 in RCS rat, which is a well-studied animal model for hereditary retinal degeneration. An antibody against Bcl-2 was used for its immunohistochemical localization in dystrophic RCS rat retinae from postnatal (PN) days 4, 7, 13, 35, 45, 70, 202 and 14 months. Results were compared with Bcl-2 localization in congenic non-dystrophic rats from PN 4, 7, 13, 44, 202 and 14 months. Bcl-2 immunoreactivity in non-dystrophic retinae was already present in PN 4 retinae in the nerve fiber layer (presumably in the endfeet of immature Müller cells) and in the proximal parts of certain radially aligned neuroepithelial cells/immature Müller cell radial processes. With increasing age the immunoreactivity in relatively more mature Müller cell radial processes spread distally towards the outer retina and between PN 13 and 44 it reached the adult distribution. No cell bodies in the ganglion cell layer were found to be immunoreactive. Expression of Bcl-2 immunoreactivity in dystrophic RCS rat retinae closely resembled that of non-dystrophic retinae. No immunoreactivity was seen in photoreceptors or retinal pigment epithelium in dystrophic or non-dystrophic retinae. In conclusion, Bcl-2 expression is not altered, either in terms of its chronology or the cell type expressing it, during retinal degeneration in RCS rats.

  3. Localization of diacylglycerol lipase alpha and monoacylglycerol lipase during postnatal development of the rat retina

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    Bruno eCécyre

    2014-12-01

    Full Text Available In recent decades, there has been increased interest in the physiological roles of the endocannabinoid (eCB system and its receptors, the cannabinoid receptor types 1 (CB1R and 2 (CB2R. Exposure to cannabinoids during development results in neurofunctional alterations, which implies that the eCB system is involved in the developmental processes of the brain. Because of their lipophilic nature, eCBs are synthesized on demand and are not stored in vesicles. Consequently, the enzymes responsible for their synthesis and degradation are key regulators of their physiological actions. Therefore, knowing the localization of these enzymes during development is crucial for a better understanding of the role played by eCBs during the formation of the central nervous system.In this study, we investigated the developmental protein localization of the synthesizing and catabolic enzymes of the principal eCB, 2-arachidonoylglycerol (2-AG in the retinas of young and adult rats. The distribution of the enzymes responsible for the synthesis (DAGLα and the degradation (MAGL of 2-AG was determined for every retinal cell type from birth to adulthood. Our results indicate that DAGLα is present early in postnatal development. It is highly expressed in photoreceptor, horizontal, amacrine, and ganglion cells. MAGL appears later during the development of the retina and its presence is limited to amacrine and Müller cells. Overall, these results suggest that 2-AG is strongly present in early retinal development and might be involved in the regulation of the structural and functional maturation of the retina.

  4. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

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    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  5. Changes in expression of Class 3 Semaphorins and their receptors during development of the rat retina and superior colliculus.

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    Sharma, Anil; LeVaillant, Chrisna J; Plant, Giles W; Harvey, Alan R

    2014-07-26

    Members of the Semaphorin 3 family (Sema3s) influence the development of the central nervous system, and some are implicated in regulating aspects of visual system development. However, we lack information about the timing of expression of the Sema3s with respect to different developmental epochs in the mammalian visual system. In this time-course study in the rat, we document for the first time changes in the expression of RNAs for the majority of Class 3 Semaphorins (Sema3s) and their receptor components during the development of the rat retina and superior colliculus (SC). During retinal development, transcript levels changed for all of the Sema3s examined, as well as Nrp2, Plxna2, Plxna3, and Plxna4a. In the SC there were also changes in transcript levels for all Sema3s tested, as well as Nrp1, Nrp2, Plxna1, Plxna2, Plxna3, and Plxna4a. These changes correlate with well-established epochs, and our data suggest that the Sema3s could influence retinal ganglion cell (RGC) apoptosis, patterning and connectivity in the maturing retina and SC, and perhaps guidance of RGC and cortical axons in the SC. Functionally we found that SEMA3A, SEMA3C, SEMA3E, and SEMA3F proteins collapsed purified postnatal day 1 RGC growth cones in vitro. Significantly this is a developmental stage when RGCs are growing into and within the SC and are exposed to Sema3 ligands. These new data describing the overall temporal regulation of Sema3 expression in the rat retina and SC provide a platform for further work characterising the functional impact of these proteins on the development and maturation of mammalian visual pathways.

  6. Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

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    Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

    2017-07-01

    Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

  7. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

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    Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase.

  8. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    International Nuclear Information System (INIS)

    Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-01-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase.

  9. The effect of a hyperdynamic environment on the development of the rat retina

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    Murakami, D. M.; Fuller, C. A.

    1985-01-01

    The effects of a 2 G field on the retinal development of the layers in the rat and central visual system nuclei are investigated. The thickness of the retinal layers, ganglion cells, and brains of male and female Wistar rats suspended from an 18 foot diameter centrifuge creating a 2 G field are evaluated and compared with a control group. A decrease in the thickness of the outer nuclear layer (ONL) of 37.1 percent, of 58.5 percent in the inner nuclear layer (INL), and of 28.8 percent in the inner plexiform layer (IPL), and a reduction in body weight are observed in the 2-G rats. The data reveal that the ganglion cells and visual system nuclei activity correspond well with the control data; however, the medial terminal nucleus (MTN) activity is inhibited in the 2-G rats. It is concluded that the differences in ONL and IPL are attributed to body weight reduction, but the INL and MTN are affected by the 2-G conditions.

  10. Silencing p75NTR prevents proNGF-induced endothelial cell death and development of acellular capillaries in rat retina

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    Ahmed Y Shanab

    Full Text Available Accumulation of the nerve growth factor precursor (proNGF and its receptor p75NTR have been associated with several neurodegenerative diseases in both brain and retina. However, whether proNGF contributes to microvascular degeneration remain unexplored. This study seeks to investigate the mechanism by which proNGF/p75NTR induce endothelial cell (EC death and development of acellular capillaries, a surrogate marker of retinal ischemia. Stable overexpression of the cleavage-resistant proNGF and molecular silencing of p75NTR were utilized in human retinal EC and rat retinas in vivo. Stable overexpression of proNGF decreased NGF levels and induced retinal vascular cell death evident by 1.9-fold increase in acellular capillaries and activation of JNK and cleaved-PARP that were mitigated by p75NTRshRNA. In vitro, overexpression of proNGF did not alter TNF-α level, reduced NGF, however induced EC apoptosis evident by activation of JNK and p38 MAPK, cleaved-PARP. Silencing p75NTR using siRNA restored expression of NGF and TrkA activation and prevented EC apoptosis. Treatment of EC with human-mutant proNGF induced apoptosis that coincided with marked protein interaction and nuclear translocation of p75NTR and the neurotrophin receptor interacting factor. These effects were abolished by a selective p75NTR antagonist. Therefore, targeting p75NTR represents a potential therapeutic strategy for diseases associated with aberrant expression of proNGF.

  11. The Transient Intermediate Plexiform Layer, a Plexiform Layer-like Structure Temporarily Existing in the Inner Nuclear Layer in Developing Rat Retina.

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    Park, Hyung Wook; Kim, Hong-Lim; Park, Yong Soo; Kim, In-Beom

    2018-02-01

    The retina is a highly specialised part of the brain responsible for visual processing. It is well-laminated; three layers containing five different types of neurons are compartmentalised by two synaptic layers. Among the retinal layers, the inner nuclear layer (INL) is composed of horizontal, bipolar, and amacrine cell types. Bipolar cells form one sublayer in the distal half of the IPL, while amacrine cells form another sublayer in the proximal half, without any border-like structure. Here, we report that a plexiform layer-like structure exists temporarily in the border between the bipolar and amacrine sublayers in the INL in the rat retina during retinal development. This transient intermediate plexiform layer (TIPL) appeared at postnatal day (PD) 7 and then disappeared around PD 12. Most apoptotic cells in the INL were found near the TIPL. These results suggest that the TIPL may contribute to the formation of sublayers and the cell number limit in the INL.

  12. Distribution of photon absorption rates across the rat retina.

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    Williams, T P; Webbers, J P; Giordano, L; Henderson, R P

    1998-04-15

    1. An investigation into the distribution of light intensity across the rat retina was carried out on excised, intact rat eyes exposed to Ganzfeld illumination from a helium-neon laser (543 nm). 2. Some of the light entering the eyes exits through the sclera where its intensity can be monitored with an optical 'pick-up' that samples the intensity coming from a small region of external sclera and underlying retina. The spatial resolution of the pick-up is such that it samples light that has passed through ca 2 % of the rods in the rat eye. 3. Some of the laser light is absorbed by the rod pigment, rhodopsin, which gradually bleaches. Bleaching in the retina, in turn, causes an exponential increase in intensity emanating from the sclera. By monitoring this intensity increase, we are able to measure two important parameters in a single bleaching run: the local rhodopsin concentration and the local intensity falling on the rods. 4. With an ocular transmission photometer, we have measured both the local intensity and the local rhodopsin concentration across wide regions of rat retina. Both pigmented and albino rats were studied. 5. The distributions of rhodopsin and intensity were both nearly uniform; consequently, the product, (rhodopsin concentration) x (intensity), was similarly nearly equal across the retina. This means that the initial rate of photon absorption is about the same at all retinal locations. 6. Interpreted in terms of photostasis (the regulation of daily photon catch), this means that the rate of photon absorption is about the same in each rod, viz. 14 400 photons absorbed per rod per second. Since this rate of absorption is sufficient to saturate the rod, one possible purpose of photostasis is to maintain the rod system in a saturated state during daylight hours.

  13. Expression of Endoplasmic Reticulum Stress-Related Factors in the Retinas of Diabetic Rats

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    Shu Yan

    2012-01-01

    Full Text Available Recent reports show that ER stress plays an important role in diabetic retinopathy (DR, but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ. The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP, and synoviolin(HRD1 were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month.

  14. Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat

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    Rath, Martin F; Morin, Fabrice; Shi, Qiong

    2007-01-01

    . This confirmed the presence of Otx2 mRNA in both the embryonic retinal pigment epithelium and the developing neural retina. During development, the expression of Otx2 persists in the pigment epithelium, whereas Otx2 expression of the neural retina becomes progressively restricted to the outer nuclear layer......Otx2 and Crx are vertebrate orthologs of the orthodenticle family of homeobox genes, which are involved in retinal development. In this study, the temporal expression patterns of Otx2 and Crx in the rat retina during embryonic and postnatal stages of development were analyzed in detail...... and the outer part of the inner nuclear layer. Immunohistochemistry revealed that Otx2 protein is also present in cell bodies of the ganglion cell layer, which does not contain the Otx2 transcript, suggesting that Otx2 protein is synthesized in cell bodies of the bipolar neurons and then transported...

  15. Protective effect of melatonin in the diabetic rat retina.

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    Mehrzadi, Saeed; Motevalian, Manijeh; Rezaei Kanavi, Mozhgan; Fatemi, Iman; Ghaznavi, Habib; Shahriari, Mansoor

    2018-03-01

    Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. The aim of this study was to evaluate the effects of melatonin (MEL) on retinal injury in diabetic rats. In this study, 21 rats were randomly divided into three groups: control, diabetic, and diabetic + MEL. Streptozotocin was used to induce diabetes at a dose of 50 mg/kg, i.p., and blood glucose was measured to choose the diabetic rats for the study. MEL (20 mg/kg) was given orally for 7 weeks in diabetic rats starting 1 week after induction of diabetes. After 8 weeks, the groups were compared in terms of mean scores of fluorescein leakage, using fluorescein angiography. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were estimated in retina using commercially available assays. Structural changes in retinas were evaluated by light microscopy. Results showed that diabetes significantly increased the mean scores of fluorescein leakage, and MDA and ROS levels compared to control group. Treatment of the diabetic rats with MEL for 7 weeks prevented the alterations induced by diabetes in comparison with the diabetic control group.Based on these findings, it can be concluded that MEL might have beneficial effects in prevention of DR. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  16. Proteomic profiling of early degenerative retina of RCS rats.

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    Zhu, Zhi-Hong; Fu, Yan; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin

    2017-01-01

    To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student's t -test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

  17. Proteomic profiling of early degenerative retina of RCS rats

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    Zhi-Hong Zhu

    2017-06-01

    Full Text Available AIM: To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP. METHODS: Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs. Bioinformatics analyses, including Gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. RESULTS: In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student’s t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. CONCLUSION: We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

  18. Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

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    Husain, Shahid; Abdul, Yasir; Crosson, Craig E.

    2012-01-01

    Morphine, a broad range opioid-receptors agonist, provides retina neuroprotection against glaucomatous injury in chronic experimental rat model. Morphine-induced retina neuroprotection in glaucoma model is mediated partly via inhibition of TNF-alpha production and caspase-3 and caspase-8 activation.

  19. Microscopic hyperspectral imaging studies of normal and diabetic retina of rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A microscopic hyperspectral imager was developed based on the microscopic technology and the spectral imaging technology. Some microscopic hyperspectral images of retina sections of the normal, the diabetic, and the treated rats were collected by the new imager. Single-band images and pseudo-color images of each group were obtained and the typical transmittance spectrums were ex-tracted. The results showed that the transmittance of outer nuclear layer cells of the diabetic group was generally higher than that of the normal. A small absorption peak appeared near the 180th band in the spectrum of the diabetic group and this peak weakened or disappeared in the spectrum of the treated group. Our findings indicate that the microscopic hyperspectral images include wealthy information of retina sections which is helpful for the ophthalmologist to reveal the pathogenesis of diabetic reti-nopathy and explore the therapeutic effect of drugs.

  20. Abnormal levels of histone methylation in the retinas of diabetic rats are reversed by minocycline treatment

    DEFF Research Database (Denmark)

    Wang, Wenjun; Sidoli, Simone; Zhang, Wenquan

    2017-01-01

    67% of these marks had their relative abundance restored to non-diabetic levels after minocycline treatment. Mono-and di-methylation states of histone H4 lysine 20 (H4K20me1/me2), markers related to DNA damage response, were found to be up-regulated in the retinas of diabetic rats and restored......In this study we quantified the alterations of retinal histone post-translational modifications (PTMs) in diabetic rats using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach. Some diabetic rats were subsequently treated with minocycline, a tetracycline antibiotic, which has...... been shown to inhibit the diabetes-induced chronic inflammation in the retinas of rodents. We quantified 266 differentially modified histone peptides, including 48 out of 83 methylation marks with significantly different abundancein retinas of diabetic rats as compared to non-diabetic controls. About...

  1. Localization and Developmental Expression Patterns of CSPG in the RCS Rat Retina

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    Li-Feng Chen

    2011-05-01

    Full Text Available Purpose: Investigate changes in chondroitin sulfate proteoglycan (CSPG distribution in Royal College of Surgeons (RCS rat retinae. Could CSPGs distribution act as a physical barrier to transplanted cell migration in degenerating retinae? Methods: CSPG expression was examined in RCS and Long-Evans rat retinae from birth to postnatal day 150 (PND150 using immunofluorescence and western-blots. Results: Both groups showed a rapid rise in CSPG expression on PND14, which peaked on PND21 before declining to lower levels by PND35. CSPG expression had risen again by PND90 and remained elevated for the duration of the study (PND150. However, from PND21, CSPG expression was significantly higher (p ≤ 0.05, n = 5 in Long-Evans rat retinae. CSPG-positive cells were localized in the ganglion cell layer (GCL and the photoreceptor outer segment debris zone (DZ; CSPG expression in the DZ was the main contributor to the higher expression in older animals for both groups. Conclusions: Increased expression of CSPGs in the DZ may act as a physical barrier following retinal cellular transplantation. CSPGs in the GCL is probably related to dendritic changes. CSPG accumulation in the older retinae suggests that aging influences the microenvironment in the retina, which may affect the efficacy of cell transplantation.

  2. Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats.

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    Ari, Seyhmus; Nergiz, Yusuf; Cingü, Abdullah Kürşat; Atay, Ahmet Engin; Sahin, Alparslan; Cinar, Yasin; Caca, Ihsan

    2013-03-01

    To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO.

  3. Spontaneous activity in the developing mammalian retina: Form and function

    Science.gov (United States)

    Butts, Daniel Allison

    Spontaneous neuronal activity is present in the immature mammalian retina during the initial stages of visual system development, before the retina is responsive to light. This activity consists of bursts of action potentials fired by retinal ganglion cells, and propagates in a wavelike manner across the inner plexiform layer of the retina. Unlike waves in other neural systems, retinal waves have large variability in both their rate and direction of propagation, and individual waves only propagate across small regions of the retina. The unique properties of retinal activity arise from dynamic processes within the developing retina, and produce characteristic spatiotemporal properties. These spatiotemporal properties are of particular interest, since they are believed to play a role in visual system development. This dissertation addresses the complex spatiotemporal patterning of the retinal waves from two different perspectives. First, it proposes how the immature circuitry of the developing retina generates these patterns of activity. In order to reproduce the distinct spatiotemporal properties observed in experiments, a model of the immature retinal circuitry must meet certain requirements, which are satisfied by a coarse-grained model of the developing retina that we propose. Second, this dissertation addresses how the particular spatiotemporal patterning of the retinal waves provides information to the rest of the visual system and, as a result, can be used to guide visual system development. By measuring the properties of this information, we place constraints on the developmental mechanisms that use this activity, and show how the particular spatiotemporal properties of the retinal waves provide this information. Together, this dissertation demonstrates how the apparent complexity of retinal wave patterning can be understood both through the immature circuitry that generates it, and through the developmental mechanisms that may use it. The first three

  4. Progranulin regulates neurogenesis in the developing vertebrate retina.

    Science.gov (United States)

    Walsh, Caroline E; Hitchcock, Peter F

    2017-09-01

    We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed-retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 77: 1114-1129, 2017. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.

  5. Expression and Localization of TRK-Fused Gene Products in the Rat Brain and Retina

    International Nuclear Information System (INIS)

    Maebayashi, Hisae; Takeuchi, Shigako; Masuda, Chiaki; Makino, Satoshi; Fukui, Kenji; Kimura, Hiroshi; Tooyama, Ikuo

    2012-01-01

    The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It has been reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. However, no information regarding the localization of Tfg in rat tissues is available. In this study, we investigated the expression of Tfg mRNA in normal rat tissues using reverse transcription-polymerase chain reaction (RT-PCR). We also produced an antibody against Tfg gene products and examined the localization of TFG in the rat brain and retina. The RT-PCR experiments demonstrated that two types of Tfg mRNA were expressed in rat tissues: the conventional form of Tfg (cTfg) and a novel variant form, retinal Tfg (rTfg). RT-PCR analyses demonstrated that cTfg was ubiquitously expressed in rat tissues, while rTfg was predominantly expressed in the brain and retina. Western blot analysis demonstrated two bands with molecular weights of about 30 kDa and 50 kDa in the rat brain. Immunohistochemistry indicated that TFG proteins were predominantly expressed by neurons in the brain. In the rat retina, intense TFG-immunoreactivity was detected in the layer of rods and cones and the outer plexiform layer

  6. Effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats

    Institute of Scientific and Technical Information of China (English)

    Xiao Liu

    2016-01-01

    ABSTRACT Objective:To study the effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats.Methods:SD rats were selected as experimental animals and divided into control group, model group and ozone group, and after diabetic models were built, ozone enema was conducted. Retina tissue was collected, TUNEL kits were used to detect the number of apoptotic cells, and Elisa kits were used to detect the contents of nerve damage molecules, angiogenesis-related molecules and endoplasmic reticulum stress molecules. Results:The number of apoptotic cells in retina tissue of model group was significantly more than that of control group, and the number of apoptotic cells in retina tissue of ozone group was significantly less than that of model group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of model group were significantly higher than those of control group, and PEDF content was lower than that of control group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of ozone group were significantly lower than those of model group, and PEDF content was higher than that of model group.Conclusion:Ozone therapy can reduce the number of apoptotic cells while reduce nerve cell injury and inhibit angiogenesis and endoplasmic reticulum stress in retina tissue of diabetic rats.

  7. Functional Architecture of the Retina: Development and Disease

    Science.gov (United States)

    Hoon, Mrinalini; Okawa, Haruhisa; Santina, Luca Della; Wong, Rachel O.L.

    2014-01-01

    Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. PMID:24984227

  8. Circadian expression of clock genes and clock-controlled genes in the rat retina

    NARCIS (Netherlands)

    Kamphuis, Willem; Cailotto, Cathy; Dijk, Frederike; Bergen, Arthur; Buijs, Ruud M.

    2005-01-01

    The circadian expression patterns of genes encoding for proteins that make up the core of the circadian clock were measured in rat retina using real-time quantitative PCR (qPCR). Transcript levels of several genes previously used for normalization of qPCR assays were determined and the effect of

  9. Cellular disturbance in the rats retina after irradiation and metabolic errors during the postnatal period

    International Nuclear Information System (INIS)

    Lierse, W.; Franke, H.D.

    1982-01-01

    During the first five days of the postnatal period the retina has been vulnerable following administration of DNA blocking drugs and irradiation with conventional X-rays and fast neutrons. During this period the disturbance of lamination accompanied with pycnosis of neurons and neuroblasts has been the important morphologic reaction. During the same phase metabolic errors, like experimental phenylketonuria, have produced a swelling of photoreceptor cells and pigmentepithelium cells. The other neurons of the retina were pycnotic. Structural alterations like rosettes persisted during the rest of life. The relative minor error during the first phase of rats life may result in a persistent disease. (orig.)

  10. Post-translational processing of synaptophysin in the rat retina is disrupted by diabetes.

    Directory of Open Access Journals (Sweden)

    Travis S D'Cruz

    Full Text Available Synaptophysin, is an abundant presynaptic protein involved in synaptic vesicle recycling and neurotransmitter release. Previous work shows that its content is significantly reduced in the rat retina by streptozotocin (STZ-diabetes. This study tested the hypothesis that STZ-diabetes alters synaptophysin protein turnover and glycosylation in the rat retina. Whole explant retinas from male Sprague-Dawley rats were used in this study. Rats were made diabetic by a single intraperitoneal STZ injection (65 mg/kg body weight in 10 mM sodium citrate, pH 4.5. mRNA translation was measured using a (35S-methionine labeling assay followed by synaptophysin immunoprecipitation and autoradiography. A pulse-chase study was used to determine the depletion of newly synthesized synaptophysin. Depletion of total synaptophysin was determined after treatment with cycloheximide. Mannose rich N-glycosylated synaptophysin was detected by treating retinal lysates with endoglycosidase H followed by immunoblot analysis. Synaptophysin mRNA translation was significantly increased after 1 month (p<0.001 and 2 months (p<0.05 of STZ-diabetes, compared to age-matched controls. Newly synthesized synaptophysin degradation was significantly accelerated in the retina after 1 and 2 months of diabetes compared to controls (p<0.05. Mannose rich glycosylated synaptophysin was significantly increased after 1 month of STZ-diabetes compared to controls (p<0.05.These data suggest that diabetes increases mRNA translation of synaptophysin in the retina, resulting in an accumulation of mannose rich glycosylated synaptophysin, a transient post-translational state of the protein. This diabetes-induced irregularity in post-translational processing could explain the accelerated degradation of retinal synaptophysin in diabetes.

  11. Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

    Science.gov (United States)

    Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

    2012-01-01

    It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water

  12. Potassium-stimulated release of radiolabelled taurine and glycine from the isolated rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Smith, L.F.; Pycock, C.J.

    1982-09-01

    The release of preloaded (/sup 3/H)glycine and (/sup 3/H)taurine in response to a depolarising stimulus (12.5-50 mM KCl) has been studied in the superfused rat retina. High external potassium concentration immediately increased the spontaneous efflux of (/sup 3/H)glycine, the effect of 50 mM K+ apparently being abolished by omitting calcium from the superfusing medium. In contrast, although high potassium concentrations increased the spontaneous efflux of (/sup 3/H)taurine from the superfused rat retina, this release was not evident until the depolarising stimulus was removed from the superfusing medium. The magnitude of this late release of (/sup 3/H)taurine was dependent on external K+ concentrations, and appeared immediately after cessation of the stimulus irrespective of whether it was applied for 4, 8, or 12 min. Potassium (50 mM)-induced release of taurine appeared partially calcium-dependent, being significantly reduced (p less than 0.01) but not abolished by replacing calcium with 1 mM EDTA in the superfusate. High-affinity uptake systems for both (/sup 3/H)glycine and (/sup 3/H)taurine were demonstrated in the rat retina in vitro (Km values, 1.67 microM and 2.97 microM; Vmax values, 19.3 and 23.1 nmol/g wet weight tissue/h, respectively). The results are discussed with respect to the possible neurotransmitter roles of both amino acids in the rat retina.

  13. Possible influences of lutein and zeaxanthin on the developing retina.

    Science.gov (United States)

    Zimmer, J Paul; Hammond, Billy R

    2007-03-01

    The carotenoids lutein and zeaxanthin (LZ) are found throughout the central nervous system but reach their highest concentration within the macular region of the primate retina where they are commonly referred to as the macular pigments. Although LZ are a major integral feature of the central fovea, no information currently exists regarding the effects of variability in the concentration of these pigments on the developing retina. In particular, the long-term effects of very low levels of macular pigment are not known and potentially meaningful. Macular pigment levels depend upon dietary intake since LZ cannot be synthesized de novo. Infants with low intake of LZ (eg, infants receiving unfortified infant formula or breast milk from mothers with low carotenoid diets) would be expected to have considerably lower macular pigment compared with infants with high LZ intake (eg, breast-fed infants with mothers on carotenoid-rich diets). In this paper we discuss possible implications of this difference and the available evidence suggesting that LZ could influence the developing visual system.

  14. Direct localised measurement of electrical resistivity profile in rat and embryonic chick retinas using a microprobe

    Directory of Open Access Journals (Sweden)

    Harald van Lintel

    2010-01-01

    Full Text Available We report an alternative technique to perform a direct and local measurement of electrical resistivities in a layered retinal tissue. Information on resistivity changes along the depth in a retina is important for modelling retinal stimulation by retinal prostheses. Existing techniques for resistivity-depth profiling have the drawbacks of a complicated experimental setup, a less localised resistivity probing and/or lower stability for measurements. We employed a flexible microprobe to measure local resistivity with bipolar impedance spectroscopy at various depths in isolated rat and chick embryo retinas for the first time. Small electrode spacing permitted high resolution measurements and the probe flexibility contributed to stable resistivity profiling. The resistivity was directly calculated based on the resistive part of the impedance measured with the Peak Resistance Frequency (PRF methodology. The resistivity-depth profiles for both rat and chick embryo models are in accordance with previous mammalian and avian studies in literature. We demonstrate that the measured resistivity at each depth has its own PRF signature. Resistivity profiles obtained with our setup provide the basis for the construction of an electric model of the retina. This model can be used to predict variations in parameters related to retinal stimulation and especially in the design and optimisation of efficient retinal implants.

  15. Zinc might protect oxidative changes in the retina and pancreas at the early stage of diabetic rats

    International Nuclear Information System (INIS)

    Moustafa, Sohair A.

    2004-01-01

    It is well documented that oxidative stress is a basic mechanism behind the development of diabetic retinopathy (DR). The current study was undertaken to elucidate the possible role of zinc as an antioxidant and a biological membrane stabilizer in the protection against (DR). Male Wistar rats weighing 250 ± 50 g were made diabetic by injection with a single ip dose of alloxan (100 mg/kg). Another group of rats was simultaneously treated with alloxan (100 mg/kg) and a single ip dose of zinc chloride (ZnCl 2 ) (5 mg/kg). Blood and tissue samples were collected at 24, 48, and 72 h post-treatment in both groups. Diabetic state was confirmed by the determination of plasma glucose levels (significantly elevated at any time of the experiment when compared with controls receiving vehicle). Plasma insulin was significantly increased 24 h after treatment in both alloxan and alloxan plus ZnCl 2 -treated groups, and then decreased markedly 48 and 72 h post treatment in both groups. Alloxan treatment depleted both retinal and liver glutathione contents. The decrease in retinal and liver GSH in alloxan-treated rats was accompanied with a sustained increase in their thiobarbituric acid (TBA) content. Simultaneous treatment of rats with alloxan and ZnCl 2 blunted the sustained increment in plasma glucose induced by alloxan. The combined administration of alloxan and zinc reversed the depleting effect on retinal and hepatic GSH in alloxan-treated rats and reduced the elevations in TBA content of both retinas and livers. At variance with many other antioxidants the current results clearly indicate the beneficial effects of Zn in both controlling hyperglycemia and the protection of the retina against oxidative stress in diabetes which may help set a new direction toward the development of effective treatments of DR

  16. Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina.

    Science.gov (United States)

    Tan, Shi Z; Mullard, Graham; Hollywood, Katherine A; Dunn, Warwick B; Bishop, Paul N

    2016-08-01

    Time-dependent post-mortem biochemical changes have been demonstrated in donor cornea and vitreous, but there have been no published studies to date that objectively measure post-mortem changes in the retinal metabolome over time. The aim of the study was firstly, to investigate post-mortem, time-dependent changes in the rat retinal metabolome and secondly, to compare the metabolite composition of healthy rat ocular tissues. To study post-mortem changes in the rat retinal metabolome, globes were enucleated and stored at 4 °C and sampled at 0, 2, 4, 8, 24 and 48 h post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 °C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 h post-mortem when eyes were stored at 4 °C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 h post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 h. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were only detected in the retina and not other tissues. In conclusion, mass spectrometry-based techniques have been used for the first time to compare the metabolic composition of

  17. In vivo two-photon imaging of retina in rabbits and rats.

    Science.gov (United States)

    Jayabalan, Gopal Swamy; Wu, Yi-Kai; Bille, Josef F; Kim, Samuel; Mao, Xiao Wen; Gimbel, Howard V; Rauser, Michael E; Fan, Joseph T

    2018-01-01

    The purpose of this study was to evaluate the retina using near-infrared (NIR) two-photon scanning laser ophthalmoscopy. New Zealand white rabbits, albino rats, and brown Norway rats were used in this study. An autofluorescence image of the retina, including the retinal cells and its associated vasculatures was obtained by a real-time scan using the ophthalmoscope. Furthermore, the retinal vessels, nerve fiber layers and the non-pigmented retina were recorded with two-photon fluorescein angiography (FA); and the choroidal vasculatures were recorded using two-photon indocyanine green angiography (ICGA). Two-photon ICGA was achieved by exciting a second singlet state at ∼398 nm. Simultaneous two-photon FA and two-photon ICGA were performed to characterize the retinal and choroidal vessels with a single injection. The minimum laser power threshold required to elicit two-photon fluorescence was determined. The two-photon ophthalmoscope could serve as a promising tool to detect and monitor the disease progression in animal models. Moreover, these high-resolution images of retinal and choroidal vessels can be acquired in a real-time scan with a single light source, requiring no additional filters for FA or ICGA. The combination of FA and ICGA using the two-photon ophthalmoscope will help researchers to characterize the retinal diseases in animal models, and also to classify the types (classic, occult or mixed) of choroidal neovascularization (CNV) in macular degeneration. Furthermore, the prototype can be adapted to image the retina of rodents and rabbits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Assessment of apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy after grape polyphenols intervention

    Institute of Scientific and Technical Information of China (English)

    Sheng-Li Zhang

    2016-01-01

    Objective:To study the effect of grape polyphenols intervention on apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy (DR).Methods: SPF male SD rats were selected as experimental animals and divided into control group, diabetes group and grape polyphenols group, intraperitoneal injection of streptozotocin was adopted to establish diabetic rat models, and grape polyphenols group received intragastric administration of grape polyphenols. 60 d after model establishment, the rats were executed, and the retina tissue was collected to determine apoptosis molecules and oxidative stress indexes.Results:Bax, Caspase-3, c-fos, c-jun, ROS, MDA, 8-OHdG, PARP, Cyclophilin D, Nrf-2, ARE, ERK and PI3K content in retina tissue of diabetes group were significantly higher than those of control group while Bcl-2, CAT, SOD, GSH-Px, HO-1 and NQO1 content were significantly lower than those of control group; Bax, Caspase-3, c-fos, c-jun, ROS, MDA, 8-OHdG, PARP and Cyclophilin D content in retina tissue of grape polyphenols group were significantly lower than those of diabetes group while Bcl-2, CAT, SOD, GSH-Px, HO-1, NQO1, Nrf-2, ARE, ERK and PI3K content were significantly higher those of diabetes group.Conclusions:Grape polyphenols intervention can relieve the apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy.

  19. Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

    Directory of Open Access Journals (Sweden)

    Yan Lu

    2014-02-01

    Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

  20. Islet-1 Immunoreactivity in the Developing Retina of Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Guadalupe Álvarez-Hernán

    2013-01-01

    Full Text Available The LIM-homeodomain transcription factor Islet1 (Isl1 has been widely used as a marker of neuronal differentiation in the developing visual system of different classes of vertebrates, including mammals, birds, reptiles, and fish. In the present study, we analyzed the spatial and temporal distribution of Isl1-immunoreactive cells during Xenopus laevis retinal development and its relation to the formation of the retinal layers, and in combination with different markers of cell differentiation. The earliest Isl1 expression appeared at St29-30 in the cell nuclei of sparse differentiating neuroblasts located in the vitreal surface of the undifferentiated retina. At St35-36, abundant Isl1-positive cells accumulated at the vitreal surface of the neuroepithelium. As development proceeded and through the postmetamorphic juveniles, Isl1 expression was identified in subpopulations of ganglion cells and in subsets of amacrine, bipolar, and horizontal cells. These data together suggest a possible role for Isl1 in the early differentiation and maintenance of different retinal cell types, and Isl1 can serve as a specific molecular marker for the study of retinal cell specification in X. laevis.

  1. Expression of neurotransmitters and neurotrophins in neurogenic inflammation of the rat retina

    Directory of Open Access Journals (Sweden)

    E Bronzetti

    2009-08-01

    Full Text Available Antidromic stimulation of the rat trigeminal ganglion triggers the release of substance P (SP and calcitonin gene-related peptide (CGRP from sensory nerve terminals of the capsaicin sensitive C-fibers. These pro-inflammatory neuropeptides produce a marked hyperemia in the anterior segment of the eye, accompanied by increased intraocular pressure, breakdown of the blood-aqueous barrier and myosis. To assess the effects of neurogenic inflammation on the retina, specifically on the immunostaining of neurotransmitters and neurotrophins, as well as on the expression of neurotrophin receptors in the retina. RT-PCR was also accomplished in control and stimulated animals to confirm the immunohistochemical results. In the electrically stimulated eyes, immunostaining for SP, CGRP, VIP and nNOS demonstrated a marked increase in the RPE/POS (Retinal Pigment Epithelium/Photoreceptor Outer Segments, in the inner and outer granular layers and in the ganglion cells in comparison to the control eyes. CGRP and SP were found increased in stimulated animals and this result has been confirmed by RT- PCR. Changes in neurotrophin immunostaining and in receptor expression were also observed after electric stimulation of trigeminal ganglia. Decrease of BDNF and NT4 in the outer and inner layers and in ganglion cells was particularly marked. In stimulated rat retinas immunostaining and RT-PCR showed a NGF expression increase. Neurotrophin receptors remained substantially unchanged. These studies demonstrated, for the first time, that antidromic stimulation of the trigeminal ganglion and subsequent neurogenic inflammation affect immunostaining of retinal cell neurotransmitter/ neuropeptides and neurotrophins as well as the expression of neurotrophin receptors.

  2. Exposing primary rat retina cell cultures to γ-rays: An in vitro model for evaluating radiation responses.

    Science.gov (United States)

    Gaddini, Lucia; Balduzzi, Maria; Campa, Alessandro; Esposito, Giuseppe; Malchiodi-Albedi, Fiorella; Patrono, Clarice; Matteucci, Andrea

    2018-01-01

    Retinal tissue can receive incidental γ-rays exposure during radiotherapy either of tumors of the eye and optic nerve or of head-and-neck tumors, and during medical diagnostic procedures. Healthy retina is therefore at risk of suffering radiation-related side effects and the knowledge of pathophysiological response of retinal cells to ionizing radiations could be useful to design possible strategies of prevention and management of radiotoxicity. In this study, we have exploited an in vitro model (primary rat retinal cell culture) to study an array of biological effects induced on retinal neurons by γ-rays. Most of the different cell types present in retinal tissue - either of the neuronal or glial lineages - are preserved in primary rat retinal cultures. Similar to the retina in situ, neuronal cells undergo in vitro a maturational development shown by the formation of polarized neuritic trees and operating synapses. Since 2 Gy is the incidental dose received by the healthy retina per fraction when the standard treatment is delivered to the brain, retina cell cultures have been exposed to 1 or 2 Gy of γ-rays at different level of neuronal differentiation in vitro: days in vitro (DIV)2 or DIV8. At DIV9, retinal cultures were analyzed in terms of viability, apoptosis and characterized by immunocytochemistry to identify alterations in neuronal differentiation. After irradiation at DIV2, MTT assay revealed an evident loss of cell viability and βIII-tubulin immunostaining highlighted a marked neuritic damage, indicating that survived neurons showed an impaired differentiation. Differentiated cultures (DIV8) appeared to be more resistant with respect to undifferentiated, DIV2 cultures, both in terms of cell viability and differentiation. Apoptosis evaluated with TUNEL assay showed that irradiation at both DIV2 and DIV8 induced a significant increase in the apoptotic rate. To further investigate the effects of γ-rays on retinal neurons, we evaluated the

  3. Development of neural retina in retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Yi Luo

    2015-10-01

    Full Text Available Retinopathy of prematurity(ROPis an important cause of infant blindness and visual impairment in the world, of which main clinical characteristics are peripheral retinal vascular abnormalities, including large non-perfusion area and abnormal neovascularization. Numerous researches have demonstrated that ROP affects the differentiation and maturity of retinal photoreceptor cells, with more significantly effect on rods than cones, and later mostly caused ametropia, strabismus, amblyopia and a series of abnormal visual functions, the specific mechanism remains unclear. After treatments, even the retinal vascular proliferation lesions disappear itself, but the abnormal development of photoreceptor cells and the resulting visual dysfunction will persist. Currently the best evaluation mean of clinical assessment about retinal function is mainly visual electrophysiology, especially flash electroretinogram(f-ERG, which can reflect the whole retinal functional status before ganglion cells, has a unique significance for the evaluation of retinal photoreceptor cells function. In this review, we aims at the development of neural retina(mainly photoreceptor cellsand its related mechanisms, also the visual function changes appeared in the late period about ROP and its mechanisms, guiding us to pursuit better methods for treatment.

  4. Expression and location of mRNAs encoding multiple forms of secretory phospholipase A2 in the rat retina

    DEFF Research Database (Denmark)

    Kolko, Miriam; Christoffersen, Nanna R; Barreiro, Sebastian G

    2004-01-01

    of sPLA(2)s in neuronal signaling and survival [Kolko et al. (1996) J. Biol. Chem. 271: 32722-32728]. To date, no retinal sPLA(2)s have been cloned or characterized. We evaluated the existence and abundance of sPLA(2) subtypes in rat retina and explored their possible involvement in light...

  5. Ethambutol induces impaired autophagic flux and apoptosis in the rat retina

    Directory of Open Access Journals (Sweden)

    Shun-Ping Huang

    2015-08-01

    Full Text Available Ethambutol (EMB, an effective first-line antituberculosis agent, can cause serious visual impairment or irreversible vision loss in a significant number of patients. However, the mechanism underlying this ocular cytotoxicity remains to be elucidated. In this study, we found that there were statistically significant dose- and time-dependent increases in the number of cytoplasmic vacuoles and the level of cell death in EMB-treated RGC-5 cells (retinal ganglion cells. The protein kinase C (PKCδ inhibitor rottlerin markedly reduced the EMB-induced activation of caspase-3 and the subsequent apoptosis of RGC-5 cells. Western blot analysis revealed that the expression levels of class III PI3K, Beclin-1, p62 and LC3-II were upregulated, and LC3 immunostaining results showed activation of the early phase and inhibition of the late stage of autophagy in retinas of the EMB-intraperitoneal (IP-injected rat model. We further demonstrated that exposure to EMB induces autophagosome accumulation, which results from the impaired autophagic flux that is mediated by a PKCδ-dependent pathway, inhibits the PI3K/Akt/mTOR signaling pathway and leads to apoptotic death in retina neuronal cells. These results indicate that autophagy dysregulation in retinal neuronal cells might play a substantial role in EMB-induced optic neuroretinopathy.

  6. Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.

    Science.gov (United States)

    Bikbova, Guzel; Oshitari, Toshiyuki; Yamamoto, Shuichi

    2013-10-09

    The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in

  7. Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina

    DEFF Research Database (Denmark)

    Campos, Elisa J.; Martins, João; Brudzewsky, Dan

    2018-01-01

    1 diabetes mellitus (DM) and sitagliptin, a DPP-IV inhibitor, on the NPY system in the retina using an animal model.  Methods: Type 1 DM was induced in male Wistar rats by an intraperitoneal injection of streptozotocin. Starting 2weeks after DM onset, animals were treated orally with sitagliptin (5...... of NPY to all receptors. Sitagliptin alone reduced retinal NPY mRNA levels. The effects of DM on the NPY system were not affected by sitagliptin.  Conclusion: DM modestly affects the NPY system in the retina and these effects are not prevented by sitagliptin treatment. These observations suggest that DPP...

  8. Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.

    Science.gov (United States)

    Namihira, M; Honma, S; Abe, H; Tanahashi, Y; Ikeda, M; Honma, K

    1999-08-13

    Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness. A small but significant daily variation was detected in the Clock transcript level, but not in BMAL1. Light increased the Clock and BMAL1 expressions significantly when examined 60 min after exposure. The light-induced gene expression was phase-dependent for Clock and peaked at ZT2, while rather constant throughout the day for BMAL1. These findings suggest that Clock and BMAL1 play different roles in the generation of circadian rhytm in the retina from those in the suprachiasmatic nucleus. Different roles are also suggested between the two genes in the photic signal transduction in the retina.

  9. Defects in the outer limiting membrane are associated with rosette development in the Nrl-/- retina.

    Directory of Open Access Journals (Sweden)

    Michael W Stuck

    Full Text Available The neural retinal leucine zipper (Nrl knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrl(-/- retina, rods are converted into functional cone-like cells. The Nrl(-/- retina is characterized by large undulations of the outer nuclear layer (ONL commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrl(-/- retina. We report that rosettes first appear at postnatal day (P8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens junctions between photoreceptors and Müller glia which comprise the retinal outer limiting membrane (OLM are not uniformly formed in the Nrl(-/- retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrl(-/- retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper formation of the OLM.

  10. Comparative toxicity of 4 commonly used intravitreal corticosteroids on rat retina.

    Science.gov (United States)

    Citirik, Mehmet; Dilsiz, Nihat; Batman, Cosar; Zilelioglu, Orhan

    2009-06-01

    To investigate the effects of 4 commonly used steroids (dexamethasone, triamcinolone, betamethasone, and methylprednisolone) on 50 retinas of 25 adult pigmented rats. Experimental animal study. Twenty-five pigmented Long-Evans male rats. Each steroid drug with 2 different doses (0.025 mL and 0.050 mL) was injected into the vitreous of each eye of 5 rats. The low drug dose was injected into the right eye and the high dose was injected into the left eye. Ten eyes of 5 randomly selected rats were used as a control group and intravitreal saline was injected into these eyes. Oxidative damage and intrinsic antioxidative capacity were determined by measuring retinal malondialdehyde (MDA) and glutathione (GSH) levels, respectively. No statistically meaningful difference was observed in retinal GSH and MDA measurements in the low- and high-dose triamcinolone (1 and 2 mg), low-dose betamethasone (0.075 mg), and low-dose dexamethasone (0.1 mg) groups, compared with the control group. Both doses of methylprednisolone (1.6 mg and 3.2 mg), high-dose betamethasone (0.15 mg), and high-dose dexamethasone (0.2 mg) markedly altered retinal GSH and MDA levels. The results of our study show that the toxicity of triamcinolone is not evident even in high doses. It may be used safely. We also suggest that intravitreal use of low doses of betamethasone and dexamethasone is safer than higher doses of these drugs and both doses of methylprednisolone.

  11. Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats

    Directory of Open Access Journals (Sweden)

    Yi-Ming Ren

    2018-05-01

    Full Text Available AIM: To evaluate the intrinsic excitability of retinal ganglion cells (RGCs in degenerated retinas. METHODS: The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS rats, a common retinitis pigmentosa (RP model, in a relatively late stage of retinal degeneration (P90 were investigated. Several parameters of RGC morphologies and action potentials (APs were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. RESULTS: Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells, and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. CONCLUSION: RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies.

  12. Immunohistochemical Localization of an Isoform of TRK-Fused Gene-Like Protein in the Rat Retina

    International Nuclear Information System (INIS)

    Masuda, Chiaki; Takeuchi, Shigeko; Bisem, Naomi J.; Vincent, Steven R.; Tooyama, Ikuo

    2014-01-01

    The TRK-fused gene (TFG) was originally identified in chromosome translocation events, creating a pair of oncogenes in some cancers, and was recently demonstrated as the causal gene of hereditary motor and sensory neuropathy with proximal dominant involvement. Recently, we cloned an alternative splicing variant of Tfg from a cDNA library of the rat retina, tentatively naming it retinal Tfg (rTfg). Although the common form of Tfg is ubiquitously expressed in most rat tissues, rTfg expression is localized to the central nervous system. In this study, we produced an antibody against an rTFG-specific amino acid sequence and used it to examine the localization of rTFG-like protein in the rat retina by immunohistochemistry and Western blots. Western blot analysis showed that the antibody detected a single band of 24 kDa in the rat retina. When we examined rTFG recombinant protein, the antibody detected two bands of about 42 kDa and 24 kDa. The results suggest that the 24 kDa rTFG-like protein is a fragment of rTFG. In our immunohistochemical studies of the rat retina, rTFG-like immunoreactivity was observed in all calbindin D-28K-positive horizontal cells and in some syntaxin 1-positive amacrine cells (ACs). In addition, the rTFG-like immunopositive ACs were actually glycine transporter 1-positive glycinergic or glutamate decarboxylase-positive GABAergic ACs. Our findings indicate that this novel 24 kDa rTFG-like protein may play a specific role in retinal inhibitory interneurons

  13. Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina.

    Science.gov (United States)

    Miyawaki, Takaya; Uemura, Akiyoshi; Dezawa, Mari; Yu, Ruth T; Ide, Chizuka; Nishikawa, Shinichi; Honda, Yoshihito; Tanabe, Yasuto; Tanabe, Teruyo

    2004-09-15

    Tlx belongs to a class of orphan nuclear receptors that underlies many aspects of neural development in the CNS. However, the fundamental roles played by Tlx in the control of eye developmental programs remain elusive. By using Tlx knock-out (KO) mice, we show here that Tlx is expressed by retinal progenitor cells in the neuroblastic layer during the period of retinal layer formation, and it is critical for controlling the generation of appropriate numbers of retinal progenies through the activities of cell cycle-related molecules, cyclin D1 and p27Kip1. Tlx expression is restricted to Müller cells in the mature retina and appears to control their proper development. Furthermore, we show that Tlx is expressed by immature astrocytes that migrate from the optic nerve onto the inner surface of the retina and is required for their generation and maturation, as assessed by honeycomb network formation and expression of R-cadherin, a critical component for vasculogenesis. The impaired astrocyte network formation on the inner retinal surface is accompanied by the loss of vasculogenesis in Tlx KO retinas. Our studies thus indicate that Tlx underlies a fundamental developmental program of retinal organization and controls the generation of the proper numbers of retinal progenies and development of glial cells during the protracted period of retinogenesis.

  14. Subretinal electrical stimulation preserves inner retinal function in RCS rat retina.

    Science.gov (United States)

    Ciavatta, Vincent T; Mocko, Julie A; Kim, Moon K; Pardue, Machelle T

    2013-01-01

    Previously, studies showed that subretinal electrical stimulation (SES) from a microphotodiode array (MPA) preserves electroretinography (ERG) b-wave amplitude and regional retinal structure in the Royal College of Surgeons (RCS) rat and simultaneously upregulates Fgf2 expression. This preservation appears to be associated with the increased current produced when the MPA is exposed to ERG test flashes, as weekly ERG testing produces greater neuroprotection than biweekly or no testing. Using an infrared source to stimulate the MPA while avoiding potential confounding effects from exposing the RCS retina to high luminance white light, this study examined whether neuroprotective effects from SES increased with subretinal current in a dose-dependent manner. RCS rats (n=49) underwent subretinal implantation surgery at P21 with MPA devices in one randomly selected eye, and the other eye served as the control. Naïve RCS rats (n=25) were also studied. To increase SES current levels, implanted eyes were exposed to 15 min per session of flashing infrared light (IR) of defined intensity, frequency, and duty cycle. Rats were divided into four SES groups that received ERG testing only (MPA only), about 450 µA/cm2 once per week (Low 1X), about 450 µA/cm2 three times per week (Low 3X), and about 1350 µA/cm2 once per week (High 1X). One eye of the control animals was randomly chosen for IR exposure. All animals were followed for 4 weeks with weekly binocular ERGs. A subset of the eyes was used to measure retina Fgf2 expression with real-time reverse-transcription PCR. Eyes receiving SES showed significant preservation of b-wave amplitude, a- and b-wave implicit times, oscillatory potential amplitudes, and post-receptoral parameters (Vmax and log σ) compared to untreated eyes. All SES-treated eyes had similar preservation, regardless of increased SES from IR light exposure. SES-treated eyes tended to have greater retinal Fgf2 expression than untreated eyes, but Fgf2 expression

  15. The retina

    DEFF Research Database (Denmark)

    van Reyk, David M; Gillies, Mark C; Davies, Michael Jonathan

    2003-01-01

    A prominent and early feature of the retinopathy of diabetes mellitus is a diffuse increase in vascular permeability. As the disease develops, the development of frank macular oedema may result in vision loss. That reactive oxygen species production is likely to be elevated in the retina, and tha...

  16. Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

    Science.gov (United States)

    Tao, Zui; Zhao, Chen; Jian, Qian; Gillies, Mark; Xu, Haiwei; Yin, Zheng Qin

    2016-01-01

    Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats. PMID:27384999

  17. CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development.

    Directory of Open Access Journals (Sweden)

    Scott F Geller

    2009-08-01

    Full Text Available Mutations in the CLRN1 gene cause Usher syndrome type 3 (USH3, a human disease characterized by progressive blindness and deafness. Clarin 1, the protein product of CLRN1, is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells, and recently demonstrated to be associated with the cytoskeleton. To study Clrn1, we created a Clrn1 knockout (KO mouse and characterized the histological and functional consequences of Clrn1 deletion in the retina and cochlea. Clrn1 KO mice do not develop a retinal degeneration phenotype, but exhibit progressive loss of sensory hair cells in the cochlea and deterioration of the organ of Corti by 4 months. Hair cell stereocilia in KO animals were longer and disorganized by 4 months, and some Clrn1 KO mice exhibited circling behavior by 5-6 months of age. Clrn1 mRNA expression was localized in the retina using in situ hybridization (ISH, laser capture microdissection (LCM, and RT-PCR. Retinal Clrn1 transcripts were found throughout development and adulthood by RT-PCR, although expression peaked at P7 and declined to undetectable levels in adult retina by ISH. LCM localized Clrn1 transcripts to the retinas inner nuclear layer, and WT levels of retinal Clrn1 expression were observed in photoreceptor-less retinas. Examination of Clrn1 KO mice suggests that CLRN1 is unnecessary in the murine retina but essential for normal cochlear development and function. This may reflect a redundancy in the mouse retina not present in human retina. In contrast to mouse KO models of USH1 and USH2, our data indicate that Clrn1 expression in the retina is restricted to the Müller glia. This is a novel finding, as most retinal degeneration associated proteins are expressed in photoreceptors, not in glia. If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal

  18. Functional and Cellular Responses to Laser Injury in the Rat Snake Retina

    National Research Council Canada - National Science Library

    Glickman, Randolph D; Elliott, III, W. R; Kumar, Neeru

    2007-01-01

    .... This animal is of interest for vision research because its eye has an all-cone retina. A linear array of 5 thermal lesions was placed in the retina of anesthetized animals, near the area centralis, using a Nd:VO4 laser (532 nm...

  19. Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

    Science.gov (United States)

    Kumar, Pankaj; Nag, Tapas Chandra; Jha, Kumar Abhiram; Dey, Sanjay Kumar; Kathpalia, Poorti; Maurya, Meenakshi; Gupta, Chandan Lal; Bhatia, Jagriti; Roy, Tara Sankar; Wadhwa, Shashi

    2017-12-01

    Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The protective effects of the proteasome inhibitor bortezomib (velcade on ischemia-reperfusion injury in the rat retina.

    Directory of Open Access Journals (Sweden)

    Fang-Ting Chen

    Full Text Available PURPOSE: To evaluate the protective effects of bortezomib (Velcade on ischemia-reperfusion (IR injury in the rat retina. METHODS: The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg, or high-dose bortezomib (0.2 mg/kg before the induction of IR injury. Electroretinography (ERG was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α, anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin, and pro-apoptotic proteins (p53, bax were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein, NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. RESULTS: ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. CONCLUSIONS: Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

  1. Diurnal rodents as animal models of human central vision: characterisation of the retina of the sand rat Psammomys obsesus.

    Science.gov (United States)

    Saïdi, Tounès; Mbarek, Sihem; Chaouacha-Chekir, Rafika Ben; Hicks, David

    2011-07-01

    Cone photoreceptor-based central vision is of paramount importance in human eyesight, and the increasing numbers of persons affected by macular degeneration emphasizes the need for relevant and amenable animal models. Although laboratory mice and rats have provided valuable information on retinal diseases, they have inherent limitations for studies on macular pathology. In the present study, we extend our recent analyses of diurnal murid rodents to demonstrate that the sand rat Psammomys obesus has a remarkably cone-rich retina, and represents a useful adjunct to available animal models of central vision. Adult P. obesus were captured and transferred to animal facilities where they were maintained under standard light/dark cycles. Animals were euthanised and their eyes enucleated. Tissue was either fixed in paraformaldehyde and prepared for immunohistochemistry, or solubilized in lysis buffer and separated by SDS-PAGE and subjected to western blot analysis. Samples were labelled with a battery of antibodies against rod and cone photoreceptors, inner retinal neurones, and glia. P. obesus showed a high percentage of cones, 41% of total photoreceptor numbers in both central and peripheral retina. They expressed multiple cone-specific proteins, including short and medium-wavelength opsin and cone transducin. A second remarkable feature of the retina concerned the horizontal cells, which expressed high levels of glial fibrillar acidic protein and occludin, two proteins which are not seen in other species. The retina of P. obesus displays high numbers of morphologically and immunologically identifiable cones which will facilitate analysis of cone pathophysiology in this species. The unusual horizontal cell phenotype may be related to the cone distribution or to an alternative facet of the animals lifestyle.

  2. Effects of Dietary Iron and Gamma Radiation on the Rat Retina

    Science.gov (United States)

    Morgan, Jennifer; Marshall, Grace; Theriot, Corey A.; Chacon, Natalia; Zwart, Sara; Zanello, Susana B.

    2012-01-01

    A health risk of concern for NASA relates to radiation exposure and its synergistic effects with other space environmental factors, includi ng nutritional status of the crew. Astronauts consume almost three times the recommended daily allowance of iron due to the use of fortifie d foods aboard the International Space Station, with iron intake occa sionally exceeding six times the recommended values. Recently, NASA has become concerned with visual changes associated with spaceflight, a nd research is being conducted to elucidate the etiology of eye structure alterations in the spaceflight environment. Terrestrially, iron o verload is also associated with certain optic neuropathies. In additi on, due to its role in Fenton reactions, iron can potentiate oxidative stress, which is a recognized cause of cataract formation. As part o f a study investigating the combined effects of radiation exposure an d iron overload on multiple physiological systems, we focused on defining the effects of both treatments on eye biology. In this study, 12- week-old Sprague-Dawley rats were assigned to one of four experimental groups: normal iron/no radiation (Control/Sham), high iron/no radiat ion (Fe/Sham), normal iron/gamma radiation (3 Gy cumulative dose, fra ctionated at 0.375 Gy/d every other day for 16 d) (Control/Rad), and high iron/gamma radiation (Fe/Rad). Oxidative stress-induced DNA damag e, measured as concentration of the marker 8-hydroxy-2'-deoxyguanosine (8OHdG) in eye retinal tissue by enzyme-immunoanalysis did not show significant changes among treatments. However, there was an overall i ncrease in 8OHdG immunostaining density in retina sections due to radiation exposure (P = 0.05). Increased dietary iron and radiation expos ure had an interactive effect (P = 0.02) on 8OHdG immunostaining of t he retinal ganglion cell layer with iron diet increasing the signal in the group not exposed to radiation (P = 0.05). qPCR gene expression profiling of relevant target genes

  3. Up-regulation of DRP-3 long isoform during the induction of neural progenitor cells by glutamate treatment in the ex vivo rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Tokuda, Kazuhiro, E-mail: r502um@yamaguchi-u.ac.jp [Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Kuramitsu, Yasuhiro; Byron, Baron; Kitagawa, Takao [Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Tokuda, Nobuko [Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube (Japan); Kobayashi, Daiki; Nagayama, Megumi; Araki, Norie [Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Sonoda, Koh-Hei [Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Nakamura, Kazuyuki [Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan)

    2015-08-07

    Glutamate has been shown to induce neural progenitor cells in the adult vertebrate retina. However, protein dynamics during progenitor cell induction by glutamate are not fully understood. To identify specific proteins involved in the process, we employed two-dimensional electrophoresis-based proteomics on glutamate untreated and treated retinal ex vivo sections. Rat retinal tissues were incubated with 1 mM glutamate for 1 h, followed by incubation in glutamate-free media for a total of 24 h. Consistent with prior reports, it was found that mitotic cells appeared in the outer nuclear layer without any histological damage. Immunohistological evaluations and immunoblotting confirmed the emergence of neuronal progenitor cells in the mature retina treated with glutamate. Proteomic analysis revealed the up-regulation of dihydropyrimidinase-related protein 3 (DRP-3), DRP-2 and stress-induced-phosphoprotein 1 (STIP1) during neural progenitor cell induction by glutamate. Moreover, mRNA expression of DRP-3, especially, its long isoform, robustly increased in the treated retina compared to that in the untreated retina. These results may indicate that glutamate induces neural progenitor cells in the mature rat retina by up-regulating the proteins which mediate cell mitosis and neurite growth. - Highlights: • Glutamate induced neuronal progenitor cells in the mature rat retina. • Proteomic analysis revealed the up-regulation of DRP-3, DRP-2 and STIP1. • mRNA expression of DRP-3, especially, its long isoform, robustly increased.

  4. The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina.

    Science.gov (United States)

    Tao, Ye; Chen, Tao; Liu, Bei; Yang, Guo Qing; Peng, Guanghua; Zhang, Hua; Huang, Yi Fei

    2015-07-01

    The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Increased Expression of Intercellular Adhesion Molecule-1, Vascular Cellular Adhesion Molecule-1 and Leukocyte Common Antigen in Diabetic Rat Retina

    Institute of Scientific and Technical Information of China (English)

    Ningyan Bai; Shibo Tang; Jing Ma; Yan Luo; Shaofeng Lin

    2003-01-01

    Purpose: To understand the expression and distribution of intercellular adhesion molecule- 1(ICAM- 1),vascular cellular adhesion molecule- 1 (VCAM- 1)and CD45 (Leukocyte Common Antigen) in the control nondiabetic and various courses of diabetic rats retina. To explore the role of adhesion molecules (Ams) and the adhesion of leukocytes to vascular endothelial cells via Ams in diabetic retinopathy(DR).Methods: Sixty healthy adult male Wistar rats were randomly divided into diabetic groups(induced by Streptozotocin, STZ) and normal control groups. Rats in these two groups were further randomly divided into 3, 7, 14, 30, 90 and 180 days-group,including 5 rats respectively. The immunohistochemical studies of ICAM-1, VCAM-1 and CD45 were carried out in the retinal digest preparations or retinal paraffin sections, and the results were analyzed qualitatively, semi-quantitatively.Results: No positive reaction of VCAM-1 was found, and weak reactions of ICAM-1,CD45 were found in nondiabetic rats retina. The difference of 6 control groups had no statistical significance(P > 0.05). The increased ICAM-1 and CD45 staining pattern were detectable 3 days after diabetes induction, and a few VCAM-1 positive cells were observed in the retinal blood capillaries. The difference of diabetes and control is significant( P < 0.05).Following the course, the expressions of ICAM-1, VCAM-1 and CD45 were increasingly enhanced, reaching a peak at the 14th day.Conclusion: Increased expression of ICAM-1, VCAM-1 and leukocytes adhering and stacking in retinal capillaries are the very early events in DR. Coherence of expression and distribution of the three further accounts for it is the key point for the onset of DR that Ams mediates leukocytes adhesion and endothelial cell injury.

  6. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

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    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  7. Postconditioning with inhaled carbon monoxide counteracts apoptosis and neuroinflammation in the ischemic rat retina.

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    Nils Schallner

    Full Text Available Ischemia and reperfusion injury (I/R of neuronal structures and organs is associated with increased morbidity and mortality due to neuronal cell death. We hypothesized that inhalation of carbon monoxide (CO after I/R injury ('postconditioning' would protect retinal ganglion cells (RGC.Retinal I/R injury was performed in Sprague-Dawley rats (n = 8 by increasing ocular pressure (120 mmHg, 1 h. Rats inhaled room air or CO (250 ppm for 1 h immediately following ischemia or with 1.5 and 3 h latency. Retinal tissue was harvested to analyze Bcl-2, Bax, Caspase-3, HO-1 expression and phosphorylation of the nuclear transcription factor (NF-κB, p38 and ERK-1/2 MAPK. NF-κB activation was determined and inhibition of ERK-1/2 was performed using PD98059 (2 mg/kg. Densities of fluorogold prelabeled RGC were analyzed 7 days after injury. Microglia, macrophage and Müller cell activation and proliferation were evaluated by Iba-1, GFAP and Ki-67 staining.Inhalation of CO after I/R inhibited Bax and Caspase-3 expression (Bax: 1.9 ± 0.3 vs. 1.4 ± 0.2, p = 0.028; caspase-3: 2.0 ± 0.2 vs. 1.5 ± 0.1, p = 0.007; mean ± S.D., fold induction at 12 h, while expression of Bcl-2 was induced (1.2 ± 0.2 vs. 1.6 ± 0.2, p = 0.001; mean ± S.D., fold induction at 12 h. CO postconditioning suppressed retinal p38 phosphorylation (p = 0.023 at 24 h and induced the phosphorylation of ERK-1/2 (p<0.001 at 24 h. CO postconditioning inhibited the expression of HO-1. The activation of NF-κB, microglia and Müller cells was potently inhibited by CO as well as immigration of proliferative microglia and macrophages into the retina. CO protected I/R-injured RGC with a therapeutic window at least up to 3 h (n = 8; RGC/mm(2; mean ± S.D.: 1255 ± 327 I/R only vs. 1956 ± 157 immediate CO treatment, vs. 1830 ± 109 1.5 h time lag and vs. 1626 ± 122 3 h time lag; p<0.001. Inhibition of ERK-1/2 did not counteract the CO effects (RGC/mm(2: 1956 ± 157 vs. 1931 ± 124, mean ± S.D., p

  8. [Expression of vimentin and GFAP and development of the retina in the trout].

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    De Guevara, R; Pairault, C; Pinganaud, G

    1994-08-01

    The glial cell development was studied during the edification of the retina and the optic tract, in a teleost, the rainbow trout. The intermediate filament proteins, vimentin and glial fibrillary acidic protein (GFAP) were visualized by an indirect immunohistochemical method. Results show that both vimentin and GFAP are early expressed in the developing retina and, particularly in the Müller cells, a coexpression of vimentin and GFAP is observed from embryonic to adult stages. The ganglion cell layer and the optic fiber layer both exhibit GFAP-positive structures. The deep staining for GFAP is also seen in the optic nerve and induces us to credit astrocyte-like cells with a leading role in the pattern formation of this tract.

  9. Vision drives correlated activity without patterned spontaneous activity in developing Xenopus retina.

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    Demas, James A; Payne, Hannah; Cline, Hollis T

    2012-04-01

    Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABA(A) receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement. Copyright © 2011 Wiley Periodicals, Inc.

  10. Extracellular Matrix components regulate cellular polarity and tissue structure in the developing and mature Retina

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    Shweta Varshney

    2015-01-01

    Full Text Available While genetic networks and other intrinsic mechanisms regulate much of retinal development, interactions with the extracellular environment shape these networks and modify their output. The present review has focused on the role of one family of extracellular matrix molecules and their signaling pathways in retinal development. In addition to their effects on the developing retina, laminins play a role in maintaining Müller cell polarity and compartmentalization, thereby contributing to retinal homeostasis. This article which is intended for the clinical audience, reviews the fundamentals of retinal development, extracellular matrix organization and the role of laminins in retinal development. The role of laminin in cortical development is also briefly discussed.

  11. Changes in acetylcholine release from the chick retina are not associated with myopia development

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    Vessey, K.A.; Cotriall, C.L.; McBrien, N.A.

    2002-01-01

    Full text: The effectiveness of muscarinic receptor antagonists in inhibiting myopia progression in animal models and humans implicates cholinergic signalling in ocular growth regulation. Therefore to determine if changes in the release of acetylcholine from the retina are involved in myopia development, the efflux of acetylcholine from the in vitro retina of normal and myopic chick eyes was investigated. Chicks were monocularly deprived (MD) of pattern vision with translucent occluders for 2 or 7 days and refractive error of MD groups and age matched normals was monitored using retinoscopy (n=6 each group). 3 H-choline-Cl (1 Ci in 7μL) was injected into the vitreous of each eye under 2.5% halothane anaesthesia. After 1hr, the eyes were enucleated, under terminal anaesthesia (sodium pentobarbital, 120 mg/kg, im). Retinas were flat-mounted on acetate filter discs and superfused with oxygenated physiological saline solution (PSS) for 30min at 0.4mL/min. Five baseline fractions were collected (B1-B5), then three stimulated fractions were collected in the presence of PSS containing 50mM KCl (K1-K3) at 2min intervals. 3 H-acetylcholine ( 3 H-ACh) in each fraction was quantified by liquid scintillation counting. Significant amounts of myopia were induced in MD eyes after 2 (-5.1±0.8D) and 7 days (-18.8±2.4D) relative to control eyes (paired t-test p 3 H-ACh release was 146±15% above basal levels (K2/B1%) from retinas of normal animals. After 2 days MD, there was no significant difference between KCl-evoked release of 3 H-ACh from deprived eyes (147 39%) compared to control eyes (198±61%, paired t-test, p=0.27) or the eyes of normal animals (ANOVA, p>0.5). Similar results were obtained following 7 days MD. The results demonstrate that evoked acetylcholine release from the chick retina of myopic eyes is unaltered relative to control or normal eyes using an in vitro approach. Copyright (2002) Australian Neuroscience Society

  12. Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat.

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    Eltony, Sohair A; Abdelhameed, Sally Y

    2017-04-01

    Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Dopamine D2 receptors preferentially regulate the development of light responses of the inner retina

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    Tian, Ning; Xu, Hong-ping; Wang, Ping

    2014-01-01

    Retinal light responsiveness measured via electroretinography undergoes developmental modulation and is thought to be critically regulated by both visual experience and dopamine. The primary goal of this study is to determine whether the dopamine D2 receptor regulates the visual experience-dependent functional development of the retina. Accordingly, we recorded electroretinograms from wild type mice and mice with a genetic deletion of the gene that encodes the dopamine D2 receptor raised under normal cyclic light conditions and constant darkness. Our results demonstrate that mutation of the dopamine D2 receptors preferentially increases the amplitude of the inner retinal light responses evoked by high intensity light measured as oscillatory potentials in adult mice. During postnatal development, all three major components of electroretinograms, the a-wave, b-wave and oscillatory potentials, increase with age. Comparatively, mutation of the dopamine D2 receptors preferentially reduces the age-dependent increase of b-waves evoked by low intensity light. Light deprivation from birth reduces the amplitude of b-waves and completely diminishes the increased amplitude of oscillatory potentials. Taken together, these results demonstrate that the dopamine D2 receptor plays an important role in the activity-dependent functional development of the mouse retina. PMID:25393815

  14. Molecular Characterization of Notch1 Positive Progenitor Cells in the Developing Retina.

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    Galina Dvoriantchikova

    Full Text Available The oscillatory expression of Notch signaling in neural progenitors suggests that both repressors and activators of neural fate specification are expressed in the same progenitors. Since Notch1 regulates photoreceptor differentiation and contributes (together with Notch3 to ganglion cell fate specification, we hypothesized that genes encoding photoreceptor and ganglion cell fate activators would be highly expressed in Notch1 receptor-bearing (Notch1+ progenitors, directing these cells to differentiate into photoreceptors or into ganglion cells when Notch1 activity is diminished. To identify these genes, we used microarray analysis to study expression profiles of whole retinas and isolated from them Notch1+ cells at embryonic day 14 (E14 and postnatal day 0 (P0. To isolate Notch1+ cells, we utilized immunomagnetic cell separation. We also used Notch3 knockout (Notch3KO animals to evaluate the contribution of Notch3 signaling in ganglion cell differentiation. Hierarchical clustering of 6,301 differentially expressed genes showed that Notch1+ cells grouped near the same developmental stage retina cluster. At E14, we found higher expression of repressors (Notch1, Hes5 and activators (Dll3, Atoh7, Otx2 of neuronal differentiation in Notch1+ cells compared to whole retinal cell populations. At P0, Notch1, Hes5, and Dll1 expression was significantly higher in Notch1+ cells than in whole retinas. Otx2 expression was more than thirty times higher than Atoh7 expression in Notch1+ cells at P0. We also observed that retinas of wild type animals had only 14% (P < 0.05 more ganglion cells compared to Notch3KO mice. Since this number is relatively small and Notch1 has been shown to contribute to ganglion cell fate specification, we suggested that Notch1 signaling may play a more significant role in RGC development than the Notch3 signaling cascade. Finally, our findings suggest that Notch1+ progenitors--since they heavily express both pro-ganglion cell (Atoh7

  15. Cannabinoid Receptor Type 1 Expression in the Developing Avian Retina: Morphological and Functional Correlation With the Dopaminergic System

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    Luzia da Silva Sampaio

    2018-03-01

    Full Text Available The avian retina has been used as a model to study signaling by different neuro- and gliotransmitters. It is unclear how dopaminergic and cannabinoid systems are related in the retina. Here we studied the expression of type 1 and 2 cannabinoid receptors (CB1 and CB2, as well as monoacylglycerol lipase (MAGL, the enzyme that degrades 2-arachidonoylglycerol (2-AG, during retina development. Our data show that CB1 receptor is highly expressed from embryonic day 5 (E5 until post hatched day 7 (PE7, decreasing its levels throughout development. CB1 is densely found in the ganglion cell layer (GCL and inner plexiform layer (IPL. CB2 receptor was also found from E5 until PE7 with a decrease in its contents from E9 afterwards. CB2 was mainly present in the lamination of the IPL at PE7. MAGL is expressed in all retinal layers, mainly in the IPL and OPL from E9 to PE7 retina. CB1 and CB2 were found both in neurons and glia cells, but MAGL was only expressed in Müller glia. Older retinas (PE7 show CB1 positive cells mainly in the INL and co-expression of CB1 and tyrosine hydroxylase (TH are shown in a few cells when both systems are mature. CB1 co-localized with TH and was heavily associated to D1 receptor labeling in primary cell cultures. Finally, cyclic AMP (cAMP was activated by the selective D1 agonist SKF38393, and inhibited when cultures were treated with WIN55, 212–2 (WIN in a CB1 dependent manner. The results suggest a correlation between the endocannabinoid and dopaminergic systems (DSs during the avian retina development. Activation of CB1 limits cAMP accumulation via D1 receptor activation and may influence embryological parameters during avian retina differentiation.

  16. Functional imaging of hemodynamic stimulus response in the rat retina with ultrahigh-speed spectral / Fourier domain OCT

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    Choi, WooJhon; Baumann, Bernhard; Clermont, Allen C.; Feener, Edward P.; Boas, David A.; Fujimoto, James G.

    2013-03-01

    Measuring retinal hemodynamics in response to flicker stimulus is important for investigating pathophysiology in small animal models of diabetic retinopathy, because a reduction in the hyperemic response is thought to be one of the earliest changes in diabetic retinopathy. In this study, we investigated functional imaging of retinal hemodynamics in response to flicker stimulus in the rat retina using an ultrahigh speed spectral / Fourier domain OCT system at 840nm with an axial scan rate of 244kHz. At 244kHz the nominal axial velocity range that could be measured without phase wrapping was +/-37.7mm/s. Pulsatile total retinal arterial blood flow as a function of time was measured using an en face Doppler approach where a 200μm × 200μm area centered at the central retinal artery was repeatedly raster scanned at a volume acquisition rate of 55Hz. Three-dimensional capillary imaging was performed using speckle decorrelation which has minimal angle dependency compared to other angiography techniques based on OCT phase information. During OCT imaging, a flicker stimulus could be applied to the retina synchronously by inserting a dichroic mirror in the imaging interface. An acute transient increase in total retinal blood flow could be detected. At the capillary level, an increase in the degree of speckle decorrelation in capillary OCT angiography images could also be observed, which indicates an increase in the velocity of blood at the capillary level. This method promises to be useful for the investigation of small animal models of ocular diseases.

  17. Comparative immunolocalization of the plasma membrane calcium pump and calbindin D28K in chicken retina during embryonic development

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    N. Tolosa de Talamoni

    2010-05-01

    Full Text Available The immunolocalization of the plasma membrane calcium pump (PMCA was studied in 4-week-old chick retina in comparison with calbindin D28K (CaBP immunostaining. We have demonstrated that the monoclonal anti-PMCA antibody 5F10 from human erythrocyte plasma membrane crossreacts with a Ca2+ pump epitope of the cells from the neural retina. The immunolocalization of both proteins was also studied during the embryonic development of the chicken retina. At age 4.5 days, the cells of the retina were faintly immunoreactive to PMCA and CaBP antibodies, but the lack of cellular aggregation and differentiation did not allow discrimination between the two proteins. A clear difference in the localization was seen from the tenth day of development through post-hatching with slight variation. PMCA localized mainly in the outer and inner plexiform layers, in some cells in the ganglion layer, in the nerve fiber layer and slightly in the photoreceptor cells. CaBP was intensely stained in cones, cone pedicles and some amacrine cells. The number of CaBP positive amacrine cells declined after hatching. A few ganglion cells and several nerve fibers were CaBP 333 immunoreactive. The role of these proteins in the early stages of retinal development is unknown, but the results suggest that Ca2+ homeostasis in the retina is well regulated, probably to avoid excessive accumulation of Ca2+, which often leads to neurodegeneration.

  18. β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina

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    Meyers Jason R

    2012-08-01

    Full Text Available Abstract Background The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; second, radial glia (Müller cells occasionally divide asymmetrically to generate committed progenitors that differentiate into rod photoreceptors, which are added interstitially throughout the retina with growth. Retinal injury stimulates Müller glia to dedifferentiate, re-enter the cell cycle, and generate multipotent retinal progenitors similar to those in the CMZ to replace missing neurons. The specific signals that maintain these two distinct populations of endogenous retinal stem cells are not understood. Results We used genetic and pharmacological manipulation of the β-catenin/Wnt signaling pathway to show that it is required to maintain proliferation in the CMZ and that hyperstimulation of β-catenin/Wnt signaling inhibits normal retinal differentiation and expands the population of proliferative retinal progenitors. To test whether similar effects occur during regeneration, we developed a method for making rapid, selective photoreceptor ablations in larval zebrafish with intense light. We found that dephosphorylated β-catenin accumulates in Müller glia as they re-enter the cell cycle following injury, but not in Müller glia that remain quiescent. Activation of Wnt signaling is required for regenerative proliferation, and hyperstimulation results in loss of Müller glia from the INL as all proliferative cells move into the ONL. Conclusions β-catenin/Wnt signaling is thus required for the maintenance of retinal progenitors during both initial development and lesion-induced regeneration, and is sufficient to prevent differentiation of those progenitors and maintain them in a proliferative state. This suggests that the β-catenin/Wnt cascade is part of the shared molecular circuitry that

  19. Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina.

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    Aurélie Cubizolle

    Full Text Available In retinal pigment epithelium (RPE, RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1 is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice. The mice displayed no delay in the kinetics of regeneration of the visual chromophore 11-cis-retinal after photobleaching and had no defects in light sensitivity. However, the total retinoid content was higher in the hFATP1TG mice than in wild type mice, and the transgenic mice also displayed an age-related accumulation (up to 40% of all-trans-retinal and retinyl esters that was not observed in control mice. Consistent with these results, hFATP1TG mice were more susceptible to light-induced photoreceptor degeneration. hFATP1 overexpression also induced an ~3.5-fold increase in retinosome autofluorescence, as measured by two-photon microscopy. Interestingly, hFATP1TG retina contained ~25% more photoreceptor cells and ~35% longer outer segments than wild type mice, revealing a non-cell-autonomous effect of hFATP1 expressed in the RPE. These data are the first to show that FATP1-mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development.

  20. Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats.

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    Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

    2017-04-01

    Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. In this experimental study, 16 male Wistar rats weighing 200 - 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina.

  1. Müller glia provide essential tensile strength to the developing retina

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    MacDonald, Ryan B.; Randlett, Owen; Oswald, Julia; Yoshimatsu, Takeshi

    2015-01-01

    To investigate the cellular basis of tissue integrity in a vertebrate central nervous system (CNS) tissue, we eliminated Müller glial cells (MG) from the zebrafish retina. For well over a century, glial cells have been ascribed a mechanical role in the support of neural tissues, yet this idea has not been specifically tested in vivo. We report here that retinas devoid of MG rip apart, a defect known as retinoschisis. Using atomic force microscopy, we show that retinas without MG have decreased resistance to tensile stress and are softer than controls. Laser ablation of MG processes showed that these cells are under tension in the tissue. Thus, we propose that MG act like springs that hold the neural retina together, finally confirming an active mechanical role of glial cells in the CNS. PMID:26416961

  2. The Effect of Intravitreal Bevacizumab on Apoptosis of Rat Retina Cells

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    Özcan Kayıkçıoğlu

    2013-01-01

    Full Text Available Pur po se: To investigate the apoptotic effects of intravitreal bevacizumab on rat retinal cells. Ma te ri al and Met hod: Thirty-six male adult Swiss albino rats were randomly divided into two groups. The first group was applied 0.25 mg bevacizumab in 0.01 ml saline, and the second group received the same amount of saline intravitreally. Each group was divided into 3 subgroups. The animals were sacrificed and their globes were enucleated at the 3rd, 24th, and 72nd hours of the experiment. Enucleated eyes were preserved for histological analysis, immunohistochemical analysis of caspase-3, caspase-8, caspase-9, Fas/Fas L, VEGF and VEGF receptors (Flt-1, Flk-1, and TUNEL staining. Re sults: Histological evaluation showed no sign of retinal toxicity in both groups. In TUNEL staining, TUNEL(+ cells were detected in all subgroups, but the number of positive cells was relatively lower in bevacizumab treatment group that reached statistically significant level at 24 and 72 hours of treatment (p<0.001. Immunohistochemical analysis revealed that in saline-treated subgroups, immunoreactivity was more pronounced for all apoptosis-inducing proteins compared to bevacizumab-treated group. Also immunoreactivity of VEGF was prominent in saline treated group. For VEGF receptors, staining was only positive for Flt-1 at the 3rd hour in the control group. Dis cus si on: Bevacizumab did not have apoptosis-inducing potential compared to saline solution in short term, which was documented with TUNEL and immunohistochemical staining. (Turk J Ophthalmol 2013; 43: 39-44

  3. The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

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    Tao, Ye [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China); Chen, Tao [Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi' an 710032 (China); Liu, Bei [Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi' an (China); Yang, Guo Qing [Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi' an 710032 (China); Peng, Guanghua [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China); Zhang, Hua [Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi' an (China); Huang, Yi Fei [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China)

    2015-07-01

    The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration.

  4. The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

    International Nuclear Information System (INIS)

    Tao, Ye; Chen, Tao; Liu, Bei; Yang, Guo Qing; Peng, Guanghua; Zhang, Hua; Huang, Yi Fei

    2015-01-01

    The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration.

  5. The temporal requirement for vitamin A in the developing eye: mechanism of action in optic fissure closure and new roles for the vitamin in regulating cell proliferation and adhesion in the embryonic retina.

    Science.gov (United States)

    See, Angela Wai-Man; Clagett-Dame, Margaret

    2009-01-01

    Mammalian eye development requires vitamin A (retinol, ROL). The role of vitamin A at specific times during eye development was studied in rat fetuses made vitamin A deficient (VAD) after embryonic day (E) 10.5 (late VAD). The optic fissure does not close in late VAD embryos, and severe folding and collapse of the retina is observed at E18.5. Pitx2, a gene required for normal optic fissure closure, is dramatically downregulated in the periocular mesenchyme in late VAD embryos, and dissolution of the basal lamina does not occur at the optic fissure margin. The addition of ROL to late VAD embryos by E12.5 restores Pitx2 expression, supports dissolution of the basal lamina, and prevents coloboma, whereas supplementation at E13.5 does not. Surprisingly, ROL given as late as E13.5 completely prevents folding of the retina despite the presence of an open fetal fissure, showing that coloboma and retinal folding represent distinct VAD-dependent defects. Retinal folding due to VAD is preceded by an overall reduction in the percentage of cyclin D1 positive cells in the developing retina, (initially resulting in retinal thinning), as well as a dramatic reduction in the cell adhesion-related molecules, N-cadherin and beta-catenin. Reduction of retinal cell number combined with a loss of the normal cell-cell adhesion proteins may contribute to the collapse and folding of the retina that occurs in late VAD fetuses.

  6. Developmental and daily expression of the Pax4 and Pax6 homeobox genes in the rat retina: localization of Pax4 in photoreceptor cells

    DEFF Research Database (Denmark)

    Rath, Martin F; Bailey, Michael J; Kim, Jong-So

    2009-01-01

    Pax4 is a homeobox gene encoding Pax4, a transcription factor that is essential for embryonic development of the endocrine pancreas. In the pancreas, Pax4 counters the effects of the related transcription factor, Pax6, which is known to be essential for eye morphogenesis. In this study, we have...... in the foetal eye. Histological analysis revealed that Pax4 mRNA is exclusively expressed in the retinal photoreceptors, whereas Pax6 mRNA and protein are present in the inner nuclear layer and in the ganglion cell layer of the mature retina. In the adult retina, Pax4 transcripts exhibit a diurnal rhythm...

  7. CHANGES IN NEUROTRANSMITTER GENE EXPRESSION IN THE AGING RETINA.

    Science.gov (United States)

    To understand mechanisms of neurotoxicity in susceptible populations, we examined age-related changes in constitutive gene expression in the retinas of young (4mos), middle-aged (11 mos) and aged (23 mos) male Long Evans rats. Derived from a pouch of the forebrain during develop...

  8. Pathological changes in the retina of eyes rats with experimental 2 type diabetes mellitus and their correction by oral gels with biologically active substances

    Directory of Open Access Journals (Sweden)

    V. V. Vit

    2014-07-01

    Full Text Available Purpose: To study of therapeutic and prophylactic action on the retina of rats with experimental diabetes mellitus type 2 (DM2 oral mucosal gels containing biologically active substances (BAS.Methods: DM2 was induced by protamine method Ulyanov and Tarasova [2000]. As BAS used lysozyme, flour of grape leaves, the water extract of blueberries and quercetin. Mucosal gels containing active substances, applied to the mucous lining of the mouth for 2 weeks. The serum glucose concentration was performed and histological studies of the retina.Results: Application mucosal gels reduces BAS 8‑22 % glucose (most with blueberry extract and significantly improves retinal histology (vacuolar degeneration less pronounced ganglion cells, there are no structural changes in photoreceptor layer. Gels revealed more effective with containing extract of bilberry, grape flour and quercetin.Conclusion: Oral mucosal application of gels containing active substances, have protection of retina in diabetes mellitus type 2.

  9. Early adaptive response of the retina to a pro-diabetogenic diet: Impairment of cone response and gene expression changes in high-fructose fed rats.

    Science.gov (United States)

    Thierry, Magalie; Pasquis, Bruno; Buteau, Bénédicte; Fourgeux, Cynthia; Dembele, Doulaye; Leclere, Laurent; Gambert-Nicot, Ségolène; Acar, Niyazi; Bron, Alain M; Creuzot-Garcher, Catherine P; Bretillon, Lionel

    2015-06-01

    The lack of plasticity of neurons to respond to dietary changes, such as high fat and high fructose diets, by modulating gene and protein expression has been associated with functional and behavioral impairments that can have detrimental consequences. The inhibition of high fat-induced rewiring of hypothalamic neurons induced obesity. Feeding rodents with high fructose is a recognized and widely used model to trigger obesity and metabolic syndrome. However the adaptive response of the retina to short term feeding with high fructose is poorly documented. We therefore aimed to characterize both the functional and gene expression changes in the neurosensory retina of Brown Norway rats fed during 3 and 8 days with a 60%-rich fructose diet (n = 16 per diet and per time point). Glucose, insulin, leptin, triacylglycerols, total cholesterol, HDL-cholesterol, LDL-cholesterol and fructosamine were quantified in plasma (n = 8 in each group). Functionality of the inner retina was studied using scotopic single flash electroretinography (n = 8 in each group) and the individual response of rod and cone photoreceptors was determined using 8.02 Hz Flicker electroretinography (n = 8 in each group). Analysis of gene expression in the neurosensory retina was performed by Affymetrix genechips, and confirmed by RT-qPCR (n = 6 in each group). Elevated glycemia (+13%), insulinemia (+83%), and leptinemia (+172%) was observed after 8 days of fructose feeding. The cone photoreceptor response was altered at day 8 in high fructose fed rats (Δ = 0.5 log unit of light stimulus intensity). Affymetrix analysis of gene expression highlighted significant modulation of the pathways of eIF2 signaling and endoplasmic reticulum stress, regulation of eIF4 and p70S6K signaling, as well as mTOR signaling and mitochondrial dysfunction. RT-qPCR analysis confirmed the down regulation of Crystallins, Npy, Nid1 and Optc genes after 3 days of fructose feeding, and up regulation of End2. Meanwhile, a trend

  10. Using induced pluripotent stem cell-derived conditional medium to attenuate the light-induced photodamaged retina of rats

    Directory of Open Access Journals (Sweden)

    Hua-Ming Chang

    2015-03-01

    Conclusion: The conditional medium of iPSCs contains plenty of cytoprotective, immune-modulative and rescue chemicals, contributing to the maintenance of neuronal function and retinal layers in light-damaged retina compared with apoptotic iPSC-CM and PBS. The antiapoptotic effect of iPSC-CM also shows promise in restoring damaged neurons. This result demonstrates that iPSC-CM may serve as an alternative to cell therapy alone to treat retinal light damage and maintain functional and structural integrity of the retina.

  11. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Hiroshi, E-mail: htomita@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574 (Japan); Tabata, Kitako, E-mail: ktabata@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Takahashi, Maki, E-mail: mqdelta@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Nishiyama, Fumiaki, E-mail: t2114018@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Sugano, Eriko, E-mail: sseriko@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan)

    2016-05-13

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

  12. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    International Nuclear Information System (INIS)

    Tomita, Hiroshi; Tabata, Kitako; Takahashi, Maki; Nishiyama, Fumiaki; Sugano, Eriko

    2016-01-01

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

  13. Relationship between blood-retinal barrier development and formation of selenite nuclear cataract in rat

    Directory of Open Access Journals (Sweden)

    Ping Lu

    2017-12-01

    Full Text Available AIM: To investigate the relationship between development of blood-retinal barrier and formation of selenite nuclear cataract in rat. METHODS: Activity of GPx, MDA level in lens and selenium content in the eyeballs of different ages rats were determined. Besides, lanthanum hydroxide \\〖La(OH3\\〗 tracer method was used to detect development status of blood-retina barrier at different ages. RESULTS: The result showed that the enzyme activity of GPx was highest in young rats before open eyes, but then decreased gradually with age. Distribution of La(OH3 in retinal pigment epithelial layer of 20-day-old rats was significantly less than 11-day-old rats. Injecting sodium selenite to 9-day-old rats, lanthanum hydroxide increased obviously and extended to the inner layers of the retina after 48h, and the retinal pigment epithelial layer was damaged seriously; while injecting sodium selenite to 18-day-old rats with the same dose, number of lanthanum hydroxide decreased significantly and did not extend to the inner layer after 48h.Before opening eyes, the content of MDA in the lens of rats was the highest, and decreased significantly after opening eyes. The Se group was 5 times as that of the control group. Besides, in these groups of rats, selenium content in the eyeballs and MDA level in the lens were in agreement with the change of La(OH3 distribution. CONCLUSION: These results indicated that antioxidant capacity in the eyelid unopened rats is not the main reason for selenite induced cataract formation. The real reason is that blood-retina barrier development is not mature in the eyelid unopened rats.

  14. Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

    Science.gov (United States)

    Theriot, Corey A.; Zanello, Susana B.

    2014-01-01

    Preliminary data from a prior tissue-sharing experiment has suggested that early growth response protein-1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia- or inflammation-driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated-weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS-induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell-specific isolectin binding, coupled to Alexa-488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z-axis. This new confocal microscope has the added capability of dye separation using the Linear

  15. Expression and light sensitivity of clock genes Per1 and Per2 and immediate-early gene c-fos within the retina of early postnatal Wistar rats

    Czech Academy of Sciences Publication Activity Database

    Matějů, Kristýna; Sumová, Alena; Bendová, Zdeňka

    2010-01-01

    Roč. 518, č. 17 (2010), s. 3630-3644 ISSN 0021-9967 R&D Projects: GA ČR(CZ) GA309/08/0503; GA MŠk(CZ) LC554 EU Projects: European Commission(XE) 18741 - EUCLOCK Grant - others:GA ČR(CZ) GD309/08/H079 Institutional research plan: CEZ:AV0Z50110509 Keywords : development * retina * circadian clock Subject RIV: FH - Neurology Impact factor: 3.774, year: 2010

  16. Biological activity is the likely origin of the intersection between the photoreceptor inner and outer segments of the rat retina as determined by optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Yamauchi Y

    2011-11-01

    Full Text Available Yasuyuki Yamauchi, Hiromichi Yagi, Yoshihiko Usui, Keisuke Kimura, Tsuyoshi Agawa, Rintaro Tsukahara, Naoyuki Yamakawa, Hiroshi GotoDepartment of Ophthalmology, Tokyo Medical University Hospital, Tokyo, JapanBackground: Recent research on macular diseases has prompted investigations into the condition of the intersection between the photoreceptor inner and outer segments (IS/OS and the relationship with retinal photoreceptor abnormalities. Although the origin of the IS/OS in optical coherence tomography (OCT images is unclear, it may be related to either the cellular activity of the photoreceptors or the structure of the OS disks. To address this question, we compared the IS/OS status in OCT images of rat retinas before and after euthanasia.Methods: OCT images were taken before and after euthanasia in four eyes of two Brown Norway rats. After the OCT images were taken, the rats were used for histopathological studies to confirm that retinal structures were intact.Results: Before euthanasia, the IS/OS and external limiting membrane (ELM line were clearly identifiable on the OCT images. However, after euthanasia, neither the IS/OS nor the ELM line was evident in three out of four eyes, and a faint IS/OS and an ELM line were identified in one eye. Histopathological analysis did not show any abnormalities in the retina in any of the four eyes.Conclusion: The origin of the IS/OS identified in OCT images is likely related to the biological activities of the photoreceptor cells.Keywords: IS/OS, OCT, histopathology, biological activity

  17. Quantum photoelectron effects in the eye retina and development of colour vision theory

    International Nuclear Information System (INIS)

    Kremkov, M.V.

    2011-01-01

    The quantum semiconductor mechanism of the colour vision of mans is created. The mechanism is based on quantum effects under influence of light waves exciting valence electrons in different microelement's atoms (Zn, Cu, Fe, Co, P, Br, Se, et al.) that are presented in the photoreceptor's cells of the eye retina (columns and retorts) with the quasi-periodical disks structure. The microelement concentrations correspond to the impurity atom amount in semiconductors, and the photoelectron's current passes out its signal to the vision nerve. The mechanism explains existence of the man colour-blindness, degradation of the vision sensitivity with the man's age and other peculiarities of the colour vision. (authors)

  18. Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat.

    Science.gov (United States)

    Arakaki, Xianghong; McCleary, Paige; Techy, Matthew; Chiang, Jiarong; Kuo, Linus; Fonteh, Alfred N; Armstrong, Brian; Levy, Dan; Harrington, Michael G

    2013-03-14

    Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and -3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer.

  19. The expression of the Slit-Robo signal in the retina of diabetic rats and the vitreous or fibrovascular retinal membranes of patients with proliferative diabetic retinopathy.

    Science.gov (United States)

    Zhou, Weiyan; Wang, Hongya; Yu, Wenzhen; Xie, Wankun; Zhao, Min; Huang, Lvzhen; Li, Xiaoxin

    2017-01-01

    The Slit-Robo signal has an important role in vasculogenesis and angiogenesis. Our study examined the expression of Slit2 and its receptor, Robo1, in a rat model of streptozotocin-induced diabetes and in patients with proliferative diabetic retinopathy. Diabetes was induced in male Sprague-Dawley rats via a single, intraperitoneal injection of streptozotocin. The rats were sacrificed 1, 3 or 6 months after the injection. The expression of Slit2 and Robo1 in retinal tissue was measured by real-time reverse transcription polymerase chain reaction (RT-PCR), and protein levels were measured by western blotting and immunohistochemistry. Recombinant N-Slit2 protein was used to study the effects of Slit2 on the expression of VEGF in vivo. The concentration of Slit2 protein in human eyes was measured by enzyme-linked immunosorbent assay in 27 eyes with proliferative diabetic retinopathy and 28 eyes in control group. The expression of Slit2, Robo1 and VEGF in the excised human fibrovascular membranes was examined by fluorescence immunostaining and semi-quantitative RT-PCR. The expression of Slit2 and Robo1 in the retina was altered after STZ injection. Recombinant N-Slit2 protein did not increase the retinal VEGF expression. Vitreous concentrations of Slit2 were significantly higher in the study group than in the control group. In the human fibrovascular membranes of the study group, the co-localization of VEGF with the markers for Slit2 and Robo1was observed. The expression of Slit2 mRNA, Robo1 mRNA, and VEGF mRNA was significantly higher in human fibrovascular proliferative diabetic retinopathy membranes than in the control membranes. The alteration of Slit2 and Robo1 expression in the retinas of diabetic rats and patients with proliferative diabetic retinopathy suggests a role for the Slit-Robo signal in the various stages diabetic retinopathy. Further studies should address the possible involvement of the Slit-Robo signal in the pathophysiological progress of diabetic

  20. Selective retina therapy (SRT)

    International Nuclear Information System (INIS)

    Brinkmann, R.; Birngruber, R.

    2007-01-01

    Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Luebeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the choroid. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced. (orig.)

  1. Modifying a standard method allows simultaneous extraction of RNA and protein, enabling detection of enzymes in the rat retina with low expressions and protein levels.

    Science.gov (United States)

    Agardh, Elisabet; Gustavsson, Carin; Hagert, Per; Nilsson, Marie; Agardh, Carl-David

    2006-02-01

    The aim of the study was to evaluate messenger RNA and protein expression in limited amounts of tissue with low protein content. The Chomczynski method was used for simultaneous extraction of RNA, and protein was modified in the protein isolation step. Template mass and cycling time for the complementary DNA synthesis step of real-time reverse transcription-polymerase chain reaction (RT-PCR) for analysis of catalase, copper/zinc superoxide dismutase, manganese superoxide dismutase, the catalytic subunit of glutamylcysteine ligase, glutathione peroxidase 1, and the endogenous control cyclophilin B (CypB) were optimized before PCR. Polymerase chain reaction accuracy and efficacy were demonstrated by calculating the regression (R2) values of the separate amplification curves. Appropriate antibodies, blocking buffers, and running conditions were established for Western blot, and protein detection and multiplex assays with CypB were performed for each target. During the extraction procedure, the protein phase was dissolved in a modified washing buffer containing 0.1% sodium dodecyl sulfate, followed by ultrafiltration. Enzyme expression on real-time RT-PCR was accomplished with high reliability and reproducibility (R2, 0.990-0.999), and all enzymes except for glutathione peroxidase 1 were detectable in individual retinas on Western blot. Western blot multiplexing with CypB was possible for all targets. In conclusion, connecting gene expression directly to protein levels in the individual rat retina was possible by simultaneous extraction of RNA and protein. Real-time RT-PCR and Western blot allowed accurate detection of retinal protein expressions and levels.

  2. Association of the AMPA receptor-related postsynaptic density proteins GRIP and ABP with subsets of glutamate-sensitive neurons in the rat retina.

    Science.gov (United States)

    Gábriel, Robert; de Souza, Sunita; Ziff, Edward B; Witkovsky, Paul

    2002-07-22

    We used specific antibodies against two postsynaptic density proteins, GRIP (glutamate receptor interacting protein) and ABP (AMPA receptor-binding protein), to study their distribution in the rat retina. In the central nervous system, it has been shown that both proteins bind strongly to the AMPA glutamate receptor (GluR) 2/3 subunits, but not other GluRs, through a set of three PDZ domains. Western blots detected a single GRIP protein that was virtually identical in retina and brain, whereas retinal ABP corresponded to only one of three ABP peptides found in brain. The retinal distributions of GluR2/3, GRIP, and ABP immunoreactivity (IR) were similar but not identical. GluR2/3 immunoreactivity (IR) was abundant in both plexiform layers and in large perikarya. ABP IR was concentrated in large perikarya but was sparse in the plexiform layers, whereas GRIP IR was relatively more abundant in the plexiform layers than in perikarya. Immunolabel for these three antibodies consisted of puncta ABP IR was examined by double labeling subclasses of retinal neuron with characteristic marker proteins, e.g., calbindin. GRIP, ABP, and GluR2/3 IR were detected in horizontal cells, dopaminergic and glycinergic AII amacrine cells and large ganglion cells. Immunolabel was absent in rod bipolar and weak or absent in cholinergic amacrine cells. By using the tyramide method of signal amplification, a colocalization of GluR2/3 was found with either GRIP or ABP in horizontal cell terminals, and perikarya of amacrine and ganglion cells. Our results show that ABP and GRIP colocalize with GluR2/3 in particular subsets of retinal neuron, as was previously established for certain neurons in the brain. Copyright 2002 Wiley-Liss, Inc.

  3. Effect of epithalon on age-specific changes in the retina in rats with hereditary pigmentary dystrophy.

    Science.gov (United States)

    Khavinson, V Kh; Razumovskii, M I; Trofimova, S V; Grigor'yan, R A; Chaban, T V; Oleinik, T L; Razumovskaya, A M

    2002-01-01

    The effect of peptide bioregulator Epithalon on the course of hereditary pigmentary retinal degeneration was studied in Campbell rats. Administration of epithalon starting from birth protected morphological structure, increased its bioelectrical activity, and improved its function.

  4. The infrared retina

    International Nuclear Information System (INIS)

    Krishna, Sanjay

    2009-01-01

    As infrared imaging systems have evolved from the first generation of linear devices to the second generation of small format staring arrays to the present 'third-gen' systems, there is an increased emphasis on large area focal plane arrays (FPAs) with multicolour operation and higher operating temperature. In this paper, we discuss how one needs to develop an increased functionality at the pixel level for these next generation FPAs. This functionality could manifest itself as spectral, polarization, phase or dynamic range signatures that could extract more information from a given scene. This leads to the concept of an infrared retina, which is an array that works similarly to the human eye that has a 'single' FPA but multiple cones, which are photoreceptor cells in the retina of the eye that enable the perception of colour. These cones are then coupled with powerful signal processing techniques that allow us to process colour information from a scene, even with a limited basis of colour cones. Unlike present day multi or hyperspectral systems, which are bulky and expensive, the idea would be to build a poor man's 'infrared colour' camera. We use examples such as plasmonic tailoring of the resonance or bias dependent dynamic tuning based on quantum confined Stark effect or incorporation of avalanche gain to achieve embodiments of the infrared retina.

  5. Calbindin-D28k and calretinin in chicken inner retina during postnatal development and neuroplasticity by dim red light.

    Science.gov (United States)

    Fosser, Nicolás Sebastián; Ronco, Laura; Bejarano, Alejandro; Paganelli, Alejandra R; Ríos, Hugo

    2013-07-01

    Members of the family of calcium binding proteins (CBPs) are involved in the buffering of calcium (Ca2+) by regulating how Ca2+ can operate within synapses or more globally in the entire cytoplasm and they are present in a particular arrangement in all types of retinal neurons. Calbindin D28k and calretinin belong to the family of CBPs and they are mainly co-expressed with other CBPs. Calbindin D28k is expressed in doubles cones, bipolar cells and in a subpopulation of amacrine and ganglion neurons. Calretinin is present in horizontal cells as well as in a subpopulation of amacrine and ganglion neurons. Both proteins fill the soma at the inner nuclear layer and the neuronal projections at the inner plexiform layer. Moreover, calbindin D28k and calretinin have been associated with neuronal plasticity in the central nervous system. During pre and early postnatal visual development, the visual system shows high responsiveness to environmental influences. In this work we observed modifications in the pattern of stratification of calbindin immunoreactive neurons, as well as in the total amount of calbindin through the early postnatal development. In order to test whether or not calbindin is involved in retinal plasticity we analyzed phosphorylated p38 MAPK expression, which showed a decrease in p-p38 MAPK, concomitant to the observed decrease of calbindin D28k. Results showed in this study suggest that calbindin is a molecule related with neuroplasticity, and we suggest that calbindin D28k has significant roles in neuroplastic changes in the retina, when retinas are stimulated with different light conditions. Copyright © 2013 Wiley Periodicals, Inc.

  6. Expression of c-Fos and c-Jun in the cornea, lens, and retina after ultraviolet irradiation of the rat eye and effect of topical antisense oligodeoxynucleotides

    International Nuclear Information System (INIS)

    Gillardon, F.; Zimmermann, M.

    1995-01-01

    Aims - Immunohistochemical techniques were used to investigate c-Fos and c-Jun proto-oncogene expression in the cornea, lens, and retina after ultraviolet irradiation of the rat eye. Methods -Eyes of anaesthetised rats were exposed to 1.5 J/cm 2 of ultraviolet radiation (280-380 nm). Animals were perfused 1, 6, or 24 hours after irradiation and tissue sections were incubated with specific antiserum to c-Fos and c-Jun, respectively. Non-irradiated contralateral eyes displayed no c-Fos and c-Jun immunoreactivity. One and 6 hours after ultraviolet exposure numerous c-Fos and c-Jun immunopositive nuclei were observed mainly in the epithelial cell layers of the cornea and the lens epithelium. Scattered labelled nuclei were detectable in the retinal ganglion cell layer and the inner nuclear layer. Twenty four hours after irradiation c-Fos and c-Jun protein expression returned to near control levels. Histological signs of ultraviolet damage (for example, chromatin condensation, nuclear fragmentation) were first recognisable in the corneal epithelium 6 hours after irradiation and became more apparent at later times. The rapid and sustained activation of c-Fos and c-Jun expression in the eye after single ultraviolet exposure may represent the molecular mechanism underlying ultraviolet induced photodamage and initiation of cell death. Furthermore, topical application of a c-fos antisense oligode-oxynucleotide to the ultraviolet exposed rat eye inhibited the increase in c-Fos expression in the cornea, suggesting therapeutic activity of antisense drugs in corneal malignant and infectious diseases. (author)

  7. Connexin 30 expression and frequency of connexin heterogeneity in astrocyte gap junction plaques increase with age in the rat retina.

    Directory of Open Access Journals (Sweden)

    Hussein Mansour

    Full Text Available We investigated age-associated changes in retinal astrocyte connexins (Cx by assaying Cx numbers, plaque sizes, protein expression levels and heterogeneity of gap junctions utilizing six-marker immunohistochemistry (IHC. We compared Wistar rat retinal wholemounts in animals aged 3 (young adult, 9 (middle-aged and 22 months (aged. We determined that retinal astrocytes have gap junctions composed of Cx26, -30, -43 and -45. Cx30 was consistently elevated at 22 months compared to younger ages both when associated with parenchymal astrocytes and vascular-associated astrocytes. Not only was the absolute number of Cx30 plaques significantly higher (P<0.05 but the size of the plaques was significantly larger at 22 months compared to younger ages (p<0.05. With age, Cx26 increased significantly initially, but returned to basal levels; whereas Cx43 expression remained low and stable with age. Evidence that astrocytes alter connexin compositions of gap junctions was demonstrated by the significant increase in the number of Cx26/Cx45 gap junctions with age. We also found gap junctions comprised of 1, 2, 3 or 4 Cx proteins suggesting that retinal astrocytes use various connexin protein combinations in their gap junctions during development and aging. These data provides new insight into the dynamic and extensive Cx network utilized by retinal astrocytes for communication within both the parenchyma and vasculature for the maintenance of normal retinal physiology with age. This characterisation of the changes in astrocytic gap junctional communication with age in the CNS is crucial to the understanding of physiological aging and age-related neurodegenerative diseases.

  8. Impact of bronchopulmonary dysplasia on brain and retina

    Directory of Open Access Journals (Sweden)

    Annie Wing Hoi Poon

    2016-04-01

    Full Text Available Many premature newborns develop bronchopulmonary dysplasia (BPD, a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, ‘BPD’ group or room air (21% O2, ‘control’ group from postnatal day 4–14 (P4–14; the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001. This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=−0.49, P=0.02 and retina (r=−0.70, P=0.0008 structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

  9. Glucocorticoid-Induced Leucine Zipper Protects the Retina From Light-Induced Retinal Degeneration by Inducing Bcl-xL in Rats.

    Science.gov (United States)

    Gu, Ruiping; Tang, Wenyi; Lei, Boya; Ding, Xinyi; Jiang, Cheng; Xu, Gezhi

    2017-07-01

    The aim of the present study was to investigate the neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ) in a light-induced retinal degeneration model and to explore the underlying mechanisms. Intravitreal injection of recombinant GILZ-overexpressing lentivirus (OE-GILZ-rLV) and short hairpin RNA targeting GILZ recombinant lentivirus (shRNA-GILZ-rLV) was performed to up- and downregulate retinal GILZ, respectively. Three days after stable transduction, rats were exposed to continuous bright light (5000 lux) for 2 days. Retinal function was assessed by full-field electroretinography (ERG), and the retinal structure was examined for photoreceptor survival and death in rats kept under a 12-hour light:2-hour dark cycle following light exposure. The expression levels of retinal Bcl-xL, caspase-9, and caspase-3 were examined by Western blotting or real-time PCR at 1, 3, 5, and 7 days after light exposure. Exposure to bright light downregulated retinal GILZ in parallel with the downregulation of Bcl-xL and the upregulation of active caspase-3. Overexpression of retinal GILZ attenuated the decrease of Bcl-xL and the activation of caspase-9 and caspase-3 at 1, 3, 5, and 7 days after bright light exposure, respectively. GILZ silencing aggravated the downregulation of Bcl-xL induced by bright light exposure. Bright light exposure reduced the amplitude of ERG, increased the number of apoptotic photoreceptor cells, and decreased retinal thickness; and GILZ overexpression could attenuate all these effects. Overexpression of GILZ by OE-GILZ-rLV transduction protected the retina from light-induced cellular damage by activating antiapoptotic pathways.

  10. Retina-Inspired Filter.

    Science.gov (United States)

    Doutsi, Effrosyni; Fillatre, Lionel; Antonini, Marc; Gaulmin, Julien

    2018-07-01

    This paper introduces a novel filter, which is inspired by the human retina. The human retina consists of three different layers: the Outer Plexiform Layer (OPL), the inner plexiform layer, and the ganglionic layer. Our inspiration is the linear transform which takes place in the OPL and has been mathematically described by the neuroscientific model "virtual retina." This model is the cornerstone to derive the non-separable spatio-temporal OPL retina-inspired filter, briefly renamed retina-inspired filter, studied in this paper. This filter is connected to the dynamic behavior of the retina, which enables the retina to increase the sharpness of the visual stimulus during filtering before its transmission to the brain. We establish that this retina-inspired transform forms a group of spatio-temporal Weighted Difference of Gaussian (WDoG) filters when it is applied to a still image visible for a given time. We analyze the spatial frequency bandwidth of the retina-inspired filter with respect to time. It is shown that the WDoG spectrum varies from a lowpass filter to a bandpass filter. Therefore, while time increases, the retina-inspired filter enables to extract different kinds of information from the input image. Finally, we discuss the benefits of using the retina-inspired filter in image processing applications such as edge detection and compression.

  11. Structure of the vitreoretinal border region in spontaneously hypertensive rats (SHR rats)

    DEFF Research Database (Denmark)

    Heegaard, Steffen

    1993-01-01

    Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure......Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure...

  12. Effect of titanium dioxide nanoparticles on zebrafish embryos and developing retina

    Directory of Open Access Journals (Sweden)

    Ya-Jie Wang

    2014-12-01

    Full Text Available AIM:To investigate the impact of titanium dioxide nanoparticles (TiO2 NPs on embryonic development and retinal neurogenesis. METHODS:The agglomeration and sedimentation of TiO2 NPs solutions at different dilutions were observed, and the ultraviolet-visible spectra of their supernatants were measured. Zebrafish embryos were experimentally exposed to TiO2 NPs until 72h postfertilization (hpf. The retinal neurogenesis and distribution of the microglia were analyzed by immunohistochemistry and whole mount in situ hybridization. RESULTS: The1 mg/L was determined to be an appropriate exposure dose. Embryos exposed to TiO2 NPs had a normal phenotype. The neurogenesis was initiated on time, and ganglion cells, cones and rods were well differentiated at 72 hpf. The expression of fms mRNA and the 4C4 antibody, which were specific to microglia in the central nervous system (CNS, closely resembled their endogenous profile. CONCLUSION:These data demonstrate that short-term exposure to TiO2 NPs at a low dose does not lead to delayed embryonic development or retinal neurotoxicity.

  13. Neural retina-specific Aldh1a1 controls dorsal choroidal vascular development via Sox9 expression in retinal pigment epithelial cells.

    Science.gov (United States)

    Goto, So; Onishi, Akishi; Misaki, Kazuyo; Yonemura, Shigenobu; Sugita, Sunao; Ito, Hiromi; Ohigashi, Yoko; Ema, Masatsugu; Sakaguchi, Hirokazu; Nishida, Kohji; Takahashi, Masayo

    2018-04-03

    VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1 -/- mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1 -/- mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of Aldh1a1 -/- pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of Aldh1a1 -/- mice and RPE-specific disruption of Sox9 phenocopied Aldh1a1 -/- choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion. © 2018, Goto et al.

  14. Patterns of cell proliferation and cell death in the developing retina and optic tectum of the brown trout.

    NARCIS (Netherlands)

    Candal, E.; Anadon, R.; Grip, W.J. de; Rodriguez-Moldes, I.

    2005-01-01

    We have analyzed the patterns of cell proliferation and cell death in the retina and optic tectum of the brown trout (Salmo trutta fario) throughout embryonic and postembryonic stages. Cell proliferation was detected by immunohistochemistry with an antibody against the proliferating cell nuclear

  15. Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity.

    Science.gov (United States)

    Hong, Hye Kyoung; Lee, Hyun Ju; Ko, Jung Hwa; Park, Ji Hyun; Park, Ji Yeon; Choi, Chang Won; Yoon, Chang-Hwan; Ahn, Seong Joon; Park, Kyu Hyung; Woo, Se Joon; Oh, Joo Youn

    2014-05-15

    Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats. To induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis. We found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located. Our data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP.

  16. Desprendimiento de retina

    Directory of Open Access Journals (Sweden)

    L. Jaime Claramunt, Dr.

    2010-11-01

    Full Text Available El desprendimiento de retina (DR consiste en la separación entre la retina neurosensorial y el epitelio pigmentario subyacente. Su forma más frecuente es el DR regmatógeno, causado por una rotura en la retina. Se manifiesta generalmente como un defecto en el campo visual o mala visión. Si se pesquisa y trata oportunamente tiene buenas posibilidades de éxito. No obstante, sigue siendo una causa importante de mala visión y ceguera, por lo que su prevención tiene un rol fundamental.

  17. Desprendimiento de retina

    OpenAIRE

    L. Jaime Claramunt, Dr.

    2010-01-01

    El desprendimiento de retina (DR) consiste en la separación entre la retina neurosensorial y el epitelio pigmentario subyacente. Su forma más frecuente es el DR regmatógeno, causado por una rotura en la retina. Se manifiesta generalmente como un defecto en el campo visual o mala visión. Si se pesquisa y trata oportunamente tiene buenas posibilidades de éxito. No obstante, sigue siendo una causa importante de mala visión y ceguera, por lo que su prevención tiene un rol fundamental.

  18. Localization and regulation of dopamine receptor D4 expression in the adult and developing rat retina

    DEFF Research Database (Denmark)

    Klitten, Laura L; Rath, Martin F; Coon, Steven L

    2008-01-01

    layers but the nocturnal increase is confined to the photoreceptors. Retinal Drd4 expression is not affected by removal of the sympathetic input to the eye, but triiodothyronine treatment induces Drd4 expression in the photoreceptors. In a developmental series, we show that the expression of Drd4...

  19. A programmable artificial retina

    International Nuclear Information System (INIS)

    Bernard, T.M.; Zavidovique, B.Y.; Devos, F.J.

    1993-01-01

    An artificial retina is a device that intimately associates an imager with processing facilities on a monolithic circuit. Yet, except for simple environments and applications, analog hardware will not suffice to process and compact the raw image flow from the photosensitive array. To solve this output problem, an on-chip array of bare Boolean processors with halftoning facilities might be used, providing versatility from programmability. By setting the pixel memory size to 3 b, the authors have demonstrated both the technological practicality and the computational efficiency of this programmable Boolean retina concept. Using semi-static shifting structures together with some interaction circuitry, a minimal retina Boolean processor can be built with less than 30 transistors and controlled by as few as 6 global clock signals. The successful design, integration, and test of such a 65x76 Boolean retina on a 50-mm 2 CMOS 2-μm circuit are presented

  20. Helping the Retina Regenerate

    Science.gov (United States)

    ... the retina News Brief 03/30/17 A new report gives recommendations for regenerating retinal ganglion cells (RGCs), crucial neurons in the back of the eye that carry visual information to the brain. Authored ...

  1. Selective retina therapy (SRT); Selektive Retina-Therapie (SRT)

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, R.; Birngruber, R. [Luebeck Univ. (Germany). Inst. fuer Biomedizinische Optik; Medizinisches Laserzentrum Luebeck GmbH, Luebeck (Germany)

    2007-07-01

    Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Luebeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the choroid. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced. (orig.)

  2. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes.

    Science.gov (United States)

    Karachalias, N; Babaei-Jadidi, R; Rabbani, N; Thornalley, P J

    2010-07-01

    The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy. Diabetes was induced in male Sprague-Dawley rats by 55 mg/kg streptozotocin and moderated by insulin (2 U twice daily). Diabetic and control rats were given thiamine or benfotiamine (7 or 70 mg kg(-1) day(-1)) over 24 weeks. Plasma, urine and tissues were collected and analysed for protein damage by stable isotopic dilution analysis MS. There were two- to fourfold increases in fructosyl-lysine and AGE content of glomerular, retinal, sciatic nerve and plasma protein in diabetes. Increases in AGEs were reversed by thiamine and benfotiamine therapy but increases in fructosyl-lysine were not. Methionine sulfoxide content of plasma protein and 3-nitrotyrosine content of sciatic nerve protein were increased in diabetes. Plasma glycation free adducts were increased up to twofold in diabetes; the increases were reversed by thiamine. Urinary excretion of glycation, oxidation and nitration free adducts was increased by seven- to 27-fold in diabetes. These increases were reversed by thiamine and benfotiamine therapy. AGEs, particularly arginine-derived hydroimidazolones, accumulate at sites of microvascular complication development and have markedly increased urinary excretion rates in experimental diabetes. Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine.

  3. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    International Nuclear Information System (INIS)

    Kim, Yeoun-Hee; Chang, Yongmin; Jung, Jae-Chang

    2012-01-01

    Highlights: ► Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. ► Staurosporine mediates uPA activation during RGC differentiation in vitro. ► Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. ► Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that uPA plays a role in the staurosporine-mediated stimulation of RGC differentiation.

  4. Insulin-like activity in the retina

    International Nuclear Information System (INIS)

    Das, A.

    1986-01-01

    A number of studies have recently demonstrated that insulin or a homologous peptide may be synthesized outside the pancreas also. The present study was designed to investigate whether insulin-like activity exists in the retina, and if it exists, whether it is due to local synthesis of insulin or a similar peptide in the retina. To determine whether the insulin-like immunoreactivity in retinal glial cells is due to binding and uptake or local synthesis of insulin, a combined approach of immunocytochemistry and in situ DNA-RNA hybridization techniques was used on cultured rat retinal glial cells. Insulin-like immunoreactivity was demonstrated in the cytoplasma of these cells. In situ hybridization studies using labeled rat insulin cDNA indicated that these cells contain the mRNA necessary for de novo synthesis of insulin or a closely homologous peptide. Since human retinal cells have, as yet, not been conveniently grown in culture, an ocular tumor cell line, human Y79 retinoblastoma was used as a model to extend these investigations. The presence of insulin-like immunoreactivity as well as insulin-specific mRNA was demonstrated in this cell line. Light microscopic autoradiography following incubation of isolated rat retinal cells with 125 I-insulin showed the presence of insulin binding sites on the photoreceptors and amarcine cells. On the basis of these observations that rat retina glial cells, including Muller cells are sites of synthesis of insulin or a similar peptide, a model for the pathogenesis of dabetic retinopathy is proposed

  5. Retina image–based optic disc segmentation

    Directory of Open Access Journals (Sweden)

    Ching-Lin Wang

    2016-05-01

    Full Text Available The change of optic disc can be used to diagnose many eye diseases, such as glaucoma, diabetic retinopathy and macular degeneration. Moreover, retinal blood vessel pattern is unique for human beings even for identical twins. It is a highly stable pattern in biometric identification. Since optic disc is the beginning of the optic nerve and main blood vessels in retina, it can be used as a reference point of identification. Therefore, optic disc segmentation is an important technique for developing a human identity recognition system and eye disease diagnostic system. This article hence presents an optic disc segmentation method to extract the optic disc from a retina image. The experimental results show that the optic disc segmentation method can give impressive results in segmenting the optic disc from a retina image.

  6. Impact of MCT1 Haploinsufficiency on the Mouse Retina

    KAUST Repository

    Peachey, Neal S.

    2018-05-02

    The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

  7. Impact of MCT1 Haploinsufficiency on the Mouse Retina

    KAUST Repository

    Peachey, Neal S.; Yu, Minzhong; Han, John Y. S.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Philp, Nancy J.

    2018-01-01

    The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

  8. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2017-01-01

    Full Text Available Nerve growth factor (NGF is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC degenerate following optic-nerve crush (ONC, even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  9. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

    Science.gov (United States)

    Mesentier-Louro, Louise A; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-05

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75 NTR , TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75 NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75 NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  10. Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction in rat retina: A novel in vitro study of subarachnoid hemorrhage

    Science.gov (United States)

    Liu, Zhi; Li, Qiang; Cui, Gaoyu; Zhu, Gang; Tang, Weihua; Zhao, Hengli; Zhang, John H.; Chen, Yujie; Feng, Hua

    2016-01-01

    Previously, it was widely accepted that the delayed ischemic injury and poor clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral vasospasm. This classical theory was challenged by a clazosentan clinical trial, which failed to improve patient outcome, despite reversing angiographic vasospasm. One possible explanation for the results of this trial is the changes in microcirculation following SAH, particularly in pericytes, which are the primary cell type controlling microcirculation in the brain parenchyma. However, as a result of technical limitations and the lack of suitable models, there was no direct evidence of microvessel dysfunction following SAH. In the present study, whole-mount retinal microvasculature has been introduced to study microcirculation in the brain following experimental SAH in vitro. Artificial blood-filled cerebrospinal fluid (BSCF) was applied to the retinal microvasculature to test the hypothesis that the presence of subarachnoid blood affects the contractile properties of the pericytes containing cerebral microcirculation during the early phase of SAH. It was observed that BCSF induced retina microvessel contraction and that this contraction could be resolved by BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated collagen gel contraction and increased the expression of α-smooth muscle actin. In addition, BCSF induced an influx of calcium in cultured retinal pericytes. In conclusion, the present study demonstrates increased contractility of retinal microvessels and pericytes in the presence of BCSF in vitro. These findings suggest that pericyte contraction and microvascular dysfunction is induced following SAH, which could lead to greater susceptibility to SAH-induced ischemia. PMID:27698742

  11. The Retina Algorithm

    CERN Multimedia

    CERN. Geneva; PUNZI, Giovanni

    2015-01-01

    Charge particle reconstruction is one of the most demanding computational tasks found in HEP, and it becomes increasingly important to perform it in real time. We envision that HEP would greatly benefit from achieving a long-term goal of making track reconstruction happen transparently as part of the detector readout ("detector-embedded tracking"). We describe here a track-reconstruction approach based on a massively parallel pattern-recognition algorithm, inspired by studies of the processing of visual images by the brain as it happens in nature ('RETINA algorithm'). It turns out that high-quality tracking in large HEP detectors is possible with very small latencies, when this algorithm is implemented in specialized processors, based on current state-of-the-art, high-speed/high-bandwidth digital devices.

  12. Corpus vitreum, retina og chorioidea biopsi

    DEFF Research Database (Denmark)

    Scherfig, Erik Christian Høegh

    2002-01-01

    oftalmology, biopsy, choroid, corpus vitreum, retina, malignant melanoma, biopsy technic, retinoblastoma......oftalmology, biopsy, choroid, corpus vitreum, retina, malignant melanoma, biopsy technic, retinoblastoma...

  13. Microarray Analysis of the Developing Rat Mandible

    Institute of Scientific and Technical Information of China (English)

    Hideo KABURAGI; Naoyuki SUGANO; Maiko OSHIKAWA; Ryosuke KOSHI; Naoki SENDA; Kazuhiro KAWAMOTO; Koichi ITO

    2007-01-01

    To analyze the molecular events that occur in the developing mandible, we examined the expression of 8803 genes from samples taken at different time points during rat postnatal mandible development.Total RNA was extracted from the mandibles of 1-day-old, 1-week-old, and 2-week-old rats. Complementary RNA (cRNA) was synthesized from cDNA and biotinylated. Fragmented cRNA was hybridized to RGU34A GeneChip arrays. Among the 8803 genes tested, 4344 were detectable. We identified 148 genes with significantly increased expression, and 19 genes with significantly decreased expression. A comprehensive analysis appears to be an effective method of studying the complex process of development.

  14. Effects of perinatal asphyxia on the neurobehavioral and retinal development of newborn rats.

    Science.gov (United States)

    Kiss, Peter; Szogyi, Donat; Reglodi, Dora; Horvath, Gabor; Farkas, Jozsef; Lubics, Andrea; Tamas, Andrea; Atlasz, Tamas; Szabadfi, Krisztina; Babai, Norbert; Gabriel, Robert; Koppan, Miklos

    2009-02-19

    Perinatal asphyxia during delivery produces long-term deficits and represents a major problem in both neonatal and pediatric care. Several morphological, biochemical and behavioral changes have been described in rats exposed to perinatal asphyxia. The aim of the present study was to evaluate how perinatal asphyxia affects the complex early neurobehavioral development and retinal structure of newborn rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by cesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily during the first 3 weeks, and motor coordination tests were performed on postnatal weeks 3-5. After completion of the testing procedure, retinas were removed for histological analysis. We found that in spite of the fast catch-up-growth of asphyctic pups, nearly all examined reflexes were delayed by 1-4 days: negative geotaxis, sensory reflexes, righting reflexes, development of fore- and hindlimb grasp and placing, gait and auditory startle reflexes. Time to perform negative geotaxis, surface righting and gait reflexes was significantly longer during the first few weeks in asphyctic pups. Among the motor coordination tests, a markedly weaker performance was observed in the grid walking and footfault test and in the walk initiation test. Retinal structure showed severe degeneration in the layer of the photoreceptor and bipolar cell bodies. In summary, our present study provided a detailed description of reflex and motor development following perinatal asphyxia, showing that asphyxia led to a marked delay in neurobehavioral development and a severe retinal degeneration.

  15. Simulating the Effects of Laser Damage to the Retina

    National Research Council Canada - National Science Library

    2001-01-01

    This Phase II SBIR brought vision and signal processing researchers from the Air Force, academia and the public sector together to develop a visualization tool for modeling laser damage to the retina...

  16. Topography of ganglion cell production in the cat's retina

    International Nuclear Information System (INIS)

    Walsh, C.; Polley, E.H.

    1985-01-01

    The ganglion cells of the cat's retina form several classes distinguishable in terms of soma size, axon diameter, dendritic morphology, physiological properties, and central connections. Labeling with [ 3 H]thymidine shows that the ganglion cells which survive in the adult are produced as several temporally shifted, overlapping waves: medium-sized cells are produced before large cells, whereas the smallest ganglion cells are produced throughout the period of ganglion cell generation. Large cells and medium-sized cells show the same distinctive pattern of production, forming rough spirals around the area centralis. The oldest cells tend to lie superior and nasal to the area centralis, whereas cells in the inferior nasal retina and inferior temporal retina are, in general, progressively younger. Within each retinal quadrant, cells nearer the area centralis tend to be older than cells in the periphery, but there is substantial overlap. The retinal raphe divides the superior temporal quadrant into two zones with different patterns of cell addition. Superior temporal retina near the vertical meridian adds cells only slightly later than superior nasal retina, whereas superior temporal retina near the horizontal meridian adds cells very late, contemporaneously with inferior temporal retina. The broader wave of production of smaller ganglion cells seems to follow this same spiral pattern at its beginning and end. The presence of the area centralis as a nodal point about which ganglion cell production in the retinal quadrants pivots suggests that the area centralis is already an important retinal landmark even at the earliest stages of retinal development

  17. Neurotransmitter-Regulated Regeneration in the Zebrafish Retina

    Directory of Open Access Journals (Sweden)

    Mahesh B. Rao

    2017-04-01

    Full Text Available Summary: Current efforts to repair damaged or diseased mammalian retinas are inefficient and largely incapable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage using Müller glia (MG-derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. We show that inhibition of γ-aminobutyric acid (GABA signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect decreased ambient levels and undergo dedifferentiation. Using pharmacological and genetic approaches, we demonstrate that GABAA receptor inhibition stimulates regeneration in undamaged retinas while activation inhibits regeneration in damaged retinas. : Unlike mammals, zebrafish regenerate following retina damage from a resident adult stem cell (Müller glia. Dissecting the mechanisms that zebrafish use could lead to new therapeutic targets to treat retinal diseases. Patton and colleagues have discovered a mechanism by which decreased GABA levels are sensed by Müller glia to initiate a regenerative response. Keywords: zebrafish, retina, regeneration, Müller glia, GABA

  18. Complex computation in the retina

    Science.gov (United States)

    Deshmukh, Nikhil Rajiv

    Elucidating the general principles of computation in neural circuits is a difficult problem requiring both a tractable model circuit as well as sophisticated measurement tools. This thesis advances our understanding of complex computation in the salamander retina and its underlying circuitry and furthers the development of advanced tools to enable detailed study of neural circuits. The retina provides an ideal model system for neural circuits in general because it is capable of producing complex representations of the visual scene, and both its inputs and outputs are accessible to the experimenter. Chapter 2 describes the biophysical mechanisms that give rise to the omitted stimulus response in retinal ganglion cells described in Schwartz et al., (2007) and Schwartz and Berry, (2008). The extra response to omitted flashes is generated at the input to bipolar cells, and is separable from the characteristic latency shift of the OSR apparent in ganglion cells, which must occur downstream in the circuit. Chapter 3 characterizes the nonlinearities at the first synapse of the ON pathway in response to high contrast flashes and develops a phenomenological model that captures the effect of synaptic activation and intracellular signaling dynamics on flash responses. This work is the first attempt to model the dynamics of the poorly characterized mGluR6 transduction cascade unique to ON bipolar cells, and explains the second lobe of the biphasic flash response. Complementary to the study of neural circuits, recent advances in wafer-scale photolithography have made possible new devices to measure the electrical and mechanical properties of neurons. Chapter 4 reports a novel piezoelectric sensor that facilitates the simultaneous measurement of electrical and mechanical signals in neural tissue. This technology could reveal the relationship between the electrical activity of neurons and their local mechanical environment, which is critical to the study of mechanoreceptors

  19. The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    匡洪宇; 邹伟; 刘丹; 史榕荇; 程丽华; 殷慧清; 刘晓民

    2003-01-01

    Objective To evaluate the potential role of insulin-like growth factor-1 receptor mRNA(IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.Methods A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.Results Weak expression of IGF-IR mRNA(5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P<0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.Conclusion Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

  20. Thyroid Hormone Signaling in the Mouse Retina.

    Directory of Open Access Journals (Sweden)

    Patrick Arbogast

    Full Text Available Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3 and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells showed strong β-gal labeling. In the inner nuclear layer (INL, a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic 'starburst' amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.

  1. The Neural Retina in Retinopathy of Prematurity

    Science.gov (United States)

    Hansen, Ronald M.; Moskowitz, Anne; Akula, James D.; Fulton, Anne B.

    2016-01-01

    Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP. PMID:27671171

  2. Imaging of the peripheral retina

    Directory of Open Access Journals (Sweden)

    Marcus Kernt

    2013-01-01

    Full Text Available The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO, digital angiography, optical coherence tomography (OCT, and detection of fundus autofluorescence (FAF have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina.

  3. Monte Carlo simulation of zinc protoporphyrin fluorescence in the retina

    Science.gov (United States)

    Chen, Xiaoyan; Lane, Stephen

    2010-02-01

    We have used Monte Carlo simulation of autofluorescence in the retina to determine that noninvasive detection of nutritional iron deficiency is possible. Nutritional iron deficiency (which leads to iron deficiency anemia) affects more than 2 billion people worldwide, and there is an urgent need for a simple, noninvasive diagnostic test. Zinc protoporphyrin (ZPP) is a fluorescent compound that accumulates in red blood cells and is used as a biomarker for nutritional iron deficiency. We developed a computational model of the eye, using parameters that were identified either by literature search, or by direct experimental measurement to test the possibility of detecting ZPP non-invasively in retina. By incorporating fluorescence into Steven Jacques' original code for multi-layered tissue, we performed Monte Carlo simulation of fluorescence in the retina and determined that if the beam is not focused on a blood vessel in a neural retina layer or if part of light is hitting the vessel, ZPP fluorescence will be 10-200 times higher than background lipofuscin fluorescence coming from the retinal pigment epithelium (RPE) layer directly below. In addition we found that if the light can be focused entirely onto a blood vessel in the neural retina layer, the fluorescence signal comes only from ZPP. The fluorescence from layers below in this second situation does not contribute to the signal. Therefore, the possibility that a device could potentially be built and detect ZPP fluorescence in retina looks very promising.

  4. Development of rat telencephalic neurons after prenatal x-irradiation

    International Nuclear Information System (INIS)

    Norton, S.

    1979-01-01

    Telencephalic neurons of rats, irradiated at day 15 of gestation with 125 R, develop synaptic connections on dendrites during maturation which appear to be normal spines in Golgi-stained light microscope preparations. At six weeks of postnatal age both control and irradiated rats have spiny dendritic processes on cortical pyramidal cells and caudate Golgi type II neurons. However, when the rats are 6 months old the irradiated rats have more neurons with beaded dendritic processes that lack spines or neurons and are likely to be degenerating neurons. The apparently normal development of the neurons followed by degeneration in the irradiated rat has a parallel in previous reports of the delayed hyperactivity which develops in rats irradiated on the fifteenth gestational day

  5. Development of ELISA kit for rat albumin

    International Nuclear Information System (INIS)

    Yuan Zhigang; Han Shiquan; Liu Yibing; Xu Wenge; Jia Juanjuan

    2009-01-01

    The Anti-rat albumin serum was prepared by immunized the sheep with rat albumin. A ELISA method was established for rat albumin. The measurement range of the assay was 1-50 mg/L, sensitivity of the assay was 0.42 mg/L, recovery rate was 85.0%-106.0%. Intra-and inter-assay variation coefficients were <8.9% and <12.8% respectively. The correlation coefficients between measured and expected values were 0.999 after serial dilution of the urine samples with high concentrations of rat albumin. A good correlation was observed between the ELISA and RIA methods, and the kit for rat albumin might provide a convenience in exploitation of renal drugs and experimental injury of the kidney. (authors)

  6. Dual cameras acquisition and display system of retina-like sensor camera and rectangular sensor camera

    Science.gov (United States)

    Cao, Nan; Cao, Fengmei; Lin, Yabin; Bai, Tingzhu; Song, Shengyu

    2015-04-01

    For a new kind of retina-like senor camera and a traditional rectangular sensor camera, dual cameras acquisition and display system need to be built. We introduce the principle and the development of retina-like senor. Image coordinates transformation and interpolation based on sub-pixel interpolation need to be realized for our retina-like sensor's special pixels distribution. The hardware platform is composed of retina-like senor camera, rectangular sensor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes two cameras' acquisition and display.

  7. Towards photovoltaic powered artificial retina

    Directory of Open Access Journals (Sweden)

    Santiago Silvestre

    2011-11-01

    Full Text Available The aim of this article is to provide an overview of current and future concepts in the field of retinal prostheses, and is focused on the power supply based on solar energy conversion; we introduce the possibility of using PV minimodules as power supply for a new concept of retinal prostheses: Photovoltaic Powered Artificial Retina (PVAR. Main characteristics of these PV modules are presented showing its potential for this application.

  8. Cold Shock Proteins Are Expressed in the Retina Following Exposure to Low Temperatures.

    Directory of Open Access Journals (Sweden)

    Ignacio M Larrayoz

    Full Text Available Hypothermia has been proposed as a therapeutic intervention for some retinal conditions, including ischemic insults. Cold exposure elevates expression of cold-shock proteins (CSP, including RNA-binding motif protein 3 (RBM3 and cold inducible RNA-binding protein (CIRP, but their presence in mammalian retina is so far unknown. Here we show the effects of hypothermia on the expression of these CSPs in retina-derived cell lines and in the retina of newborn and adult rats. Two cell lines of retinal origin, R28 and mRPE, were exposed to 32°C for different time periods and CSP expression was measured by qRT-PCR and Western blotting. Neonatal and adult Sprague-Dawley rats were exposed to a cold environment (8°C and expression of CSPs in their retinas was studied by Western blotting, multiple inmunofluorescence, and confocal microscopy. RBM3 expression was upregulated by cold in both R28 and mRPE cells in a time-dependent fashion. On the other hand, CIRP was upregulated in R28 cells but not in mRPE. In vivo, expression of CSPs was negligible in the retina of newborn and adult rats kept at room temperature (24°C. Exposure to a cold environment elicited a strong expression of both proteins, especially in retinal pigment epithelium cells, photoreceptors, bipolar, amacrine and horizontal cells, Müller cells, and ganglion cells. In conclusion, CSP expression rapidly rises in the mammalian retina following exposure to hypothermia in a cell type-specific pattern. This observation may be at the basis of the molecular mechanism by which hypothermia exerts its therapeutic effects in the retina.

  9. [Lattice degeneration of the retina].

    Science.gov (United States)

    Boĭko, E V; Suetov, A A; Mal'tsev, D S

    2014-01-01

    Lattice degeneration of the retina is a clinically important type of peripheral retinal dystrophies due to its participation in the pathogenesis of rhegmatogenous retinal detachment. In spite of extensive epidemiological, morphological, and clinical data, the question on causes of this particular type of retinal dystrophies currently remains debatable. Existing hypotheses on pathogenesis of retinal structural changes in lattice degeneration explain it to a certain extent. In clinical ophthalmology it is necessary to pay close attention to this kind of degenerations and distinguish between cases requiring preventive treatment and those requiring monitoring.

  10. Lattice degeneration of the retina.

    Science.gov (United States)

    Byer, N E

    1979-01-01

    Lattice degeneration of the retina is the most important of all clinically distinct entities that effect the peripheral fundus and are related to retinal detachment. The purpose of this review is to survey the extensive literature, to evaluate the many diverse opinions on this subject, and to correlate and summarize all the known facts regarding this disease entity. The disease is fully defined and described, both clinically and histologically. Some aspects of the disease are still poorly understood, and some remain controversial, especially in the area of management. For this reason, the indications for treatment are discussed under eight subsections, with a view toward providing practical guidelines for recommendations in management.

  11. Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter.

    Directory of Open Access Journals (Sweden)

    Jake Bedore

    Full Text Available Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina.A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina- targeted (embryonic day 12.5 deletion of VAChT (VAChTSix3-Cre-flox/flox and littermate controls at 5 and 12 months of age. VAChTSix3-Cre-flox/flox mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChTSix3-Cre-flox/flox mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses.This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina.

  12. [Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

    Science.gov (United States)

    Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

    2017-12-01

    Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

  13. The retina of Spalax ehrenbergi: novel histologic features supportive of a modified photosensory role.

    NARCIS (Netherlands)

    Cernuda-Cernuda, R.; Grip, W.J. de; Cooper, H.M.; Nevo, E.; Garcia-Fernandez, J.M.

    2002-01-01

    PURPOSE: The retina of the blind mole rat Spalax ehrenbergi was compared with other vertebrate photosensitive organs in an attempt to correlate its histologic organization with a presumptive nonvisual photoreceptor role. METHODS: The eyes of eight adult animals were analyzed by light and electron

  14. Neural Responses to Injury: Prevention, Protection and Repair; Volume 7: Role Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury

    National Research Council Canada - National Science Library

    Bazan, Nicolas

    1996-01-01

    ...: Prevention, Protection, and Repair, Subproject: Role of Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury, are as follows: Species Rat(Albino Wistar), Number Allowed...

  15. Acetylcholine receptors in the human retina

    International Nuclear Information System (INIS)

    Hutchins, J.B.; Hollyfield, J.G.

    1985-01-01

    Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand 3 H-propylbenzilylcholine mustard ( 3 H-PrBCM) to label muscarinic receptors. 3 H- or 125 I-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that 3 H-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer of the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. This study provides evidence for cholinergic neurotransmission in the human retina

  16. RETINOBASE: a web database, data mining and analysis platform for gene expression data on retina

    Directory of Open Access Journals (Sweden)

    Léveillard Thierry

    2008-05-01

    Full Text Available Abstract Background The retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina. Description RETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression meta-data and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed

  17. Gluconeogenesis in rat placenta during foetal development

    International Nuclear Information System (INIS)

    Bagewadikar, R.S.; Sharma, C.; Nadkarni, G.B.

    1977-01-01

    Variations in glycogen levels in rat placenta have been correlated with gluconeogenesis in this tissue. Placental homogenate could synthesize substantial amounts of glucose from L-alanine-U- 14 C in early pregnancy. This has been substantiated by the observed enhancement in the activities of glucose 6-phosphatase, fructose 1, 6-diphosphatase and phosphoenolpyruvate carboxykinase. Gluconeogenic activity in placenta could proceed till the foetal liver was able to take over this function. The increase or decrease in placental glycogen is concomitant with glycogen synthetase, but not phosphorylase, activity. The reversible catalytic properties of placental aldolase also show subtle functional changes during and late phases of gestation. (author)

  18. Gluconeogenesis in rat placenta during foetal development

    Energy Technology Data Exchange (ETDEWEB)

    Bagewadikar, R S; Sharma, C; Nadkarni, G B [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

    1977-01-01

    Variations in glycogen levels in rat placenta have been correlated with gluconeogenesis in this tissue. Placental homogenate could synthesize substantial amounts of glucose from L-alanine-U-/sup 14/C in early pregnancy. This has been substantiated by the observed enhancement in the activities of glucose 6-phosphatase, fructose 1, 6-diphosphatase and phosphoenolpyruvate carboxykinase. Gluconeogenic activity in placenta could proceed till the foetal liver was able to take over this function. The increase or decrease in placental glycogen is concomitant with glycogen synthetase, but not phosphorylase, activity. The reversible catalytic properties of placental aldolase also show subtle functional changes during and late phases of gestation.

  19. Increased intraretinal PO2 in short-term diabetic rats.

    Science.gov (United States)

    Lau, Jennifer C M; Linsenmeier, Robert A

    2014-12-01

    In diabetic retinopathy, neovascularization is hypothesized to develop due to hypoxia in the retina. However, evidence for retinal hypoxia is limited, and the progressive changes in oxygenation are unknown. The objective of this study was to determine if retinal hypoxia occurs early in the development of diabetes. Intraretinal oxygen (PO2) profiles were recorded with oxygen-sensitive microelectrodes in control and diabetic Long-Evans rats at 4 and 12 weeks after induction of diabetes. Diabetes did not affect oxygen consumption in the photoreceptors in either dark or light adaptation. Oxygenation of the inner retina was not affected after 4 weeks of diabetes, although vascular endothelial growth factor levels increased. At 12 weeks, average inner retinal PO2, normalized to choriocapillaris PO2, was higher in diabetic rats than in age-matched controls, which was opposite to what was expected. Thus retinal hypoxia is not a condition of early diabetes in rat retina. Increased inner retinal PO2 may occur because oxygen consumption decreases in the inner retina. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Cytogenesis in the monkey retina

    International Nuclear Information System (INIS)

    La Vail, M.M.; Rapaport, D.H.; Rakic, P.

    1991-01-01

    Time of cell origin in the retina of the rhesus monkey (Macaca mulatta) was studied by plotting the number of heavily radiolabeled nuclei in autoradiograms prepared from 2- to 6-month-old animals, each of which was exposed to a pulse of 3H-thymidine (3H-TdR) on a single embryonic (E) or postnatal (P) day. Cell birth in the monkey retina begins just after E27, and approximately 96% of cells are generated by E120. The remaining cells are produced during the last (approximately 45) prenatal days and into the first several weeks after birth. Cell genesis begins near the fovea, and proceeds towards the periphery. Cell division largely ceases in the foveal and perifoveal regions by E56. Despite extensive overlap, a class-specific sequence of cell birth was observed. Ganglion and horizontal cells, which are born first, have largely congruent periods of cell genesis with the peak between E38 and E43, and termination around E70. The first labeled cones were apparent by E33, and their highest density was achieved between E43 and E56, tapering to low values at E70, although some cones are generated in the far periphery as late as E110. Amacrine cells are next in the cell birth sequence and begin genesis at E43, reach a peak production between E56 and E85, and cease by E110. Bipolar cell birth begins at the same time as amacrines, but appears to be separate from them temporally since their production reaches a peak between E56 and E102, and persists beyond the day of birth. Mueller cells and rod photoreceptors, which begin to be generated at E45, achieve a peak, and decrease in density at the same time as bipolar cells, but continue genesis at low density on the day of birth. Thus, bipolar, Mueller, and rod cells have a similar time of origin

  1. Autoradiography of 90Sr in developing rats

    International Nuclear Information System (INIS)

    Olsen, I.; Jonsen, J.

    1979-01-01

    The distribution patterns of 90 Sr in five littermate, 8-day-old Wistar rats were studied by whole body autoradiography. Rats were killed 15 min, 1, 4, 24, and 72 h after a single intraperitoneal injection of the isotope. Immediately after administration, 90 Sr was distributed throughout most of the soft tissues of the body. The soft tissue deposits had practically disappeared after 4 h. In the hard tissues of the body 90 Sr accumulated up to 24-72 h. Fifteen minutes after injection the uptake of 90 Sr in the enamel of the teeth was highest in the occlusal and incisal regions. 90 Sr gradually accumulated throughout the enamel and after 72 h its distribution in this layer was fairly uniform. Immediately after injection a narrow zone of radioactivity appeared in the dentin near the pulp. This zone broadened with time towards the dentinoenamel junction and included the intire dentin layer 72 h after injection. Initially, the uptake of 90 Sr was higher in the dentin than in the enamel, particularly in the cervical areas of the crown. This difference became less apparent with time. There was good correlation between the uptake in the teeth and bones, supporting the use of teeth as indicators of the 90 Sr body burden. (author)

  2. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    International Nuclear Information System (INIS)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-01-01

    Autoradiography using 125 I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat

  3. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-04-01

    Autoradiography using /sup 125/I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.

  4. Simultaneous in vivo imaging of melanin and lipofuscin in the retina with multimodal photoacoustic ophthalmoscopy

    Science.gov (United States)

    Zhang, Xiangyang; Zhang, Hao F.; Zhou, Lixiang; Jiao, Shuliang

    2012-02-01

    We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective vs. exacerbate) in the RPE in the aging process. We successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

  5. Postnatal development of plasma amino acids in hyperphagic rats.

    Science.gov (United States)

    Salvadó, M J; Segués, T; Arola, L

    1991-01-01

    The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30.

  6. Clonal origins of cells in the pigmented retina of the zebrafish eye

    International Nuclear Information System (INIS)

    Streisinger, G.; Coale, F.; Taggart, C.; Walker, C.; Grunwald, D.J.

    1989-01-01

    Mosaic analysis has been used to study the clonal basis of the development of the pigmented retina of the zebrafish, Brachydanio rerio. Zebrafish embryos heterozygous for a recessive mutation at the gol-1 locus were exposed to gamma-irradiation at various developmental stages to create mosaic individuals consisting of wild-type pigmented cells and a clone of pigmentless (golden) cells in the eye. The contribution of individual embryonic cells to the pigmented retina was measured and the total number of cells in the embryo that contributed descendants to this tissue was determined. Until the 32-cell stage, almost every blastomere has some descendants that participate in the formation of the pigmented retina of the zebrafish. During subsequent cell divisions, up to the several thousand-cell stage, the number of ancestral cells is constant: approximately 40 cells are present that will give rise to progeny in the pigmented retina. Analysis of the size of clones in the pigmented retina indicates that the cells of this tissue do not arise through a rigid series of cell divisions originating in the early embryo. The findings that each cleavage stage cell contributes to the pigmented retina and yet the contribution of such cells is highly variable are consistent with the interpretation that clonal descendants of different blastomeres normally intermix extensively prior to formation of the pigmented retina

  7. An analog silicon retina with multichip configuration.

    Science.gov (United States)

    Kameda, Seiji; Yagi, Tetsuya

    2006-01-01

    The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

  8. Development of the rat larynx: a histological study.

    Science.gov (United States)

    Alli, Opeyemi; Berzofsky, Craig; Sharma, Sansar; Pitman, Michael J

    2013-12-01

    To evaluate and describe the cartilaginous and muscular development of the rat larynx. Histologic evaluation. The larynges of Sprague Dawley rats of embryonic day (E) 13, 15, 17, 19, 21, postnatal day 0, 14, and adult of 250 gm were collected. Four larynges of each age were harvested, cut into 15-μm serial sections, stained with hematoxylin and eosin, and evaluated under light microscopy. Representative digital images were recorded and evaluated at the preglottic (supraglottic in humans), glottic, and postglottic (subglottic in humans) levels. Brachial arches were observed at E13. At E17, immature structures of the larynx, including skeletal muscle, cartilage, and the lumen were identifiable. Chondrification and muscle formation were clearly seen by E19. The muscular and cartilagenous components of the larynx were well established by E21. During the span between birth and adult maturation, the size of the larynx increased from a height of 1.10 mm to 2.90 mm, and from a width of 1.80 mm to 5.40 mm, and from a length of 1.38 mm to 4.77 mm in the stained section. Although developed at E21, the laryngeal structures continued to grow by approximately 30%. Rat laryngeal development parallels that in mice and humans. In the rat, at E17 immature structures of the larynx are identifiable, they are well developed at birth and grow by approximately 30% into adulthood. Understanding the chronology and morphology of the embryogenesis of the rat laryngeal musculature is essential and will allow for further evaluation of the embryologic innervation of these muscles. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Development of antibodies against the rat brain somatostatin receptor.

    Science.gov (United States)

    Theveniau, M; Rens-Domiano, S; Law, S F; Rougon, G; Reisine, T

    1992-05-15

    Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation of motor activity and cognition. It induces its physiological actions by interacting with receptors. We have developed antibodies against the receptor to investigate its structural properties. Rabbit polyclonal antibodies were generated against the rat brain SRIF receptor. These antibodies (F4) were able to immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT-20. The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108, which express high densities of SRIF receptors. They did not detect immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high densities of SRIF receptors. However, F4 did not interact with proteins from cerebellum and brain stem, which express few SRIF receptors. Immunoreactive material cannot be detected in rat pancreas or pituitary, which have been reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60-kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes are immunologically distinct. The availability of antibodies that selectively detect native and denatured brain SRIF receptors provides us with a feasible approach to clone the brain SRIF receptor gene(s).

  10. Phenomenon of hormesis on γ-irradiated developing rat pups

    International Nuclear Information System (INIS)

    Ruda, V.P.; Kuzin, A.M.

    1991-01-01

    Development of rat pups was shown to accelerate body mass up 121% of control) afetr γ-irradiation on day 21 of the postnatal development (2.88 cGy, dose-rate of 0.12 cGy/h). Higher cumulative doses (14.4 and 144 cGy) did not influence the body mass growth, and inhibition was only caused by doses exceeding 150 cGy

  11. Some indications of structural damage in retina by heavy ion radiation

    International Nuclear Information System (INIS)

    Nelson, A.C.; Hayes, T.L.; Tobias, C.A.; Yang, T.C.

    1981-01-01

    At the Lawrence Berkeley Laboratory Bevalac Facility, iron nuclei were accelerated to an energy of 600 MeV/amu. The beam of iron thus obtained was used to irradiate living biological specimens in order to study possible microscopic tissue damage with the aid of SEM. The experiments involved total head irradiation of live rats which were subsequently returned to their cages to remain for 1 day and 30 days before further examination. After the 1 day and 30 day waits, both eyes were enucleated and placed in chemical fixative followed by ethanol dehydration and critical point drying. Retinas were carefully removed from the eye cups and loaded separately on aluminum stubs which were sputter coated. SEM of the 1 day and 30 day retinas revealed lesions which were not found at all in control retinas. The 1 day and 30 day retinas manifest regions where outer rod segments were missing or rearranged. A single energetic iron nucleus may be capable of generating a retinal lesion which becomes enlarged as biological processes intervene during the 1 day and 30 day waits. Being composed of highly specialized nerve cells, retinas cannot regenerate following irradiation which severely damages the rod cells. Thus one would expect the observed radiation induced retinal lesions to correspond to permanent tissue damage and possible loss of visual acuity in the intact animal

  12. Increased expression of IRE1α and stress-related signal transduction proteins in ischemia-reperfusion injured retina

    Directory of Open Access Journals (Sweden)

    Natsuyo Hata

    2008-08-01

    Full Text Available Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1, SAPK/ERK kinase 1 (SEK1 and c-Jun N-terminal kinase (JNK is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

  13. Histopathological effects on the eye development during perinatal growth of albino rats maternally treated with experimental phenylketonuria during pregnancy

    Directory of Open Access Journals (Sweden)

    Hany A. Hefty

    2016-04-01

    Full Text Available Phenylketonuria (PKU is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. Although, this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known about the mechanisms involved in the pathology of PKU during neonatal brain development. Elevated concentrations of plasma phenylalanine were induced in pregnant rats by oral administration of 50mg/100g body weight alpha-methylphenylalanine plus phenylalanine supplementation at a dosage of 60mg/100g body weight two times daily after 6th day of onset of gestation till 14 & 16 days prenatal as well as at parturition. Treatment with alpha-methylphenylalanine resulted in significant reduction of retinal cell layers of prenatal fetuses and delivered newborns.   Histological abnormalities were detected manifested by either hyaline degeneration of lens structure or inducing lens cataract as well as comparative atrophy of retina associated with the development of malignant polypoid mass in the ganglionic cell layers in contact with the lens.

  14. Radioadaptive Cytoprotective Pathways in the Mouse Retina

    Science.gov (United States)

    Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.

    2010-01-01

    Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

  15. Modeling and Simulation of Microelectrode-Retina Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Beckerman, M

    2002-11-30

    The goal of the retinal prosthesis project is the development of an implantable microelectrode array that can be used to supply visually-driven electrical input to cells in the retina, bypassing nonfunctional rod and cone cells, thereby restoring vision to blind individuals. This goal will be achieved through the study of the fundamentals of electrical engineering, vision research, and biomedical engineering with the aim of acquiring the knowledge needed to engineer a high-density microelectrode-tissue hybrid sensor that will restore vision to millions of blind persons. The modeling and simulation task within this project is intended to address the question how best to stimulate, and communicate with, cells in the retina using implanted microelectrodes.

  16. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)

    1977-01-01

    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  17. Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

    Directory of Open Access Journals (Sweden)

    ROBERTO PAES-DE-CARVALHO

    2002-09-01

    Full Text Available The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity or A2 receptors that directly activate the enzyme. Experiments using retinal cell cultures revealed that adenosine is taken up by specific cell populations that when stimulated by depolarization or neurotransmitters such as dopamine or glutamate, release the nucleoside through calcium-dependent transporter-mediated mechanisms. The presence of adenosine in the extracellular medium and the long-term activation of adenosine receptors is able to regulate the survival of retinal neurons and blocks glutamate excitoxicity. Thus, adenosine besides working as a neurotransmitter or neuromodulator in the mature retina, is considered as an important signaling molecule during retinal development having important functions such as regulation of neuronal survival and differentiation.O nucleosídeo adenosina apresenta um importante papel como neurotransmissor ou neuromodulador no sistema nervoso central, inclusive na retina. Neste artigo apresentamos uma revisão das evidências que mostram que a adenosina é uma molécula sinalizadora na retina em desenvolvimento. Na retina de pinto, transportadores de adenosina estão presentes desde estágios precoces do desenvolvimento, antes do aparecimento dos receptores A1 que modulam a atividade adenilato ciclase dependente de dopamina ou dos receptores A2 que ativam diretamente a enzima. Experimentos usando culturas de células de retina revelaram que a adenosina é captada por populações celulares específicas que, quando estimuladas por despolarização ou por

  18. Passive stiffness of rat skeletal muscle undernourished during fetal development

    Directory of Open Access Journals (Sweden)

    Ana Elisa Toscano

    2010-01-01

    Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

  19. Non-invasive imaging and monitoring of rodent retina using simultaneous dual-band optical coherence tomography

    Science.gov (United States)

    Cimalla, Peter; Burkhardt, Anke; Walther, Julia; Hoefer, Aline; Wittig, Dierk; Funk, Richard; Koch, Edmund

    2011-03-01

    Spectral domain dual-band optical coherence tomography for simultaneous imaging of rodent retina in the 0.8 μm and 1.3 μm wavelength region and non-invasive monitoring of the posterior eye microstructure in the field of retinal degeneration research is demonstrated. The system is illuminated by a supercontinuum laser source and allows three-dimensional imaging with high axial resolution better than 3.8 μm and 5.3 μm in tissue at 800 nm and 1250 nm, respectively, for precise retinal thickness measurements. A fan-shaped scanning pattern with the pivot point close to the eye's pupil and a contact lens are applied to obtain optical access to the eye's fundus. First in vivo experiments in a RCS (royal college of surgeons) rat model with gene-related degeneration of the photoreceptor cells show good visibility of the retinal microstructure with sufficient contrast for thickness measurement of individual retinal layers. An enhanced penetration depth at 1250 nm is clearly identifiable revealing sub-choroidal structures that are not visible at 800 nm. Furthermore, additional simultaneous imaging at 1250 nm improves image quality by frequency compounding speckle noise reduction. These results are encouraging for time course studies of the rodent retina concerning its development related to disease progression and treatment response.

  20. Elucidation of Inflammation Processes Exacerbating Neuronal Cell Damage to the Retina and Brain Visual Centers as Quest for Therapeutic Drug Targets in Rat Model of Blast Overpressure Wave Exposure

    Science.gov (United States)

    2016-10-01

    Righting Reflex of rats following double blast exposure. 0 4 8 12 16 20 R ig ht in g Re fle x (m in ut es ) PLACEBO FISH OIL Total Lived Died...experiments. Funding Support: Geneva Foundation contractor – WRAIR Name: Joseph B. Long, Ph.D. Project Role: Co-Investigator – WRAIR Researcher...Funding Support: Clinical Research Management contractor Name: Andrew B. Batuure Project Role: Technician - WRAIR Researcher Identifier (e.g. ORCID

  1. Fibronectin distribution during the development of fetal rat skin

    DEFF Research Database (Denmark)

    Gibson, W T; Couchman, J R; Weaver, A C

    1983-01-01

    Fibronectin distribution during fetal rat skin development has been studied immunocytochemically at the light and electron microscope level from 16 days of gestation to birth. The dermal-epidermal junction, the dermis, and connective tissue around developing muscle were shown by light microscopy......, and there was also staining associated with the underlying fine collagen fibrils. These observations are further evidence for the proposed role of fibronectin as a mediator of the cell-matrix interactions which are of importance for tissue development and maintenance....

  2. The role of cell cycle in retinal development: cyclin-dependent kinase inhibitors co-ordinate cell-cycle inhibition, cell-fate determination and differentiation in the developing retina.

    Science.gov (United States)

    Bilitou, Aikaterini; Ohnuma, Shin-ichi

    2010-03-01

    The mature retina is formed through multi-step developmental processes, including eye field specification, optic vesicle evagination, and cell-fate determination. Co-ordination of these developmental events with cell-proliferative activity is essential to achieve formation of proper retinal structure and function. In particular, the molecular and cellular dynamics of the final cell cycle significantly influence the identity that a cell acquires, since cell fate is largely determined at the final cell cycle for the production of postmitotic cells. This review summarizes our current understanding of the cellular mechanisms that underlie the co-ordination of cell-cycle and cell-fate determination, and also describes a molecular role of cyclin-dependent kinase inhibitors (CDKIs) as co-ordinators of cell-cycle arrest, cell-fate determination and differentiation. Copyright (c) 2010 Wiley-Liss, Inc.

  3. Neurotransmitter properties of the newborn human retina

    International Nuclear Information System (INIS)

    Hollyfield, J.G.; Frederick, J.M.; Rayborn, M.E.

    1983-01-01

    Human retinal tissue from a newborn was examined autoradiographically for the presence of high-affinity uptake and localization of the following putative neurotransmitters: dopamine, glycine, GABA, aspartate, and glutamate. In addition, the dopamine content of this newborn retina was measured by high pressure liquid chromatography. Our study reveals that specific uptake mechanisms for 3 H-glycine, 3 H-dopamine, and 3 H-GABA are present at birth. However, the number and distribution of cells labeled with each of these 3 H-transmitters are not identical to those observed in adult human retinas. Furthermore, the amount of endogenous dopamine in the newborn retina is approximately 1/20 the adult level. Photoreceptor-specific uptake of 3 H-glutamate and 3 H-aspartate are not observed. These findings indicate that, while some neurotransmitter-specific properties are present at birth, significant maturation of neurotransmitter systems occurs postnatally

  4. HIV-1 transgenic rats develop T cell abnormalities

    International Nuclear Information System (INIS)

    Reid, William; Abdelwahab, Sayed; Sadowska, Mariola; Huso, David; Neal, Ashley; Ahearn, Aaron; Bryant, Joseph; Gallo, Robert C.; Lewis, George K.; Reitz, Marvin

    2004-01-01

    HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-γ following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC - CD62L - ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naieve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process

  5. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Katsuda

    2014-01-01

    Full Text Available We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam. The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

  6. Development of neuropeptide Y-mediated heart innervation in rats.

    Science.gov (United States)

    Masliukov, Petr M; Moiseev, Konstantin; Emanuilov, Andrey I; Anikina, Tatyana A; Zverev, Alexey A; Nozdrachev, Alexandr D

    2016-02-01

    Neuropeptide Y (NPY) plays a trophic role in the nervous and vascular systems and in cardiac hypertrophy. However, there is no report concerning the expression of NPY and its receptors in the heart during postnatal development. In the current study, immunohistochemistry and Western blot analysis was used to label NPY, and Y1R, Y2R, and Y5R receptors in the heart tissue and intramural cardiac ganglia from rats of different ages (newborn, 10 days old, 20 days old, 30 days old, 60 days old, 1 year old, and 2 years old).The obtained data suggest age-dependent changes of NPY-mediated heart innervation. The density of NPY-immunoreactive (IR) fibers was the least in newborn animals and increased in the first 20 days of life. In the atria of newborn and 10-day-old rats, NPY-IR fibers were more abundant compared with the ventricles. The vast majority of NPY-IR fibers also contained tyrosine hydroxylase, a key enzyme in catecholamine synthesis.The expression of Y1R increased between 10 and 20 days of life. Faint Y2R immunoreactivity was observed in the atria and ventricles of 20-day-old and older rats. In contrast, the highest level of the expression of Y5R was found in newborn pups comparing with more adult rats. All intramural ganglionic neurons were also Y1R-IR and Y5R-IR and Y2R-negative in all studied animals.Thus, the increasing of density of NPY-containing nerve fibers accompanies changes in relation of different subtypes of NPY receptors in the heart during development.

  7. [Degenerative lesions of the peripheral retina].

    Science.gov (United States)

    Conart, J-B; Baron, D; Berrod, J-P

    2014-01-01

    Degenerative lesions of the peripheral retina are present from teenage years onwards and increase with age. These abnormabilities are frequent, some of them being benign while others predispose to retinal tears and detachment. In the latter case, the lesions are rhegmatogenous and may justify prophylactic treatment by laser photocoagulation. We distinguish congenital lesions of the peripheral retina and intraretinal, chorioretinal and vitreoretinal degenerations. The holes and tears observed in 2% of the population consist of round atrophic holes, "horseshoe" tears, oral dialyses and giant tears. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Genetics of lattice degeneration of the retina.

    Science.gov (United States)

    Murakami, F; Ohba, N

    1982-01-01

    First-degree relatives of proband patients with lattice degeneration of the retina revealed a significantly higher prevalence of the disease than the prevalence in the general population: the former had the disease about three times as frequently as the latter. The observed data were analyzed in terms of their accordance with recognized genetic models. The inheritance pattern did not fit well to a monogenic mode of inheritance, and it was hypothesized that a polygenic or multifactorial mode of inheritance is the most likely for lattice degeneration of the retina.

  9. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Science.gov (United States)

    Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2017-01-01

    Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

  10. Expression and localization of ionotropic glutamate receptor subunits in the goldfish retina--an in situ hybridization and immunocytochemical study

    NARCIS (Netherlands)

    Vandenbranden, C. A.; Kamphuis, W.; Nunes Cardozo, B.; Kamermans, M.

    2000-01-01

    The expression and distribution of AMPA, kainate and NMDA glutamate receptor subunits was studied in the goldfish retina. For the immunocytochemical localization of the AMPA receptor antisera against GluR2, GluR2/3 and GluR4 were used, and for in situ hybridization rat specific probes for GluR1 and

  11. Peripheral and central arterial pressure and its relationship to vascular target organ damage in carotid artery, retina and arterial stiffness. Development and validation of a tool. The Vaso risk study

    Directory of Open Access Journals (Sweden)

    Patino-Alonso Maria C

    2011-04-01

    Full Text Available Abstract Background Ambulatory blood pressure monitoring (ABPM shows a better correlation to target organ damage and cardiovascular morbidity-mortality than office blood pressure. A loss of arterial elasticity and an increase in carotid artery intima-media thickness (IMT has been associated with increased cardiovascular morbidity-mortality. Tools have been developed that allow estimation of the retinal arteriovenous index but not all studies coincide and there are contradictory results in relation to the evolution of the arteriosclerotic lesions and the caliber of the retinal vessels. The purpose of this study is to analyze the relationship between peripheral and central arterial pressure (clinic and ambulatory and vascular structure and function as evaluated by the carotid artery intima-media thickness, retina arteriovenous index, pulse wave velocity (PWV and ankle-brachial index in patients with and without type 2 diabetes. In turn, software is developed and validated for measuring retinal vessel thickness and automatically estimating the arteriovenous index. Methods/Design A cross-sectional study involving a control group will be made, with a posterior 4-year follow-up period in primary care. The study patients will be type 2 diabetics, with a control group of non-diabetic individuals. Consecutive sampling will be used to include 300 patients between 34-75 years of age and no previous cardiovascular disease, one-half being assigned to each group. Main measurements: age, gender, height, weight and abdominal circumference. Lipids, creatinine, microalbuminuria, blood glucose, HbA1c, blood insulin, high sensitivity C-reactive protein and endothelial dysfunction markers. Clinic and ambulatory blood pressure monitoring. Carotid ultrasound to evaluate IMT, and retinography to evaluate the arteriovenous index. ECG to assess left ventricle hypertrophy, ankle-brachial index, and pulse wave analysis (PWA and pulse wave velocity (PWV with the Sphigmocor

  12. Instant website optimization for retina displays how-to

    CERN Document Server

    Larson, Kyle J

    2013-01-01

    Written in an accessible and practical manner which quickly imparts the knowledge you want to know. As a How-to book it will use applied examples and teach you to optimize websites for retina displays. This book is for web designers and developers who are familiar with HTML, CSS, and editing graphics who would like to improve their existing website or their next web project with high-resolution images. You'll need to have a high-definition device to be able to test the examples in this book and a server to upload your code to if you're not developing it on that device.

  13. Effect of lead acetate on neurobehavioral development of rats

    Directory of Open Access Journals (Sweden)

    Mello C.F.

    1998-01-01

    Full Text Available We investigated the effects of lead exposure during the pre- and postnatal period on the neurobehavioral development of female Wistar rats (70-75 days of age, 120-150 g using a protocol of lead intoxication that does not affect weight gain. Wistar rats were submitted to lead acetate intoxication by giving their dams 1.0 mM lead acetate. Control dams received deionized water. Growth and neuromotor development were assessed by monitoring daily the following parameters in 20 litters: body weight, ear unfolding, incisor eruption, eye opening, righting, palmar grasp, negative geotaxis, cliff avoidance and startle reflex. Spontaneous alternation was assessed on postnatal day 17 using a T maze. The animals' ability to equilibrate on a beaker rim was measured on postnatal day 19. Lead intoxication was confirmed by measuring renal, hepatic and cerebral lead concentration in dams and litters. Lead treatment hastened the day of appearance of the following parameters: eye opening (control: 13.5 ± 0.6, N = 88; lead: 12.9 ± 0.6, N = 72; P<0.05, startle reflex (control: 13.0 ± 0.8, N = 88; lead: 12.0 ± 0.7, N = 72; P<0.05 and negative geotaxis. On the other hand, spontaneous alternation performance was hindered in lead-exposed animals (control: 37.6 ± 19.7; lead: 57.5 ± 28.3% of alternating animals; P<0.05. These results suggest that lead exposure without concomitant undernutrition alters rat development, affecting specific subsets of motor skills.

  14. Information processing in the outer retina of fish

    NARCIS (Netherlands)

    Endeman, D.

    2017-01-01

    The retina translates light into neuronal activity. Thus, it renders visual information of the external environment. The retina can only send a limited amount of information to the brain within a given period. To use this amount optimally, light stimuli are strongly processed in the retina. This

  15. Wistar-Kyoto Female Rats Are More Susceptible to Develop Sugar Binging: A Comparison with Wistar Rats

    Directory of Open Access Journals (Sweden)

    Helena Papacostas-Quintanilla

    2017-05-01

    Full Text Available The hedonic component of the feeding behavior involves the mesolimbic reward system and resembles addictions. Nowadays, the excessive consumption of sucrose is considered addictive. The Wistar-Kyoto (WKY rat strain is prone to develop anxiety and addiction-like behavior; nevertheless, a lack of information regarding their vulnerability to develop sugar binging-like behavior (SBLB and how it affects the reward system persist. Therefore, the first aim of the present study was to compare the different predisposition of two rat strains, Wistar (W and WKY to develop the SBLB in female and male rats. Also, we studied if the SBLB-inducing protocol produces changes in anxiety-like behavior using the plus-maze test (PMT and, analyzed serotonin (5-HT and noradrenaline (NA concentrations in brain areas related to anxiety and ingestive behavior (brain stem, hypothalamus, nucleus accumbens, and amygdala. Finally, we evaluated whether fluoxetine, a drug that has been effective in reducing the binge-eating frequency, body weight, and severity of binge eating disorder, could also block this behavior. Briefly, WKY and W female rats were exposed to 30% sucrose solution (2 h, 3 days/week for 4 weeks, and fed up ad libitum. PMT was performed between the last two test periods. Immediately after the last test where sucrose access was available, rats were decapitated and brain areas extracted for high-performance liquid chromatography analysis. The results showed that both W and WKY female and male rats developed the SBLB. WKY rats consumed more calories and ingested a bigger amount of sucrose solution than their W counterpart. This behavior was reversed by using fluoxetine, rats exposed to the SBLB-inducing protocol presented a rebound effect during the washout period. On female rats, the SBLB-inducing protocol induced changes in NA concentrations on WKY, but not on W rats. No changes were found in 5-HT levels. Finally, animals that developed SBLB showed increased

  16. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

  17. Developing a Speaker Identification System for the DARPA RATS Project

    DEFF Research Database (Denmark)

    Plchot, O; Matsoukas, S; Matejka, P

    2013-01-01

    This paper describes the speaker identification (SID) system developed by the Patrol team for the first phase of the DARPA RATS (Robust Automatic Transcription of Speech) program, which seeks to advance state of the art detection capabilities on audio from highly degraded communication channels. ...... such as CFCCs out-perform MFCC front-ends on noisy audio, and (c) fusion of multiple systems provides 24% relative improvement in EER compared to the single best system when using a novel SVM-based fusion algorithm that uses side information such as gender, language, and channel id....

  18. Olfactory granule cell development in normal and hyperthyroid rats.

    Science.gov (United States)

    Brunjes, P C; Schwark, H D; Greenough, W T

    1982-10-01

    Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.

  19. Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice.

    Science.gov (United States)

    Wang, Yanhe; Yin, Zhiyuan; Gao, Lixiong; Sun, Dayu; Hu, Xisu; Xue, Langyue; Dai, Jiaman; Zeng, YuXiao; Chen, Siyu; Pan, Boju; Chen, Min; Xie, Jing; Xu, Haiwei

    2017-01-01

    Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP. © 2017 The Author(s). Published by S. Karger AG, Basel.

  20. Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

    Directory of Open Access Journals (Sweden)

    Yanhe Wang

    2017-11-01

    Full Text Available Background/Aims: Retinitis pigmentosa (RP is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1 mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

  1. Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.

    Science.gov (United States)

    Omori, Yoshihiro; Katoh, Kimiko; Sato, Shigeru; Muranishi, Yuki; Chaya, Taro; Onishi, Akishi; Minami, Takashi; Fujikado, Takashi; Furukawa, Takahisa

    2011-01-01

    In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease.

  2. Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Omori

    Full Text Available In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease.

  3. Pancreatic morphogenesis and extracellular matrix organization during rat development.

    Science.gov (United States)

    Hisaoka, M; Haratake, J; Hashimoto, H

    1993-07-01

    We investigated the rat pancreatic morphology at various developmental stages ranging from 12 days of gestation to the neonatal stage, with special emphasis on alterations in extracellular matrix organization in vivo. The rat pancreatic development in utero could be divided into four representative stages as follows: (1) initial epithelial buds (12 days of gestation), (2) elongated and branching epithelium (13-14 days), (3) tubular structure (15-16 days), and (4) acinar structure (17 days or more). Ultrastructurally, the fetal and neonatal pancreata were almost constantly encompassed by continuous basal lamina, except for the earliest stage, in which minute disruptions of basal lamina were observed. Through the disruption, the direct epithelial-mesenchymal contact was formed between an endocrine cell and an adjacent mesenchymal cell, which implied epithelial-mesenchymal interactions in processes of endocrine cell differentiation. Collagen fibrils were frequently accumulated at the cleft (branchpoint) of the branching epithelium during the second and third stages mentioned above. Immunohistochemically, fibronectin and collagen type-I were localized particularly beside the neck (narrow part) or cleft of the pancreatic epithelium at these stages, although continuous linear localization of these matrices was noted around the initial pancreatic bud. This was in contrast to invariable linear localization of laminin and collagen type-IV at the epithelial/mesenchymal interface throughout the pancreatic development. Diffuse fibrillar localization of fibronectin and collagen type-I in the mesenchyme was pronounced at the later stages and after birth. Collagen type-III was only focally detectable around the pancreatic epithelium from the second stage, and its distinct localization was noted in the interlobular connective tissue after birth. Thus, chronological changes in extracellular matrix organization seemed to be closely related to morphogenetic processes of the rat

  4. Activation of retinal stem cells in the proliferating marginal region of RCS rats during development of retinitis pigmentosa.

    Science.gov (United States)

    Jian, Qian; Xu, Haiwei; Xie, Hanping; Tian, Chunyu; Zhao, Tongtao; Yin, ZhengQin

    2009-11-06

    Retinal stem cells (RSCs) have been demonstrated at the proliferating marginal regions from the pars plana of ciliary body to the ciliary marginal zone (CMZ) in adult lower vertebrates and mammals. Investigations in the lower vertebrates have provided some evidence that RSCs can proliferate following retinal damage; however, the evidence that this occurs in mammals is not clear. In this study, we explored RSCs proliferation potential of adult mammalian in proliferating marginal regions of Royal College of Surgeons (RCS) rats, an animal model for retinitis pigmentosa (RP). The proliferation was evaluated using BrdU labeling, and Chx-10 as markers to discern progenitor cell of CMZ in Long-Evan's and RCS rats at different postnatal day (PND) after eye opening. We found that few Chx-10 and BrdU labeled cells in the proliferating marginal regions of Long-Evan's rats, which significantly increased in RCS rats at PND30 and PND60. Consistent with this, Chx-10/Vimentin double staining cells in the center retina of RCS rats increased significantly at PND30 after eye opening. In addition, mRNA expression of Shh, Ptch1 and Smo was up-regulated in RCS rats at PND60 compared to age-matched Long-Evan's rats, which revealed Shh/ptc pathway involving in the activation of RSCs. These results suggest that RSCs in the mammalian retinal proliferating marginal regions has the potential to regenerate following degeneration.

  5. Optimization of reagent concentration for radioiodination of rat C-peptide II in development of radioimmunoassay procedure for rats

    Directory of Open Access Journals (Sweden)

    B R Manupriya

    2018-01-01

    Full Text Available Rat C-peptide is a polypeptide molecule made up of 31 amino acids and secreted from pancreas into circulation in two isoforms I and II. Quantification of rat C-peptide II in rat serum is important as it is directly related to the diagnosis of carbohydrate metabolism abnormalities, pancreatic performance analysis, monitoring of hypoglycemia, and diabetes-related illness in rat model. The aim of the present work is to develop a tracer by chloramine-T method for radioimmunoassay (RIA procedure and to determine the optimum amount of chloramine-T required for the preparation of stable radioiodinated product with a specific activity of around 24.97 MBq/μg, corresponding to 1 125I atom per molecule of the peptide. Tyrosylated rat C-peptide II was selected for the radioiodination procedure as rat C-peptide II does not contain either tyrosine or histidine which is mandatory for the incorporation of 125I atom to the rat C-peptide II. Tyrosylated rat C-peptide II was subjected to radioiodination by chloramine-T method with different concentrations of chloramine-T and sodium metabisulfite (MBS to obtain a stable radiolabeled compound. Optimized reaction conditions relating to the concentration of chloramine-T (10 μg and MBS (20 μg yielded a stable 125I-rat C-peptide II with specific activity of 21.01 MBq/μg corresponding to 0.84 125I atoms per molecule of the peptide. Preparation of high integrity tracer of rat C-peptide II was achieved by combining one molecule of oxidant (chloramine-T and two molecule of reductant (MBS.

  6. Simultaneous in vivo imaging of melanin and lipofuscin in the retina with photoacoustic ophthalmoscopy and autofluorescence imaging

    Science.gov (United States)

    Zhang, Xiangyang; Zhang, Hao F.; Puliafito, Carmen A.; Jiao, Shuliang

    2011-08-01

    We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective versus exacerbate) in the RPE in the aging process. We have successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

  7. Training and professional profile of retinologists in Spain: Retina 2 project, Report 4.

    Science.gov (United States)

    Pastor, J Carlos; Fernández, Itziar; Rojas, Jimena; Coco, Rosa; Sanabria, Maria R; Rodríguez-de la Rúa, Enrique; Sánchez, Diego; Valverde, Carmen; Sala-Puigdollers, Anna

    2011-01-01

    Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties. After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined. Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%). Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5%) practiced anterior segment surgery, and 78.7% declared skills in vitrectomy. We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.

  8. Investigations into localized re-treatment of the retina with a 3-nanosecond laser.

    Science.gov (United States)

    Chidlow, Glyn; Plunkett, Malcolm; Casson, Robert J; Wood, John P M

    2016-08-01

    additional risk of developing visual scotomas, choroidal neovascularizations, or inflammatory events. Indeed, the collated results indicate that the metabolic and structural disruption to the RPE-retina caused by short pulse duration laser treatment is resolved within a short time frame such that re-treatment elicits a phenotype indistinguishable from single treatment. Lasers Surg. Med. 48:602-615, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  10. [The effects of strontium in drinking water on growth and development of rat bone].

    Science.gov (United States)

    Xu, F; Zhang, X; Liu, J; Fan, M

    1997-05-01

    Effects of strontium at a high level in drinking water on growth and development of rat bone were studied. The results showed that Sr2+ concentration from 5 to 500 mg/L in drinking water could increase the contents of strontium in blood serum, urine, femur, mixilla and tooth in Wistar rats exposed to Sr2+ for 12 weeks with an obvious dose-response relationship. In addition, strontium at over 50 mg/L could decrease the contents of calcium in bone, increase the contents of calcium in tooth and bone density, and decrease the levels of calcium in blood serum except female rats at the 12th week. Effects of Sr2+ on body weight, body length, AKP activity of serum, calcium content of urine and breaking load of bended femur for rats were not found. However, there are differences in the effects of strontium on growth and development of bone between male and female rats. At the 12th week the content of calcium in blood serum decreased in male rats but increased in female rats in exposed groups. At the 4th and 8th weeks, urine Hop/Cr in male rats increased but it remained normal level in female rats. Sr2+ increased the bone density of mixilla in male rats but it did not increase that of femur in female rats. It is suggested that such changes may be a result of the differences in endocritic regulation and metabolic process between two sexes.

  11. Direct transdifferentiation in the vertebrate retina.

    Science.gov (United States)

    Opas, M; Dziak, E

    1998-03-01

    Transdifferentiation is the process by which differentiated cells alter their identity to become other, distinct cell types. The conversion of neural retina into lens epithelium is one of the most spectacular examples of transdifferentiation. We show that the redirection of cell fate from neural retina to lens and subsequent transdifferentiation is independent of cell replication as it occurs in growth-arrested cell populations. Using DNA ratiometry of individual cells in these cultures we show that, indeed, individual amitotic cells do transdifferentiate. Hence, choice of fate in transdifferentiating cells does not rely on a "community effect" but instead can be categorized as a leadership effect> For lack of overt lens progenitors, and most importantly, for its mitotic independence, we conclude that lens colony formation in vitro does occur by direct transdifferentiation and not by clonal proliferation of progenitor cells.

  12. 17β-Estradiol up-regulates Nrf2 via PI3K/AKT and estrogen receptor signaling pathways to suppress light-induced degeneration in rat retina.

    Science.gov (United States)

    Zhu, C; Wang, S; Wang, B; Du, F; Hu, C; Li, H; Feng, Y; Zhu, R; Mo, M; Cao, Y; Li, A; Yu, X

    2015-09-24

    Human age-related retinal diseases, such as age-related macular degeneration (AMD), are intimately associated with decreased tissue oxygenation and hypoxia. Different antioxidants have been investigated to reverse AMD. In the present study, we describe the antioxidant 17β-estradiol (βE2) and investigate its protective effects on retinal neurons. Fourteen days after ovariectomy, adult Sprague-Dawley rats were exposed to 8000-lux light for 12h to induce retinal degeneration. Reactive oxygen species (ROS) levels were assessed by confocal fluorescence microscopy using 2,7-dichlorofluorescein diacetate. Nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant enzyme mRNA expression were detected by real-time PCR. Western blotting was used to evaluate NRF2 activation. NRF2 translocation was determined by immunohistochemistry, with morphological changes monitored by hematoxylin and eosin staining. Following light exposure, βE2 significantly reduced ROS production. βE2 also up-regulated NRF2 mRNA and protein levels, with maximal expression at 4 and 12h post-exposure, respectively. Interestingly, following βE2 administration, NRF2 was translocated from the cytoplasm to the nucleus, primarily in the outer nuclear layer. βE2 also up-regulated NRF2, which triggered phase-2 antioxidant enzyme expression (superoxide dismutases 1 and 2, catalase, glutaredoxins 1 and 2, and thioredoxins 1 and 2), reduced ROS production, and ameliorated retinal damage. However, the beneficial effects of βE2 were markedly suppressed by pretreatment with LY294002 or ICI182780, specific inhibitors of the phosphatidylinositol 3-kinase-Akt (PI3K/AKT), and estrogen receptor (ER) signaling pathways, respectively. Taken together, these observations suggest that βE2 exerts antioxidative effects following light-induced retinal degeneration potentially via NRF2 activation. This protective mechanism may depend on two pathways: a rapid, non-genomic-type PI3K/AKT response, and a genomic-type ER

  13. Critical androgen-sensitive periods of rat penis and clitoris development

    OpenAIRE

    Welsh, M.; Macleod, D. J.; Walker, M.; Smith, L. B.; Sharpe, R. M.

    2010-01-01

    Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during t...

  14. Connecting the Retina to the Brain

    Directory of Open Access Journals (Sweden)

    Lynda Erskine

    2014-12-01

    Full Text Available The visual system is beautifully crafted to transmit information of the external world to visual processing and cognitive centers in the brain. For visual information to be relayed to the brain, a series of axon pathfinding events must take place to ensure that the axons of retinal ganglion cells, the only neuronal cell type in the retina that sends axons out of the retina, find their way out of the eye to connect with targets in the brain. In the past few decades, the power of molecular and genetic tools, including the generation of genetically manipulated mouse lines, have multiplied our knowledge about the molecular mechanisms involved in the sculpting of the visual system. Here, we review major advances in our understanding of the mechanisms controlling the differentiation of RGCs, guidance of their axons from the retina to the primary visual centers, and the refinement processes essential for the establishment of topographic maps and eye-specific axon segregation. Human disorders, such as albinism and achiasmia, that impair RGC axon growth and guidance and, thus, the establishment of a fully functioning visual system will also be discussed.

  15. The mammalian retina as a clock

    Science.gov (United States)

    Tosini, Gianluca; Fukuhara, Chiaki

    2002-01-01

    Many physiological, cellular, and biochemical parameters in the retina of vertebrates show daily rhythms that, in many cases, also persist under constant conditions. This demonstrates that they are driven by a circadian pacemaker. The presence of an autonomous circadian clock in the retina of vertebrates was first demonstrated in Xenopus laevis and then, several years later, in mammals. In X. laevis and in chicken, the retinal circadian pacemaker has been localized in the photoreceptor layer, whereas in mammals, such information is not yet available. Recent advances in molecular techniques have led to the identification of a group of genes that are believed to constitute the molecular core of the circadian clock. These genes are expressed in the retina, although with a slightly different 24-h profile from that observed in the central circadian pacemaker. This result suggests that some difference (at the molecular level) may exist between the retinal clock and the clock located in the suprachiasmatic nuclei of hypothalamus. The present review will focus on the current knowledge of the retinal rhythmicity and the mechanisms responsible for its control.

  16. Simultaneous optical coherence tomography and lipofuscin autofluorescence imaging of the retina with a single broadband light source at 480nm.

    Science.gov (United States)

    Jiang, Minshan; Liu, Tan; Liu, Xiaojing; Jiao, Shuliang

    2014-12-01

    We accomplished spectral domain optical coherence tomography and auto-fluorescence microscopy for imaging the retina with a single broadband light source centered at 480 nm. This technique is able to provide simultaneous structural imaging and lipofuscin molecular contrast of the retina. Since the two imaging modalities are provided by the same group of photons, their images are intrinsically registered. To test the capabilities of the technique we periodically imaged the retinas of the same rats for four weeks. The images successfully demonstrated lipofuscin accumulation in the retinal pigment epithelium with aging. The experimental results showed that the dual-modal imaging system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

  17. PBN (Phenyl-N-Tert-Butylnitrone-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

    Directory of Open Access Journals (Sweden)

    Megan Stiles

    Full Text Available A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD, and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control. In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat

  18. PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

    Science.gov (United States)

    Stiles, Megan; Moiseyev, Gennadiy P; Budda, Madeline L; Linens, Annette; Brush, Richard S; Qi, Hui; White, Gary L; Wolf, Roman F; Ma, Jian-Xing; Floyd, Robert; Anderson, Robert E; Mandal, Nawajes A

    2015-01-01

    A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from

  19. Three dimensional reconstruction of tomographic images of the retina

    International Nuclear Information System (INIS)

    Glittenberg, C.; Zeiler, F.; Falkner, C.; Binder, S.; Povazay, B.; Hermann, B.; Drexler, W.

    2007-01-01

    The development of a new display system for the three-dimensional visualization of tomographic images in ophthalmology. Specifically, a system that can use stacks of B-mode scans from an ultrahigh resolution optical tomography examination to vividly display retinal specimens as three-dimensional objects. Several subroutines were programmed in the rendering and raytracing program Cinema 4D XL 9.102 Studio Bundle (Maxon Computer Inc., Friedrichsburg, Germany), which could process stacks of tomographic scans into three-dimensional objects. Ultrahigh resolution optical coherence tomography examinations were performed on patients with various retinal pathologies and post processed with the subroutines that had been designed. All ultrahigh resolution optical coherence tomographies were performed with a titanium: sapphire based ultra broad bandwidth (160 nm) femtosecond laser system (INTEGRAL, Femtolasers Productions GmbH. Vienna Austria) with an axial resolution of 3 μm. A new three dimensional display system for tomographic images in ophthalmology was developed, which allows a highly vivid display of physiological and pathological structures of the retina. The system also distinguishes itself through its high interactivity and adaptability. This new display system allows the visualization of physiological and pathological structures of the retina in a new way, which will give us new insight into their morphology and development. (author) [de

  20. The utilization of glutamine by the retina: an autoradiographic and metabolic study

    International Nuclear Information System (INIS)

    Voaden, M.J.; Lake, N.; Marshall, J.; Morjaria, B.

    1978-01-01

    The cells able to accumulate exogenously applied [ 3 H] glutamine in rat, cat, frog, pigeon and guinea pig retinas have been located by autoradiography, and the fate of the labelled glutamine, as regards its incorporation into aspartic, glutamic and γ-amino-butyric acids, followed for 60 min. The results support the notion of glutamine as a precursor of transmitter amino acids in some neurones. In particular, it would appear to be a source of a relatively stable pool of GABA which may be located, with species variation, in amacrine or ganglion cells. In the pigeon retina glutamate pool incorporates and retains a major percentage of the label, and perikarya in the middle of the inner nuclear layer of the tissue are predominantly labelled. (author)

  1. Utilization of glutamine by the retina: an autoradiographic and metabolic study

    Energy Technology Data Exchange (ETDEWEB)

    Voaden, M J; Lake, N; Marshall, J; Morjaria, B [Institute of Ophthalmology, London (UK). Dept. of Visual Science

    1978-10-01

    The cells able to accumulate exogenously applied (/sup 3/H) glutamine in rat, cat, frog, pigeon and guinea pig retinas have been located by autoradiography, and the fate of the labelled glutamine, as regards its incorporation into aspartic, glutamic and ..gamma..-amino-butyric acids, followed for 60 min. The results support the notion of glutamine as a precursor of transmitter amino acids in some neurones. In particular, it would appear to be a source of a relatively stable pool of GABA which may be located, with species variation, in amacrine or ganglion cells. In the pigeon retina glutamate pool incorporates and retains a major percentage of the label, and perikarya in the middle of the inner nuclear layer of the tissue are predominantly labelled.

  2. FPGA-Based Real Time, Multichannel Emulated-Digital Retina Model Implementation

    Directory of Open Access Journals (Sweden)

    Zsolt Vörösházi

    2009-01-01

    Full Text Available The function of the low-level image processing that takes place in the biological retina is to compress only the relevant visual information to a manageable size. The behavior of the layers and different channels of the neuromorphic retina has been successfully modeled by cellular neural/nonlinear networks (CNNs. In this paper, we present an extended, application-specific emulated-digital CNN-universal machine (UM architecture to compute the complex dynamic of this mammalian retina in video real time. The proposed emulated-digital implementation of multichannel retina model is compared to the previously developed models from three key aspects, which are processing speed, number of physical cells, and accuracy. Our primary aim was to build up a simple, real-time test environment with camera input and display output in order to mimic the behavior of retina model implementation on emulated digital CNN by using low-cost, moderate-sized field-programmable gate array (FPGA architectures.

  3. Autofluorescence from the outer retina and subretinal space: hypothesis and review.

    Science.gov (United States)

    Spaide, Richard

    2008-01-01

    To review the pathophysiologic principles underlying increased autofluorescence from the outer retina and subretinal space using selected diseases as examples. The ocular imaging information and histopathologic features, when known, were integrated for diseases causing increased autofluorescence from the outer retina and subretinal space. Inferences were taken from this information and used to create a classification scheme. These diseases are principally those that cause separation of the outer retina from the retinal pigment epithelium, thereby preventing proper phagocytosis of photoreceptor outer segments. The separation can arise from increased exudation into the subretinal space or inadequate removal of fluid from the subretinal space. Lack of normal outer segment processing initially leads to increased accumulation of outer segments on the outer retina and subretinal space. Over time, this material is visible as an increasingly thick coating on the outer retina, is yellow, and is autofluorescent. Over time, atrophy develops with thinning of the deposited material and decreasing autofluorescence. The accumulated material is ultimately capable of inducing damage to the retinal pigment epithelium. Diseases causing accumulation of the material include central serous chorioretinopathy, vitelliform macular dystrophy, acute exudative polymorphous vitelliform maculopathy, choroidal tumors, and vitreomacular traction syndrome. The physical separation of the retinal outer segments from the retinal pigment epithelium hinders proper phagocytosis of the outer segments. Accumulation of the shed but not phagocytized outer segments plays a role in disease manifestations for a number of macular diseases.

  4. Proteomic interactions in the mouse vitreous-retina complex.

    Directory of Open Access Journals (Sweden)

    Jessica M Skeie

    Full Text Available Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina.Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software.We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor.Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.

  5. Proteomic interactions in the mouse vitreous-retina complex.

    Science.gov (United States)

    Skeie, Jessica M; Mahajan, Vinit B

    2013-01-01

    Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina. Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software. We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor. Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.

  6. Oral Morphine Consumption Reduces Lens Development in Rat Embryos

    Directory of Open Access Journals (Sweden)

    Hossein Bahadoran

    2012-07-01

    Full Text Available Objective: Consumption of morphine, during pregnancy, in addition to inducing defects in the mother’s nervous system function, caused defects or delays in the formation and evolution of embryonic visual system. In the present study, changes in lens development was assessed in embryos exposed in utero to morphine. Material and Methods: Female Wistar rats (250-300 g were mated with male rats and pregnancy was determined by sperm observation in vaginal smear. This day was considered as embryonic day zero (E0. The females were then divided randomly into the experimental and the control groups. The control group received tap water and the experimental group received morphine (0.05 mg/ml in their water. On embryonic day 13 ( E13, blood samples were collected from the retro-orbital sinus of all animals for plasma corticosterone detection. On embryonic day 17(E17, the animals were killed by an overdose of chloroform and the embryos were taken out surgically. The embryos were fixed in 10% formalin for 30 days. At this time, the head of the embryos were removed for tissue processing and Hematoxylin- Eosin (H&E staining. The samples were evaluated using light microscope and MOTIC software. Results: Our data indicated that plasma corticosterone level was dramatically increased and the lens was thinner in the experimental group. (Although the proliferation of lens cells increased in the experiment group but that lens had delay in removing the proliferated and elongation cells with abnormal density in the lateral part of the lens in compare with control group. I have no idea what the authors are stating here. Moreover, the opening of the eyelids was delayed in the off springs of the mothers who received morphine. Conclusions: This study showed that morphine consumption during pregnancy leads to defects in fetal visual system development, particularly in the lens, and eyelids.

  7. Adaptive Optical System for Retina Imaging Approaches Clinic Applications

    Science.gov (United States)

    Ling, N.; Zhang, Y.; Rao, X.; Wang, C.; Hu, Y.; Jiang, W.; Jiang, C.

    We presented "A small adaptive optical system on table for human retinal imaging" at the 3rd Workshop on Adaptive Optics for Industry and Medicine. In this system, a 19 element small deformable mirror was used as wavefront correction element. High resolution images of photo receptors and capillaries of human retina were obtained. In recent two years, at the base of this system a new adaptive optical system for human retina imaging has been developed. The wavefront correction element is a newly developed 37 element deformable mirror. Some modifications have been adopted for easy operation. Experiments for different imaging wavelengths and axial positions were conducted. Mosaic pictures of photoreceptors and capillaries were obtained. 100 normal and abnormal eyes of different ages have been inspected.The first report in the world concerning the most detailed capillary distribution images cover ±3° by ± 3° field around the fovea has been demonstrated. Some preliminary very early diagnosis experiment has been tried in laboratory. This system is being planned to move to the hospital for clinic experiments.

  8. Finestructure of the retina in Garra rufa (cypriniae, Teleostei)

    International Nuclear Information System (INIS)

    Al-Adhami, A. M.; Mir, S.

    1999-01-01

    The light - and dark-adapted retina of the freshwater, bottom-dweller tele ost, Ga rra rufa (Heck el, 1843) was studied under light and electron microscopes. The fish is a fist record in having both falcifrom process and vit real blood circulation and the hyaloid artery from which it developers. A number of acute vision areas represented by increased density of ganglion cell soma ta are evident. The dark-adapted retina is characterized by notably large photoreceptor terminals (rod spherules and cone placidas). A rod spherules has single synaptic ribbon, whereas a cone pedicle has three to four. The inner nuclear layer is composed of the so meta of horizontal, bipolar and amsacrine cells in addition to nuclei of Muller cells. The outer nuclear layer, on the other hand, is composed of two-three rows of rod nuclei and one row of cone nuclei. The photoreceptor cells include rods and single and double cones. The rod outer segments have deep and/or shallow incisor. Cone ellipsoid may have ellipsosomes. These are shown to develop from one of the apical mitochondria of the ellipsoid- Retinomotor movement involves both the photoreceptor cells and the pigment epithelium. (authors). 11 refs., 14 figs

  9. Rapid development of Leydig cell tumors in a Wistar rat substrain

    NARCIS (Netherlands)

    Teerds, K. J.; de rooij, D. G.; de Jong, F. H.; Rommerts, F. F.

    1991-01-01

    In 78% of the Wistar rats (substrain U) studied, spontaneous Leydig cell tumors developed between the ages of 12 and 30 months. The first signs of tumor development, in the form of nodules of Leydig cells, were already apparent in 1-month-old U-rats. These nodules of Leydig cells were found in all

  10. Training and professional profile of retinologists in Spain: Retina 2 project, Report 4

    Directory of Open Access Journals (Sweden)

    Pastor JC

    2011-04-01

    Full Text Available J Carlos Pastor1,3, Itziar Fernández2, Jimena Rojas1, Rosa Coco1, Maria R Sanabria1, Enrique Rodríguez-de la Rúa1,3, Diego Sánchez3, Carmen Valverde3, Anna Sala Puigdollers1,31University Institute of Applied Ophthalmobiology (IOBA, Retina Group, 2Ministry of Science and Innovation CIBER-BBN, Statistics Department, 3Clinic University Hospital, University of Valladolid, Valladolid, SpainBackground: Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties.Methods: After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined.Results: Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%. Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5% practiced anterior segment surgery, and 78.7% declared skills in vitrectomy.Conclusion: We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.Keywords: clinical activity, fellowship, mastership, professional profile, retinologist training

  11. Common Variants in the COL4A4 Gene Confer Susceptibility to Lattice Degeneration of the Retina

    OpenAIRE

    Meguro, Akira; Ideta, Hidenao; Ota, Masao; Ito, Norihiko; Ideta, Ryuichi; Yonemoto, Junichi; Takeuchi, Masaki; Uemoto, Riyo; Nishide, Tadayuki; Iijima, Yasuhito; Kawagoe, Tatsukata; Okada, Eiichi; Shiota, Tomoko; Hagihara, Yuta; Oka, Akira

    2012-01-01

    Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite...

  12. Peripheral Avascular Retina in a Term Male Neonate With Microvillus Inclusion Disease and Pancreatic Insufficiency.

    Science.gov (United States)

    Paulus, Yannis M; Alcorn, Deborah M; Gaynon, Michael; Moshfeghi, Darius M

    2015-05-01

    The authors present the first case of peripheral avascular retina in a term male neonate with pancreatic exocrine insufficiency, atypical microvillus inclusion disease, flat tympanograms, and recurrent urinary tract infections. Clinical examination showed avascular peripheral retina to posterior zone II temporally, with a flat stage 1-like demarcation line, and no plus disease. Genetic testing results were normal. The patient developed peripheral neovascularization and underwent panretinal photocoagulation. This case likely represents mild Norrie disease, familial exudative vitreoretinopathy, or incontinentia pigmenti due to a Wnt signaling abnormality. While these conditions are usually more severe, a variable spectrum of Wnt abnormalities exists throughout the body. Copyright 2015, SLACK Incorporated.

  13. An experimental platform for systemic drug delivery to the retina.

    LENUS (Irish Health Repository)

    Campbell, Matthew

    2009-10-20

    Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-\\/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.

  14. The development of radioimmunoassay kit for rat albumin

    International Nuclear Information System (INIS)

    Yuan Zhigang; Han Shiquan; Liu Yibing; Xu Wenge

    2006-01-01

    The Anti-rat albumin serum is prepared by immunized the sheep with rat albumin. A radioimmunoassay method is established for rat albumin. The measurement range of the assay is 1-50 mg/L, sensitivity of the assay is 0.12 mg/L, recovery rate is 97.8%- 108.4%. Intra- and inter-assay variation coefficients are <4.0% and <8.2% respectively. The correlation coefficients between measured and expected values are more than 0.990 after serial dilution of the urine samples with high concentrations of rat albumin. The kit for rat albumin might provide a convenience in exploitation of renal drugs and experimental in- jury of the kidney. (authors)

  15. Lactate Transport and Receptor Actions in Retina

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vosborg, Fia; Henriksen, Jens Ulrik Lütken

    2016-01-01

    known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions......In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also...

  16. Modeling laser damage to the retina

    Science.gov (United States)

    Clark, Clifton D.

    This dissertation presents recent progress in several areas related to modeling laser damage to the retina. In Chapter 3, we consider the consequences of using the Arrhenius damage model to predict the damage thresholds of multiple pulse, or repetitive pulse, exposures. We have identified a few fundamental trends associated with the multiple pulse damage predictions made by the Arrhenius model. These trends differ from what would be expected by non-thermal mechanisms, and could prove useful in differentiating thermal and non-thermal damage. Chapter 4 presents a new rate equation damage model hypothesized to describe photochemical damage. The model adds a temperature dependent term to the simple rate equation implied by the principle of reciprocity that is characteristic of photochemical damage thresholds. A recent damage threshold study, conducted in-vitro, has revealed a very sharp transition between thermal and photochemical damage threshold trends. For the wavelength used in the experiment (413 nm), thermal damage thresholds were observed at exposure levels that were twice the expected photochemical damage threshold, based on the traditional understanding of photochemical damage. Our model accounts for this observed trend by introducing a temperature dependent quenching, or repair, rate to the photochemical damage rate. For long exposures that give a very small temperature rise, the model reduces to the principle of reciprocity. Near the transition region between thermal and photochemical damage, the model allows the damage threshold to be set by thermal mechanisms, even at exposure above the reciprocity exposure. In Chapter 5, we describe a retina damage model that includes thermal lensing in the eye by coupling beam propagation and heat transfer models together. Thermal lensing has recently been suggested as a contributing factor to the large increase in measured retinal damage thresholds in the near infrared. The transmission of the vitreous decreases

  17. Epidermal growth factor and lung development in the offspring of the diabetic rat

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    2000-01-01

    Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes...... in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had...... and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining...

  18. Development of obesity in Zucker obese (fafa) rat in absence of hyperphagia.

    Science.gov (United States)

    Cleary, M P; Vasselli, J R; Greenwood, M R

    1980-03-01

    The free-feeding, genetically obese rat is hyperphagic, hyperinsulinemic, and hypertriglyceridemic and has increased fat cell size and number compared to its lean littermate. These experiments demonstrate that, when fafa rats are prevented from expressing hyperphagia throughout life, the complete obese "syndrome" still develops. Furthermore, life-long food restriction does not prevent increased lipoprotein lipase in the fafa rat. The data support the concept that a peripheral metabolic adaptation, probably in lipid metabolism, results in preferential shunting of dietary substrate in the restricted obese rats to adipose tissue with concomitant decreases in other tissues.

  19. Tartrazine and the developing nervous system of rats.

    Science.gov (United States)

    Sobotka, T J; Brodie, R E; Spaid, S L

    1977-05-01

    Rat dams were exposed to the artificial food color tartrazine (FD&C Yellow no. 5) at dietary levels of 0, 1, and 2% during gestation and lactation. The experimental offspring were continued on the same diets for approximately 3 months after weaning. No adverse physical or behavioral effects were noted in the dams. Fetal development and postnatal viability of the offspring were also normal. The only effect on postnatal development of the central nervous system (CNS) was a small transient change in neuromotor clinging ability of female offspring. The limited effect of tartrazine on the CNS was further evidenced by the facts that (1) the neurobehavioral profiles of the experimental weanlings revealed no significant abnormalities, and (2) morphochemical analysis of brain tissue, as well as brain weights, revealed no abnormalities. Tartrazine did appear to exert more general signs of toxicity in the offspring--namely, depressed body weight, an apparent reduction in thymus weight, and a slight elevation of red blood cells and hemoglobin.

  20. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....

  1. Effects of prenatal exposure to xylene on postnatal development and behavior in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, S. P.; Simonsen, L.

    1995-01-01

    The effects of prenatal exposure to the organic solvent xylene (dimethylbenzene, GAS-no 1330-20-7) on postnatal development and behavior in rats were studied. Pregnant rats (Mol:WIST) were exposed to 500 ppm technical xylene 6 h per day on gestation days 7-20. The dose level was selected so as no...

  2. Glycinergic pathways in the goldfish retina

    International Nuclear Information System (INIS)

    Marc, R.E.; Lam, D.M.

    1981-01-01

    Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish has been used to study some anatomical and physiological properties of potentially glycinergic neurons. There are two classes of retinal cells exhibiting high affinity glycine uptake: Aa amacrine cells and I2 interplexiform cells. Aa amacrine cells constitute about 20% of the somas in the amacrine cell layer and send their dendrites to the middle of the inner plexiform layer. There they are both pre- and postsynaptic primarily to other amacrine cells. Photic modulation of glycine uptake indicates that they are probably red-hyperpolarizing/green-depolarizing neurons. I2 interplexiform cells are a newly discovered type of interplexiform cell; in the outer plexiform layer, they receive direct synaptic input from the somas of red-dominated GABAergic H1 horizontal cells and are apparently presynaptic to dendrites of unidentified types of horizontal cells. The connections of I2 interplexiform cells have not been successfully characterized in the inner plexiform layer. These findings extend our knowledge of neurochemically specific pathways in the cyprinid retina and indicate that glycine, like GABA, is a neurotransmitter primarily involved with circuits coding ''red'' information

  3. Resonant imaging of carotenoid pigments in the human retina

    Science.gov (United States)

    Gellermann, Werner; Emakov, Igor V.; McClane, Robert W.

    2002-06-01

    We have generated high spatial resolution images showing the distribution of carotenoid macular pigments in the human retina using Raman spectroscopy. A low level of macular pigments is associated with an increased risk of developing age-related macular degeneration, a leading cause of irreversible blindness. Using excised human eyecups and resonant excitation of the pigment molecules with narrow bandwidth blue light from a mercury arc lamp, we record Raman images originating from the carbon-carbon double bond stretch vibrations of lutein and zeaxanthin, the carotenoids comprising human macular pigments. Our Raman images reveal significant differences among subjects, both in regard to absolute levels as well as spatial distribution within the macula. Since the light levels used to obtain these images are well below established safety limits, this technique holds promise for developing a rapid screening diagnostic in large populations at risk for vision loss from age-related macular degeneration.

  4. Dual odontogenic origins develop at the early stage of rat maxillary incisor development.

    Science.gov (United States)

    Kriangkrai, Rungarun; Iseki, Sachiko; Eto, Kazuhiro; Chareonvit, Suconta

    2006-03-01

    Developmental process of rat maxillary incisor has been studied through histological analysis and investigation of tooth-related gene expression patterns at initial tooth development. The tooth-related genes studied here are fibroblast growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium and/or ectomesenchyme at the stage of epithelial thickening to the early bud stage of tooth development. Both the histological observation and tooth-related gene expression patterns during early stage of maxillary incisor development demonstrate that dual odontogenic origins aligned medio-laterally in the medial nasal process develop, subsequently only single functional maxillary incisor dental placode forms. The cascade of tooth-related gene expression patterns in rat maxillary incisor studied here is quite similar to those of the previous studies in mouse mandibular molar, even though the origins of oral epithelium and ectomesenchyme involved in development of maxillary incisor and mandibular molar are different. Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development.

  5. Prenatal development toxicity study of zinc oxide nanoparticles in rats

    Directory of Open Access Journals (Sweden)

    Hong JS

    2014-12-01

    Full Text Available Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+ NPs] zinc oxide nanoparticles, positively charged, 20 nm on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+ NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%; resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after

  6. Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2 diabetes mellitus model

    Directory of Open Access Journals (Sweden)

    Rui-Jin Ran

    2016-11-01

    Full Text Available AIM: To examine the expression of high mobility group box-1 (HMGB-1 and intercellular adhesion molecule-1 (ICAM-1 in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier (BRB and blood-brain barrier (BBB in a rat model of type 2 diabetes. METHODS: The type-2 diabetes mellitus (DM model was established with a high-fat and high-glucose diet combined with streptozotocin (STZ. Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay (ELISA. RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection (P<0.01. The serum levels of fasting insulin, Insulin resistance homeostatic model assessment (IRHOMA, total cholesterol (TC, total triglycerides (TG and low density lipoprotein cholesterol (LDL-C in the DM rats significantly higher than those in the controls (all P<0.01. HMGB-1 (0.96±0.03, P<0.01 and ICAM-1 (0.76±0.12, P<0.05 levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1 (0.83±0.13, P<0.01 and ICAM-1 (1.15±0.08, P<0.01 levels in the hippocampal tissues in the DM rats were also significantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls (P<0.01. However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats. CONCLUSION: BRB permeability increases significantly

  7. Imagen de retina de campo ultra-amplio

    Directory of Open Access Journals (Sweden)

    Gerardo García-Aguirre

    2017-11-01

    Conclusión: Las imágenes de campo ultra-amplio han revolucionado la forma en la que estudiamos y entendemos la enfermedad de la retina. A medida que la tecnología para obtenerlas se haga más accesible, formará parte del armamentario de rutina para estudiar las enfermedades de la retina.

  8. Human cadaver retina model for retinal heating during corneal surgery with a femtosecond laser

    Science.gov (United States)

    Sun, Hui; Fan, Zhongwei; Yun, Jin; Zhao, Tianzhuo; Yan, Ying; Kurtz, Ron M.; Juhasz, Tibor

    2014-02-01

    Femtosecond lasers are widely used in everyday clinical procedures to perform minimally invasive corneal refractive surgery. The intralase femtosecond laser (AMO Corp. Santa Ana, CA) is a common example of such a laser. In the present study a numerical simulation was developed to quantify the temperature rise in the retina during femtosecond intracorneal surgery. Also, ex-vivo retinal heating due to laser irradiation was measured with an infrared thermal camera (Fluke Corp. Everett, WA) as a validation of the simulation. A computer simulation was developed using Comsol Multiphysics to calculate the temperature rise in the cadaver retina during femtosecond laser corneal surgery. The simulation showed a temperature rise of less than 0.3 degrees for realistic pulse energies for the various repetition rates. Human cadaver retinas were irradiated with a 150 kHz Intralase femtosecond laser and the temperature rise was measured withan infrared thermal camera. Thermal camera measurements are in agreement with the simulation. During routine femtosecond laser corneal surgery with normal clinical parameters, the temperature rise is well beneath the threshold for retina damage. The simulation predictions are in agreement with thermal measurements providing a level of experimental validation.

  9. Retinal, visual, and refractive development in retinopathy of prematurity

    Science.gov (United States)

    Moskowitz, Anne; Hansen, Ronald M; Fulton, Anne B

    2016-01-01

    The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human ROP and have evaluated these presumptions in a series on non-invasive investigations of the photoreceptor and post-receptor peripheral and central retina in infants and children. Key results are slowed kinetics of phototransduction and deficits in photoreceptor sensitivity that persist years after ROP has completely resolved based on clinical criteria. On the other hand, deficits in post-receptor sensitivity are present in infancy regardless of the severity of the ROP but are not present in older children if the ROP was so mild that it never required treatment and resolved without a clinical trace. Accompanying the persistent deficits in photoreceptor sensitivity, there is increased receptive field size and thickening of the post-receptor retinal laminae in the peripheral retina of ROP subjects. In the late maturing central retina, which mediates visual acuity, attenuation of multifocal electroretinogram activity in the post-receptor retina led us to the discovery of a shallow foveal pit and significant thickening of the post-receptor retinal laminae in the macular region; this is most likely due to failure of the normal centrifugal movement of the post-receptor cells during foveal development. As for refractive development, myopia, at times high, is more common in ROP subjects than in control subjects, in accord with refractive findings in other populations of former preterms. This information about the neurosensory retina enhances understanding of vision in patients with a history of ROP, and taken as a whole, raises the possibility that the neurosensory retina is a target for therapeutic intervention. PMID:28539805

  10. Wavefront optimized nonlinear microscopy of ex vivo human retinas

    Science.gov (United States)

    Gualda, Emilio J.; Bueno, Juan M.; Artal, Pablo

    2010-03-01

    A multiphoton microscope incorporating a Hartmann-Shack (HS) wavefront sensor to control the ultrafast laser beam's wavefront aberrations has been developed. This instrument allowed us to investigate the impact of the laser beam aberrations on two-photon autofluorescence imaging of human retinal tissues. We demonstrated that nonlinear microscopy images are improved when laser beam aberrations are minimized by realigning the laser system cavity while wavefront controlling. Nonlinear signals from several human retinal anatomical features have been detected for the first time, without the need of fixation or staining procedures. Beyond the improved image quality, this approach reduces the required excitation power levels, minimizing the side effects of phototoxicity within the imaged sample. In particular, this may be important to study the physiology and function of the healthy and diseased retina.

  11. De rijping van het cerebellum; a study of the postnatal development of the rat cerebellum.

    NARCIS (Netherlands)

    Ebels, E.J.

    1969-01-01

    Chapter I: INTRODUCTION In this investigation the development of the rat cerebellum from 0 -30 days after birth is studied morphologically, by means of enzymchistochemistry and electronmicroscopy. Enzymchistochemistry and electronmicroscopy were chosen because changes in enzyme content or enzyme

  12. Adaptive optics imaging of the retina

    Directory of Open Access Journals (Sweden)

    Rajani Battu

    2014-01-01

    Full Text Available Adaptive optics is a relatively new tool that is available to ophthalmologists for study of cellular level details. In addition to the axial resolution provided by the spectral-domain optical coherence tomography, adaptive optics provides an excellent lateral resolution, enabling visualization of the photoreceptors, blood vessels and details of the optic nerve head. We attempt a mini review of the current role of adaptive optics in retinal imaging. PubMed search was performed with key words Adaptive optics OR Retina OR Retinal imaging. Conference abstracts were searched from the Association for Research in Vision and Ophthalmology (ARVO and American Academy of Ophthalmology (AAO meetings. In total, 261 relevant publications and 389 conference abstracts were identified.

  13. Development of rat visual system after prenatal X-irradiation

    International Nuclear Information System (INIS)

    Brueckner, G.; Biesold, D.; Mares, V.

    1980-01-01

    Rats pregnant for 16 or 19 days (ED 16 or 19) were irradiated with 1 Gy and killed after 24 hrs or at age 24 or 180 days. The primary influence of X-rays consists in a lethal lesion of cells located in the periventricular zone as well as some of the more differentiated cells in the brain parenchyma. After irradiation on ED 16, the acute damage was greater in the cerebral cortex and the superior colliculus (SC) than in the lateral geniculate nucleus (LGN). Irradiation on ED 19 damaged mainly the cortical part of the visual system. In adult animals the acute radiation damage results in a deficit in packing density and the total number of neurons. Animals irradiated on ED 16 revealed more pronounced changes in deep layers of the cortex (L VI) than in the superficial layers. The deficit was smaller in the SC, and in the LGN an increase in the packing density of nerve cells was found. In animals irradiated on ED 19, the deficit in neurons density occurred mainly in more superficial layers of the cortex, with a maximum deficit in layer IV. From comparison of acute and final changes it may be concluded that the damage of preneuroblastic cell populations is compensated during later embryonic development, while the damage induced in populations already at early neuroblast stage is irreversible and leads to a permanent deficit. Glia cell population is altered in a similar way as the number of neurons in regions poor in myelin, while in regions rich in myelin the number of glia cells seems to depend on changes in the number of efferent and afferent nerve fibres. (author)

  14. Curcumin Alleviates Diabetic Retinopathy in Experimental Diabetic Rats.

    Science.gov (United States)

    Yang, Fang; Yu, Jinqiang; Ke, Feng; Lan, Mei; Li, Dekun; Tan, Ke; Ling, Jiaojiao; Wang, Ying; Wu, Kaili; Li, Dai

    2018-03-29

    To investigate the potential protective effects of curcumin on the retina in diabetic rats. An experimental diabetic rat model was induced by a low dose of streptozotocin combined with a high-energy diet. Rats which had blood glucose levels ≥11.6 mmol/L were used as diabetic rats. The diabetic rats were randomly divided into 3 groups: diabetic rats with no treatment (DM), diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally administered daily for 16 weeks. After 16 weeks of administration, the rats were euthanized, and eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes of retinal ganglion cells, inner layer cells, retinal capillary, and membranous disks were observed by electron microscopy. Malondialdehyde, superoxide dismutase, and total antioxidant capacity were measured by ELISA. Expression levels of vascular endothelial growth factor (VEGF) in retina tissues were examined by immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in retina tissues were determined by immunohistochemical staining and Western blotting. Curcumin reduced the blood glucose levels of diabetic rats and decreased diabetes-induced body weight loss. Curcumin prevented attenuation of the retina in diabetic rats and ameliorated diabetes-induced ultrastructure changes of the retina, including thinning of the retina, apoptosis of the retinal ganglion cells and inner nuclear layer cells, thickening of retinal capillary basement membrane and disturbance of photoreceptor cell membranous disks. We also found that curcumin has a strong antioxidative ability in the retina of diabetic rats. It was observed that curcumin attenuated the expression of VEGF in the retina of diabetic rats. We also discovered that curcumin had an antiapoptotic effect by upregulating the expression of Bcl-2 and downregulating

  15. Quantitative analysis of retina layer elasticity based on automatic 3D segmentation (Conference Presentation)

    Science.gov (United States)

    He, Youmin; Qu, Yueqiao; Zhang, Yi; Ma, Teng; Zhu, Jiang; Miao, Yusi; Humayun, Mark; Zhou, Qifa; Chen, Zhongping

    2017-02-01

    Age-related macular degeneration (AMD) is an eye condition that is considered to be one of the leading causes of blindness among people over 50. Recent studies suggest that the mechanical properties in retina layers are affected during the early onset of disease. Therefore, it is necessary to identify such changes in the individual layers of the retina so as to provide useful information for disease diagnosis. In this study, we propose using an acoustic radiation force optical coherence elastography (ARF-OCE) system to dynamically excite the porcine retina and detect the vibrational displacement with phase resolved Doppler optical coherence tomography. Due to the vibrational mechanism of the tissue response, the image quality is compromised during elastogram acquisition. In order to properly analyze the images, all signals, including the trigger and control signals for excitation, as well as detection and scanning signals, are synchronized within the OCE software and are kept consistent between frames, making it possible for easy phase unwrapping and elasticity analysis. In addition, a combination of segmentation algorithms is used to accommodate the compromised image quality. An automatic 3D segmentation method has been developed to isolate and measure the relative elasticity of every individual retinal layer. Two different segmentation schemes based on random walker and dynamic programming are implemented. The algorithm has been validated using a 3D region of the porcine retina, where individual layers have been isolated and analyzed using statistical methods. The errors compared to manual segmentation will be calculated.

  16. Expression and location of α-fetoprotein during rat colon development

    Science.gov (United States)

    Liu, Xiao-Yan; Dong, Dan; Sun, Peng; Du, Jun; Gu, Luo; Ge, Ying-Bin

    2009-01-01

    AIM: To investigate the expression of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, and its involvement during rat colon development. METHODS: Colons from Sprague-Dawley rat fetuses, young and adult (8 wk old) animals were used in this study. Expression levels of AFP in colons of different development stage were detected by reverse-transcriptase PCR (RT-PCR) and Western blotting. To identify the cell location of AFP in the developing rat colons, double-immunofluorescent staining was performed using antibodies to specific cell markers and AFP, respectively. RESULTS: The highest levels of AFP mRNA were detected in colons of rats at embryonic day 18.5 (e18.5). Compared to e18.5 d, the AFP expression was significantly decreased during rat development [85% for e20.5, P colon from the embryo to the weaning stage by immunofluorescence and presents 72-kDa isoform in the developing rat colons by Western blotting. The dynamic expression of AFP in the various developmental stages of the colon indicates that AFP might be involved in many aspects of colon development. PMID:19360917

  17. The rat with oxygen-induced retinopathy is myopic with low retinal dopamine.

    Science.gov (United States)

    Zhang, Nan; Favazza, Tara L; Baglieri, Anna Maria; Benador, Ilan Y; Noonan, Emily R; Fulton, Anne B; Hansen, Ronald M; Iuvone, P Michael; Akula, James D

    2013-12-19

    Dopamine (DA) is a neurotransmitter implicated both in modulating neural retinal signals and in eye growth. Therefore, it may participate in the pathogenesis of the most common clinical sequelae of retinopathy of prematurity (ROP), visual dysfunction and myopia. Paradoxically, in ROP myopia the eye is usually small. The eye of the rat with oxygen-induced retinopathy (OIR) is characterized by retinal dysfunction and short axial length. There have been several investigations of the early maturation of DA in rat retina, but little at older ages, and not in the OIR rat. Therefore, DA, retinal function, and refractive state were investigated in the OIR rat. In one set of rats, the development of dopaminergic (DAergic) networks was evaluated in retinal cross-sections from rats aged 14 to 120 days using antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in the biosynthesis of DA). In another set of rats, retinoscopy was used to evaluate spherical equivalent (SE), electoretinography (ERG) was used to evaluate retinal function, and high-pressure liquid chromatography (HPLC) was used to evaluate retinal contents of DA, its precursor levodopamine (DOPA), and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). The normally rapid postnatal ramification of DAergic neurons was disrupted in OIR rats. Retinoscopy revealed that OIR rats were relatively myopic. In the same eyes, ERG confirmed retinal dysfunction in OIR. HPLC of those eyes' retinae confirmed low DA. Regression analysis indicated that DA metabolism (evaluated by the ratio of DOPAC to DA) was an important additional predictor of myopia beyond OIR. The OIR rat is the first known animal model of myopia in which the eye is smaller than normal. Dopamine may modulate, or fail to modulate, neural activity in the OIR eye, and thus contribute to this peculiar myopia.

  18. In Silico Ocular Pharmacokinetic Modeling: Delivery of Topical FK962 to Retina.

    Science.gov (United States)

    Mori, Ayumi; Yabuta, Chiho; Kishimoto, Yayoi; Kozai, Seiko; Ohtori, Akira; Shearer, Thomas R; Azuma, Mitsuyoshi

    2017-09-01

    To establish the in silico ocular pharmacokinetic modeling for eye drops, and to simulate the dose regimen for FK962 in human choroid/retinal diseases. Pharmacokinetics for FK962 in vivo was performed by a single instillation of drops containing 0.1% 14 C-FK962 in rabbit eyes. Permeation of FK962 across the cornea, sclera, and choroid/retina was measured in vitro. Neurite elongation by FK962 was measured in cultured rat retinal ganglion cells. Parameters from the experimental data were used in an improved in silico model of ocular pharmacokinetics of FK962 in man. The mean concentration of FK962 in ocular tissues predicted by in silico modeling was consistent with in vivo results, validating the in silico model. FK962 rapidly penetrated into the anterior and posterior segments of the eye and then diffused into the vitreous body. The in silico pharmacokinetic modeling also predicted that a dose regimen of 0.0054% FK962 twice per day would produce biologically effective concentrations of FK962 in the choroid/retina, where FK962 facilitates rat neurite elongation. Our in silico model for ocular pharmacokinetics is useful (1) for predicting drug concentrations in specific ocular tissues after topical instillation, and (2) for suggesting the optimal dose regimens for eye drops. The pharmacodynamics for FK962 produced by this model may be useful for clinical trials against retinal neuropathy.

  19. Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina

    Science.gov (United States)

    Zhang, Yan; Rha, Jungtae; Jonnal, Ravi S.; Miller, Donald T.

    2005-06-01

    Although optical coherence tomography (OCT) can axially resolve and detect reflections from individual cells, there are no reports of imaging cells in the living human retina using OCT. To supplement the axial resolution and sensitivity of OCT with the necessary lateral resolution and speed, we developed a novel spectral domain OCT (SD-OCT) camera based on a free-space parallel illumination architecture and equipped with adaptive optics (AO). Conventional flood illumination, also with AO, was integrated into the camera and provided confirmation of the focus position in the retina with an accuracy of ±10.3 μm. Short bursts of narrow B-scans (100x560 μm) of the living retina were subsequently acquired at 500 Hz during dynamic compensation (up to 14 Hz) that successfully corrected the most significant ocular aberrations across a dilated 6 mm pupil. Camera sensitivity (up to 94 dB) was sufficient for observing reflections from essentially all neural layers of the retina. Signal-to-noise of the detected reflection from the photoreceptor layer was highly sensitive to the level of cular aberrations and defocus with changes of 11.4 and 13.1 dB (single pass) observed when the ocular aberrations (astigmatism, 3rd order and higher) were corrected and when the focus was shifted by 200 μm (0.54 diopters) in the retina, respectively. The 3D resolution of the B-scans (3.0x3.0x5.7 μm) is the highest reported to date in the living human eye and was sufficient to observe the interface between the inner and outer segments of individual photoreceptor cells, resolved in both lateral and axial dimensions. However, high contrast speckle, which is intrinsic to OCT, was present throughout the AO parallel SD-OCT B-scans and obstructed correlating retinal reflections to cell-sized retinal structures.

  20. Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina.

    Science.gov (United States)

    Beier, Corinne; Palanker, Daniel; Sher, Alexander

    2018-06-04

    Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    International Nuclear Information System (INIS)

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

    2011-01-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

  2. Tissue-specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat

    OpenAIRE

    1991-01-01

    Fibronectin isoforms are generated by the alternative splicing of a primary transcript derived from a single gene. In rat at least three regions of the molecule are involved: EIIIA, EIIIB, and V. This study investigated the splicing patterns of these regions during development and aging, by means of ribonuclease protection analysis. Between fetal and adult rat, the extent of inclusion of the EIIIA and/or EIIIB region in fibronectin mRNA varied according to the type of tissue analyzed; but the...

  3. Characteristic lesions in mouse retina irradiated with accelerated iron particles

    International Nuclear Information System (INIS)

    Malachowski, M.J.; Philpott, D.E.; Corbett, R.L.; Tobias, C.A.

    1981-01-01

    A program is underway to determine the radiation hazards of HZE particles using the Bevalac, a heavy-ion accelerator at LBL. Our earlier work with helium, carbon, neon, and argon particles, and exposure to rats to HZE particles in space flight demonstrated some deleterious biological effects. TEM studies have shown that some visual cells were missing and dislocated; these were termed channel lesions. Recently obtained is evidence that a single iron HZE particle may affect a series of cells. Mice were irradiated with 0.1, 0.3, 1, 10, or 25 rad of 590 MeV/amu initial kinetic energy iron particles in groups of 10 animals per dose point. Irradiated and control animals were sacrificed at intervals from one week to two years postirradiation. The eye samples were dehydrated, critical points dried with freon, fractured, and Au-Pd coated for SEM, or plastic embedded, sectioned, and stained for TEM. Additionally, dry fractured samples viewed with the SEM were embedded in plastic, sectioned, and stained for the TEM. Characteristic tunnel shaped lesions were observed with the SEM. Stereo pairs showed tunnels of various lengths up to 100 μm. Light microscopy of serially cut sections from the same material had vacuoles (V) extending the same length. TEM of the same specimen and specimens prepared only for TEM exhibited large vacuoles, greater than or equal to 2 μm, in the inner segment (IS) and outer segment (OS) layers. Severe membrane disruption was found bordering the vacuoles and gross nuclear degeneration (ND) and loose tissue (LT) were seen in the outer nuclear layer (ONL). The number of lesions increased with increasing dose. Microscopy of the control retina failed to demonstrate similar lesions

  4. Effects of enriched uranium on developing brain damage of neonatal rats

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Wang Liuyi; Yang Shuqin; Zhu Lingli

    2001-01-01

    The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium 235 U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 β (IL- β), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells

  5. Effects of enriched uranium on developing brain damage of neonatal rats

    Energy Technology Data Exchange (ETDEWEB)

    Guixiong, Gu; Shoupeng, Zhu; Liuyi, Wang; Shuqin, Yang; Lingli, Zhu [Suzhou Medical College, Suzhou (China)

    2001-04-01

    The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium {sup 235}U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 {beta} (IL- {beta}), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells.

  6. The effect of prenatal exposure to diazepam on aspects of postnatal development and behavior in rats.

    Science.gov (United States)

    Gai, N; Grimm, V E

    1982-01-01

    In the present study the effects of chronic treatment of pregnant rats with diazepam on the physical and behavioral development of their offspring were investigated. Rats that were diazepam-exposed prenatally were compared to age-matched controls in terms of the following: number of littermates; birth weight and weight gain until weaning: motor development and coordination; simple motor learning; open field activity; performance on learning tasks of varying complexity; retention of these tasks. Nulliparous Wistar rats were injected s.c. for 16 days of their pregnancy was either 2.5, 5, of 10 mg/kg diazepam or an equal volume of vehicle. Prenatal diazepam treatment did not alter litter size, birth weight, or the righting reflex, but seemed to retard early motor development transiently. Diazepam pups showed longer latencies and less rearing in the open field. There were no differences between animals exposed to drug and vehicle in simple motor learning or in acquiring a simple successive discrimination task. However, there were significant dose-dependent differences on a complex six-choice simultaneous discrimination learning task, the diazepam-exposed rats making more errors and taking more time to reach the goal. A significant difference was seen again between diazepam- and vehicle-exposed rats on the retention test 10 days later. The results indicate that diazepam administered to pregnant rats has long-range effects on the behavior of the offspring, some becoming manifest even in maturity.

  7. Perinatal and chronic hypothyroidism impair behavioural development in male and female rats.

    NARCIS (Netherlands)

    Wijk, van N.; Rijntjes, E.; Heijning, van de B.J.

    2008-01-01

    Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. EXP PHYSIOL 00(0) 000-000, 0000. - A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the

  8. Sexual dimorphism in development of kidney damage in aging Fischer-344 rats.

    Science.gov (United States)

    Sasser, Jennifer M; Akinsiku, Oladele; Moningka, Natasha C; Jerzewski, Katie; Baylis, Chris; LeBlanc, Amanda J; Kang, Lori S; Sindler, Amy L; Muller-Delp, Judy M

    2012-08-01

    Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide. Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys. We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress. There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability. The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3

  9. Vitreous in lattice degeneration of retina.

    Science.gov (United States)

    Foos, R Y; Simons, K B

    1984-05-01

    A localized pocket of missing vitreous invariably overlies lattice degeneration of the retina. Subjects with lattice also have a higher rate of rhegmatogenous retinal detachment, which is usually a complication of retinal tears. The latter are in turn a result of alterations in the central vitreous--that is, synchysis senilis leading to posterior vitreous detachment. In order to determine if there is either an association or a deleterious interaction between the local and central lesions of the vitreous in eyes with lattice, a comparison was made in autopsy eyes with and without lattice the degree of synchysis and rate of vitreous detachment. Results show no association between the local and central vitreous lesions, indicating that a higher rate of vitreous detachment is not the basis for the higher rate of retinal detachment in eyes with lattice. Also, there was no suggestion of deleterious interaction between the local and central vitreous lesions, either through vitreodonesis as a basis for precocious vitreous detachment, or through a greater degree of synchysis as a basis for interconnection of local and central lacunae (which could extend the localized retinal detachment in eyes with holes in lattice degeneration).

  10. Mouse embryonic retina delivers information controlling cortical neurogenesis.

    Directory of Open Access Journals (Sweden)

    Ciro Bonetti

    2010-12-01

    Full Text Available The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal. Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.

  11. Simple Experiments on the Physics of Vision: The Retina

    Science.gov (United States)

    Cortel, Adolf

    2005-01-01

    Many simple experiments can be performed in the classroom to explore the physics of vision. Students can learn of the two types of receptive cells (rods and cones), their distribution on the retina and the existence of the blind spot.

  12. Enhancement of Spatial Learning-Memory in Developing Rats via Mozart Music

    Institute of Scientific and Technical Information of China (English)

    Jian-Gao Yao; Yang Xia; Sheng-Jun Dai; Guang-Zhan Fang; Hua Guo; De-Zhong Yao

    2009-01-01

    This paper studies the effect of musical stimulations on the capability of the spatial learning-memory in developing rats by behavioral and electro-physiological techniques.Rats,which are exposed to Mozart's Sonata for Two Pianos in D Major,complete learning tasks of the Moriss water maze with significantly shorter latencies,and the power spectrum of alpha band of electrohippocampogram (EHG) significantly increase,compared with the control rats and rats exposed to the horror music.The results indicate that if given the stimulation of Mozart music in the developmental period of the auditory cortex,the capability of the spatial learning-memory can be significantly changed.The enhancement of alpha band of EHG may be related to the change of this function mainly.

  13. Retina damage after exposure to UVA radiation on the early developmental stages of the Egyptian toad Bufo regularis Reuss

    Directory of Open Access Journals (Sweden)

    Alaa El-Din H. Sayed

    2016-10-01

    Full Text Available The present study was carried out to investigate the histological and histochemical changes in the retina on different developmental stages of Egyptian toad Bufo regularis. Our experiment started when tadpoles begin to feed. The adapted embryos are divided into 3 large tanks of 200 embryos each, collections of samples started from feeding age every three days. Both histological and histochemical results showed that the general architecture of the retina organ is correlated with the state of development. Therefore, it displayed different characteristic features depending on the investigated developmental stage starting from the larval stage (feeding began, stage 44 and ending with the post-metamorphic stage 66. Also, the present work aimed to study the chronic effects of UVA on the retina structure of B. regularis during development and metamorphosis for the first time.

  14. Free radical activity during development of insulin-dependent diabetes mellitus in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Pitkaenen, O.M.; Akerblom, H.K.; Sariola, H.; Andersson, S.M. (Univ. of Helsinki (Finland)); Martin, J.M. (Hospital for Sick Children, Toronto, Ontario (Canada)); Hallman, M. (Univ. of California, Irvine (United States))

    1991-01-01

    Free radical-induced lipid peroxidation was quantified by measuring expired pentane from diabetic prone BB Wistar rats of 45-90 d of age. Insulin-dependent diabetes mellitus was manifest at the age of 71 {plus minus} 8 d. Expired pentane increased from 2.1 {plus minus} 0.7 to 5.0 {plus minus}3.0 pmol/100g/min (p <0.01) at manifestation of the disease and remained high throughout the test period. In healthy age-matched control rats it persisted low. In rats made diabetic with streptozotocin, expired pentane remained low. The changes in expired pentane suggest that the development of endogenous insulin-dependent diabetes mellitus in BB rats is associated with increased free radical activity. This is not due to hyperglycemia or ketosis per se, and reflects a fundamental difference in the free radical activity between the spontaneously diabetic BB rats and the disease produced by streptozotocin. Development of spontaneous insulin-dependent diabetes in BB rats is associated with increased free radical activity that persists after the manifestation of the disease.

  15. Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression.

    Directory of Open Access Journals (Sweden)

    Anton M Markovets

    Full Text Available UNLABELLED: The incidence of age-related macular degeneration (AMD, the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1 is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF and its antagonist pigment epithelium-derived factor (PEDF genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.

  16. Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Tracy Ho

    Full Text Available Amyloid precursor protein (APP is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.

  17. Quantitative analysis of development and aging of genital corpuscles in glans penis of the rat.

    Science.gov (United States)

    Shiino, Mizuho; Hoshi, Hideo; Kawashima, Tomokazu; Ishikawa, Youichi; Takayanagi, Masaaki; Murakami, Kunio; Kishi, Kiyoshi; Sato, Fumi

    2015-02-01

    The aim of the present postnatal developmental study was to determine densities of unique genital corpuscles (GCs) in glans penis of developing and aged rats. GCs were identified as corpuscular endings consisting of highly branched and coiled axons with many varicosities, which were immunoreactive for protein gene product 9.5. In addition, GCs were immunoreactive for calcitonin gene-related peptide and substance P, but not for vasoactive intestinal polypeptide and neuropeptide Y. GCs were not found in the glans penis of 1 week old rats. Densities of GCs were low at 3 weeks, significantly increased at 5 and 10 weeks, reached the peak of density at 40 weeks, and tended to decrease at 70 and 100 weeks. Sizes of GCs were small in 3 weeks old rats, increased at 5 and 10 weeks, reached the peak-size at 40 weeks and reduced in size at 70 and 100 weeks. Considering sexual maturation of the rat, the results reveal that GCs of the rat begins to develop postnatal and reaches to the peak of their development after puberty and continues to exist until old age, in contrast to prenatal and early postnatal development of other sensory receptors of glabrous skin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Segmentasi Pembuluh Darah Retina Pada Citra Fundus Menggunakan Gradient Based Adaptive Thresholding Dan Region Growing

    Directory of Open Access Journals (Sweden)

    Deni Sutaji

    2016-07-01

    , segmentasi. AbstractSegmentation of blood vessels in the retina fundus image becomes substantial in the medical, because it can be used to detect diseases, such as diabetic retinopathy, hypertension, and cardiovascular. Doctor takes about two hours to detect the blood vessels of the retina, so screening methods are needed to make it faster. The previous methods are able to segment the blood vessels that are sensitive to variations in the size of the width of blood vessels, but there is over-segmentation in the area of pathology. Therefore, this study aims to develop a segmentation method of blood vessels in retinal fundus images which can reduce over-segmentation in the area of pathology using Gradient Based Adaptive Thresholding and Region Growing. The proposed method consists of three stages, namely the segmentation of the main blood vessels, detection area of pathology and segmentation thin blood vessels. Main blood vessels segmentation using high-pass filtering and tophat reconstruction on the green channel which adjusted of contras image that results the clearly between object and background. Detection area of pathology using Gradient Based Adaptive thresholding method. Thin blood vessels segmentation using Region Growing based on the information main blood vessel segmentation and detection of pathology area. Output of the main blood vessel segmentation and thin blood vessels are then combined to reconstruct an image of the blood vessels as output system.This method is able to segment the blood vessels in retinal fundus images DRIVE with an accuracy of 95.25% and the value of Area Under Curve (AUC in the relative operating characteristic curve (ROC of 74.28%.Keywords: Blood vessel, fundus retina image, gradient based adaptive thresholding, pathology, region growing, segmentation.

  19. Fundus autofluorescence and the bisretinoids of retina.

    Science.gov (United States)

    Sparrow, Janet R; Wu, Yalin; Nagasaki, Takayuki; Yoon, Kee Dong; Yamamoto, Kazunori; Zhou, Jilin

    2010-11-01

    Imaging of the human fundus of the eye with excitation wavelengths in the visible spectrum reveals a natural autofluorescence, that in a healthy retina originates primarily from the bisretinoids that constitute the lipofuscin of retinal pigment epithelial (RPE) cells. Since the intensity and distribution of fundus autofluorescence is altered in the presence of retinal disease, we have examined the fluorescence properties of the retinal bisretinoids with a view to aiding clinical interpretations. As is also observed for fundus autofluorescence, fluorescence emission from RPE lipofuscin was generated with a wide range of exciting wavelengths; with increasing excitation wavelength, the emission maximum shifted towards longer wavelengths and spectral width was decreased. These features are consistent with fluorescence generation from a mixture of compounds. While the bisretinoids that constitute RPE lipofuscin all fluoresced with maxima that were centered around 600 nm, fluorescence intensities varied when excited at 488 nm, the excitation wavelength utilized for fundus autofuorescence imaging. For instance the fluorescence efficiency of the bisretinoid A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE) was greater than A2E and relative to both of the latter, all-trans-retinal dimer-phosphatidylethanolamine was weakly fluorescent. On the other hand, certain photooxidized forms of the bisretinoids present in both RPE and photoreceptor cells were more strongly fluorescent than the parent compound. We also sought to evaluate whether diffuse puncta of autofluorescence observed in some retinal disorders of monogenic origin are attributable to retinoid accumulation. However, two retinoids of the visual cycle, all-trans-retinyl ester and all-trans-retinal, did not exhibit fluorescence at 488 nm excitation.

  20. Asthma pregnancy alters postnatal development of chromaffin cells in the rat adrenal medulla.

    Directory of Open Access Journals (Sweden)

    Xiu-Ming Wu

    Full Text Available Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown.This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3 to postnatal day 60 (P60. Asthmatic pregnant rats (AP, nerve growth factor (NGF-treated pregnant rats (NP and NGF antibody-treated pregnant rats (ANP were sensitized and challenged with ovalbumin (OVA; NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP, offspring from AP (OAP, offspring from NP (ONP, and offspring from ANP (OANP. The expressions of phenylethanolamine N-methyltransferase (PNMT protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI, corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP.Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.

  1. Impact of environmental noise on growth and neuropsychological development of newborn rats.

    Science.gov (United States)

    Zheng, Yanyan; Meng, Meng; Zhao, Congmin; Liao, Wei; Zhang, Yuping; Wang, Liyan; Wen, Enyi

    2014-05-01

    We aimed to investigate the effects of environmental noise exposure on the growth and neuropsychological development in neonatal rats. Twenty-four postnatal 7-day-old Sprague-Dawley rats were randomly assigned into control, high-noise and reduced noise groups. The rats in the high-noise group were exposed to 90 dB white noise, and those in the control group were grown under standard condition, while those in the reduced noise group were exposed to standard condition with sound-absorbing cotton. Ten, 15, and 20 days post noise exposure, both the body weight and length of the rats in high-noise group were lower than those in the control and reduced noise groups, respectively. The secretion of growth hormone was significantly decreased in the rats exposed to high noise environment, compared to those exposed to standard condition and reduced noise. More interestingly, the swimming distance was apparently increased and the swimming speed was significantly decreased in high-noise group compared with those in control and reduced noise groups. Importantly, the mRNA and protein levels of SYP in the rats hippocampus were significantly decreased in high-noise group compare with those in control and reduced noise groups. Similarly, the positive expression of SYP in the CA1 region of hippocampus was also significantly decreased in the high noise group rats. In conclusion, our results demonstrated that high noise exposure could decrease the production of growth hormone and SYP in neonatal rats, which may retard the growth of weight and length and the capability of learning and memory. Copyright © 2014 Wiley Periodicals, Inc.

  2. Spontaneous motor activity during the development and maintenance of diet-induced obesity in the rat.

    Science.gov (United States)

    Levin, B E

    1991-09-01

    More than 80% of most daily spontaneous activities (assessed in an Omnitech activity monitor) occurred during the last hour of light and 12 h of the dark phase in 8 chow-fed male Sprague-Dawley rats. Thirty additional rats were, therefore, monitored over this 13-h period to assess the relationship of activity to the development and maintenance of diet-induced obesity (DIO) on a diet high in energy, fat and sucrose (CM diet). Nine of 20 rats became obese after 3 months on the CM diet, with 71% greater weight gain than 10 chow-fed controls. Eleven of 20 rats were diet resistant (DR), gaining the same amount of weight as chow-fed rats. Neither initial activity levels nor initial body weights on chow (Period I) differed significantly across retrospectively identified groups. After 3 months on CM diet or chow (Period II), as well as after an additional 3 months after CM diet-fed rats returned to chow (Period III), there were significant inverse correlations (r = -.606 to -.370) between body weight at the time of testing and various measures of movement in the horizontal plane. There was no relationship to dietary content nor consistent correlations of body weight or diet group to vertical movements, an indirect measure of ingestive behavior. Patterns of time spent in the vertical position were significantly different for DIO vs. DR rats in Period III, however. Thus, differences in food intake and metabolic efficiency, rather than differences in nocturnal activity, are probably responsible for the greater weight gain in DIO-prone rats placed on CM diet.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Diet composition determines course of hyperphagia in developing Zucker obese rats.

    Science.gov (United States)

    Vasselli, J R; Maggio, C A

    1990-12-01

    Previous observations from this laboratory indicate that, during growth, the hyperphagia of the male genetically obese Zucker rat reaches a peak or "breakpoint" and then declines. To examine the effect of dietary macronutrient content on the course of hyperphagia, groups of male lean and obese rats were maintained from 5-28 weeks of age on powdered chow, or isocaloric diets (3.6 kcal/g) containing 72% of calories as corn oil, dextrose, or soy isolate protein (n = 5 lean and obese rats/diet). On chow, hyperphagia was maintained at a level of 7-8 g above lean control intake until a "breakpoint" was reached at 17 weeks, and obese intake declined to lean control level. On the fat diet, hyperphagia was increased to 10 g/day when a breakpoint was reached at 8 weeks. On the dextrose and protein diets, hyperphagia at a level of 3-4 g/day reached breakpoints at weeks 18 and 16, respectively. On all diets, the intakes of obese rats were precisely equal to the intakes of lean control rats by weeks 19-20. These data show that the magnitude and duration of hyperphagia in the developing obese rat are influenced by diet composition. Previously, we have proposed that the obese rat's hyperphagia arises from rapid adipocyte filling. Since high-fat diets facilitate adipocyte enlargement, the early "breakpoint" of hyperphagia seen with the high-fat diet may indicate that this feeding stimulation decreases as the fat cells of the obese rat approach maximal size.

  4. Retina Image Analysis and Ocular Telehealth: The Oak Ridge National Laboratory-Hamilton Eye Institute Case Study

    Energy Technology Data Exchange (ETDEWEB)

    Karnowski, Thomas Paul [ORNL; Giancardo, Luca [ORNL; Li, Yaquin [University of Tennessee, Knoxville (UTK); Tobin Jr, Kenneth William [ORNL; Chaum, Edward [University of Tennessee, Knoxville (UTK)

    2013-01-01

    Automated retina image analysis has reached a high level of maturity in recent years, and thus the question of how validation is performed in these systems is beginning to grow in importance. One application of retina image analysis is in telemedicine, where an automated system could enable the automated detection of diabetic retinopathy and other eye diseases as a low-cost method for broad-based screening. In this work we discuss our experiences in developing a telemedical network for retina image analysis, including our progression from a manual diagnosis network to a more fully automated one. We pay special attention to how validations of our algorithm steps are performed, both using data from the telemedicine network and other public databases.

  5. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina.

    Science.gov (United States)

    Young, T L; Matsuda, T; Cepko, C L

    2005-03-29

    With the advent of genome-wide analyses, it is becoming evident that a large number of noncoding RNAs (ncRNAs) are expressed in vertebrates. However, of the thousands of ncRNAs identified, the functions of relatively few have been established. In a screen for genes upregulated by taurine in developing retinal cells, we identified a gene that appears to be a ncRNA. Taurine Upregulated Gene 1 (TUG1) is a spliced, polyadenylated RNA that does not encode any open reading frame greater than 82 amino acids in its full-length, 6.7 kilobase (kb) RNA sequence. Analyses of Northern blots and in situ hybridization revealed that TUG1 is expressed in the developing retina and brain, as well as in adult tissues. In the newborn retina, knockdown of TUG1 with RNA interference (RNAi) resulted in malformed or nonexistent outer segments of transfected photoreceptors. Immunofluorescent staining and microarray analyses suggested that this loss of proper photoreceptor differentiation is a result of the disregulation of photoreceptor gene expression. A function for a newly identified ncRNA, TUG1, has been established. TUG1 is necessary for the proper formation of photoreceptors in the developing rodent retina.

  6. An artificial retina processor for track reconstruction at the LHC crossing rate

    Science.gov (United States)

    Bedeschi, F.; Cenci, R.; Marino, P.; Morello, M. J.; Ninci, D.; Piucci, A.; Punzi, G.; Ristori, L.; Spinella, F.; Stracka, S.; Tonelli, D.; Walsh, J.

    2017-10-01

    The goal of the INFN-RETINA R&D project is to develop and implement a computational methodology that allows to reconstruct events with a large number (> 100) of charged-particle tracks in pixel and silicon strip detectors at 40 MHz, thus matching the requirements for processing LHC events at the full bunch-crossing frequency. Our approach relies on a parallel pattern-recognition algorithm, dubbed artificial retina, inspired by the early stages of image processing by the brain. In order to demonstrate that a track-processing system based on this algorithm is feasible, we built a sizable prototype of a tracking processor tuned to 3 000 patterns, based on already existing readout boards equipped with Altera Stratix III FPGAs. The detailed geometry and charged-particle activity of a large tracking detector currently in operation are used to assess its performances. We report on the test results with such a prototype.

  7. A New Rat Model of Epileptic Spasms Based on Methylazoxymethanol-Induced Malformations of Cortical Development

    Directory of Open Access Journals (Sweden)

    Eun-Hee Kim

    2017-06-01

    Full Text Available Malformations of cortical development (MCDs can cause medically intractable epilepsies and cognitive disabilities in children. We developed a new model of MCD-associated epileptic spasms by treating rats prenatally with methylazoxymethanol acetate (MAM to induce cortical malformations and postnatally with N-methyl-d-aspartate (NMDA to induce spasms. To produce cortical malformations to infant rats, two dosages of MAM (15 mg/kg, intraperitoneally were injected to pregnant rats at gestational day 15. In prenatally MAM-exposed rats and the controls, spasms were triggered by single (6 mg/kg on postnatal day 12 (P12 or 10 mg/kg on P13 or 15 mg/kg on P15 or multiple doses (P12, P13, and P15 of NMDA. In prenatally MAM-exposed rats with single NMDA-provoked spasms at P15, we obtain the intracranial electroencephalography and examine the pretreatment response to adrenocorticotropic hormone (ACTH or vigabatrin. Rat pups prenatally exposed to MAM exhibited a significantly greater number of spasms in response to single and multiple postnatal NMDA doses than vehicle-exposed controls. Vigabatrin treatment prior to a single NMDA dose on P15 significantly suppressed spasms in MAM group rats (p < 0.05, while ACTH did not. The MAM group also showed significantly higher fast oscillation (25–100 Hz power during NMDA-induced spasms than controls (p = 0.047. This new model of MCD-based epileptic spasms with corresponding features of human spasms will be valuable for future research of the developmental epilepsy.

  8. Development of rat female genital cortex and control of female puberty by sexual touch.

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    Constanze Lenschow

    2017-09-01

    Full Text Available Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  9. Development of rat female genital cortex and control of female puberty by sexual touch.

    Science.gov (United States)

    Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

    2017-09-01

    Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  10. Developmentally Regulated Production of meso-Zeaxanthin in Chicken Retinal Pigment Epithelium/Choroid and Retina.

    Science.gov (United States)

    Gorusupudi, Aruna; Shyam, Rajalekshmy; Li, Binxing; Vachali, Preejith; Subhani, Yumna K; Nelson, Kelly; Bernstein, Paul S

    2016-04-01

    meso-Zeaxanthin is a carotenoid that is rarely encountered in nature outside of the vertebrate eye. It is not a constituent of a normal human diet, yet this carotenoid comprises one-third of the primate macular pigment. In the current study, we undertook a systematic approach to biochemically characterize the production of meso-zeaxanthin in the vertebrate eye. Fertilized White Leghorn chicken eggs were analyzed for the presence of carotenoids during development. Yolk, liver, brain, serum, retina, and RPE/choroid were isolated, and carotenoids were extracted. The samples were analyzed on C-30 or chiral HPLC columns to determine the carotenoid composition. Lutein and zeaxanthin were found in all studied nonocular tissues, but no meso-zeaxanthin was ever detected. Among the ocular tissues, the presence of meso-zeaxanthin was consistently observed starting at embryonic day 17 (E17) in the RPE/choroid, several days before its consistent detection in the retina. If RPE/choroid of an embryo was devoid of meso-zeaxanthin, the corresponding retina was always negative as well. This is the first report of developmentally regulated synthesis of meso-zeaxanthin in a vertebrate system. Our observations suggest that the RPE/choroid is the primary site of meso-zeaxanthin synthesis. Identification of meso-zeaxanthin isomerase enzyme in the developing chicken embryo will facilitate our ability to determine the biochemical mechanisms responsible for production of this unique carotenoid in other higher vertebrates, such as humans.

  11. Lack of toxic effect of technical azadirachtin during postnatal development of rats.

    Science.gov (United States)

    Srivastava, M K; Raizada, R B

    2007-03-01

    Azadirachtin, a biopesticide has been evaluated for its possible toxic effects during postnatal development of rats over two generations. Rats were fed 100, 500 and 1000ppm technical azadirachtin through diet which is equivalent to 5, 25 and 50mg/kg body weight of rats. Technical azadirachtin has not produced any adverse effects on reproductive function and data were comparable to control animals over two generations. There were no toxicological effect in parent rats as evidenced by clinical signs of toxicity, enzymatic parameters like AST, ALT, ALP, S. bilirubin, S. cholesterol, total protein and histopathology of liver, brain, kidney and testes/ovary. The litters of F(1B) and F(2B) generations were devoid of any morphological, visceral and teratological changes. The percent cumulative loss and growth index of pups were also comparable to respective controls in successive growth period of 0, 4, 7, 14 and 21 days in two generations. There were no major malformations in fetuses while some insignificant minor skeletal variations like missing 5th sternebrae and bipartite thoracic centre found were not compound or dose related. No significant pathomorphological changes were observed in liver, kidney, brain and gonads of F(2B) pups. In conclusion rats fed technical azadirachtin showed no evidence of cumulative effects on postnatal development and reproductive performance over two generations. Absence of any major adverse reproductive effects in adults as well as in 21 days old pups of F(2B) generation suggest the safe use of technical azadirachtin as a biopesticide.

  12. Development of T Lymphocytes in the Nasal-associated Lymphoid Tissue (NALT from Growing Wistar Rats

    Directory of Open Access Journals (Sweden)

    Gustavo A. Sosa

    2004-01-01

    Full Text Available The aim of the present report was to study the development of several T-lymphocyte subsets in the nasal-associated lymphoid tissue (NALT of growing Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A predominance of CD8α+ over CD4+ T cells was found from 7 to 45 days but from 45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most relevant findings by immunohistochemistry are: (1 the predominance of TCRγδ+ and CD8α+ cells at 7 days postpartum over all the other T-cell subpopulations; and (2 that TCRγβ+ outnumbered TCRαβ+ T cells from 7 to 45 days postpartum whereas αβ T cells predominated in 45- and 60-day-old rats. Besides, cytometric studies have shown that the percentages of TCRγ+, CD8+, as well as the population coexpressing both phenotypes (TCRγδ+CD8α+, were significantly higher in rats at 7 days postpartum when compared to 60 day-old rats. In the present study, the finding of a high number of γδ+ and CD8+ T cells early in NALT development may indicate the importance of these subpopulations in the protection of the nasal mucosa in suckling and weaning Wistar rats.

  13. Towards metabolic mapping of the human retina.

    Science.gov (United States)

    Schweitzer, D; Schenke, S; Hammer, M; Schweitzer, F; Jentsch, S; Birckner, E; Becker, W; Bergmann, A

    2007-05-01

    = 190 ps) originates from the retinal pigment epithelium and the second lifetime (t2 = 1,000 ps) from the neural retina. The lifetime t3 approximately 5.5 ns might be influenced by the long decay of the fluorescence in the crystalline lens. In vitro analysis of the spectral properties of expected fluorophores under the condition of the living eye lightens the interpretation of in vivo measurements. Taking into account the transmission of the ocular media, the excitation of NADH is unlikely at the fundus. Copyright 2007 Wiley-Liss, Inc.

  14. Retina neural circuitry seen with particle detector technology

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    Using particle physics techniques, high energy physics researchers have recently provided new insight into neural circuits inside the retina. After uncovering a new type of retinal cell and mapping how the retina deals with colours, the team from Santa Cruz (US), Krakow and Glasgow is now turning its attention to more complex issues such as how the retina gets wired up and how the brain deals with the signals it receives from the retina. All this using technology derived from high-density, multistrip silicon detectors…   Seen from the point of view of a particle physicist, eyes are image detectors that can gather many different types of data: light and dark, different colours, motion, etc. In particular, the retina, a thin tissue that lines the back of the eye, is a biological pixel detector that detects light and converts it to electrical signals that travel through the optic nerve to the brain. Neurobiologists know that many different cell types are involved in these processes, but they...

  15. The Analysis of Artificial Retina Organization for Signal Processing

    Institute of Scientific and Technical Information of China (English)

    WEIHui

    2004-01-01

    Machine vision is an active branch of artificial intelligence. An important problem in this area is the trade-off among efficiency, accuracy and computation complexity. The human visual system can keep watchfulness to the perimeter of a viewing field while at the same time focus on the center of the field for fine information processing. This mechanism of appropriate assignment of computing resources can reduce the demand for huge and complex hardware structure. Therefore, the design of a computer model based on the biological visual mechanism is an effective approach to resolve problems in machine vision. In this paper, a multi-layer neural model is developed based on the features of receptive field of ganglion in retina to simulate multi-scale perceptive fields of ganglion cell. The neural model can maintain alert on the outer area of the image while capturing and processing more important information in the central part. It may provide valuable inspiration for the implementation of real-time processing and avoidance of huge computation in machine vision.

  16. HMGB1 promotes the development of pulmonary arterial hypertension in rats.

    Directory of Open Access Journals (Sweden)

    Yukari Sadamura-Takenaka

    Full Text Available Pulmonary arterial hypertension (PAH is characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. However, the molecular and cellular mechanisms driving inflammation have not been fully elucidated.To elucidate the roles of high mobility group box 1 protein (HMGB1, a ubiquitous DNA-binding protein with extracellular pro-inflammatory activity, in a rat model of PAH.Male Sprague-Dawley rats were administered monocrotaline (MCT. Concentrations of HMGB1 in bronchoalveolar lavage fluid (BALF and serum, and localization of HMGB1 in the lung were examined over time. The protective effects of anti-HMGB1 neutralizing antibody against MCT-induced PAH were tested.HMGB1 levels in BALF were elevated 1 week after MCT injection, and this elevation preceded increases of other pro-inflammatory cytokines, such as TNF-α, and the development of PAH. In contrast, serum HMGB1 levels were elevated 4 weeks after MCT injection, at which time the rats began to die. Immunohistochemical analyses indicated that HMGB1 was translocated to the extranuclear space in periarterial infiltrating cells, alveolar macrophages, and bronchial epithelial cells of MCT-injected rats. Anti-HMGB1 neutralizing antibody protected rats against MCT-induced lung inflammation, thickening of the pulmonary artery wall, and elevation of right ventricular systolic pressure, and significantly improved the survival of the MCT-induced PAH rats.Our results identify extracellular HMGB1 as a promoting factor for MCT-induced PAH. The blockade of HMGB1 activity improved survival of MCT-induced PAH rats, and thus might be a promising therapy for the treatment of PAH.

  17. Regulation of glutamate dehydrogenase expression in the developing rat liver: control at different levels in the prenatal period

    NARCIS (Netherlands)

    Das, A. T.; Salvadó, J.; Boon, L.; Biharie, G.; Moorman, A. F.; Lamers, W. H.

    1996-01-01

    To study the regulation of the expression of glutamate dehydrogenase (Glu-DH) in rat liver during development, the Glu-DH mRNA concentration in the liver of rats ranging in age from 14 days prenatal development to 3 months after birth was determined. This concentration increased up to two days

  18. Disrupted social development enhances the motivation for cocaine in rats

    NARCIS (Netherlands)

    Baarendse, P.J.J.; Limpens, J.H.W.; Vanderschuren, L.J.M.J.|info:eu-repo/dai/nl/126514917

    2014-01-01

    for behavioural development. In particular, social play behaviour during post-weaning development is thought to facilitate the attainment of social, emotional and cognitive capacities. Conversely, social insults during development can cause longlasting behavioural impairments and increase the

  19. Chronic intermittent hyperoxia alters the development of the hypoxic ventilatory response in neonatal rats.

    Science.gov (United States)

    Logan, Sarah; Tobin, Kristina E; Fallon, Sarah C; Deng, Kevin S; McDonough, Amy B; Bavis, Ryan W

    2016-01-01

    Chronic exposure to sustained hyperoxia alters the development of the respiratory control system, but the respiratory effects of chronic intermittent hyperoxia have rarely been investigated. We exposed newborn rats to short, repeated bouts of 30% O2 or 60% O2 (5 bouts h(-1)) for 4-15 days and then assessed their hypoxic ventilatory response (HVR; 10 min at 12% O2) by plethysmography. The HVR tended to be enhanced by intermittent hyperoxia at P4 (early phase of the HVR), but it was significantly reduced at P14-15 (primarily late phase of the HVR) compared to age-matched controls; the HVR recovered when individuals were returned to room air and re-studied as adults. To investigate the role of carotid body function in this plasticity, single-unit carotid chemoafferent activity was recorded in vitro. Intermittent hyperoxia tended to decrease spontaneous action potential frequency under normoxic conditions but, contrary to expectations, hypoxic responses were only reduced at P4 (not at P14) and only in rats exposed to higher O2 levels (i.e., intermittent 60% O2). Rats exposed to intermittent hyperoxia had smaller carotid bodies, and this morphological change may contribute to the blunted HVR. In contrast to rats exposed to intermittent hyperoxia beginning at birth, two weeks of intermittent 60% O2 had no effect on the HVR or carotid body size of rats exposed beginning at P28; therefore, intermittent hyperoxia-induced respiratory plasticity appears to be unique to development. Although both intermittent and sustained hyperoxia alter carotid body development and the HVR of rats, the specific effects and time course of this plasticity differs. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Expression and function of Delta-like ligand 4 in a rat model of retinopathy of prematurity

    Institute of Scientific and Technical Information of China (English)

    Shaoyang Shi; Xun Li; You Li; Cunwen Pei; Hongwei Yang; Xiaolong Chen

    2013-01-01

    The Delta-like ligand 4/Notch signaling pathway was shown to participate in the process of retinal development and angiogenesis. However, the function of the Delta-like ligand 4/Notch signaling pathway in retinopathy of prematurity requires further study. Retinopathy of prematurity was induced in 5-day-old Sprague-Dawley rats exposed to hyperoxia for 7 days, and then returned to room air. Reverse transcription-PCR and western blot revealed that Delta-like ligand 4 levels decreased at postnatal day 12 and increased at postnatal day 17 in retinopathy of prematurity rats. Flat-mounted adenosine diphosphatase stained retina and hematoxylin-eosin stained retinal tissue slices showed that the clock hour scores and the nuclei counts in retinopathy of prematurity rats were significantly different compared to normal control rats. After retinopathy of prematurity rats were intravitreally injected with Delta-like ligand 4 monoclonal antibody to inhibit the Delta-like ligand 4/Notch signaling pathway, there was a significant increase in the severity of retinal neovascularization (clock hours) in the intravitreally injected eyes. The nuclei count was highly correlated with the clock hour score. These results suggest that Delta-like ligand 4/Notch signaling plays an essential role in the process of physiological and pathological angiogenesis in the retina.

  1. Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina.

    Directory of Open Access Journals (Sweden)

    Hideto Osada

    Full Text Available Excessive exposure to light promotes degenerative and blinding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. However, the underlying mechanisms of photo-induced retinal degeneration are not fully understood, and a generalizable preventive intervention has not been proposed. Bilberry extract is an antioxidant-rich supplement that ameliorates ocular symptoms. However, its effects on photo-stressed retinas have not been clarified. In this study, we examined the neuroprotective effects of bilberry extract against photo-stress in murine retinas. Light-induced visual function impairment recorded by scotopic and phototopic electroretinograms showing respective rod and cone photoreceptor function was attenuated by oral administration of bilberry extract through a stomach tube in Balb/c mice (750 mg/kg body weight. Bilberry extract also suppressed photo-induced apoptosis in the photoreceptor cell layer and shortening of the outer segments of rod and cone photoreceptors. Levels of photo-induced reactive oxygen species (ROS, oxidative and endoplasmic reticulum (ER stress markers, as measured by real-time reverse transcriptase polymerase chain reaction, were reduced by bilberry extract treatment. Reduction of ROS by N-acetyl-L-cysteine, a well-known antioxidant also suppressed ER stress. Immunohistochemical analysis of activating transcription factor 4 expression showed the presence of ER stress in the retina, and at least in part, in Müller glial cells. The photo-induced disruption of tight junctions in the retinal pigment epithelium was also attenuated by bilberry extract, repressing an oxidative stress marker, although ER stress markers were not repressed. Our results suggest that bilberry extract attenuates photo-induced apoptosis and visual dysfunction most likely, and at least in part, through ROS reduction, and subsequent ER stress attenuation in the retina. This study can help understand the mechanisms of photo

  2. Development of pulmonary oxygen toxicity in rats after hyperoxic exposure

    Directory of Open Access Journals (Sweden)

    Siermontowski Piotr

    2014-06-01

    Full Text Available The aim of the study was to examine the effects of hyperbaric oxygen on lung aeration on an animal experimental model and compare the obtained results with the anticipated scope of damage to pulmonary parenchyma in humans under the same exposure conditions. The research was carried out on Black Hood rats that were kept in a hyperbaric chamber designed for animals in an atmosphere of pure oxygen and at overpressures of 0.15, 0.2, 0.3, 0.4, and 0.5 MPa for 1, 2 or 4 h. After sacrificing the animals, histopathological specimens were obtained encompassing cross-sections of entire lungs, which were subjected to qualitative and quantitative examination with the use of the 121-point Haug grid. A statistically significant decrease in pulmonary parenchyma was observed as a result of an increasing oxygen partial pressure as well as with prolonged exposure time. The intensification of changes observed was much higher than expected on the basis of calculations performed with the use of tables.

  3. Non-mydriatic video ophthalmoscope to measure fast temporal changes of the human retina

    Science.gov (United States)

    Tornow, Ralf P.; Kolář, Radim; Odstrčilík, Jan

    2015-07-01

    The analysis of fast temporal changes of the human retina can be used to get insight to normal physiological behavior and to detect pathological deviations. This can be important for the early detection of glaucoma and other eye diseases. We developed a small, lightweight, USB powered video ophthalmoscope that allows taking video sequences of the human retina with at least 25 frames per second without dilating the pupil. Short sequences (about 10 s) of the optic nerve head (20° x 15°) are recorded from subjects and registered offline using two-stage process (phase correlation and Lucas-Kanade approach) to compensate for eye movements. From registered video sequences, different parameters can be calculated. Two applications are described here: measurement of (i) cardiac cycle induced pulsatile reflection changes and (ii) eye movements and fixation pattern. Cardiac cycle induced pulsatile reflection changes are caused by changing blood volume in the retina. Waveform and pulse parameters like amplitude and rise time can be measured in any selected areas within the retinal image. Fixation pattern ΔY(ΔX) can be assessed from eye movements during video acquisition. The eye movements ΔX[t], ΔY[t] are derived from image registration results with high temporal (40 ms) and spatial (1,86 arcmin) resolution. Parameters of pulsatile reflection changes and fixation pattern can be affected in beginning glaucoma and the method described here may support early detection of glaucoma and other eye disease.

  4. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

    DEFF Research Database (Denmark)

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie

    2015-01-01

    Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action. Pregnant rat dams were exposed during gestation and lactation to mixtures...

  5. Effects of prenatal exposure to toluene on postnatal development and behavior in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Hass, Ulla; Lund, S. P.

    1999-01-01

    Development and neurobehavioral effects of prenatal exposure to toluene (CAS 108-88-3) were studied after exposing pregnant rats (Mol:WIST) to 1800 ppm of the solvent for 6 h daily on days 7-20 of gestation. Body weights of exposed offspring were lower until day 10 after parturition. Neurobehavio...

  6. Selenium prevents tumor development in a rat model for chemical carcinogenesis

    DEFF Research Database (Denmark)

    Bjorkhem-Bergman, L.; Torndal, U. B.; Eken, S.

    2005-01-01

    Previous studies in animals and humans have shown that selenium compounds can prevent cancer development. In this work we studied the tumor preventive effect of selenium supplementation, administrated as selenite, in the initiation, promotion and progression phases in a synchronized rat model for...

  7. Cortical interhemispheric responses to rhythmic stimulation are influenced by status epilepticus in developing rats

    Czech Academy of Sciences Publication Activity Database

    Tsenov, Grygoriy; Mareš, Pavel

    2005-01-01

    Roč. 46, č. S6 (2005), s. 209-210 ISSN 0013-9580. [International Epilepsy Congress /26./. 28.08.2005-01.09.2005, Paris] Institutional research plan: CEZ:AV0Z50110509 Keywords : status epilepticus * interhemispheric responses * developing rats Subject RIV: ED - Physiology

  8. Influence of age and immunization on development of gingivitis in rats

    DEFF Research Database (Denmark)

    Lekic, P; Klausen, B; Friis-Hasché, E

    1989-01-01

    To study the effect of age and antigenic priming on the development of gingivitis, 33 healthy rats were placed in contact with Streptococcus mutans, Actinomyces viscosus, Fusobacterium nucleatum, and Bacteroides gingivalis. On days 0, 3, 7, and 14 after inoculation, the gingival condition...

  9. Postnatal development and behaviour of Wistar rats after prenatal toluene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thiel, R. [Fachbereich Humanmedizin, Universitaetsklinikum Benjamin Franklin, Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany); Chahoud, I. [Fachbereich Humanmedizin, Universitaetsklinikum Benjamin Franklin, Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany)

    1997-02-01

    Pregnant Wistar rats were treated with different concentrations of toluene by inhalation (300, 600, 1000 and 1200 ppm) from day 9 to day 21 of pregnancy for 6 h a day in a whole-body inhalation chamber (controls inhaled fresh air only). From day 22, rats were kept single-caged and were allowed to deliver. Besides a detailed evaluation of the physical development of the offspring we performed the following tests: forelimb-grasp reflex, righting reflex, cliff-drop aversion reflex, maintainance of balance on a rotating rod, measurement of locomotor activity and learning ability in a discrimination learning test. A toluene exposure of 1200 ppm resulted in a reduced body weight of rat dams and offspring and a higher mortality until weaning. The physical development (incisor eruption, eye opening and vaginal opening) was retarded in this group. There were no clear-cut and concentration-dependent differences in the development of reflexes, rota rod performance and locomotor activity between the offspring of animals exposed to toluene and the controls. Likewise, no effects were found on learning ability in the operant conditioning task. Compared to the controls there were no differences in mating, fertility and pregnancy indexes in the F{sub 1}-generation. The tests performed have provided no evidence that toluene exposures {<=} 1200 ppm induce adverse effects on the behaviour of rat offspring exposed during late embryonic and fetal development. (orig.). With 8 figs., 7 tabs.

  10. Effects of metabotropic glutamate receptor 5 antagonist MPEP on learning in developing rats

    Czech Academy of Sciences Publication Activity Database

    Mikulecká, Anna; Mareš, Pavel

    2007-01-01

    Roč. 18, Suppl. 1 (2007), S48-S48 ISSN 0955-8810. [Biennial Meeting of the European Behavioural Pharmacology Society /12./. 31.08.2007-03.09.2007, Tübingen] Institutional research plan: CEZ:AV0Z50110509 Keywords : MPEP * developing rats * behavioral parameters Subject RIV: ED - Physiology

  11. Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, Jiří; Vytášek, Richard; Uhlík, Jiří; Vajner, Luděk

    2016-01-01

    Roč. 2016, č. 2016 (2016), č. článku 5057610. ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP303/11/0298 Institutional support: RVO:67985823 Keywords : oxidative stress * developing rat brain * lipid peroxidation Subject RIV: ED - Physiology Impact factor: 4.593, year: 2016

  12. IPRODIONE DELAYS MALE RAT PUBERTAL DEVELOPMENT, REDUCING SERUM TESTOSTERONE AND EX VIVO TESTOSTERONE PRODUCTION

    Science.gov (United States)

    Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to the androgen receptor (AR) antagonist vinclozolin. The current studies were designed to determine if IPRO would delay male rat pubertal development like vinclozolin and to identify the mechanism(s) of action...

  13. Extinction, Reacquisition, and Rapid Forgetting of Eyeblink Conditioning in Developing Rats

    Science.gov (United States)

    Brown, Kevin L.; Freeman, John H.

    2014-01-01

    Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory. However, age differences in extinction and subsequent reacquisition have yet to be studied using this model. The present study examined extinction and reacquisition of eyeblink conditioning in developing rats. In…

  14. Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

    Science.gov (United States)

    Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

    2006-05-01

    The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

  15. Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity

    Directory of Open Access Journals (Sweden)

    Ploj Karolina

    2005-09-01

    Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance. Methods Our objectives in this study were (1 to estimate sympathetic-adrenal medullary (SAM activity by measuring mean systolic blood pressure (MSAP in rats with estradiol valerate (EV-induced PCO; (2 to estimate alpha1a and alpha2a adrenoceptor expression in a brain area thought to mediate central effects on MSAP regulation and in the adrenal medulla; (3 to assess hypothalamic-pituitary-adrenal (HPA axis regulation by measuring adrenocorticotropic hormone (ACTH and corticosterone (CORT levels in response to novel-environment stress; and (4 to measure abdominal obesity, sex steroids, and insulin sensitivity. Results The PCO rats had significantly higher MSAP than controls, higher levels of alpha1a adrenoceptor mRNA in the hypothalamic paraventricular nucleus (PVN, and lower levels of alpha2a adrenoceptor mRNA in the PVN and adrenal medulla. After exposure to stress, PCO rats had higher ACTH and CORT levels. Plasma testosterone concentrations were lower in PCO rats, and no differences in insulin sensitivity or in the weight of intraabdominal fat depots were found. Conclusion Thus, rats with EV-induced PCO develop hypertension and increased sympathetic and HPA-axis activity without reduced insulin sensitivity, obesity, or hyperandrogenism. These findings may have implications for mechanisms underlying hypertension in PCOS.

  16. Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Kaneko, Mika K; Nakamura, Takuro; Ichii, Osamu; Konnai, Satoru; Kato, Yukinari

    2017-04-01

    Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG 2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG 2a , which was derived from rat PMab-1 mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.

  17. Disturbed sensorimotor and electrophysiological patterns in lead intoxicated rats during development are restored by curcumin I.

    Directory of Open Access Journals (Sweden)

    Hind Benammi

    Full Text Available Lead poisoning is one of the most significant health problem of environmental origin. It is known to cause different damages in the central and peripheral nervous system which could be represented by several neurophysiological and behavioral symptoms. In this study we firstly investigated the effect of lead prenatal exposure in rats to (3g/L, from neonatal to young age, on the motor/sensory performances, excitability of the spinal cord and gaits during development. Then we evaluated neuroprotective effects of curcumin I (Cur I against lead neurotoxicity, by means of grasping and cliff avoidance tests to reveal the impairment of the sensorimotor functions in neonatal rats exposed prenatally to lead. In addition, extracellular recordings of motor output in spinal cord revealed an hyper-excitability of spinal networks in lead treated rats. The frequency of induced fictive locomotion was also increased in treated rats. At the young age, rats exhibited an impaired locomotor gait. All those abnormalities were attenuated by Cur I treatment at a dose of 16g/kg. Based on our finding, Cur I has shown features of a potent chemical compound able to restore the neuronal and the relative locomotor behaviors disturbances induced by lead intoxication. Therefore, this chemical can be recommended as a new therapeutic trial against lead induced neurotoxicity.

  18. Effects of combined exposure to anti-androgens on development and sexual dimorphic behaviour in rats

    DEFF Research Database (Denmark)

    Christiansen, Sofie

    Summary Background: Androgens are key regulators of male sexual differentiation during the in utero and early postnatal development. Exposure to endocrine disrupting chemicals (EDCs) that counteract androgen action at some stage in these periods can permanently demasculinise male foetuses and lead......?  Is sexually dimorphic behaviour in rats affected at lower dose levels of anti-androgens and thereby a more sensitive endpoint than morphological effects on the male external reproductive organs? The thesis is based on the results of in vivo studies where mated female Wistar rats were exposed to anti......-androgens either alone or in mixtures during pregnancy and lactation. The endpoints examined for anti-androgenic effects in the offspring were: Anogenital distance (AGD), nipple retention (NR), and external (morphological) malformations in pups and sexually mature male rats. Furthermore, the effects of the anti...

  19. [Lattice degeneration of the peripheral retina: ultrastructural study].

    Science.gov (United States)

    Bec, P; Malecaze, F; Arne, J L; Mathis, A

    1985-01-01

    The ultrastructural study of a case of snail track degeneration shows the presence of lipid inclusions in both the glial and the macrophage cells in every layer of the retina, and the existence of intraretinal fibers different from collagen fibers appearing to be glial filaments similar to those found in astrocytic gliomes and to the Rosenthal fibers observed in senile nervous cells. Other features were thinning of the retina and absence of blood vessels in the retina. There are no abnormalities of the vitreo-retinal juncture. All the lesions are in agreement with those observed by Daicker [Ophthalmologica, Basel 165: 360-365, 1972; Klin. Mbl. Augenheilk. 172: 581-583, 1978] with some differences, however. They are different from those found in lattice degeneration. They show that snail track degeneration is a specific form of peripheral retinal degeneration which is quite different from lattice degeneration and must not be considered similar.

  20. Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas.

    Science.gov (United States)

    Zhang, Lin; Chen, Wei; Dai, Yuee; Zhu, Ziyang; Liu, Qianqi

    2016-07-01

    Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. © 2016 by the Society for Experimental Biology and Medicine.

  1. Effects of iron supplementation on growth, gut microbiota, metabolomics and cognitive development of rat pups.

    Directory of Open Access Journals (Sweden)

    Erica E Alexeev

    Full Text Available Iron deficiency is common during infancy and therefore iron supplementation is recommended. Recent reports suggest that iron supplementation in already iron replete infants may adversely affect growth, cognitive development, and morbidity.Normal and growth restricted rat pups were given iron daily (30 or 150 μg/d from birth to postnatal day (PD 20, and followed to PD56. At PD20, hematology, tissue iron, and the hepatic metabolome were measured. The plasma metabolome and colonic microbial ecology were assessed at PD20 and PD56. T-maze (PD35 and passive avoidance (PD40 tests were used to evaluate cognitive development.Iron supplementation increased iron status in a dose-dependent manner in both groups, but no significant effect of iron on growth was observed. Passive avoidance was significantly lower only in normal rats given high iron compared with controls. In plasma and liver of normal and growth-restricted rats, excess iron increased 3-hydroxybutyrate and decreased several amino acids, urea and myo-inositol. While a profound difference in gut microbiota of normal and growth-restricted rats was observed, with iron supplementation differences in the abundance of strict anaerobes were observed.Excess iron adversely affects cognitive development, which may be a consequence of altered metabolism and/or shifts in gut microbiota.

  2. Studies on the postnatal development of the rat liver plasma membrane following maternal ethanol ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Rovinski, B

    1984-01-01

    Studies on the developing rat liver and on the structure and function of the postnatal rat liver plasma membrane were carried out following maternal consumption of alcohol during pregnancy and lactation. A developmental study of alcohol dehydrogenase (ADH) indicated that both the activity and certain kinetic properties of the enzyme from the progeny of alcohol-fed and pair-fed mothers were similar. Fatty liver, however, developed in the alcoholic progeny only after ADH appeared on a day 19 of gestation. Further studies on structural and functional changes were then undertaken on the postnatal development of the rat liver plasma membrane. Radioligand binding studies performed using the hapatic alpha{sub 1}-adrenergic receptor as a plasma membrane probe demonstrated a significant decrease in receptor density in the alcoholic progeny, but no changes in binding affinity. Finally, the fatty acid composition of constituent phospholipids and the cholesterol content of rat liver plasma membranes were determined. All these observations suggest that membrane alterations in the newborn may be partially responsible for the deleterious action(s) of maternal alcoholism at the molecular level.

  3. Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

    Science.gov (United States)

    Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

    2015-04-01

    Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

  4. Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

    Science.gov (United States)

    Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

    2016-09-01

    Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

  5. Image Signal Transfer Method in Artificial Retina using Laser

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, I.Y.; Lee, B.H.; Kim, S.J. [Seoul National University, Seoul (Korea)

    2002-05-01

    Recently, the research on artificial retina for the blind is active. In this paper a new optical link method for the retinal prosthesis is proposed. Laser diode system was chosen to transfer image into the eye in this project and the new optical system was designed and evaluated. The use of laser diode array in artificial retina system makes system simple for lack of signal processing part inside of the eyeball. Designed optical system is enough to focus laser diode array on photodiode array in 20X20 application. (author). 11 refs., 7 figs., 2 tabs.

  6. Retina-like sensor image coordinates transformation and display

    Science.gov (United States)

    Cao, Fengmei; Cao, Nan; Bai, Tingzhu; Song, Shengyu

    2015-03-01

    For a new kind of retina-like senor camera, the image acquisition, coordinates transformation and interpolation need to be realized. Both of the coordinates transformation and interpolation are computed in polar coordinate due to the sensor's particular pixels distribution. The image interpolation is based on sub-pixel interpolation and its relative weights are got in polar coordinates. The hardware platform is composed of retina-like senor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes the real-time image acquisition, coordinate transformation and interpolation.

  7. EVALUATION OF INHOMOGENEITIES IN HISTOLOGICAL STRUCTURES (CARTILAGE, RETINA

    Directory of Open Access Journals (Sweden)

    Lutz Muche

    2011-05-01

    Full Text Available This paper investigates histological tissues by means of image analysis and spatial statistics. For the quantification of cell frequencies and accumulations two statistical characteristics, intensity function and cluster density, are suggested. The samples are histological sections of human articular cartilage and human retina considered in view of changes during the ageing process. The articular cartilage is characterized by continuous changes of both functions, the cell intensity as well as the clusterization. In contrast, the retina is a trilaminar structure formed in the early embryonic stage without changes by ageing.

  8. Functional characterization of rs2229094 (T>C polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project

    Directory of Open Access Journals (Sweden)

    Pastor-Idoate S

    2017-05-01

    Full Text Available Salvador Pastor-Idoate,1,2 Irene Rodríguez-Hernández,2,3 Jimena Rojas,1 Lucia Gonzalez-Buendia,1 Santiago Delgado-Tirado,1,4 Jose Carlos López,1 Rogelio González-Sarmiento,2,3 Jose C Pastor1,4 1IOBA Eye Institute, University of Valladolid, Valladolid, 2Molecular Medicine Unit, Department of Medicine, 3Molecular and Cellular Cancer Biology Institute, High Council of Scientific Research, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, 4Department of Ophthalmology, Hospital Clínico Universitario, Valladolid, Spain Purpose: The objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R (T>C, previously associated with proliferative vitreoretinopathy (PVR development.Materials and methods: Total RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD and three healthy control eyes were subjected to immunohistochemistry (IHC with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed.Results: RT-PCR analysis revealed no significant levels of messenger RNA (mRNA LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells.Conclusion: Although results suggest lack of functionality, the differences found in IHC study and its strong association

  9. Activation of the Nrf2/HO-1 Antioxidant Pathway Contributes to the Protective Effects of Lycium Barbarum Polysaccharides in the Rodent Retina after Ischemia-Reperfusion-Induced Damage

    Science.gov (United States)

    Chang, Raymond Chuen-Chung; So, Kwok-Fai; Brecha, Nicholas C.; Pu, Mingliang

    2014-01-01

    Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are protective to retina after ischemia-reperfusion (I/R). The antioxidant response element (ARE)–mediated antioxidant pathway plays an important role in maintaining the redox status of the retina. Heme oxygenase-1 (HO-1), combined with potent AREs in its promoter, is a highly effective therapeutic target for the protection against neurodegenerative diseases, including I/R-induced retinal damage. The aim of our present study was to investigate whether the protective effect of LBP after I/R damage was mediated via activation of the Nrf2/HO-1-antioxidant pathway in the retina. Retinal I/R was induced by an increase in intraocular pressure to 130 mm Hg for 60 minutes. Prior to the induction of ischemia, rats were orally treated with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. For specific experiments, zinc protoporphyrin (ZnPP, 20 mg/kg), an HO-1 inhibitor, was intraperitoneally administered at 24 h prior to ischemia. The protective effects of LBP were evaluated by quantifying ganglion cell and amacrine cell survival, and by measuring cell apoptosis in the retinal layers. In addition, HO-1 expression was examined using Western blotting and immunofluorescence analyses. Cytosolic and nuclear Nrf2 was measured using immunofluorescent staining. LBP treatment significantly increased Nrf2 nuclear accumulation and HO-1 expression in the retina after I/R injury. Increased apoptosis and a decrease in the number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment. The HO-1 inhibitor, ZnPP, diminished the LBP treatment-induced protective effects in the retina after I/R. Taken together, these results suggested that LBP partially exerted its beneficial neuroprotective effects via the activation of Nrf2 and an increase in HO-1 protein expression. PMID:24400114

  10. Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

    Directory of Open Access Journals (Sweden)

    Saito Felipe H

    2010-04-01

    Full Text Available Abstract Background Experimental models are necessary to elucidate diabetes pathophysiological mechanisms not yet understood in humans. Objective: To evaluate the repercussions of the mild diabetes, considering two methodologies, on the pregnancy of Wistar rats and on the development of their offspring. Methods In the 1st induction, female offspring were distributed into two experimental groups: Group streptozotocin (STZ, n = 67: received the β-cytotoxic agent (100 mg STZ/kg body weight - sc on the 1st day of the life; and Non-diabetic Group (ND, n = 14: received the vehicle in a similar time period. In the adult life, the animals were mated. After a positive diagnosis of pregnancy (0, female rats from group STZ presenting with lower glycemia than 120 mg/dL received more 20 mg STZ/kg (ip at day 7 of pregnancy (2nd induction. The female rats with glycemia higher than 120 mg/dL were discarded because they reproduced results already found in the literature. In the mornings of days 0, 7, 14 and 21 of the pregnancy glycemia was determined. At day 21 of pregnancy (at term, the female rats were anesthetized and killed for maternal reproductive performance and fetal development analysis. The data were analyzed using Student-Newman-Keuls, Chi-square and Zero-inflated Poisson (ZIP Tests (p Results STZ rats presented increased rates of pre (STZ = 22.0%; ND = 5.1% and post-implantation losses (STZ = 26.1%; ND = 5.7%, reduced rates of fetuses with appropriate weight for gestational age (STZ = 66%; ND = 93% and reduced degree of development (ossification sites. Conclusion Mild diabetes led a negative impact on maternal reproductive performance and caused intrauterine growth restriction and impaired fetal development.

  11. Motor System Development Depends on Experience: A Microgravity Study of Rats

    Science.gov (United States)

    Walton, Kerry D.; Llinas, Rodolfo R.; Kalb, Robert; Hillman, Dean; DeFelipe, Javier; Garcia-Segura, Luis Miguel

    2003-01-01

    Animals move about their environment by sensing their surroundings and making adjustments according to need. All animals take the force of gravity into account when the brain and spinal cord undertake the planning and execution of movements. To what extent must animals learn to factor in the force of gravity when making neural calculations about movement? Are animals born knowing how to respond to gravity, or must the young nervous system learn to enter gravity into the equation? To study this issue, young rats were reared in two different gravitational environments (the one-G of Earth and the microgravity of low Earth orbit) that necessitated two different types of motor operations (movements) for optimal behavior. We inquired whether those portions of the young nervous system involved in movement, the motor system, can adapt to different gravitational levels and, if so, the cellular basis for this phenomenon. We studied two groups of rats that had been raised for 16 days in microgravity (eight or 14 days old at launch) and compared their walking and righting (ability to go from upside down to upright) and brain structure to those of control rats that developed on Earth. Flight rats were easily distinguished from the age-matched ground control rats in terms of both motor function and central nervous system structure. Mature surface righting predominated in control rats on the day of landing (R+O), while immature righting predominated in the flight rats on landing day and 30 days after landing. Some of these changes appear to be permanent. Several conclusions can be drawn from these studies: (1) Many aspects of motor behavior are preprogrammed into the young nervous system. In addition, several aspects of motor behavior are acquired as a function of the interaction of the developing organism and the rearing environment; (2) Widespread neuroanatomical differences between one-G- and microgravity-reared rats indicate that there is a structural basis for the adaptation

  12. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    International Nuclear Information System (INIS)

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-01-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

  13. Artificial Retina Project: Final Report for CRADA ORNL 01-0625

    Energy Technology Data Exchange (ETDEWEB)

    Greenbaum, E; Little, J [Second Sight Medical Products

    2011-09-01

    The U.S. Department of Energy’s Artificial Retina Project is a collaborative, multi-institutional effort to develop an implantable microelectronic retinal prosthesis that restores useful vision to people blinded by retinal diseases. The ultimate goal of the project is to restore reading ability, facial recognition, and unaided mobility in people with retinitis pigmentosa and age-related macular degeneration. The project taps into the unique research technologies and resources developed at DOE national laboratories to surmount the many technical challenges involved with developing a safe, effective, and durable product. The research team includes six DOE national laboratories, four universities, and private industry.

  14. Altered placental development in undernourished rats: role of maternal glucocorticoids

    Directory of Open Access Journals (Sweden)

    Chen Chun-Hung

    2011-08-01

    Full Text Available Abstract Maternal undernutrition (MUN during pregnancy may lead to fetal intrauterine growth restriction (IUGR, which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1, 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1 predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC to corticosterone, although can sometimes drive the opposing (inactivating reaction, and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents in control and MUN rats at embryonic day 20 (E20. Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3 and amino acids (SLC38A1, 2, and 4. Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC

  15. Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract

    Directory of Open Access Journals (Sweden)

    Madhoosudan A. Patil

    2014-01-01

    Full Text Available Type 2 diabetes (T2D generally follows prediabetes (PD conditions such as impaired fasting glucose (IFG and/or impaired glucose tolerance (IGT. Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70% of nSTZ injected pups developed IGT (nSTZ-PD by two months but not cataract even after seven months, remaining (30% nSTZ rats developed hyperglycemia (nSTZ-D by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities.

  16. Effect of Marine Collagen Peptides on Physiological and Neurobehavioral Development of Male Rats with Perinatal Asphyxia

    Directory of Open Access Journals (Sweden)

    Linlin Xu

    2015-06-01

    Full Text Available Asphyxia during delivery produces long-term deficits in brain development. We investigated the neuroprotective effects of marine collagen peptides (MCPs, isolated from Chum Salmon skin by enzymatic hydrolysis, on male rats with perinatal asphyxia (PA. PA was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 15 min. Caesarean-delivered pups were used as controls. PA rats were intragastrically administered with 0.33 g/kg, 1.0 g/kg and 3.0 g/kg body weight MCPs from postnatal day 0 (PND 0 till the age of 90-days. Behavioral tests were carried out at PND21, PND 28 and PND 90. The results indicated that MCPs facilitated early body weight gain of the PA pups, however had little effects on early physiological development. Behavioral tests revealed that MCPs facilitated long-term learning and memory of the pups with PA through reducing oxidative damage and acetylcholinesterase (AChE activity in the brain, and increasing hippocampus phosphorylated cAMP-response element binding protein (p-CREB and brain derived neurotrophic factor (BDNF expression.

  17. Gross hepatic changes in developing albino rats exposed to valproic acid

    International Nuclear Information System (INIS)

    Khan, M.; Khattak, S.T.; Elahi, M.

    2011-01-01

    Background: Valproid Acid (VPA) is a broad spectrum antiepileptic drug. Its use during pregnancy has been associated with congenital anomalies and hepatotoxicity. This study was designed to assess the effects of VPA on the gross structure of liver in developing albino rats exposed to the drug during various trimesters of pregnancy. Methods: In this experimental study 40 pregnant rats were divided into 4 equal groups A, B, C and D. Group A received VPA in a dose of 500 mg/Kg/day intraperitonealy (I/P) on days 3, 4 and 5 of gestation. Group B received the drug in a dose of 500 mg/Kg/day I/P on days 8, 9 and 10 of gestation. Group C received VPA in a dose of 500 mg/Kg/day I/P on days 16, 17 and 18 of gestation. Group D received no treatment and was kept as a control group. On day 21, the rats were euthanised by cervical dislocation. The liver of the foetuses were dissected out for the assessment of their gross structure. Results: Foetal liver of the experimental groups showed significant decrease in weight as well as relative tissue weight index (RTWI) as compared to the control group, although the gross appearance of the foetal liver was normal in all the groups. Conclusion: The use of VPA during various trimesters of pregnancy produces hepatotoxicity in the developing rats. So, the use of this drug during pregnancy should be carefully decided. (author)

  18. Protective effect of pomegranate juice on retinal oxidative stress in streptozotocin-induced diabetic rats

    OpenAIRE

    Betul Tugcu; Senay Asik Nacaroglu; Asuman Gedikbasi; Mehmet Uhri; Nur Acar; Hakan Ozdemir

    2017-01-01

    AIM: To investigate the effect of pomegranate juice (PJ) intake on overall oxidation status in retinas of diabetic rats. METHODS: Twenty-seven rats were divided into four groups as control (CO), diabetic (DM), control treated with PJ (CO-PJ), and diabetic treated with PJ (DM-PJ).The retina tissues were used to determine 8-hydroxy-2’-deoxyguanosine (8OHdG), malondialdehyde (MDA), reduced glutathione (GSH) levels, and the enzyme activities of superoxide dismutase (SOD) and glutathione peroxi...

  19. GENE EXPRESSION PROFILES IN THE DEVELOPING RAT CEREBELLUM AND HIPPOCAMPUS

    Science.gov (United States)

    Development of the nervous system is a complex program, involving coordinated growth of axons and their targets. In rodents, rapid brain growth occurs during early postnatal development. At this time, several fundamental processes, such as dendritic and axonal outgrowth and the e...

  20. Development and adaptation to resection of infant rat gut

    NARCIS (Netherlands)

    J.E. de Vries

    1982-01-01

    textabstractInfants with malrotation of the gut easily develop midgut volvuluse If this volvulus is not treated immediately, ischemic necrosis of the small bowel may develop rapidly. The treatment of these children requires extensive small bowel resection. Infrequently, children are born with

  1. Endogenous synthesis of taurine and GABA in rat ocular tissues

    Energy Technology Data Exchange (ETDEWEB)

    Heinaemaeki, A.A.

    1988-01-01

    The endogenous production of taurine and ..gamma..-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine on the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye.

  2. Endogenous synthesis of taurine and GABA in rat ocular tissues

    International Nuclear Information System (INIS)

    Heinaemaeki, A.A.

    1988-01-01

    The endogenous production of taurine and γ-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine on the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye. (author)

  3. The importance of dietary control in the development of a peanut allergy model in Brown Norway rats

    NARCIS (Netherlands)

    Jonge, J.D. de; Knippels, L.M.J.; Ezendam, J.; Odink, J.; Penninks, A.H.; Loveren, H. van

    2007-01-01

    This report describes the further development of a peanut allergy model in Brown Norway (BN) rats and in particular the importance of allergen-free breeding of the laboratory animals for the allergen to be used. For this purpose BN rats were bred for 3 generations on soy- and peanut-free feed since

  4. Cytomegalovirus-enhanced development of transplant arteriosclerosis in the rat; effect of timing of infection and recipient responsiveness

    NARCIS (Netherlands)

    Hillebrands, JL; van Dam, JG; Onuta, G; Klatter, FA; Grauls, G; Bruggeman, CA; Rozing, J

    Cytomegalovirus (CMV) is put forward as a risk factor for transplant arteriosclerosis (TA). In this article, we studied CMV-enhanced development of TA in rats in different donor/recipient combinations in relation to the timing of infection. Recipient rats transplanted with an aortic allograft (BN to

  5. Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat

    NARCIS (Netherlands)

    Dijkstra, G.; de rooij, D. G.; de Jong, F. H.; van den Hurk, R.

    1996-01-01

    The aim of this study was to examine the effects of prepubertal hypothyroidism on ovarian development in rats. Therefore, from birth up to day 40 postpartum, rats were given 6-propyl-2-thiouracil (PTU) via the drinking water of mothers and pups. At ages ranging from 12 to 40 days, ovarian weights

  6. Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

    DEFF Research Database (Denmark)

    Hass, Ulla; Boberg, Julie; Christiansen, Sofie

    2012-01-01

    The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase...... and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans....

  7. Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in retina.

    Science.gov (United States)

    Suzuki-Kerr, Haruna; Iwagawa, Toshiro; Sagara, Hiroshi; Mizota, Atsushi; Suzuki, Yutaka; Watanabe, Sumiko

    2018-06-01

    During development of the retina, common retinal progenitor cells give rise to six classes of neurons that subsequently further diversify into more than 55 subtypes of neuronal subtypes. Here, we have investigated the expression and function of Fezf2, Fez zinc finger family of protein, in the developing mouse retina. Expression of Fezf2 transcripts was strongly observed in the embryonic retinal progenitors at E14.5 and declined quickly in subsequent development of retina. Then, in postnatal stage at around day 8, Fezf2 was transiently expressed then declined again. Loss-of-function analysis using retinas from mice in which Fezf2 coding region was substituted with β-galactosidase showed that Fezf2 is expressed in a subset of cone OFF bipolar cells and required for their differentiation. Using electroretinogram, we found that Fezf2 knockout retina exhibited significantly reduced photopic b-wave, suggesting functional abnormality of cone ON bipolar cells. Furthermore, reduced expression of synaptic protein Trpm1 and structural alteration of ON bipolar cell invagination, both of which affected cone photoreceptor terminal synaptic activity, was identified by transmission electron microscopy and immunohistochemistry, respectively. Taken together, our results show that Fezf2 is indispensable in differentiation of bipolar precursors into cone OFF bipolar cells and in functional maturation of cone ON bipolar cells during development of mouse retina. These results contribute to our understanding of how diversity of neuronal subtypes and hence specificity of neuronal connections are established in the retina by intrinsic cues. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Eye Controlled Simulation of Scotoma Effects on the Retina

    Science.gov (United States)

    1990-07-01

    movements since the central region of the viewing. The PRLs were positioned near the retina, the macula , and its center, the fovea, have scotoma boundary...scotoma area; as macular degeneration increases in size. near to the fovea as possible to maximize acuity, Feedback of failures to detect targets might

  9. Near UV radiation effect on the lens and retina

    International Nuclear Information System (INIS)

    Zigman, S.

    1987-01-01

    The discussion presented in this paper indicates that the retina of a diurnal animal with a natural UV-absorbing lens (ie: the gray squirrel) is susceptible to near-UV damage from environmental sources only after the lens has been removed. This suggests that it is very important to protect against near-UV exposure of human eyes after cataract surgery

  10. A digital retina-like low-level vision processor.

    Science.gov (United States)

    Mertoguno, S; Bourbakis, N G

    2003-01-01

    This correspondence presents the basic design and the simulation of a low level multilayer vision processor that emulates to some degree the functional behavior of a human retina. This retina-like multilayer processor is the lower part of an autonomous self-organized vision system, called Kydon, that could be used on visually impaired people with a damaged visual cerebral cortex. The Kydon vision system, however, is not presented in this paper. The retina-like processor consists of four major layers, where each of them is an array processor based on hexagonal, autonomous processing elements that perform a certain set of low level vision tasks, such as smoothing and light adaptation, edge detection, segmentation, line recognition and region-graph generation. At each layer, the array processor is a 2D array of k/spl times/m hexagonal identical autonomous cells that simultaneously execute certain low level vision tasks. Thus, the hardware design and the simulation at the transistor level of the processing elements (PEs) of the retina-like processor and its simulated functionality with illustrative examples are provided in this paper.

  11. The effects of microwave radiation on rabbit's retina

    Directory of Open Access Journals (Sweden)

    Mohammad R. Talebnejad

    2018-03-01

    Conclusions: Histopathologically, cell phone simulated MW irradiation had no significant detrimental effect on the retina. However, ciliary body congestion was observed in greater fraction of those who received higher MW doses. Although there was no significant difference between post-treatment mean ERG values, there were statistically non-significant trends toward greater changes in the MW irradiated eyes.

  12. GABA sensitivity of spectrally classified horizontal cells in goldfish retina

    NARCIS (Netherlands)

    Verweij, J.; Kamermans, M.; Negishi, K.; Spekreijse, H.

    1998-01-01

    We studied the GABA sensitivity of horizontal cells in the isolated goldfish retina. After the glutamatergic input to the horizontal cells was blocked with DNQX, GABA depolarized the monophasic and biphasic horizontal cells. The pharmacology of these GABA-induced depolarizations was tested with the

  13. Localization and characterization of immunocompetent cells in the human retina

    NARCIS (Netherlands)

    Yang, P.; Das, P. K.; Kijlstra, A.

    2000-01-01

    Recent studies have shown that experimental uveitis can be induced by the appropriate administration of various retinal antigens. Little is known about the in-situ interactions between immune cells in the retina as a prerequisite for understanding the mechanisms involving the presentation of

  14. Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina?

    OpenAIRE

    Widomska, Justyna; Subczynski, Witold K

    2014-01-01

    Age-related macular degeneration (AMD) is associated with a low level of macular carotenoids in the eye retina. Only two carotenoids, namely lutein and zeaxanthin are selectively accumulated in the human eye retina from blood plasma where more than twenty other carotenoids are available. The third carotenoid which is found in the human retina, meso-zeaxanthin is formed directly in the retina from lutein. All these carotenoids, named also macular xanthophylls, play key roles in eye health and ...

  15. Expression patterns and role of PTEN in rat peripheral nerve development and injury.

    Science.gov (United States)

    Chen, Hui; Xiang, Jianping; Wu, Junxia; He, Bo; Lin, Tao; Zhu, Qingtang; Liu, Xiaolin; Zheng, Canbin

    2018-05-29

    Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Role of the nucleolus in neurodegenerative diseases with particular reference to the retina: a review.

    Science.gov (United States)

    Sia, Paul I; Wood, John Pm; Chidlow, Glyn; Sharma, Shiwani; Craig, Jamie; Casson, Robert J

    2016-04-01

    The nucleolus has emerged as a key regulator of cellular growth and the response to stress, in addition to its traditionally understood function in ribosome biogenesis. The association between nucleolar function and neurodegenerative disease is increasingly being explored. There is also recent evidence indicating that the nucleolus may well be crucial in the development of the eye. In this present review, the role of the nucleolus in retinal development as well as in neurodegeneration with an emphasis on the retina is discussed. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

  17. Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: alleviation by CRF₁ receptor antagonism.

    Science.gov (United States)

    Edwards, Scott; Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Wee, Sunmee; Park, Paula E; Schulteis, Gery; Koob, George F

    2012-02-01

    Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol. The emergence of mechanical hypersensitivity with heroin and ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and pain-related states may provide insight into mechanisms underlying the transition to drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety.

    Science.gov (United States)

    Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C; Fant, Andrew D; Simmons, Rebecca K; Akil, Huda; Kerman, Ilan A; Clinton, Sarah M

    2015-01-01

    The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel.

  19. Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats

    Directory of Open Access Journals (Sweden)

    Lin CM

    2015-08-01

    Full Text Available Chien-Min Lin,1,* Jo-Ting Tsai,2,* Chen Kuei Chang,1 Juei-Tang Cheng,3 Jia-Wei Lin11Department of Neurosurgery, 2Department of Radiation Oncology, Shuang Ho Hospital-Taipei Medical University, 3Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan City, Taiwan*These authors contributed equally to this workBackground: Decrease of peroxisome proliferator-activated receptors-δ (PPARδ expression has been observed after spinal cord injury (SCI. Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application.Methods: In the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage.Results: Recovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI.Conclusion: The obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.Keywords: PPARδ, AMPK, spinal cord injury, angiotensin receptor blocker, metformin

  20. Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

    Science.gov (United States)

    Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

    2017-06-01

    Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control ( n = 36) and experimental ( n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 wk old in control and experimental groups ( n = 9 per group per time point). Repeated-measures multivariate ANOVA was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 wk, but there was no significant difference between 9 and 11 wk of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity. NEW & NOTEWORTHY Unilateral nasal obstruction in rats during growth periods induced changes in arterial oxygen saturation (SpO 2 ) and altered development of the motor representation within the face primary cortex. Unilateral nasal obstruction occurring during growth periods may greatly affect not only respiratory function but also craniofacial function in rats. Nasal obstruction should be treated

  1. [Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain].

    Science.gov (United States)

    Feng, Er-Cui; Jiang, Li

    2017-12-01

    To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. A total of 80 neonatal rats were randomly divided into 3 groups: sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. There was no significant difference in the survival rate of rats between the three groups (P>0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (Pmemory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.

  2. Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R.

    Science.gov (United States)

    Cai, Siwei; Yang, Qianhui; Hou, Mengzhu; Han, Qian; Zhang, Hanyu; Wang, Jiantao; Qi, Chen; Bo, Qiyu; Ru, Yusha; Yang, Wei; Gu, Zhongxiu; Wei, Ruihua; Cao, Yunshan; Li, Xiaorong; Zhang, Yan

    2018-01-01

    Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH's anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH's protection. Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested

  3. A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability.

    Science.gov (United States)

    Calabrese, Evan; Badea, Alexandra; Watson, Charles; Johnson, G Allan

    2013-05-01

    There has been growing interest in the role of postnatal brain development in the etiology of several neurologic diseases. The rat has long been recognized as a powerful model system for studying neuropathology and the safety of pharmacologic treatments. However, the complex spatiotemporal changes that occur during rat neurodevelopment remain to be elucidated. This work establishes the first magnetic resonance histology (MRH) atlas of the developing rat brain, with an emphasis on quantitation. The atlas comprises five specimens at each of nine time points, imaged with eight distinct MR contrasts and segmented into 26 developmentally defined brain regions. The atlas was used to establish a timeline of morphometric changes and variability throughout neurodevelopment and represents a quantitative database of rat neurodevelopment for characterizing rat models of human neurologic disease. Published by Elsevier Inc.

  4. Postdependent state in rats as a model for medication development in alcoholism.

    Science.gov (United States)

    Meinhardt, Marcus W; Sommer, Wolfgang H

    2015-01-01

    Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review. © 2014 Society for the Study of Addiction.

  5. Effects of hyper- and hypothyroidism on the development and proliferation of testicular cells in prepubertal rats.

    Science.gov (United States)

    Fadlalla, Mohamed Babo; Wei, Quanwei; Fedail, Jaafar Sulieman; Mehfooz, Asif; Mao, Dagan; Shi, Fangxiong

    2017-12-01

    Thyroid hormones are important in the development and regulation of testes. This study was conducted to determine the effects of hyper- and hypothyroidism on testicular development in prepubertal rats aged 20-70 days. Weaning male rats (20 days old) until day 70 age were randomly divided into four groups: control, hyperthyroid (hyper-T), hypothyroid (hypo-T) and hypothyroid treated with thyroxine (T4) (hypo-T+T4). The results indicated that thyroid hormones caused a significant effect in body and testis weights, and food and water consumption. In addition there were changes in serum concentrations of tri-iodothyronine, T4, thyroid stimulating hormone (TSH) and testosterone. Histomorphology showed a significant decrease in seminiferous tubule diameter in hyper-T compared to the other groups. Leydig cell numbers showed a significant elevation in hyper-T but not in hypo-T groups. Immunostaining indicated that TSH receptor (TSHR), thyroid hormone receptors α/β (TRαβ) and proliferating cell nuclear antigen (PCNA) have the roles in testicular development. Our findings suggest that hyper- and hypo-thyroidism regulate testicular cell proliferation and spermatogenesis in prepubertal rats, indicating that expression of TSHR, TRαβ and PCNA may be regulated by thyroid hormones that are involved in testicular development; and that the administration of T4 to the hypo-T+T4 group leads to an improvement in the testicular condition. © 2017 Japanese Society of Animal Science.

  6. Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

    Science.gov (United States)

    Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

    2016-01-15

    Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Locomotion and physical development in rats treated with ionizing radiation in utero

    International Nuclear Information System (INIS)

    Zaman, M.S.; Hupp, E.W.; Lancaster, F.E.

    1993-01-01

    Effects of ionizing radiation on the emergence of locomotor skill, and physical development were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Results indicated that relatively moderate (15 rad) to high (150 rad) doses of radiation had effects on certain locomotion and physical development parameters. Exposure to 150 rad delayed pivoting, cliff-avoidance, upper jaw tooth eruption, and decreased body weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption were marginally delayed in the 150 rad treated animals. Exposure to 15 rad delayed pivoting and cliff-avoidance

  8. Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

    Science.gov (United States)

    Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

    2010-01-01

    Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

  9. Early postnatal development of rat brain is accompanied by generation of lipofuscin-like pigments

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, J.; Ivica, J.; Kagan, Dmytro; Svoboda, Petr

    2011-01-01

    Roč. 347, 1-2 (2011), s. 157-162 ISSN 0300-8177 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA500110606 Institutional research plan: CEZ:AV0Z50110509 Keywords : brain * early development * lipofuscin-like pigments * fluorescence * rat Subject RIV: CE - Biochemistry Impact factor: 2.057, year: 2011

  10. Anticonvulsant action of two antagonists of NMDA receptors in developing rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Lojková, Denisa; Mikulecká, Anna

    2006-01-01

    Roč. 47, č. S4 (2006), s. 314-314 ISSN 0013-9580. [Annual Meeting of the American Epilepsy Society and Canadian League against Epilepsy. 01.12.2006-05.12.2006, San Diego, CA] R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : memantine * ifenprodil * developing rats Subject RIV: ED - Physiology

  11. Development of the acoustic startle response in rats and its change after early acoustic trauma

    Czech Academy of Sciences Publication Activity Database

    Rybalko, Natalia; Chumak, Tetyana; Bureš, Zbyněk; Popelář, Jiří; Šuta, Daniel; Syka, Josef

    2015-01-01

    Roč. 286, jul 1 (2015), s. 212-221 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GAP303/12/1347; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : auditory system * rat * acoustic startle reflex * development * critical period * noise exposure Subject RIV: FH - Neurology Impact factor: 3.002, year: 2015

  12. Generation of hydrogen peroxide in the developing rat heart: the role of elastin metabolism

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, J.; Ošťádalová, Ivana; Vytášek, R.; Vajner, L.

    2011-01-01

    Roč. 358, 1-2 (2011), s. 215-220 ISSN 0300-8177 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:GA ČR(CZ) GAP303/11/0298 Program:GA Institutional research plan: CEZ:AV0Z50110509 Keywords : rat heart * ontogenetic development * hydrogen peroxide * elastin * fluorescence Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.057, year: 2011

  13. Periodization of the early postnatal development in the rat with particular attention to the weaning period

    Czech Academy of Sciences Publication Activity Database

    Ošťádalová, Ivana; Babický, A.

    2012-01-01

    Roč. 61, Suppl.1 (2012), S1-S7 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GAP303/12/1162 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat * ontogenic development * presuckling period * suckling period * weaning period Subject RIV: ED - Physiology Impact factor: 1.531, year: 2012

  14. Olanzapine-induced weight gain: lessons learned from developing rat models

    OpenAIRE

    van der Zwaal, E.M.

    2011-01-01

    Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying mechanisms. Therefore, this thesis describes the development of a number of rat models that were designed to determine the effects of olanzapine on different aspects of energy balance. In both short- a...

  15. Development of a bio-magnetic measurement system and sensor configuration analysis for rats

    Science.gov (United States)

    Kim, Ji-Eun; Kim, In-Seon; Kim, Kiwoong; Lim, Sanghyun; Kwon, Hyukchan; Kang, Chan Seok; Ahn, San; Yu, Kwon Kyu; Lee, Yong-Ho

    2017-04-01

    Magnetoencephalography (MEG) based on superconducting quantum interference devices enables the measurement of very weak magnetic fields (10-1000 fT) generated from the human or animal brain. In this article, we introduce a small MEG system that we developed specifically for use with rats. Our system has the following characteristics: (1) variable distance between the pick-up coil and outer Dewar bottom (˜5 mm), (2) small pick-up coil (4 mm) for high spatial resolution, (3) good field sensitivity (45 ˜ 80 fT /cm/√{Hz} ) , (4) the sensor interval satisfies the Nyquist spatial sampling theorem, and (5) small source localization error for the region to be investigated. To reduce source localization error, it is necessary to establish an optimal sensor layout. To this end, we simulated confidence volumes at each point on a grid on the surface of a virtual rat head. In this simulation, we used locally fitted spheres as model rat heads. This enabled us to consider more realistic volume currents. We constrained the model such that the dipoles could have only four possible orientations: the x- and y-axes from the original coordinates, and two tangentially layered dipoles (local x- and y-axes) in the locally fitted spheres. We considered the confidence volumes according to the sensor layout and dipole orientation and positions. We then conducted a preliminary test with a 4-channel MEG system prior to manufacturing the multi-channel system. Using the 4-channel MEG system, we measured rat magnetocardiograms. We obtained well defined P-, QRS-, and T-waves in rats with a maximum value of 15 pT/cm. Finally, we measured auditory evoked fields and steady state auditory evoked fields with maximum values 400 fT/cm and 250 fT/cm, respectively.

  16. Standard anatomical and visual space for the mouse retina: computational reconstruction and transformation of flattened retinae with the Retistruct package.

    Directory of Open Access Journals (Sweden)

    David C Sterratt

    Full Text Available The concept of topographic mapping is central to the understanding of the visual system at many levels, from the developmental to the computational. It is important to be able to relate different coordinate systems, e.g. maps of the visual field and maps of the retina. Retinal maps are frequently based on flat-mount preparations. These use dissection and relaxing cuts to render the quasi-spherical retina into a 2D preparation. The variable nature of relaxing cuts and associated tears limits quantitative cross-animal comparisons. We present an algorithm, "Retistruct," that reconstructs retinal flat-mounts by mapping them into a standard, spherical retinal space. This is achieved by: stitching the marked-up cuts of the flat-mount outline; dividing the stitched outline into a mesh whose vertices then are mapped onto a curtailed sphere; and finally moving the vertices so as to minimise a physically-inspired deformation energy function. Our validation studies indicate that the algorithm can estimate the position of a point on the intact adult retina to within 8° of arc (3.6% of nasotemporal axis. The coordinates in reconstructed retinae can be transformed to visuotopic coordinates. Retistruct is used to investigate the organisation of the adult mouse visual system. We orient the retina relative to the nictitating membrane and compare this to eye muscle insertions. To align the retinotopic and visuotopic coordinate systems in the mouse, we utilised the geometry of binocular vision. In standard retinal space, the composite decussation line for the uncrossed retinal projection is located 64° away from the retinal pole. Projecting anatomically defined uncrossed retinal projections into visual space gives binocular congruence if the optical axis of the mouse eye is oriented at 64° azimuth and 22° elevation, in concordance with previous results. Moreover, using these coordinates, the dorsoventral boundary for S-opsin expressing cones closely matches

  17. Abnormal expression of ephrin-A5 affects brain development of congenital hypothyroidism rats.

    Science.gov (United States)

    Suo, Guihai; Shen, Feifei; Sun, Baolan; Song, Honghua; Xu, Meiyu; Wu, Youjia

    2018-05-14

    EphA5 and its ligand ephrin-A5 interaction can trigger synaptogenesis during early hippocampus development. We have previously reported that abnormal EphA5 expression can result in synaptogenesis disorder in congenital hypothyroidism (CH) rats. To better understand its precise molecular mechanism, we further analyzed the characteristics of ephrin-A5 expression in the hippocampus of CH rats. Our study revealed that ephrin-A5 expression was downregulated by thyroid hormone deficiency in the developing hippocampus and hippocampal neurons in rats. Thyroxine treatment for hypothyroid hippocampus and triiodothyronine treatment for hypothyroid hippocampal neurons significantly improved ephrin-A5 expression but could not restore its expression to control levels. Hypothyroid hippocampal neurons in-vitro showed synaptogenesis disorder characterized by a reduction in the number and length of neurites. Furthermore, the synaptogenesis-associated molecular expressions of NMDAR-1 (NR1), PSD95 and CaMKII were all downregulated correspondingly. These results suggest that ephrin-A5 expression may be decreased in CH, and abnormal activation of ephrin-A5/EphA5 signaling affects synaptogenesis during brain development. Such findings provide an important basis for exploring the pathogenesis of CH genetically.

  18. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

    Science.gov (United States)

    Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P hydrocephalus development. PMID:26848844

  19. Low-dose effects of bisphenol A on early sexual development in male and female rats

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Petersen, Marta Axelstad; Boberg, Julie

    2014-01-01

    the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25 mg/kg bw per day). Time-mated Wistar rats (n=22) were...... in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5 mg/kg for BPA, which is used as the basis for establishment of the current tolerable......Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine...

  20. In utero exposure to chloroquine alters sexual development in the male fetal rat

    International Nuclear Information System (INIS)

    Clewell, Rebecca A.; Pluta, Linda; Thomas, Russell S.; Andersen, Melvin E.

    2009-01-01

    Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.

  1. Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats.

    Science.gov (United States)

    Nakano, Ayuki; Nakahara, Tsutomu; Mori, Asami; Ushikubo, Hiroko; Sakamoto, Kenji; Ishii, Kunio

    2016-02-01

    Retinal arterial tortuosity and venous dilation are hallmarks of plus disease, which is a severe form of retinopathy of prematurity (ROP). In this study, we examined whether short-term interruption of vascular endothelial growth factor (VEGF) signals leads to the formation of severe ROP-like abnormal retinal blood vessels. Neonatal rats were treated subcutaneously with the VEGF receptor (VEGFR) tyrosine kinase inhibitors, KRN633 (1, 5, or 10 mg/kg) or axitinib (10 mg/kg), on postnatal day (P) 7 and P8. The retinal vasculatures were examined on P9, P14, or P21 in retinal whole-mounts stained with an endothelial cell marker. Prevention of vascular growth and regression of some preformed capillaries were observed on P9 in retinas of rats treated with KRN633. However, on P14 and P21, density of capillaries, tortuosity index of arterioles, and diameter of veins significantly increased in KRN633-treated rats, compared to vehicle (0.5% methylcellulose)-treated animals. Similar observations were made with axitinib-treated rats. Expressions of VEGF and VEGFR-2 were enhanced on P14 in KRN633-treated rat retinas. The second round of KRN633 treatment on P11 and P12 completely blocked abnormal retinal vascular growth on P14, but thereafter induced ROP-like abnormal retinal blood vessels by P21. These results suggest that an interruption of normal retinal vascular development in neonatal rats as a result of short-term VEGFR inhibition causes severe ROP-like abnormal retinal vascular growth in a VEGF-dependent manner. Rats treated postnatally with VEGFR inhibitors could serve as an animal model for studying the mechanisms underlying the development of plus disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Genetic Regulation of Development of Thymic Lymphomas Induced by N‐Propyl‐N‐nitrosourea in the Rat

    Science.gov (United States)

    Fukami, Hiroko; Nishimura, Mayumi; Matsuyama, Mutsushi

    1995-01-01

    To clarify the linkage between Hbb and Tls‐1 (thymic lymphoma susceptible‐1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N‐propyl‐N‐nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls‐1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY × BUF) × WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls‐3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls‐3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls‐3 may not be identical with Tls‐1 and other genes known to be relevant to thymic tumors, but its relationship with Tls‐2 remains obscure. PMID:7559080

  3. Alterations of sodium and potassium channels of RGCs in RCS rat with the development of retinal degeneration.

    Science.gov (United States)

    Chen, Zhongshan; Song, Yanping; Yao, Junping; Weng, Chuanhuang; Yin, Zheng Qin

    2013-11-01

    All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.

  4. Segmental neuropathic pain does not develop in male rats with complete spinal transections.

    Science.gov (United States)

    Hubscher, Charles H; Kaddumi, Ezidin G; Johnson, Richard D

    2008-10-01

    In a previous study using male rats, a correlation was found between the development of "at-level" allodynia in T6-7 dermatomes following severe T8 spinal contusion injury and the sparing of some myelinated axons within the core of the lesion epicenter. To further test our hypothesis that this sparing is important for the expression of allodynia and the supraspinal plasticity that ensues, an injury that severs all axons (i.e., a complete spinal cord transection) was made in 15 male rats. Behavioral assessments were done at level throughout the 30-day recovery period followed by terminal electrophysiological recordings (urethane anesthesia) from single medullary reticular formation (MRF) neurons receiving convergent nociceptive inputs from receptive fields above, at, and below the lesion level. None of the rats developed signs of at-level allodynia (versus 18 of 26 male rats following severe contusion). However, the terminal recording (206 MRF neurons) data resembled those obtained previously post-contusion. That is, there was evidence of neuronal hyper-excitability (relative to previous data from intact controls) to high- and low-threshold mechanical stimulation for "at-level" (dorsal trunk) and "above-level" (eyelids and face) cutaneous territories. These results, when combined with prior data on intact controls and severe/moderate contusions, indicate that (1) an anatomically incomplete injury (some lesion epicenter axonal sparing) following severe contusion is likely important for the development of allodynia and (2) the neuronal hyper-excitability at the level of the medulla is likely involved in nociceptive processes that are not directly related to the conscious expression of pain-like avoidance behaviors that are being used as evidence of allodynia.

  5. Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

    Science.gov (United States)

    Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael

    2014-02-01

    Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.

  6. Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Siti Rosmani Md Zin

    2013-01-01

    Full Text Available OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i a control group that received vehicle (distilled water and Tween 80; (ii a group treated with 10 mg/kg body weight (BW of Genistein (Gen 10; and (iii a group treated with a higher dose of Genistein (Gen 100. The rats were treated daily for three weeks from postnatal day 22 (P22 to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05. These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

  7. Impaired brain development in the rat following prenatal exposure to methylazoxymethanol acetate at gestational day 17 and neurotrophin distribution

    NARCIS (Netherlands)

    Fiore, M; Grace, AA; Korf, J; Stampachiacchiere, B; Aloe, L

    2004-01-01

    Several neuropsychiatric disorders, including schizophrenia, are the consequence of a disrupted development of the CNS. Accordingly, intrauterine exposure to toxins may increase the risk for psychopathology. We investigated whether prenatal exposure of rats to the neurotoxin methylaxoxymethanol

  8. Early changes in retinal structure and BMP2 expression in the retina and crystalline lens of streptozotocin-induced diabetic pigs.

    Science.gov (United States)

    Jeong, Jae Seung; Lee, Woon-Kyu; Moon, Yeon Sung; Kim, Na Rae

    2017-09-01

    This study aims to evaluate early changes in retinal structure and BMP2 expression in the retina and crystalline lens by comparing streptozotocin-induced diabetic pigs and normal control group pigs. Five eye samples from five diabetic Micro-pigs (Medikinetics, Pyeongtaek, Korea) and five eye samples from five control pigs bred in a specific pathogen-free area were used. Diabetes was developed through intravenous injection of nicotinamide and streptozotocin, and the average fasting glucose level was maintained at 250 mg/dL or higher for 16 weeks. To evaluate BMP2 expression in the retina and crystalline lens, Western blotting was performed. In Hematoxylin and Eosin staining, most diabetic pigs showed structural abnormalities in the inner plexiform layer. The number of nuclei in the ganglion cell layer within the range of 10 4 µm 2 was 3.78±0.60 for diabetic pigs and 5.57±1.07 for control group pigs, showing a statistically significant difference. In immunohistochemical staining, diabetic retinas showed an overall increase in BMP2 expression. In Western blotting, the average BMP2/actin level of diabetic retinas was 1.19±0.05, showing a significant increase compared to the 1.06±0.03 of the control group retinas ( P =0.016). The BMP2/actin level of diabetic crystalline lenses was similar to the control group crystalline lenses ( P =0.730). Compared to control group pigs, the number of nuclei in the inner nuclear layer of retinas from streptozotocin-induced diabetic pigs decreased, while an increase in BMP2 expression was observed in the retina of diabetic pigs.

  9. Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration.

    Science.gov (United States)

    Plaas, Mario; Seppa, Kadri; Reimets, Riin; Jagomäe, Toomas; Toots, Maarja; Koppel, Tuuliki; Vallisoo, Tuuli; Nigul, Mait; Heinla, Indrek; Meier, Riho; Kaasik, Allen; Piirsoo, Andres; Hickey, Miriam A; Terasmaa, Anton; Vasar, Eero

    2017-08-31

    Wolfram syndrome (WS) is a rare autosomal-recessive disorder that is caused by mutations in the WFS1 gene and is characterized by juvenile-onset diabetes, optic atrophy, hearing loss and a number of other complications. Here, we describe the creation and phenotype of Wfs1 mutant rats, in which exon 5 of the Wfs1 gene is deleted, resulting in a loss of 27 amino acids from the WFS1 protein sequence. These Wfs1-ex5-KO232 rats show progressive glucose intolerance, which culminates in the development of diabetes mellitus, glycosuria, hyperglycaemia and severe body weight loss by 12 months of age. Beta cell mass is reduced in older mutant rats, which is accompanied by decreased glucose-stimulated insulin secretion from 3 months of age. Medullary volume is decreased in older Wfs1-ex5-KO232 rats, with the largest decreases at the level of the inferior olive. Finally, older Wfs1-ex5-KO232 rats show retinal gliosis and optic nerve atrophy at 15 months of age. Electron microscopy revealed axonal degeneration and disorganization of the myelin in the optic nerves of older Wfs1-ex5-KO232 rats. The phenotype of Wfs1-ex5-KO232 rats indicates that they have the core symptoms of WS. Therefore, we present a novel rat model of WS.

  10. Effects of chronic treatment with valproate and oxcarbazepine on testicular development in rats.

    Science.gov (United States)

    Cansu, Ali; Ekinci, Ozgür; Serdaroglu, Ayse; Gürgen, Seren Gulsen; Ekinci, Ozalp; Erdogan, Deniz; Coskun, Zafer Kutay; Tunc, Lutfi

    2011-04-01

    The aim of this study was to examine the potential effects of valproate (VPA) and oxcarbazepine (OXC) on testicular development in rats. Forty-two Wistar rats were randomly divided into three groups of 14 rats each. Each group received the following via gavage over 90 days: group 1, tap water (control group); group 2, VPA (300mg/kg/day); group 3, OXC (100mg/kg/day). After sacrifice, body, testicular and epididymidis weights were measured. Testes were sampled, fixed and processed, and quantitative morphometric analysis of Sertoli cells, spermatocytes and spermatids was performed in stages II, V and XII by histopathological examination. Immunohistochemical staining was performed to transform growth factor beta 1 (TGF-β1) and p53, and the apoptotic index was assessed using the TUNEL method. Testis and relative testis weights were significantly lower in the VPA group compared to the control group (p0.05). Apoptotic cell counts and p53 immunoreaction were significantly high and TGF-β1 expression was significantly lower in the VPA group compared to that of the control group (p0.05). Our results show that VPA treatment from prepuberty to adulthood significantly negatively affects spermatogenesis, not only by reducing testicular weight, but also by increasing apoptotic death and p53 and decreasing TGF-β1 activation. OXC has a minimal side effect on testicular development. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. Curative effects of sodium fusidate on the development of dinitrobenzenesulfonic acid-induced colitis in rats

    DEFF Research Database (Denmark)

    Di Marco, Roberto; Mangano, Katia; Quattrocchi, Cinzia

    2003-01-01

    Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunomodulatory activities in vitro and in vivo. In this study we have evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid (DNB)-induced colitis in rats that serves....... These entailed a significant reduction in body weight loss, smaller increase in colon weights, milder macroscopic damage, and lower histological scores. In addition, when sacrificed at the end of the study, fusidin-treated rats had significantly lower blood levels of tumor necrosis factor alpha and interferon......-gamma compared with untreated controls. The present findings concur with the beneficial actions of fusidin in a pilot study conducted in patients with Crohn's disease and warrant controlled studies in humans with IBD....

  12. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of 3 H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author)

  13. In vivo and in vitro study of /sub 90/Sr in developing rat molar enamel

    International Nuclear Information System (INIS)

    White, B.A.; Deaton, T.G.; Bawden, J.W.

    1980-01-01

    The uptake patterns of /sub 90/Sr in developing rat molar enamel were studied in vivo and in vitro. Autoradiographic methods were used that preclude loss or translocation of tracers associated with water-soluble compounds in the sections. In eight-day-old rats injected with the tracer, /sub 90/Sr uptake in the enamel was significantly less than for dentin and bone, particularly at early sacrifice times. The uptake pattern of 90Sr was somewhat different from that previously observed for /sub 45/Ca. The in vitro experiments indicated that the viable intact enamel organ limits uptake of /sub 90/Sr by enamel in both the secretory and maturation phases of enamel formation

  14. Morphological and Histopathological Changes in Orofacial Structures of Experimentally Developed Acromegaly-Like Rats: An Overview

    Directory of Open Access Journals (Sweden)

    Masahiro Iikubo

    2012-01-01

    Full Text Available Tongue enlargement and mandibular prognathism are clinically recognized in almost all patients with acromegaly. An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I was used to investigate morphological and histopathological changes in orofacial structures and to clarify whether these changes were reversible. Exogenous administration of IGF-I evoked specific enlargement of the tongue with identifiable histopathological changes (increased muscle bundle width, increased space between muscle bundles, and increased epithelial thickness, elongation of the mandibular alveolar bone and ascending ramus, and lateral expansion of the mandibular dental arch. Regarding histopathological changes in the mandibular condyle, the cartilaginous layer width, bone matrix ratio, and number of osteoblasts were all significantly greater in this rat model. After normalization of the circulating IGF-I level, tongue enlargement and histopathological changes in the tongue and mandibular condyle were reversible, whereas morphological skeletal changes in the mandible remained.

  15. Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

    Science.gov (United States)

    Donoghue, John P.; Sanes, Jerome N.

    1987-02-01

    We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

  16. Development of Eimeria nieschulzi (Coccidia, Apicomplexa Gamonts and Oocysts in Primary Fetal Rat Cells

    Directory of Open Access Journals (Sweden)

    Hong Chen

    2013-01-01

    Full Text Available The in vitro production of gametocytes and oocysts of the apicomplexan parasite genus Eimeria is still a challenge in coccidiosis research. Until today, an in vitro development of gametocytes or oocysts had only been shown in some Eimeria species. For several mammalian Eimeria species, partial developments could be achieved in different cell types, but a development up to gametocytes or oocysts is still lacking. This study compares several permanent cell lines with primary fetal cells of the black rat (Rattus norvegicus concerning the qualitative in vitro development of the rat parasite Eimeria nieschulzi. With the help of transgenic parasites, the developmental progress was documented. The selected Eimeria nieschulzi strain constitutively expresses the yellow fluorescent protein and a macrogamont specific upregulated red tandem dimer tomato. In the majority of all investigated host cells the development stopped at the second merozoite stage. In a mixed culture of cells derived from inner fetal organs the development of schizont generations I-IV, macrogamonts, and oocysts were observed in crypt-like organoid structures. Microgamonts and microgametes could not be observed and oocysts did not sporulate under air supply. By immunohistology, we could confirm that wild-type E. nieschulzi stages can be found in the crypts of the small intestine. The results of this study may be helpful for characterization of native host cells and for development of an in vitro cultivation system for Eimeria species.

  17. Exposure to urban PM1 in rats: development of bronchial inflammation and airway hyperresponsiveness.

    Science.gov (United States)

    Filep, Ágnes; Fodor, Gergely H; Kun-Szabó, Fruzsina; Tiszlavicz, László; Rázga, Zsolt; Bozsó, Gábor; Bozóki, Zoltán; Szabó, Gábor; Peták, Ferenc

    2016-03-10

    Several epidemiological and laboratory studies have evidenced the fact that atmospheric particulate matter (PM) increases the risk of respiratory morbidity. It is well known that the smallest fraction of PM (PM1 - particulate matter having a diameter below 1 μm) penetrates the deepest into the airways. The ratio of the different size fractions in PM is highly variable, but in industrial areas PM1 can be significant. Despite these facts, the health effects of PM1 have been poorly investigated and air quality standards are based on PM10 and PM2.5 (PM having diameters below 10 μm and 2.5 μm, respectively) concentrations. Therefore, this study aimed at determining whether exposure to ambient PM1 at a near alert threshold level for PM10 has respiratory consequences in rats. Rats were either exposed for 6 weeks to 100 μg/m(3) (alert threshold level for PM10 in Hungary) urban submicron aerosol, or were kept in room air. End-expiratory lung volume, airway resistance (Raw) and respiratory tissue mechanics were measured. Respiratory mechanics were measured under baseline conditions and following intravenous methacholine challenges to characterize the development of airway hyperresponsiveness (AH). Bronchoalveolar lavage fluid (BALF) was analyzed and lung histology was performed. No significant differences were detected in lung volume and mechanical parameters at baseline. However, the exposed rats exhibited significantly greater MCh-induced responses in Raw, demonstrating the progression of AH. The associated bronchial inflammation was evidenced by the accumulation of inflammatory cells in BALF and by lung histology. Our findings suggest that exposure to concentrated ambient PM1 (mass concentration at the threshold level for PM10) leads to the development of mild respiratory symptoms in healthy adult rats, which may suggest a need for the reconsideration of threshold limits for airborne PM1.

  18. Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum.

    Science.gov (United States)

    McDougall, Annie R A; Wiradjaja, Vanny; Azhan, Aminath; Li, Anqi; Hale, Nadia; Wlodek, Mary E; Hooper, Stuart B; Wallace, Megan J; Tolcos, Mary

    2017-01-01

    Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR. © 2017 S. Karger AG, Basel.

  19. Cell Cycle Regulation and Apoptotic Responses of the Embryonic Chick Retina by Ionizing Radiation.

    Directory of Open Access Journals (Sweden)

    Margot Mayer

    Full Text Available Ionizing radiation (IR exerts deleterious effects on the developing brain, since proliferative neuronal progenitor cells are highly sensitive to IR-induced DNA damage. Assuming a radiation response that is comparable to mammals, the chick embryo would represent a lower vertebrate model system that allows analysis of the mechanisms underlying this sensitivity, thereby contributing to the reduction, refinement and replacement of animal experiments. Thus, this study aimed to elucidate the radiation response of the embryonic chick retina in three selected embryonic stages. Our studies reveal a lack in the radiation-induced activation of a G1/S checkpoint, but rapid abrogation of G2/M progression after IR in retinal progenitors throughout development. Unlike cell cycle control, radiation-induced apoptosis (RIA showed strong variations between its extent, dose dependency and temporal occurrence. Whereas the general sensitivity towards RIA declined with ongoing differentiation, its dose dependency constantly increased with age. For all embryonic stages RIA occurred during comparable periods after irradiation, but in older animals its maximum shifted towards earlier post-irradiation time points. In summary, our results are in good agreement with data from the developing rodent retina, strengthening the suitability of the chick embryo for the analysis of the radiation response in the developing central nervous system.

  20. An analog VLSI chip emulating polarization vision of Octopus retina.

    Science.gov (United States)

    Momeni, Massoud; Titus, Albert H

    2006-01-01

    Biological systems provide a wealth of information which form the basis for human-made artificial systems. In this work, the visual system of Octopus is investigated and its polarization sensitivity mimicked. While in actual Octopus retina, polarization vision is mainly based on the orthogonal arrangement of its photoreceptors, our implementation uses a birefringent micropolarizer made of YVO4 and mounted on a CMOS chip with neuromorphic circuitry to process linearly polarized light. Arranged in an 8 x 5 array with two photodiodes per pixel, each consuming typically 10 microW, this circuitry mimics both the functionality of individual Octopus retina cells by computing the state of polarization and the interconnection of these cells through a bias-controllable resistive network.

  1. Infrared reflectance as a diagnostic adjunct for subclinical commotio retinae

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    Nicholas H Andrew

    2014-01-01

    Full Text Available Commotio retinae (CR is an outer retinal disorder following blunt trauma to the eye. Histologically it is characterized by disruption of the photoreceptor outer segments (OS, typically without injury to other retinal layers. Using spectral-domain optical coherence tomography (OCT the condition is visible as hyper-reflectivity of the OS. Most cases of CR are associated with transient grey-white discoloration of the retina and are easily diagnosed clinically, but there have been reports of OCT-confirmed CR without retinal discoloration. It is likely that this subclinical variant of CR is under-recognized as the OCT features of CR are subtle. Here, we report a case of OCT-confirmed subclinical CR that demonstrated prominent infrared hypo-reflectance, using the infrared protocol of the SPECTRALIS® OCT, Heidelberg Engineering. This case suggests that infrared reflectance may have a role in diagnosing cases of subclinical CR.

  2. Erythropoetin receptor expression in the human diabetic retina

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    Tsang Stephen H

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests erythropoietin (EPO and the erythropoietin receptor (EPOR may play a direct role in the pathogenesis of diabetic retinopathy. Better characterization of the EPO-EPOR signaling system in the ischemic retina may offer a new therapeutic modality for ischemic ophthalmic diseases. This study was performed to identify EPOR mRNA expression in the human diabetic eye. Findings EPOR antisense RNA probes were validated on human pancreas tissue. In the normal eye, EPOR was expressed in the retinal ganglion cell layer. Minimal expression was observed in the inner and outer nuclear layer. Under conditions of diabetic retinopathy, EPOR expression shifted to photoreceptor cells. Increased expression was also observed in the peripheral retina. Conclusion EPOR expression may be a biomarker or contribute to disease mechanisms in diabetic retinopathy.

  3. Study on developing brain damage of neonatal rats induced by enriched uranium

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Yang Shuqin

    2000-01-01

    Objective: The injurious effects of enriched uranium 235 U on developing brain of neonatal Wistar pure bred rats were studied. Methods: The model of irradiation induced brain damage in vivo was settled. The effects of cerebrum exposure by 235 U on somatic growth and neuro-behavior development of neonatal rats were examined by thirteen index determination of multiple parameters. The dynamic retention of autoradiographic tracks of 235 U in cells of developing brain was observed. The changes of NSE, IL-1β, SOD, and ET in cerebral cortex, hippocampus, diencephalon, cerebellum after expose to 235 U were examined with radioimmunoassay. Results: The somatic growth such as increase of body weight and brain weight was lower significantly. The retardation of development was found such as eye opening, sensuous function as auditory startle, movement and coordination function and activity as swimming, physiological reflexes as negative geotaxis, surface righting, grasping reflex suspension and the tendency behavior. The data showed delayed growth and abnormal neuro-behavior. The micro-autoradiographic tracing showed that the tracks of 235 U were mainly accumulated in the nucleus of developing brain. At the same time only few tracks appeared in the cytoplasm and interval between cells. Experimental study showed that when the dose of 235 U irradiation was increased, the level of NSE was decreased and the IL-1β was increased. However, the results indicated that SOD and ET can be elevated by the low dose irradiation of 235 U, and can be inhibited by the high dose. Conclusion: The behavior of internal irradiation from 235 U on the developing brain damage of neonatal rats were of sensibility and compensation in nervous cells

  4. Enhanced inhibitory effects of TBT chloride on the development of F1 rats.

    Science.gov (United States)

    Asakawa, H; Tsunoda, M; Kaido, T; Hosokawa, M; Sugaya, C; Inoue, Y; Kudo, Y; Satoh, T; Katagiri, H; Akita, H; Saji, M; Wakasa, M; Negishi, T; Tashiro, T; Aizawa, Y

    2010-05-01

    Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which

  5. Heidelberg Retina Tomograph for the Detection of Glaucoma

    Directory of Open Access Journals (Sweden)

    Barbara Cvenkel

    2012-06-01

    Full Text Available Heidelberg Retina Tomograph (HRT is a confocal scanning laser ophthalmoscope which acquires and analyzes 3-dimensional images of the optic nerve head. The latest instrument HRT3 includes software with larger ethinic-specific normative database. This review summarizes relevant published literature on HRT in diagnosing glaucoma, detecting glaucoma progression, the diagnostic accuracy of HRT among other imaging devices and its role in clinical practice.

  6. Effects and Responses to Spaceflight in the Mouse Retina

    Science.gov (United States)

    Zanello, Susana B.; Theriot, Corey; Westby, Christian; Boyle, Richard

    2011-01-01

    Several stress environmental factors are combined in a unique fashion during spaceflight, affecting living beings widely across their physiological systems. Recently, attention has been placed on vision changes in astronauts returning from long duration missions. Alterations include hyperoptic shift, globe flattening, choroidal folds and optic disc edema, which are probably associated with increased intracranial pressure. These observations justify a better characterization of the ocular health risks associated with spaceflight. This study investigates the impact of spaceflight on the biology of the mouse retina. Within a successful tissue sharing effort, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (Animal Enclosure Module) mice were used as ground controls. Oxidative stress-induced DNA damage was higher in the flight samples compared to controls on R+1, and decreased on R+7. A trend toward higher oxidative and cellular stress response gene expression was also observed on R+1 compared to AEM controls, and these levels decreased on R+7. Several genes coding for key antioxidant enzymes, namely, heme-oxygenase-1, peroxiredoxin, and catalase, were among those upregulated after flight. Likewise, NF B and TGFbeta1, were upregulated in one flight specimen that overall showed the most elevated oxidative stress markers on R+1. In addition, retinas from vivarium control mice evidenced higher oxidative stress markers, NF B and TGFbeta1, likely due to the more intense illumination in vivarium cages versus the AEM. These preliminary data suggest that spaceflight represents a source of environmental stress that translates into oxidative and cellular stress in the retina, which is partially reversible upon return to Earth. Further work is needed to dissect the contribution of the various spaceflight factors (microgravity, radiation) and to

  7. The development of the glucocorticoid receptor system in the rat limbic brain. 2

    International Nuclear Information System (INIS)

    Meaney, M.J.; Sapolsky, R.M.; McEwen, B.S.

    1985-01-01

    The authors report the results of an autoradiographic analysis of the postnatal development of the hippocampal glucocorticoid receptor system in the rat brain. Quantitative analysis of the autoradiograms revealed a varied pattern of gradual development towards adult receptor concentrations during the second week of life. Receptor concentrations in the dentate gyrus increased dramatically between Days 9 and 15, while the changes during this period in the pyramidal layers of Ammon's horn seemed to reflect both structural changes in these regions as well as increases in receptor concentrations. (orig.)

  8. Effect of tritium (tritium water) on prenatal and postnatal development of rats

    International Nuclear Information System (INIS)

    Bajrakova, A.; Baev, I.; Yagova, A.

    1983-01-01

    Female rats were injected intraperitoneally on the first day after their fecundation with 3,7 kBq/g b.w. tritium water - activity which under these conditions does not increase prenatal death rate. The postnatal development of the born alive was traced in respect to the lethality rate and growth rate (mean bodily weight in dynamics up to the 60-th day p.p.) and compared with that of the offsprings from the control group. It was shown that the used activity tritium water during the initial stages of embryonic development does not result in deviations from the norm. (authors)

  9. Gene expression changes in the retina following subretinal injection of human neural progenitor cells into a rodent model for retinal degeneration.

    Science.gov (United States)

    Jones, Melissa K; Lu, Bin; Saghizadeh, Mehrnoosh; Wang, Shaomei

    2016-01-01

    Retinal degenerative diseases (RDDs) affect millions of people and are the leading cause of vision loss. Although treatment options for RDDs are limited, stem and progenitor cell-based therapies have great potential to halt or slow the progression of vision loss. Our previous studies have shown that a single subretinal injection of human forebrain derived neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) retinal degenerate rat offers long-term preservation of photoreceptors and visual function. Furthermore, neural progenitor cells are currently in clinical trials for treating age-related macular degeneration; however, the molecular mechanisms of stem cell-based therapies are largely unknown. This is the first study to analyze gene expression changes in the retina of RCS rats following subretinal injection of hNPCs using high-throughput sequencing. RNA-seq data of retinas from RCS rats injected with hNPCs (RCS(hNPCs)) were compared to sham surgery in RCS (RCS(sham)) and wild-type Long Evans (LE(sham)) rats. Differential gene expression patterns were determined with in silico analysis and confirmed with qRT-PCR. Function, biologic, cellular component, and pathway analyses were performed on differentially expressed genes and investigated with immunofluorescent staining experiments. Analysis of the gene expression data sets identified 1,215 genes that were differentially expressed between RCS(sham) and LE(sham) samples. Additionally, 283 genes were differentially expressed between the RCS(hNPCs) and RCS(sham) samples. Comparison of these two gene sets identified 68 genes with inverse expression (termed rescue genes), including Pdc, Rp1, and Cdc42ep5. Functional, biologic, and cellular component analyses indicate that the immune response is enhanced in RCS(sham). Pathway analysis of the differential expression gene sets identified three affected pathways in RCS(hNPCs), which all play roles in phagocytosis signaling. Immunofluorescent staining

  10. Light regulation of the insulin receptor in the retina.

    Science.gov (United States)

    Rajala, Raju V S; Anderson, Robert E

    2003-10-01

    The peptide hormone insulin binds its cognate cell-surface receptors to activate a coordinated biochemical-signaling network and to induce intracellular events. The retina is an integral part of the central nervous system and is known to contain insulin receptors, although their function is unknown. This article, describes recent studies that link the photobleaching of rhodopsin to tyrosine phosphorylation of the insulin receptor and subsequent activation of phosphoinositide 3- kinase (PI3K). We recently found a light-dependent increase in tyrosine phosphorylation of the insulin receptor-beta-subunit (IR beta) and an increase in PI3K enzyme activity in isolated rod outer segments (ROS) and in anti-phosphotyrosine (PY) and anti-IR beta immunoprecipitates of retinal homogenates. The light effect, which was localized to photoreceptor neurons, is independent of insulin secretion. Our results suggest that light induces tyrosine phosphorylation of IR beta in outer-segment membranes, which leads to the binding of p85 through its N-terminal SH2 domain and the generation of PI-3,4,5-P3. We suggest that the physiological role of this process may be to provide neuroprotection of the retina against light damage by activating proteins that protect against stress-induced apoptosis. The studies linking PI3K activation through tyrosine phosphorylation of IR beta now provide physiological relevance for the presence of these receptors in the retina.

  11. Identification of endogenous flurophores in the layered retina

    Science.gov (United States)

    Xu, Gaixia; Chen, Danni; Sun, Yiwen; Qu, Junle; Lin, Ziyang; Ding, Zhihua; Niu, Hanben

    2007-05-01

    In this paper, we measured and analyzed the characteristic of endogenous fluorophores in porcine layered retina by using advanced fluorescence spectroscopy and microscopy imaging technology. It was found that there were obvious contrasts corresponding to the different layers of retina, which may be important for fundus disease diagnosis. The retinal pigment epithelium cells exhibited strong autofluorescence with as emission peak of 600+/-10nm when excited with 860-nm light. The emission peak of photoreceptors was at 652+/-5nm, and the emission peak of retinal vessels layer was weak and at 640~700nm, when excited with 488-nm light. Autofluorescence images of three layers of retina were obtained using the same setup. We concluded that the main endogenous fluorophore in PRE was lipofuscin and that in retinal vessels was porphyrin. What's more, the FMHW (full width at half. maximum) of retinal fluorescence spectrum was broad, which suggested that there wasn't only one endogenous fluorophores of tissues excited.

  12. A biochemical basis for induction of retina regeneration by antioxidants.

    Science.gov (United States)

    Echeverri-Ruiz, Nancy; Haynes, Tracy; Landers, Joseph; Woods, Justin; Gemma, Michael J; Hughes, Michael; Del Rio-Tsonis, Katia

    2018-01-15

    The use of antioxidants in tissue regeneration has been studied, but their mechanism of action is not well understood. Here, we analyze the role of the antioxidant N-acetylcysteine (NAC) in retina regeneration. Embryonic chicks are able to regenerate their retina after its complete removal from retinal stem/progenitor cells present in the ciliary margin (CM) of the eye only if a source of exogenous factors, such as FGF2, is present. This study shows that NAC modifies the redox status of the CM, initiates self-renewal of the stem/progenitor cells, and induces regeneration in the absence of FGF2. NAC works as an antioxidant by scavenging free radicals either independently or through the synthesis of glutathione (GSH), and/or by reducing oxidized proteins through a thiol disulfide exchange activity. We dissected the mechanism used by NAC to induce regeneration through the use of inhibitors of GSH synthesis and the use of other antioxidants with different biochemical structures and modes of action, and found that NAC induces regeneration through its thiol disulfide exchange activity. Thus, our results provide, for the first time, a biochemical basis for induction of retina regeneration. Furthermore, NAC induction was independent of FGF receptor signaling, but dependent on the MAPK (pErk1/2) pathway. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Light pollution: the possible consequences of excessive illumination on retina.

    Science.gov (United States)

    Contín, M A; Benedetto, M M; Quinteros-Quintana, M L; Guido, M E

    2016-02-01

    Light is the visible part of the electromagnetic radiation within a range of 380-780 nm; (400-700 on primates retina). In vertebrates, the retina is adapted to capturing light photons and transmitting this information to other structures in the central nervous system. In mammals, light acts directly on the retina to fulfill two important roles: (1) the visual function through rod and cone photoreceptor cells and (2) non-image forming tasks, such as the synchronization of circadian rhythms to a 24 h solar cycle, pineal melatonin suppression and pupil light reflexes. However, the excess of illumination may cause retinal degeneration or accelerate genetic retinal diseases. In the last century human society has increased its exposure to artificial illumination, producing changes in the Light/Dark cycle, as well as in light wavelengths and intensities. Although, the consequences of unnatural illumination or light pollution have been underestimated by modern society in its way of life, light pollution may have a strong impact on people's health. The effects of artificial light sources could have direct consequences on retinal health. Constant exposure to different wavelengths and intensities of light promoted by light pollution may produce retinal degeneration as a consequence of photoreceptor or retinal pigment epithelium cells death. In this review we summarize the different mechanisms of retinal damage related to the light exposure, which generates light pollution.

  14. MiR-200a is involved in rat epididymal development by targeting β-catenin mRNA

    Institute of Scientific and Technical Information of China (English)

    Xiaojiang Wu; Botao Zhao; Wei Li; Yue Chen; Ruqiang Liang; Lin Li; Youxin Jin; Kangcheng Ruan

    2012-01-01

    The expression of 350 microRNAs (miRNAs) in epididymis of rat from postnatal development to adult (from postnatal days 7-70) was profiled with home-made miRNA microarray.Among them,48 miRNAs changed significantly, in which the expression of miR-200a increased obviously with time,in a good agreement with that obtained from northern blot analysis.The real-time quantitative-polymerase chain reaction result indicated that temporal expression of rat β-catenin was exactly inversed to that of miR-200a during rat epididymal development,implying that miR-200a might also target β-catenin mRNA in rat epididymis as reported by Saydam et al.in humans.The bioinformatic analysis indicated that 3' untranslated region of rat β-catenin mRNA did contain a putative binding site for miR-200a.Meanwhile,it was found that the sequence of this binding site was different from that of human β-catenin mRNA with a deletion of two adjacent nucleotides (U and C).But the results of luciferase targeting assay in HEK 293T cells and the overexpression of miR-200a in rat NRK cells demonstrated that miR-200a did target rat β-catenin mRNA and cause the suppression of its expression.All these results show that miR-200a should be involved in rat epididymal development by targeting β-catenin mRNA of rat and suppressing its expression.

  15. Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway.

    Directory of Open Access Journals (Sweden)

    Hong Pan

    Full Text Available Retinal ischemia-reperfusion (I/R injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF, which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2-mediated induction of heme oxygenase-1 (HO-1. This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p. injected with SF (12.5 mg/kg or vehicle (corn oil once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II (ZnPP, 30 mg/kg, i.p. treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL, and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway.

  16. Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

    Science.gov (United States)

    Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

    2010-03-01

    Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

  17. Effects of maternal separation on the neurobehavioral development of newborn Wistar rats.

    Science.gov (United States)

    Farkas, Jozsef; Reglodi, Dora; Gaszner, Balazs; Szogyi, Donat; Horvath, Gabor; Lubics, Andrea; Tamas, Andrea; Frank, Falko; Besirevic, Dario; Kiss, Peter

    2009-05-29

    Animal models of neonatal stress, like maternal separation, may provide important correlation with human stress-related disorders. Early maternal deprivation has been shown to cause several short- and long-term neurochemical and behavioral deficits. Little is known about the early neurobehavioral development after postnatal stress. The aim of the present study was to investigate the development of reflexes and motor coordination in male and female pups subjected to maternal deprivation. Pups were removed from their mothers from postnatal day 1-14, for 3h daily. Somatic development (weight gain, eye opening, ear unfolding, incisor eruption) and reflex development was tested during the first 3 weeks. The appearance of the following reflexes was investigated: crossed extensor, grasping, placing, gait, righting and sensory reflexes, and negative geotaxis. Timely performance of negative geotaxis, righting and gait were also tested daily during the first 3 weeks. Motor coordination and open-field tests were performed on postnatal weeks 3-5 (rotarod, elevated grid-walk, footfault, rope suspension, inclined board and walk initiation tests). The results revealed that a 3-h-long daily maternal separation did not lead to a marked delay or enhancement in reflex development and motor coordination. A subtle enhancement was observed in the appearance of hindlimb grasp and gait reflexes, and a better performance in footfault test in male rats suffering from maternal deprivation. In contrast, female maternally deprived (MD) rats displayed a slight delay in forelimb grasp and air righting reflex appearance, and surface righting performance. Open-field activity was not changed in maternally deprived rats. In summary, our present observations indicate that maternal deprivation does not induce drastic changes in early neurodevelopment, therefore, further research is needed to determine the onset of behavioral alterations in subject with maternal deprivation history. Gender differences

  18. Adaptation in Coding by Large Populations of Neurons in the Retina

    Science.gov (United States)

    Ioffe, Mark L.

    A comprehensive theory of neural computation requires an understanding of the statistical properties of the neural population code. The focus of this work is the experimental study and theoretical analysis of the statistical properties of neural activity in the tiger salamander retina. This is an accessible yet complex system, for which we control the visual input and record from a substantial portion--greater than a half--of the ganglion cell population generating the spiking output. Our experiments probe adaptation of the retina to visual statistics: a central feature of sensory systems which have to adjust their limited dynamic range to a far larger space of possible inputs. In Chapter 1 we place our work in context with a brief overview of the relevant background. In Chapter 2 we describe the experimental methodology of recording from 100+ ganglion cells in the tiger salamander retina. In Chapter 3 we first present the measurements of adaptation of individual cells to changes in stimulation statistics and then investigate whether pairwise correlations in fluctuations of ganglion cell activity change across different stimulation conditions. We then transition to a study of the population-level probability distribution of the retinal response captured with maximum-entropy models. Convergence of the model inference is presented in Chapter 4. In Chapter 5 we first test the empirical presence of a phase transition in such models fitting the retinal response to different experimental conditions, and then proceed to develop other characterizations which are sensitive to complexity in the interaction matrix. This includes an analysis of the dynamics of sampling at finite temperature, which demonstrates a range of subtle attractor-like properties in the energy landscape. These are largely conserved when ambient illumination is varied 1000-fold, a result not necessarily apparent from the measured low-order statistics of the distribution. Our results form a consistent

  19. An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA.

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

    2008-10-01

    Full Text Available The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER

  20. Designing and testing scene enhancement algorithms for patients with retina degenerative disorders

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    Downes Susan M

    2010-06-01

    Full Text Available Abstract Background Retina degenerative disorders represent the primary cause of blindness in UK and in the developed world. In particular, Age Related Macular Degeneration (AMD and Retina Pigmentosa (RP diseases are of interest to this study. We have therefore created new image processing algorithms for enhancing the visual scenes for them. Methods In this paper we present three novel image enhancement techniques aimed at enhancing the remaining visual information for patients suffering from retina dystrophies. Currently, the only effective way to test novel technology for visual enhancement is to undergo testing on large numbers of patients. To test our techniques, we have therefore built a retinal image processing model and compared the results to data from patient testing. In particular we focus on the ability of our image processing techniques to achieve improved face detection and enhanced edge perception. Results Results from our model are compared to actual data obtained from testing the performance of these algorithms on 27 patients with an average visual acuity of 0.63 and an average contrast sensitivity of 1.22. Results show that Tinted Reduced Outlined Nature (TRON and Edge Overlaying algorithms are most beneficial for dynamic scenes such as motion detection. Image Cartoonization was most beneficial for spatial feature detection such as face detection. Patient's stated that they would most like to see Cartoonized images for use in daily life. Conclusions Results obtained from our retinal model and from patients show that there is potential for these image processing techniques to improve visual function amongst the visually impaired community. In addition our methodology using face detection and efficiency of perceived edges in determining potential benefit derived from different image enhancement algorithms could also prove to be useful in quantitatively assessing algorithms in future studies.

  1. Characterization of Pax2 expression in the goldfish optic nerve head during retina regeneration.

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    Marta Parrilla

    Full Text Available The Pax2 transcription factor plays a crucial role in axon-guidance and astrocyte differentiation in the optic nerve head (ONH during vertebrate visual system development. However, little is known about its function during regeneration. The fish visual system is in continuous growth and can regenerate. Müller cells and astrocytes of the retina and ONH play an important role in these processes. We demonstrate that pax2a in goldfish is highly conserved and at least two pax2a transcripts are expressed in the optic nerve. Moreover, we show two different astrocyte populations in goldfish: Pax2(+ astrocytes located in the ONH and S100(+ astrocytes distributed throughout the retina and the ONH. After peripheral growth zone (PGZ cryolesion, both Pax2(+ and S100(+ astrocytes have different responses. At 7 days after injury the number of Pax2(+ cells is reduced and coincides with the absence of young axons. In contrast, there is an increase of S100(+ astrocytes in the retina surrounding the ONH and S100(+ processes in the ONH. At 15 days post injury, the PGZ starts to regenerate and the number of S100(+ astrocytes increases in this region. Moreover, the regenerating axons reach the ONH and the pax2a gene expression levels and the number of Pax2(+ cells increase. At the same time, S100(+/GFAP(+/GS(+ astrocytes located in the posterior ONH react strongly. In the course of the regeneration, Müller cell vitreal processes surrounding the ONH are primarily disorganized and later increase in number. During the whole regenerative process we detect a source of Pax2(+/PCNA(+ astrocytes surrounding the posterior ONH. We demonstrate that pax2a expression and the Pax2(+ astrocyte population in the ONH are modified during the PGZ regeneration, suggesting that they could play an important role in this process.

  2. Vitamin D-dependent rat renal calcium-binding protein: development of a radioimmunoassay, tissue distribution, and immunologic identification

    International Nuclear Information System (INIS)

    Sonnenberg, J.; Pansini, A.R.; Christakos, S.

    1984-01-01

    A sensitive double antibody RIA has been developed for the 28,000 mol wt rat renal vitamin D-dependent calcium-binding protein. Using this assay, concentrations of calcium-binding protein (CaBP) as low as 30 ng can be measured. The assay is precise (intraassay variability, 5.0%) and reproductible (interassay variability, 8.2%). Measurements of renal CaBP by RIA showed a good correlation with measurements of CaBP by the chelex resin assay and by polyacrylamide gel analysis by densitometric tracing using a purified CaBP marker. The concentration of CaBP in the vitamin D-replete rat kidney is 7.3 +/- 1.0 (mean +/- SEM) micrograms/mg protein. In vitamin D-deficient rats the level of renal CaBP is 2.6 +/- 0.3 micrograms/mg protein. Tissue distribution of immunoreactive rat renal CaBP showed the highest concentration of CaBP in the rat cerebellum (38.3 +/- 5.1 micrograms/mg protein). Lower concentrations of immunoreactive CaBP were detected in several other rat tissues. No immunoreactive CaBP was detected in rat or human serum. In necropsy human kidney and cerebellum, high levels of immunoreactive CaBP were also detected (1.5 +/- 0.1 and 27.3 +/- 2.1 micrograms/mg protein, respectively). When extracts of rat kidney and brain and human cerebellum and kidney were assayed at several dilutions, immunodisplacement curves parallel to that of pure renal CaBP were observed, indicating immunochemical similarity. Fractionation of extracts of rat cerebellum, human kidney, and human cerebellum on Sephadex G-100 revealed immunoreactivity and calcium-binding activity in the 28,000 mol wt region similar to rat kidney

  3. Simple explant culture of the embryonic chicken retina with long-term preservation of photoreceptors.

    Science.gov (United States)

    Thangaraj, Gopenath; Greif, Alexander; Layer, Paul G

    2011-10-01

    Structurally stable in vitro-model systems are indispensible to analyse neural development during embryogenesis, follow cellular differentiation and evaluate neurotoxicological or growth factor effects. Here we describe a three-dimensional, long-term in vitro-culture system of the embryonic chick retina which supports photoreceptor development. Retinal tissue was isolated from E6 chick eye, and cultured as explants by continuous orbital rotation to allow free floatation without any supporting materials. Young stage (E6) immature retinas were cultured for various time periods in order to follow the differentiation of cell types and plexiform layers by immunocytochemical methods. These explants could be cultured for at least 2-3 weeks with remarkable retention of retinal architecture. Interestingly, photoreceptors developed in the absence of pigment epithelium. Electron microscopic studies revealed formation of structures resembling photoreceptor outer segments, a feature not reported previously. Thus, the verification of photoreceptors, Müller cells, inner retinal cells and the inner plexiform layer described in our study establishes this explant culture as a valuable in vivo-like model system. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  4. Interaction of renal failure and dyslipidaemia in the development of calcific aortic valve disease in rats.

    Science.gov (United States)

    Gillis, Kris; Roosens, Bram; Bala, Gezim; Remory, Isabel; Hernot, Sophie; Delvenne, Philippe; Mestrez, Fabienne; Droogmans, Steven; Cosyns, Bernard

    2017-10-01

    Calcific aortic valve disease (CAVD) is currently the most common heart valve disease worldwide and is known to be an active process. Both renal failure and dyslipidaemia are considered to be promoting factors for the development of valvular calcifications. The aim of this study is to prospectively evaluate the respective contribution and interaction of renal failure and dyslipidaemia on CAVD in a rat model, using echocardiography and compared with histology. Sixty-eight male Wistar rats were prospectively divided in eight groups, each fed a different diet to induce renal failure alone and combined with hyperlipidaemia or hypercholesterolemia. CAVD was detected and quantified by calibrated integrated backscatter of ultrasound (cIB) and compared with the histological calcium score. The study follow-up was 20 weeks. At the end of the study, the cIB value and the calcium score of the aortic valve were significantly increased in the group with isolated renal failure but not with dyslipidaemia. The combination of renal failure with high cholesterol or high-fat diet did not significantly increase calcifications further. Renal failure alone does induce aortic valve calcifications in a rat model of CAVD, whereas dyslipidaemia alone does not. The combination of renal failure with dyslipidaemia does not increase calcification further. These findings suggest that a combination of atherosclerotic and calcifying factors is not required to induce aortic valve calcifications in this model.

  5. A neurorobotic platform for locomotor prosthetic development in rats and mice

    Science.gov (United States)

    von Zitzewitz, Joachim; Asboth, Leonie; Fumeaux, Nicolas; Hasse, Alexander; Baud, Laetitia; Vallery, Heike; Courtine, Grégoire

    2016-04-01

    Objectives. We aimed to develop a robotic interface capable of providing finely-tuned, multidirectional trunk assistance adjusted in real-time during unconstrained locomotion in rats and mice. Approach. We interfaced a large-scale robotic structure actuated in four degrees of freedom to exchangeable attachment modules exhibiting selective compliance along distinct directions. This combination allowed high-precision force and torque control in multiple directions over a large workspace. We next designed a neurorobotic platform wherein real-time kinematics and physiological signals directly adjust robotic actuation and prosthetic actions. We tested the performance of this platform in both rats and mice with spinal cord injury. Main Results. Kinematic analyses showed that the robotic interface did not impede locomotor movements of lightweight mice that walked freely along paths with changing directions and height profiles. Personalized trunk assistance instantly enabled coordinated locomotion in mice and rats with severe hindlimb motor deficits. Closed-loop control of robotic actuation based on ongoing movement features enabled real-time control of electromyographic activity in anti-gravity muscles during locomotion. Significance. This neurorobotic platform will support the study of the mechanisms underlying the therapeutic effects of locomotor prosthetics and rehabilitation using high-resolution genetic tools in rodent models.

  6. Chronic consumption of trans fat can facilitate the development of hyperactive behavior in rats.

    Science.gov (United States)

    Pase, C S; Roversi, Kr; Trevizol, F; Kuhn, F T; Dias, V T; Roversi, K; Vey, L T; Antoniazzi, C T; Barcelos, R C S; Bürger, M E

    2015-02-01

    In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Mobile phone radiation during pubertal development has no effect on testicular histology in rats.

    Science.gov (United States)

    Tumkaya, Levent; Kalkan, Yildiray; Bas, Orhan; Yilmaz, Adnan

    2016-02-01

    Mobile phones are extensively used throughout the world. There is a growing concern about the possible public health hazards posed by electromagnetic radiation emitted from mobile phones. Potential health risk applies particularly to the most intensive mobile phone users-typically, young people. The aim of this study was to investigate the effects of mobile phone exposure to the testes, by assessing the histopathological and biochemical changes in the testicular germ cells of rats during pubertal development. A total of 12 male Sprague Dawley rats were used. The study group (n = 6) was exposed to a mobile phone for 1 h a day for 45 days, while the control group (n = 6) remained unexposed. The testes were processed with routine paraffin histology and sectioned. They were stained with hematoxylin-eosin, caspase 3, and Ki-67 and then photographed. No changes were observed between the groups (p > 0.05). The interstitial connective tissue and cells of the exposed group were of normal morphology. No abnormalities in the histological appearance of the seminiferous tubules, including the spermatogenic cycle stage, were observed. Our study demonstrated that mobile phones with a low specific absorption rate have no harmful effects on pubertal rat testicles. © The Author(s) 2013.

  8. Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.

    Science.gov (United States)

    Dong, Hongxin; Csernansky, Cynthia A; Chu, Yunxiang; Csernansky, John G

    2003-10-10

    The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.

  9. Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat

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    Jianan Geng

    2018-01-01

    Full Text Available Diabetic nephropathy (DN is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2 and the expression of tissue transglutaminase (tTG, which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.

  10. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chih-Chung, E-mail: cchuang@mail.ncku.edu.tw [Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan (China); Chen, Wei-Tsen [Department of Electrical Engineering, Fu Jen Catholic University, New Taipei City 24205, Taiwan (China)

    2014-01-15

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals.

  11. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    International Nuclear Information System (INIS)

    Huang, Chih-Chung; Chen, Wei-Tsen

    2014-01-01

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals

  12. ATLAS helps shed light on the retina

    CERN Multimedia

    2007-01-01

    Technology developed for high-energy physics has led to the discovery of a retinal cell that eluded biologists for 40 years. The 512 electrode array, inspired by silicon microstrip detector technology in ATLAS, records the electrical activity of retinal neurones.ATLAS expertise have crossed over to biology enabling the discovery of a retinal cell type that may help humans see motion. The research, carried out by ATLAS collaborators at the University of California, Santa Cruz, and by neurobiologists at the Salk Institute in La Jolla, California, appeared in the 10 October issue of the Journal of Neuroscience and may help open biologists’ eyes to the uses of techniques developed in high-energy physics. At least 22 different types of primate retinal output cell are known from anatomical studies, but the functions of only a handful of these have been determined. The cells discovered have been ca...

  13. Increased risk of cataract development in WNIN-obese rats due to accumulation of intralenticular sorbitol.

    Science.gov (United States)

    Reddy, Paduru Yadagiri; Giridharan, Nappan Veettil; Balakrishna, Nagalla; Validandi, Vakdevi; Pullakhandam, Raghu; Reddy, Geereddy Bhanuprakash

    2013-05-01

    Epidemiological studies have reported an association between obesity and increased incidence of ocular complications including cataract, yet the underlying biochemical and molecular mechanisms remained unclear. Previously we had demonstrated accumulation of sorbitol in the lens of obese rats (WNIN/Ob) and more so in a related strain with impaired glucose tolerance (WNIN/GR-Ob). However, only a few (15-20%) WNIN/Ob and WNIN/GR-Ob rats develop cataracts spontaneously with age. To gain further insights, we investigated the susceptibility of eye lens proteins of these obese rat strains to heat- and UV-induced aggregation in vitro, lens opacification upon glucose-mediated sorbitol accumulation ex vivo, and onset and progression of cataract was followed by galactose feeding and streptozotocin (STZ) injection. The results indicated increased susceptibility toward heat- or UV-induced aggregation of lens proteins in obese animals compared to their littermate lean controls. Further, in organ culture studies glucose-induced sorbitol accumulation was found to be higher and thus the lens opacification was faster in obese animals compared to their lean littermates. Also, the onset and progression of galactose- or STZ-induced cataractogenesis was faster in obese animals compared to lean control. These results together with our previous observations suggest that obesity status could lead to hyperaccumulation of sorbitol in eye lens, predisposing them to cataract, primarily by increasing their susceptibility to environmental and/or physiological factors. Further, intralenticular sorbitol accumulation beyond a threshold level could lead to cataract in WNIN/Ob and WNIN/GR-Ob rats. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  14. NADPH-diaphorase expression in the Meibomian glands of rat palpebra in postnatal development

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    D. Kluchova

    2010-11-01

    Full Text Available In the current study, we aimed at investigating the presence of nitric oxide synthase (NOS positive nerve fibers in rat meibomian glands (MGs at various stages of development. There is good evidence to suggest that nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d is a surrogate for neuronal nitric oxide synthase (NOS. Sections of the central, upper eyelids of Wistar rats were processed histochemically for NADPH-d to investigate the presence and distribution of NOS-positive nerve fibers at the following time points: day 1 and weeks 1, 2 and 3 post partum, and in adult controls. At day 1, MG acini were lightly stained and located at a distance from the mucosal border. Vessels were accompanied by intensely stained NADPH-d positive nerve fibers. At the week 1 time point, both the vessels and the NADPH-d positive fibers were still present, but less numerous. MGs were now closer to the mucosa, so that the submucosa was thinner. The acini were mostly pale but occasionally darker. At week 3, there were fewer blood vessels in both the submucosa and within the septa. Darker acini were more common than lightly stained acini. NADPH-d positive dots were observed in the vicinity of the MGs. At the week 3 time point, MGs were adjacent to the mucosal border and stained more intensely than at earlier times; almost all acini were stained. The microscopic appearances were almost identical with those of adult palpebra. Submucosal and septal blood vessels and NADPH-d positive nerve fibers were less numerous. NADPH-d histochemical staining confirmed differences in the density of stained nerve fibers at different developmental stages. The greatest density of NADPH-d -positive nerve fibers occurred in 1-day-old rats whereas they were less numerous in adult rat eyelids. Nerves innervating MGs utilize nitric oxide (NO as a neurotransmitter mostly in early developmental stages and this need thereafter decreases and stabilizes at 3 weeks postnatally.

  15. Meduloepitelioma teratóide da retina: relato de caso Teratoid medulloepithelioma of the retina: case report

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    Ramon Coral Ghanem

    2004-06-01

    Full Text Available O meduloepitelioma é um tumor intra-ocular congênito originário do epitélio medular primitivo que, por sua vez, é responsável pela formação do epitélio não pigmentado do corpo ciliar. Ocorre geralmente na infância, de forma unilateral, acometendo o corpo ciliar. O objetivo deste trabalho é documentar um caso raro de meduloepitelioma teratóide originário da retina. Paciente de nove anos, feminina, apresentava baixa acuidade visual (AV, estrabismo e leucocoria no olho esquerdo (OE. A AV era de 1,0 no olho direito e movimentos de mão no OE. Foi observada tumoração retrocristaliniana branco-acinzentada no OE, aparentemente subretiniana, vascularizada, de grande extensão, com alterações císticas na sua superfície. Foram realizadas tomografia de crânio e órbitas e ecografia ocular. A paciente foi submetida à enucleação com suspeita clínica de retinoblastoma. Pelo aspecto histopatológico foi feito o diagnóstico de meduloepitelioma teratóide benigno originário da retina. Na maioria dos casos apresentados na literatura o meduloepitelioma tem origem a partir do epitélio não pigmentado do corpo ciliar. No nosso caso, a neoplasia parece ter tido origem a partir da retina, já que os cortes revelaram epitélio do corpo ciliar preservado e não foi reconhecida a estrutura normal da retina. Embora o tumor apresentado neste relato tenha sido classificado como benigno, o fato de ser lesão de grandes proporções e de crescimento aparentemente recente, justifica a conduta cirúrgica empregada. O tratamento do meduloepitelioma deve objetivar a intervenção cirúrgica precoce, na tentativa de se evitar a disseminação extra-ocular.Medulloepithelioma is a congenital intraocular tumor that usually arises from the primitive medullary epithelium that is destined to form the nonpigmented ciliary epithelium of the ciliary body. It occurs most frequently in early childhood and is unilateral. This report documents a rare case of

  16. The potential of cell sheet technique on the development of hepatocellular carcinoma in rat models.

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    Alaa T Alshareeda

    Full Text Available Hepatocellular carcinoma (HCC is considered the 3rd leading cause of death by cancer worldwide with the majority of patients were diagnosed in the late stages. Currently, there is no effective therapy. The selection of an animal model that mimics human cancer is essential for the identification of prognostic/predictive markers, candidate genes underlying cancer induction and the examination of factors that may influence the response of cancers to therapeutic agents and regimens. In this study, we developed a HCC nude rat models using cell sheet and examined the effect of human stromal cells (SCs on the development of the HCC model and on different liver parameters such as albumin and urea.Transplanted cell sheet for HCC rat models was fabricated using thermo-responsive culture dishes. The effect of human umbilical cord mesenchymal stromal cells (UC-MSCs and human bone marrow mesenchymal stromal cells (BM-MSCs on the developed tumour was tested. Furthermore, development of tumour and detection of the liver parameter was studied. Additionally, angiogenesis assay was performed using Matrigel.HepG2 cells requires five days to form a complete cell sheet while HepG2 co-cultured with UC-MSCs or BM-MSCs took only three days. The tumour developed within 4 weeks after transplantation of the HCC sheet on the liver of nude rats. Both UC-MSCs and BM-MSCs improved the secretion of liver parameters by increasing the secretion of albumin and urea. Comparatively, the UC-MSCs were more effective than BM-MSCs, but unlike BM-MSCs, UC-MSCs prevented liver tumour formation and the tube formation of HCC.Since this is a novel study to induce liver tumour in rats using hepatocellular carcinoma sheet and stromal cells, the data obtained suggest that cell sheet is a fast and easy technique to develop HCC models as well as UC-MSCs have therapeutic potential for liver diseases. Additionally, the data procured indicates that stromal cells enhanced the fabrication of HepG2

  17. Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat.

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    Angelina Swali

    Full Text Available Poor iron status is a global health issue, affecting two thirds of the world population to some degree. It is a particular problem among pregnant women, in both developed and developing countries. Feeding pregnant rats a diet deficient in iron is associated with both hypertension and reduced nephron endowment in adult male offspring. However, the mechanistic pathway leading from iron deficiency to fetal kidney development remains elusive. This study aimed to establish the underlying processes associated with iron deficiency by assessing gene and protein expression changes in the rat embryo, focussing on the responses occurring at the time of the nutritional insult. Analysis of microarray data showed that iron deficiency in utero resulted in the significant up-regulation of 979 genes and down-regulation of 1545 genes in male rat embryos (d13. Affected processes associated with these genes included the initiation of mitosis, BAD-mediated apoptosis, the assembly of RNA polymerase II preinitiation complexes and WNT signalling. Proteomic analyses highlighted 7 proteins demonstrating significant up-regulation with iron deficiency and the down-regulation of 11 proteins. The main functions of these key proteins included cell proliferation, protein transport and folding, cytoskeletal remodelling and the proteasome complex. In line with our recent work, which identified the perturbation of the proteasome complex as a generalised response to in utero malnutrition, we propose that iron deficiency alone leads to a more specific failure in correct protein folding and transport. Such an imbalance in this delicate quality-control system can lead to cellular dysfunction and apoptosis. Therefore these findings offer an insight into the underlying mechanisms associated with the development of the embryo during conditions of poor iron status, and its health in adult life.

  18. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Science.gov (United States)

    Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

    2016-01-01

    Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  19. Critical androgen-sensitive periods of rat penis and clitoris development.

    Science.gov (United States)

    Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

    2010-02-01

    Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW +/- postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5-e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1-24 or at puberty (d15-24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14-postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15-24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its

  20. {sup 26}Al incorporation into the brain of rat fetuses through the placental barrier and subsequent metabolism in postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, Sakae, E-mail: yumoto-s@viola.ocn.ne.j [Yumoto Institute of Neurology, Kawadacho 6-11, Shinjuku-ku, Tokyo 162-0054 (Japan); Nagai, Hisao [College of Humanities and Sciences, Nihon University, Tokyo (Japan); Kakimi, Shigeo [Faculty of Medicine, Nihon University, Tokyo (Japan); Matsuzaki, Hiroyuki [School of Engineering, The University of Tokyo, Tokyo (Japan)

    2010-04-15

    Aluminium (Al) inhibits prenatal and postnatal development of the brain. We used {sup 26}Al as a tracer, and measured {sup 26}Al incorporation into rat fetuses through the placental barrier by accelerator mass spectrometry (AMS). From day 15 to day 18 of gestation, {sup 26}AlCl{sub 3} was subcutaneously injected into pregnant rats. Considerable amounts of {sup 26}Al were measured in the tissues of newborn rats immediately after birth. The amounts of {sup 26}Al in the liver and kidneys decreased rapidly during postnatal development. However, approximately 15% of {sup 26}Al incorporated into the brain of fetuses remained in the brain of adult rats 730 days after birth.

  1. What the laboratory rat has taught us about social play behavior: role in behavioral development and neural mechanisms.

    Science.gov (United States)

    Vanderschuren, Louk J M J; Trezza, Viviana

    2014-01-01

    Social play behavior is the most vigorous and characteristic form of social interaction displayed by developing mammals. The laboratory rat is an ideal species to study this behavior, since it shows ample social play that can be easily recognized and quantified. In this chapter, we will first briefly describe the structure of social play behavior in rats. Next, we will discuss studies that used social isolation rearing during the period in life when social play is most abundant to investigate the developmental functions of social play behavior in rats, focusing on the consequences of play deprivation on social, cognitive, emotional, and sensorimotor development. Last, we will discuss the neural substrates of social play behavior in rats, with emphasis on the limbic corticostriatal circuits that underlie emotions and their influence on behavior.

  2. Wnt signaling in form deprivation myopia of the mice retina.

    Directory of Open Access Journals (Sweden)

    Mingming Ma

    Full Text Available BACKGROUND: The canonical Wnt signaling pathway plays important roles in cellular proliferation and differentiation, axonal outgrowth, cellular maintenance in retinas. Here we test the hypothesis that elements of the Wnt signaling pathway are involved in the regulation of eye growth and prevention of myopia, in the mouse form-deprivation myopia model. METHODOLOGY/PRINCIPAL FINDINGS: (1 One hundred twenty-five C57BL/6 mice were randomly distributed into form-deprivation myopia and control groups. Form-deprivation myopia (FDM was induced by suturing the right eyelid, while the control group received no treatment. After 1, 2, and 4 weeks of treatment, eyes were assessed in vivo by cycloplegic retinoscopic refraction and axial length measurement by photography or A-scan ultrasonography. Levels of retinal Wnt2b, Fzd5 and β-catenin mRNA and protein were evaluated using RT-PCR and western blotting, respectively. (2 Another 96 mice were divided into three groups: control, drugs-only, and drugs+FDM (by diffuser. Experimentally treated eyes in the last two groups received intravitreal injections of vehicle or the proteins, DKK-1 (Wnt-pathway antagonist or Norrin (Wnt-pathway agonist, once every three days, for 4 injections total. Axial length and retinoscopic refraction were measured on the 14th day of form deprivation. Following form-deprivation for 1, 2, and 4 weeks, FDM eyes had a relatively myopic refractive error, compared with contralateral eyes. There were no significant differences in refractive error between right and left eye in control group. The amounts of Wnt2b, Fzd5 and β-catenin mRNA and protein were significantly greater in form-deprived myopia eyes than in control eyes.DKK-1 (antagonist reduced the myopic shift in refractive error and increase in axial elongation, whereas Norrin had the opposite effect in FDM eyes. CONCLUSIONS/SIGNIFICANCE: Our studies provide the first evidence that the Wnt2b signaling pathway may play a role in the

  3. Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome.

    Science.gov (United States)

    Aleman, Tomas S; Ventura, Camila V; Cavalcanti, Milena M; Serrano, Leona W; Traband, Anastasia; Nti, Akosua A; Gois, Adriana L; Bravo-Filho, Vasco; Martins, Thayze T; Nichols, Charles W; Maia, Mauricio; Belfort, Rubens

    2017-10-01

    A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS). To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency. The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles. Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (<30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer

  4. Distribution of light in the human retina under natural viewing conditions

    Science.gov (United States)

    Gibert, Jorge C.

    Age-related macular degeneration (AMD) is the leading cause of blindness inAmerica. The fact that AMD wreaks most of the damage in the center of the retina raises the question of whether light, integrated over long periods, is more concentrated in the macula. A method, based on eye-tracking, was developed to measure the distribution of light in the retina under natural viewing conditions. The hypothesis was that integrated over time, retinal illumination peaked in the macula. Additionally a possible relationship between age and retinal illumination was investigated. The eye tracker superimposed the subject's gaze position on a video recorded by a scene camera. Five informed subjects were employed in feasibility tests, and 58 naive subjects participated in 5 phases. In phase 1 the subjects viewed a gray-scale image. In phase 2, they observed a sequence of photographic images. In phase 3 they viewed a video. In phase 4, they worked on a computer; in phase 5, the subjects walked around freely. The informed subjects were instructed to gaze at bright objects in the field of view and then at dark objects. Naive subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, and the video provided by the scene camera, the cumulative light distribution on the retina was calculated for ˜15° around the fovea. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark objects respectively. The light distribution maps obtained from the naive subjects presented a tendency to peak in the macula for phases 1, 2, and 3, a consistent tendency in phase 4 and a variable tendency in phase 5. The feasibility of using an eye-tracker system to measure the distribution of light in the retina was demonstrated, thus helping to understand the role played by light exposure in the etiology of AMD. Results showed that a tendency for light to peak in the macula is a characteristic of some

  5. A Comparative Analysis of Perinatal Development of Barrel Cortex in Rat, Mouse and Guinea Pig Using Acetylcholinesterase Histochemistry

    OpenAIRE

    ŞENDEMİR, Erdoğan

    2014-01-01

    The role of acetylcholinesterase (AChE) in the developing neocortex was reexamined by comparing its expression in rats, mice and guinea pigs, following the protocol for acetylcholinesterase histochemistry (described in Sendemir et al., 1996) in order to determine the suitability of the breeding colony at UludaÛ University for use as an animal model. A total of 103 pups as well as two adult animals of each species were used. In the rat pups, acetylcholinesterase-rich patches were d...

  6. Resistant starch but not enzymatic treated waxy maize delays development of diabetes in Zucker Diabetic Fatty rats

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou; Hermansen, Kjeld; Pedersen, Sven

    2017-01-01

    excretion during week 8 in rats fed the GLU and EMS diets than that of rats fed S and RS showed that they were diabetic. Urinary nontargeted metabolomics revealed that the diabetic state of rats fed S, GLU, and EMS diets influenced microbial metabolism, as well as amino acid, lipid, and vitamin metabolism......Background: The incidence of type 2 diabetes (T2D) is increasing worldwide, and nutritional management of circulating glucose may be a strategic tool in the prevention of T2D. Objective: We studied whether enzymatically modified waxy maize with an increased degree of branching delayed the onset...... glucose concentrations in feed-deprived rats, none of the groups developed diabetes. However, in week 9, plasma glucose after feed deprivation was significantly lower in rats fed the S and RS diets (13.5 mmol/L) than in rats fed the GLU and EMS diets (17.0–18.9 mmol/L), and rats fed RS had lower HbA1c (4...

  7. Patterns of x-radiation-induced Schwann cell development in spinal cords of immature rats

    International Nuclear Information System (INIS)

    Gilmore, S.A.; Heard, J.K.; Leiting, J.E.

    1983-01-01

    Schwann cells, Schwann cell myelin, and connective tissue components develop in the spinal cord of the immature rat following exposure to x-rays. For the purposes of this paper, these intraspinal peripheral nervous tissue constituents are referred to as IPNT. A series of investigations are in progress to elucidate factors related to the development of IPNT, and the present study is a light microscopic evaluation of the relationship between the amount of radiation administered (1,000-3,000R) to the lumbosacral spinal cord in 3-day-old rats and the incidence and distribution of IPNT at intervals up to 60 days postirradiation (P-I). The results showed that IPNT was present in only 33% of the rats exposed to 1,000R, whereas its presence was observed in 86% or more of those in the 2,000-, 2,500-, and 3,000R groups. The distribution of IPNT was quite limited in the 1,000R group, where it was restricted to the spinal cord-dorsal root junction and was found in only a few sections within the irradiated area. The distribution was more widespread with increasing amounts of radiation, and IPNT occupied substantial portions of the dorsal funiculi and extended into the dorsal gray matter in the 3,000R group. In all aR mals developing IPNT in the groups receiving 2,000R or more, the IPNT was present in essentially all sections from the irradiated area. Further studies will compare in detail spinal cords exposed to 1,000R in which IPNT is an infrequent, limited occurrence with those exposed to higher doses where IPNT occurs in a more widespread fashion in essentially all animals

  8. Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring.

    Science.gov (United States)

    Mychasiuk, R; Harker, A; Ilnytskyy, S; Gibb, R

    2013-06-25

    Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global DNA methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered DNA methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and DNA methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. The effect of food hardness on the development of dental caries in alloxan-induced diabetic rats.

    Science.gov (United States)

    Nakahara, Yutaka; Sano, Tomoya; Kodama, Yasushi; Ozaki, Kiyokazu; Matsuura, Tetsuro

    2013-01-01

    We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.

  10. The Effect of Food Hardness on the Development of Dental Caries in Alloxan-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Yutaka Nakahara

    2013-01-01

    Full Text Available We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.

  11. Low-dose effects of bisphenol A on mammary gland development in rats

    DEFF Research Database (Denmark)

    Egebjerg, Karen Mandrup; Boberg, Julie; Isling, Louise Krag

    2016-01-01

    was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose–response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg...... intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may...

  12. [The dinitrosyl-iron complexes with cysteine block the development of experimental endometriosis in rats].

    Science.gov (United States)

    Burgova, E N; Tkachev, N A; Vanin, A F

    2012-01-01

    It has been shown that the administration of 0,5 ml of 5 mM aqueous solution of dinitrosyl-iron complexes (DNIC) with cysteine alleviated the development of experimental endometriosis in rats induced by surgical way: the size of endometriomes decreased 1.85 times when the DNIC was added every day during 10 days. The effect was suggested to be due to cytotoxic action of NO molecules and nitrosonium ions (NO+) released from rapidly decomposed DNIC in animal organism on endometriome tissues.

  13. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury

    DEFF Research Database (Denmark)

    Lee, I. Hui; Lindqvist, Eva; Kiehn, Ole

    2005-01-01

    Spinal cord injury induces a complex cascade of degenerative and remodeling events evolving over time. The possible roles of changed intercellular communication via gap junctions after spinal cord injury (SCI) have remained relatively unexplored. We investigated the temporospatial expression...... patterns of gap junctional genes and proteins, connexin 43 (Cx43), Cx36, and Cx32, by in situ hybridization and immunohistochemistry in the rat neonatal, adult normal, and adult injured spinal cord. Cx36 was strongly expressed in immature neurons, and levels declined markedly during development, whereas Cx...

  14. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    DEFF Research Database (Denmark)

    Dean, Afshan; van den Driesche, Sander; Wang, Yili

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development...... smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise...

  15. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    International Nuclear Information System (INIS)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh; Godbole, Madan M.

    2010-01-01

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1α, NRF-1α and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  16. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Godbole, Madan M., E-mail: madangodbole@yahoo.co.in [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India)

    2010-07-02

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  17. Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar Suman

    2016-01-01

    Full Text Available Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD and low dose of streptozotocin (STZ at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia (increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide, and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP, decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.

  18. Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats.

    Science.gov (United States)

    Suman, Rajesh Kumar; Ray Mohanty, Ipseeta; Borde, Manjusha K; Maheshwari, Ujwala; Deshmukh, Y A

    2016-01-01

    Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.

  19. Physical and behavioral development in rats after late prenatal exposure to diazepam.

    Science.gov (United States)

    Lall, S B; Sahoo, R N

    1990-01-01

    The effect of late prenatal exposure to diazepam (DZP) on physical and behavioral development of rat pups was investigated. Prenatal exposure to DZP (20 mg/kg, sc, in last week of pregnancy) did not alter litter size and no gross malformations were noted at birth. Body weight at birth and subsequent weight gain was significantly less in these animals. The development of reflexes and neuromuscular maturation was normal. Open field locomotor activity and rearing scores were significantly decreased. Test of social play in juvenile rats revealed normal pattern of sexual dimorphism with increased masculinized behavior. Acquisition and retention of passive avoidance task was not affected by DZP exposure, however, retention of brightness discrimination task was significantly decreased. The hypnotic effect of a challenge dose of DZP and convulsive effect of pentylene tetrazole remained unaltered. Open field activity test in adult animals revealed increased ambulation. Probe dose of amphetamine in these animals caused paradoxical decrease in activity. It is concluded that exposure to high dose of DZP during late prenatal period may not manifest in physical or neuromuscular impairment during early development period, except for weight loss, however, it may have long term effects on behavior becoming manifest in adolescence and at maturity.

  20. Physiological properties of afferents to the rat cerebellum during normal development and after postnatal x irradiation

    International Nuclear Information System (INIS)

    Puro, D.G.

    1975-01-01

    The consequences of an altered cerebellar cortical development on afferent transmission and terminal organization were analyzed in adult rats which had received x irradiation to the cerebellum postnatally. Rats, anesthetized with 0.5 percent halothane, were studied in various ages from day 3 to adult. The ascending mossy and climbing fiber systems were activated by electrical stimulation of the limbs with needle electrodes. Stimulation of the motor cortex activated the descending climbing fiber pathways. Extracellular responses from cerebellar Purkinje cells were observed on an oscilloscope as poststimulus time histograms were constructed ''on-line''. Conclusions and assertions include: (1) Synaptogenesis between incoming afferent fibers and target neurons takes place early in cerebellar cortical development. (2) Mossy fiber transmission is mature before the bulk of cerebellar synaptogenesis occurs. (3) The ascending and descending components of the climbing fiber system mature, with respect to latency, in synchrony. (4) The terminal synaptic organization has little effect on the development of transmission characteristics in these afferent systems. (5) One possible mechanism by which an adult neural structure can have an abnormal synaptic organization is to maintain immature synaptic relationships due to the neonatal loss of interneurons

  1. Immunologic differentiation of two high-affinity neurotensin receptor isoforms in the developing rat brain.

    Science.gov (United States)

    Boudin, H; Lazaroff, B; Bachelet, C M; Pélaprat, D; Rostène, W; Beaudet, A

    2000-09-11

    Earlier studies have demonstrated overexpression of NT1 neurotensin receptors in rat brain during the first 2 weeks of life. To gain insight into this phenomenon, we investigated the identity and distribution of NT1 receptor proteins in the brain of 10-day-old rats by using two different NT1 antibodies: one (Abi3) directed against the third intracellular loop and the other (Abi4) against the C-terminus of the receptor. Immunoblot experiments that used Abi3 revealed the presence of two differentially glycosylated forms of the NT1 receptor in developing rat brain: one migrating at 54 and the other at 52 kDa. Whereas the 54-kDa form was expressed from birth to adulthood, the 52-kDa form was detected only at 10 and 15 days postnatal. Only the 52-kDa isoform was recognized by Abi4. By immunohistochemistry, both forms of the receptor were found to be predominantly expressed in cerebral cortex and dorsal hippocampus, in keeping with earlier radioligand binding and in situ hybridization data. However, whereas Abi4 immunoreactivity was mainly concentrated within nerve cell bodies and extensively colocalized with the Golgi marker alpha-mannosidase II, Abi3 immunoreactivity was predominantly located along neuronal processes. These results suggest that the transitorily expressed 52-kDa protein corresponds to an immature, incompletely glycosylated and largely intracellular form of the NT1 receptor and that the 54-kDa protein corresponds to a mature, fully glycosylated, and largely membrane-associated form. They also indicate that antibodies directed against different sequences of G-protein-coupled receptors may yield isoform-specific immunohistochemical labeling patterns in mammalian brain. Finally, the selective expression of the short form of the NT1 receptor early in development suggests that it may play a specific role in the establishment of neuronal circuitry. Copyright 2000 Wiley-Liss, Inc.

  2. Development of a hyperpolarized 129Xe system on 3T for the rat lungs

    International Nuclear Information System (INIS)

    Sato, Hiroshi; Enmi, Jun-ichiro; Hayashi, Takuya

    2004-01-01

    MRI (magnetic resonance imaging) with 129 Xe has gained much attention as a diagnostic methodology because of its affinity for lipids and possible polarization. The quantitative estimation of net detectability and stability of hyperpolarized 129 Xe in the dissolved phase in vivo is valuable to the development of clinical applications. The goal of this study was to develop a stable hyperpolarized 129 Xe experimental 3T system to statistically analyze the dissolved-phase 129 Xe signal in the rat lungs. The polarization of 129 Xe with buffer gases at the optical pumping cell was measured under adiabatic fast passage against the temperature of an oven and laser absorption at the cell. The gases were insuffiated into the lungs of Sprague-Dawley rats (n=15, 400-550 g) through an endotracheal tube under spontaneous respiration. Frequency-selective spectroscopy was performed for the gas phase and dissolved phase. We analyzed the 129 Xe signal in the dissolved phase to measure the chemical shift, T 2 * , delay and its ratio in a rat lungs on 3T. The polarizer was able to produce polarized gas (1.1±0.47%, 120 cm 3 ) hundreds of times with the laser absorption ratio (25%) kept constant at the cell. The optimal buffer gas ratio of 25-50% rendered the maximum signal in the dissolved phase. Two dominant peaks of 211.8±0.9 and 201.1±0.6 ppm were observed with a delay of 0.4±0.9 and 0.9±1.0 s from the gas phase spectra. The ratios of their average signal to that of the gas phase were 5.6±5.2% and 4.4±4.7%, respectively. The T 2 * of the air space in the lungs was 2.5±0.5 ms, which was 3.8 times shorter than that in a syringe. We developed a hyperpolarized 129 Xe experimental system using a 3T MRI scanner that yields sufficient volume and polarization and quantitatively analyzed the dissolved-phase 129 Xe signal in the rat lungs. (author)

  3. Evidence for RPE65-independent vision in the cone-dominated zebrafish retina.

    Science.gov (United States)

    Schonthaler, Helia B; Lampert, Johanna M; Isken, Andrea; Rinner, Oliver; Mader, Andreas; Gesemann, Matthias; Oberhauser, Vitus; Golczak, Marcin; Biehlmaier, Oliver; Palczewski, Krzysztof; Neuhauss, Stephan C F; von Lintig, Johannes

    2007-10-01

    An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.

  4. Toward automated selective retina treatment (SRT): an optical microbubble detection technique

    Science.gov (United States)

    Seifert, Eric; Park, Young-Gun; Theisen-Kunde, Dirk; Roh, Young-Jung; Brinkmann, Ralf

    2018-02-01

    Selective retina therapy (SRT) is an ophthalmological laser technique, targeting the retinal pigment epithelium (RPE) with repetitive microsecond laser pulses, while causing no thermal damage to the neural retina, the photoreceptors as well as the choroid. The RPE cells get damaged mechanically by microbubbles originating, at the intracellular melanosomes. Beneficial effects of SRT on Central Serous Retinopathy (CSR) and Diabetic Macula Edema (DME) have already been shown. Variations in the transmission of the anterior eye media and pigmentation variation of RPE yield in intra- and inter- individual thresholds of the pulse energy required for selective RPE damage. Those selective RPE lesions are not visible. Thus, dosimetry-systems, designed to detect microbubbles as an indicator for RPE cell damage, are demanded elements to facilitate SRT application. Therefore, a technique based on the evaluation of backscattered treatment light has been developed. Data of 127 spots, acquired during 10 clinical treatments of CSR patients, were assigned to a RPE cell damage class, validated by fluorescence angiography (FLA). An algorithm has been designed to match the FLA based information. A sensitivity of 0.9 with a specificity close to 1 is achieved. The data can be processed within microseconds. Thus, the process can be implemented in existing SRT lasers with an automatic pulse wise increasing energy and an automatic irradiation ceasing ability to enable automated treatment close above threshold to prevent adverse effects caused by too high pulse energy. Alternatively, a guidance procedure, informing the treating clinician about the adequacy of the actual settings, is possible.

  5. Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina.

    Science.gov (United States)

    Choi, Hannah; Zhang, Lei; Cembrowski, Mark S; Sabottke, Carl F; Markowitz, Alexander L; Butts, Daniel A; Kath, William L; Singer, Joshua H; Riecke, Hermann

    2014-09-15

    In many forms of retinal degeneration, photoreceptors die but inner retinal circuits remain intact. In the rd1 mouse, an established model for blinding retinal diseases, spontaneous activity in the coupled network of AII amacrine and ON cone bipolar cells leads to rhythmic bursting of ganglion cells. Since such activity could impair retinal and/or cortical responses to restored photoreceptor function, understanding its nature is important for developing treatments of retinal pathologies. Here we analyzed a compartmental model of the wild-type mouse AII amacrine cell to predict that the cell's intrinsic membrane properties, specifically, interacting fast Na and slow, M-type K conductances, would allow its membrane potential to oscillate when light-evoked excitatory synaptic inputs were withdrawn following photoreceptor degeneration. We tested and confirmed this hypothesis experimentally by recording from AIIs in a slice preparation of rd1 retina. Additionally, recordings from ganglion cells in a whole mount preparation of rd1 retina demonstrated that activity in AIIs was propagated unchanged to elicit bursts of action potentials in ganglion cells. We conclude that oscillations are not an emergent property of a degenerated retinal network. Rather, they arise largely from the intrinsic properties of a single retinal interneuron, the AII amacrine cell. Copyright © 2014 the American Physiological Society.

  6. TOPOGRAPHIC ORGANIZATION AND SPECIALIZED AREAS IN THE RETINA OF Callopistes palluma: GANGLION CELL LAYER

    OpenAIRE

    Inzunza, Oscar; Barros B., Zitta; Bravo, Hermes

    1998-01-01

    In this paper we analyze the topographic distribution and cell body size of neurons (ganglion and displaced amacrine) of layer 8 of the retina in the chilean reptile Callopistes palluma; using whole mount retinaswith nissl stain. Callopistes palluma retina has an area centralis without fovea in which the ganglion cell density amounts 20.000 cells / µm2 while the displaced amacrine neurons is about 7.000 cells / µm2. This neural density decreased gradually towards the peripheral retina. A hor...

  7. Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina.

    Science.gov (United States)

    Meguro, Akira; Ideta, Hidenao; Ota, Masao; Ito, Norihiko; Ideta, Ryuichi; Yonemoto, Junichi; Takeuchi, Masaki; Uemoto, Riyo; Nishide, Tadayuki; Iijima, Yasuhito; Kawagoe, Tatsukata; Okada, Eiichi; Shiota, Tomoko; Hagihara, Yuta; Oka, Akira; Inoko, Hidetoshi; Mizuki, Nobuhisa

    2012-01-01

    Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6), OR = 0.63 and Pc = 1.0 × 10(-5), OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

  8. Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina.

    Directory of Open Access Journals (Sweden)

    Akira Meguro

    Full Text Available Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4 gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6, OR = 0.63 and Pc = 1.0 × 10(-5, OR = 0.69 in a total of 574 patients and 608 controls, respectively. Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

  9. Low endogenous glucocorticoid allows induction of kidney cortical cyclooxygenase-2 during postnatal rat development

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Stubbe, Jane; Skøtt, Ole

    2004-01-01

    COX-2 in these cells. Thus low plasma concentrations of corticosterone allowed for cortical and medullary COX-2 induction during postnatal kidney development. Increased circulating glucocorticoid in the postnatal period may damage late renal development through inhibition of COX-2.......In postnatal weeks 2-4, cyclooxygenase-2 (COX-2) is induced in the rat kidney cortex where it is critically involved in final stages of kidney development. We examined whether changes in circulating gluco- or mineralocorticosteroids or in their renal receptors regulate postnatal COX-2 induction....... Plasma corticosterone concentration peaked at birth, decreased to low levels at days 3-13, and increased to adult levels from day 22. Aldosterone peaked at birth and then stabilized at adult levels. Gluco- and mineralocorticoid receptor (GR and MR) mRNAs were expressed stably in kidney before, during...

  10. [VEGF expression in dog retina after chorioretinal venous anastomosis].

    Science.gov (United States)

    Lu, Ning; Li, Zhihui; Sun, Xianli; Wang, Guanglu; Zhang, Feng; Peng, Xiaoyan

    2002-09-01

    To identify changes in vascular endothelial growth factor (VEGF) expression in the dog retina after laser-induced chorioretinal venous anastomosis (CRVA), in order to find out the relationship between CRVA treatment and the related neovascular complications. Immediately after branch retinal vein occlusion (BRVO) model was made in 5 eyes of 5 normal dogs, CRVA treatment was done over a small tributary vein in the drainage distribution of the occluded vein. In each eye, there were 2 - 3 treatment sites. Four to six weeks later, a repeated treatment was given if the first treatment failed to show the anastomosis. The treatment sites with successful CRVA were divided into two groups: the small laser spot group, which received one treatment and the big laser spot group, which received more than one treatment. The expression of VEGF was investigated immunohistochemically in the treatment sites with successful anastomoses and in the 5 normal fellow eyes (control). There were totally 10 successful anastomoses in the 5 experimental eyes, among which, five received one treatment and the other 5 received more than one treatment. On fundus examination, the small laser spots were round and small, and the big laser spots were large with local proliferation. VEGF immunoreactivity was absent/weak in the normal dog retina, and remained unchanged in the small laser spot group, but somewhat increased in the big laser spot group. No neovascular complications occurred. All immunostaining experiments were accompanied by proper controls and none of the negative controls showed any immunoreactivity. Proper laser treatment can induce CRVA quite safely in nonischemic dog retina, which does not cause changes in the expression of VEGF, but severe laser damage in the treatment site can cause increased VEGF expression which may be related to neovascular complications.

  11. Survey of intravitreal injection techniques among retina specialists in Israel

    Directory of Open Access Journals (Sweden)

    Segal O

    2016-06-01

    Full Text Available Ori Segal,1,2 Yael Segal-Trivitz,1,3 Arie Y Nemet,1,2 Noa Geffen,1,2 Ronit Nesher,1,2 Michael Mimouni4 1Department of Ophthalmology, Meir Medical Center, Kfar Saba, 2The Sackler School of Medicine, Tel Aviv University, Tel Aviv, 3Department of Psychiatry, Geha Psychiatric Hospital, Petah Tikva, 4Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel Purpose: The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. Methods: All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. Results: Overall, 66% (52/79 completed the survey. Most (98% do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71% use sterile surgical draping. All respondents apply topical analgesics and a majority (69% measure the distance from the limbus to the injection site. A minority (21% displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%. Less than half routinely assess postinjection optic nerve perfusion (44%. A majority (92% apply prophylactic antibiotics immediately after the injection. Conclusion: The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques

  12. Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex

    International Nuclear Information System (INIS)

    Guo, Bao-Qiang; Yan, Chong-Huai; Cai, Shi-Zhong; Yuan, Xiao-Bing; Shen, Xiao-Ming

    2013-01-01

    Highlights: ► Low level MeHg exposure causes migratory defect of rat cerebrocortical neurons. ► The migration defect is due to the impact of MeHg on the neuronal migration itself. ► Rho GTPases seem to be involved in MeHg-induced disruption of neuronal migration. -- Abstract: We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11–21. Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats. Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself. Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway. In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg

  13. Sex difference in mecp2 expression during a critical period of rat brain development.

    Science.gov (United States)

    Kurian, Joseph R; Forbes-Lorman, Robin M; Auger, Anthony P

    2007-09-01

    Pervasive developmental disorder is a classification covering five related conditions including the neurodevelopmental disorder Rett syndrome (RTT) and autism. Of these five conditions, only RTT has a known genetic cause with mutations in Methyl-CpG-binding protein 2 (MeCP2), a global repressor of gene expression, responsible for the majority of RTT cases. However, recent evidence indicates that reduced MeCP2 expression or activity is also found in autism and other disorders with overlapping phenotypes. Considering the sex difference in autism diagnosis, with males diagnosed four times more often than females, we questioned if a sex difference existed in the expression of MeCP2, in particular within the amygdala, a region that develops atypically in autism. We found that male rats express significantly less mecp2 mRNA and protein than females within the amygdala, as well as the ventromedial hypothalamus (VMH), but not within the preoptic area (POA) on post-natal day 1 (PN1). At PN10 these differences were gone; however, on this day males had more mecp2 mRNA than females within the POA. The transient sex difference of mecp2 expression during the steroid-sensitive period of brain development suggests that mecp2 may participate in normal sexual differentiation of the rat brain. Considering the strong link between MeCP2 and neurodevelopmental disorders, the lower levels of mecp2 expression in males may also underlie a biological risk for mecp2-related neural disorders.

  14. Brain manganese, catecholamine turnover, and the development of startle in rats prenatally exposed to manganese

    International Nuclear Information System (INIS)

    Kontur, P.J.; Fechter, L.D.

    1985-01-01

    Manganese (Mn) can be neurotoxic when present in high concentrations. Neonatal animals show differential absorption, accumulation, and excretion of Mn relative to adults. If similar kinetic differences exist during gestation, then fetal animals may be susceptible to Mn neurotoxicity. The objective of this study was to examine maternal-fetal Mn transfer and the susceptibility of prenatal animals to Mn neurotoxicity. This was approached by studying the ability of Mn to cross the placenta and reach the fetal central nervous system using radiotracer and atomic absorption spectroscopy techniques. Manganese is thought to disrupt catecholamine neurotransmission in the central nervous system. This was examined in newborn rats by alpha-methyl-para-tyrosine induced catecholamine turnover and the development of the acoustic startle response. The results suggest that there are limits on fetal Mn accumulation under conditions of both normal and excessive dietary Mn levels. Manganese accumulation in the fetal brain after exposure to increased dietary Mn does not alter either dopamine or norepinephrine turnover or the development of the acoustic startle response. Excess Mn does not appear to be neurotoxic to fetal rats in spite of its limited accumulation in nervous tissue after gestational exposure

  15. Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

    Directory of Open Access Journals (Sweden)

    Raj K. Singh Badhan

    2014-03-01

    Full Text Available Central nervous system (CNS drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB, blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF, choroidal epithelial and total cerebrospinal fluid (CSF compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain and CSF:plasma ratio (CSF:Plasmau using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways.

  16. Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

    Science.gov (United States)

    Kunko, P M; Smith, J A; Wallace, M J; Maher, J R; Saady, J J; Robinson, S E

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of me