Current Search: Retina (x)
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Title
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The outer retina and tapetum lucidum of the snook Centropomus undecimalis (Teleostei).
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Creator
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Eckelbarger, Kevin J., Scalan, R., Nicol, J. A. C., Harbor Branch Oceanographic Institute
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Date Issued
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1980
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PURL
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http://purl.flvc.org/FCLA/DT/3342217
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Subject Headings
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Centropomus undecimalis, Tapetum lucidum, Retina, Snook
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Format
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Document (PDF)
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Title
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A CELL BIOLOGICAL AND ELECTROPHYSIOLOGICAL STUDY OF MOUSE RETINA.
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Creator
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Sullivan, James P., Shen, Wen, Prentice, Howard, Florida Atlantic University, Center for Complex Systems and Brain Sciences, Charles E. Schmidt College of Science
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Abstract/Description
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Both proliferative diabetic retinopathy and exudative age-related macular degeneration are major causes of blindness which are caused by growth of defective, leaky and tortuous blood vessels in the retina. Hypoxia is implicated in triggering both of these diseases and results in induction of HIF-1alpha transcription factor in addition to the angiogenic factor VEGF. Müller cells are the major glial cell in the retina and they contribute to neovascularization in hypoxic regions of the retina...
Show moreBoth proliferative diabetic retinopathy and exudative age-related macular degeneration are major causes of blindness which are caused by growth of defective, leaky and tortuous blood vessels in the retina. Hypoxia is implicated in triggering both of these diseases and results in induction of HIF-1alpha transcription factor in addition to the angiogenic factor VEGF. Müller cells are the major glial cell in the retina and they contribute to neovascularization in hypoxic regions of the retina through eliciting secretion of growth factors, cytokines and angiogenic factors. As Müller cells span the breadth of the retina they can secrete angiostatic factors as well as neuroprotective trophic factors, the Müller cell is a valuable cell type for targeting by potential new gene therapies. The current investigation tests the hypoxia responsiveness of an AAV vector containing a hybrid hypoxia response element together with a GFAP promoter, and this vector encodes the angiostatic protein decorin, a well characterized multi-receptor tyrosine kinase inhibitor. Decorin may have advantages over other key angiostatic factors such as endostatin or angiostatin by virtue of its multiple anti-angiogenic signaling modalities. We employed Q-RT-PCR to evaluate the cell specificity and hypoxia responsiveness of an AAV-Vector termed AAV-REG-Decorin containing a hybrid HRE and GFAP promoter driving expression of the decorin transgene. The vector also contains a silencer element between the HRE and the GFAP domains to enable low basal expression in normoxia as well as high level inducibility in hypoxia. AAV-REGDecorin was found to elicit high level expression of decorin mRNA in hypoxia with greater than 9 – fold induction of the transgene in hypoxic conditions in astrocytes by comparison to normoxic astrocytes. AAV-REG-Decorin showed low levels of transgene expression by comparison to the positive control vector AAV-CMV -decorin containing the ubiquitously active CMV-promoter. The expression levels of decorin mRNA from AAV-REG-Decorin and from AAV-GFAP-Decorin were low in the PC12 neuronal cell model and in the ARPE19 line of retinal pigment epithelial cells with respect to those of AAV-CMV-decorin and no induction of Decorin mRNA was found with AAV-REGDecorin in these two control cell lines. Our novel gene therapy vector will serve as a platform for testing efficacy in rodent disease models (OIR and laser induced choroidal neovascularization) for assessment of the benefits of tightly regulated antiangiogenic gene therapy eliciting decorin transgene expression, both in terms of timing and the cellular source of production, during the progression of the retinal pathophysiology.
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Date Issued
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2021
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PURL
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http://purl.flvc.org/fau/fd/FA00013725
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Subject Headings
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Macular Degeneration, Retina, Gene therapy, Decorin
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Format
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Document (PDF)
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Title
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Function of glycinergic interplexiform cells in rod synaptic transmission.
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Creator
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Jiang, Zheng., Charles E. Schmidt College of Science, Department of Biological Sciences
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Abstract/Description
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The interplexiform cells(IP cells) are the most recently discovered neurons in the retina and their function is to provide centrifugal feedback in retina. The anatomical structure of the IP cells has been well studied, but the function of these neurons is largely unknown. I systematically studied the excitatory and inhibitory inputs from IP cells in salamander retina. I found that L-EPSCs in IP cells are mediated by AMPA and NMDA receptors; in addition, L-IPSCs are mediated by glycine...
Show moreThe interplexiform cells(IP cells) are the most recently discovered neurons in the retina and their function is to provide centrifugal feedback in retina. The anatomical structure of the IP cells has been well studied, but the function of these neurons is largely unknown. I systematically studied the excitatory and inhibitory inputs from IP cells in salamander retina. I found that L-EPSCs in IP cells are mediated by AMPA and NMDA receptors; in addition, L-IPSCs are mediated by glycine receptors and GABAC receptors. In response to light, IP cells reaction potentials transiently at the onset and onset of light stimulation. The major neural transmitter of IP cells in salamander retina is glycine. We also studied the distribution and function of glycine transporters. Our result indicates that GlyT1- and GlyT2-like transporters were present in Muller cells and neurons. The glycine feedback at outer plexiform layer (OPL) has effects on both the bipolar cell dendrites and rod photoreceptor terminals. At bipolar cell dendrites, glycine selectively depolarizes rod-dominant On-bipolar cells, and hyperpolarizes Off- bipolar cells. At rod photoreceptor terminals, 10 M glycine activates voltage-gated Ca2+ channels. These effects facilitated glutamate vesicle release in photoreceptors. It increases the sEPSC in OFF bipolar cells. The combined effect of glycine at rod terminals and bipolar cell dendrites leads to enhanced dim light signal transduction in the rod photoreceptor to ganglion cell pathway. This study provides a model that displays the function of centrifugal feedback through IP cells in the retina.
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Date Issued
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2009
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PURL
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http://purl.flvc.org/FAU/2708369
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Subject Headings
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Cellular signal transduction, Neurochemistry, Neuroplasticity, Synapses, Retina, Cytology, Visual pathways
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Format
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Document (PDF)
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Title
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PHOTORECEPTOR DEGENERATION AND ABNORMAL RETINAL VASCULOGENESIS.
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Creator
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Nguyen, Matthew, Shen, Wen, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
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Abstract/Description
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Abnormal vasculature in the retina, specifically tortuous blood vessels, are common to many of the most prevalent retinal degenerative diseases currently affecting millions across the world. The mechanisms of their formation and development in the context of retinal degenerative disease, however, are still poorly understood. The rd1 and rd10 mice are relatively well-studied animal models of retinal degenerative disease, however, there lacks a systematic characterization of vascular changes co...
Show moreAbnormal vasculature in the retina, specifically tortuous blood vessels, are common to many of the most prevalent retinal degenerative diseases currently affecting millions across the world. The mechanisms of their formation and development in the context of retinal degenerative disease, however, are still poorly understood. The rd1 and rd10 mice are relatively well-studied animal models of retinal degenerative disease, however, there lacks a systematic characterization of vascular changes co-related to photoreceptor degeneration in the rd1 and rd10 retina. Here, we utilize advancements in confocal microscopy, immunohistochemistry, and image analysis software in order to systematically characterize vascular changes before and after retinal development in the rd1 and rd10 mice. We show that there are plexus specific changes in the retinal vasculature that parallel photoreceptor degeneration. Such information will be of particular use to future studies investigating the role of vascular changes in retinal degenerative disease therapies.
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Date Issued
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2021
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PURL
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http://purl.flvc.org/fau/fd/FA00013818
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Subject Headings
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Retinal Degeneration, Retinal Vessels--pathology, Retina—Diseases, Photoreceptors
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Format
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Document (PDF)
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Title
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An investigation of membrane transporter proteins in the distal vertebrate retina: excitatory amino acid transporters and sodium potassium chloride cotransporters.
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Creator
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Purpura, Lauren Angeline, Shen, Wen, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
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Abstract/Description
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Neurons are able to maintain membrane potential and synaptic integrity by an intricate equilibrium of membrane transporter proteins and ion channels. Two membrane proteins of particular importance in the vertebrate retina are the excitatory amino acid transporters (EAATs) which are responsible for the reuptake of glutamate into both glial and neuronal cells and the sodium potassium chloride cotransporters (NKCCs) that are responsible for the uptake of chloride ions into the cell. NKCCs are...
Show moreNeurons are able to maintain membrane potential and synaptic integrity by an intricate equilibrium of membrane transporter proteins and ion channels. Two membrane proteins of particular importance in the vertebrate retina are the excitatory amino acid transporters (EAATs) which are responsible for the reuptake of glutamate into both glial and neuronal cells and the sodium potassium chloride cotransporters (NKCCs) that are responsible for the uptake of chloride ions into the cell. NKCCs are electro-neutral with the uptake of 2 Cl- coupled to an exchange of a potassium and Na+ ion into the cells. Therefore, there is little change of cell membrane potential in the action of NKCCs. In this study the localization and function of EAATs in the distal retina is investigated. Whole cell patch clamp recordings in lower vertebrate retina have demonstrated that EAAT2 is the main synaptic EAATs in rod photoreceptors and it is localized to the axon terminals. Furthermore, the action of the transporter seems to be modified by intracellular calcium concentration. There is also evidence that EAAT2 might be regulated by feedback from the neuron network by glycinergic and GABAergic mechanisms. The second half of this study investigates expression of NKCCs in the retina by western blot analysis and quantitative polymerase chain reaction. There are two forms of NKCCs, NKCC1 and NKCC2. NKCC1 is mostly expressed in the central nervous system and NKCC2 was thought to only be expressed in the kidneys. NKCC1 is responsible for the majority of chloride uptake into neuronal and epithelial cells and NKCC1 is expressed in the distal retina where photoreceptors synapse on second order horizontal and bipolar cells. This study found the expression of NKCC1 in the distal retina to be regulated by temporal light and dark adaptation. Light adaptation increased phosphorylated NKCC1 expression (the active form of the cotransporter). The increase in NKCC1 expression during light adaptation was modulated by dopamine. Specifically, a D1 receptor agonist increased phosphorylated NKCC1 expression. Dopamine is an essential chemical and receptor known for initiating light adaptation in retina. Finally, an NKCC1 knockout mouse model was examined and it revealed that both forms of NKCC are expressed in the vertebrate retina.
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Date Issued
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2014
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PURL
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http://purl.flvc.org/fau/fd/FA00004224, http://purl.flvc.org/fau/fd/FA00004224
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Subject Headings
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Biological transport, Carrier proteins, Cellular signal transduction, Neural receptors, Retina -- Cytology
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Format
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Document (PDF)
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Title
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Regulation of rapid signaling at the cone ribbon synapse via distinct pre- and postsynaptic mechanisms.
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Creator
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Rowan, Matthew JM., Charles E. Schmidt College of Science, Department of Biological Sciences
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Abstract/Description
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Background: Light-adaptation is a multifaceted process in the retina that helps adjust the visual system to changing illumination levels. Many studies are focused on the photochemical mechanism of light-adaptation. Neural network adaptation mechanisms at the photoreceptor synapse are largely unknown. We find that large, spontaneous Excitatory Amino Acid Transporter (EAATs) activity in cone terminals may contribute to cone synaptic adaptation, specifically with respect to how these signals...
Show moreBackground: Light-adaptation is a multifaceted process in the retina that helps adjust the visual system to changing illumination levels. Many studies are focused on the photochemical mechanism of light-adaptation. Neural network adaptation mechanisms at the photoreceptor synapse are largely unknown. We find that large, spontaneous Excitatory Amino Acid Transporter (EAATs) activity in cone terminals may contribute to cone synaptic adaptation, specifically with respect to how these signals change in differing conditions of light. EAATs in neurons quickly transport glutamate from the synaptic cleft, and also elicit large thermodynamically uncoupled Cl- currents when activated. We recorded synaptic EAAT currents from cones to study glutamate-uptake events elicited by glutamate release from the local cone, and from adjacent photoreceptors. We find that cones are synaptically connected via EAATs in dark ; this synaptic connection is diminished in light-adapted cones. Methods: Whole-cell patch-clamp was performed on dark- and transiently light-adapted tiger salamander cones. Endogenous EAAT currents were recorded in cones with a short depolarization to -10mV/2ms, while spontaneous transporter currents from network cones were observed while a local cone holding at -70mV constantly. DHKA, a specific transporter inhibitor, was used to identify EAAT2 currents in the cone terminals, while TBOA identified other EAAT subtypes. GABAergic and glycinergic network inputs were always blocked with picrotoxin and strychnine. Results: Spontaneous EAAT currents were observed in cones held constantly at -70mV in dark, indicating that the cones received glutamate inputs from adjacent photoreceptors. These spontaneous EAAT currents disappeared in presence of a strong light, possibly because the light suppressed glutamate releases from the adjacent photoreceptors. The spontaneous EAAT currents were blocked with TBOA, but not DHKA, an inhibitor for EAAT2 subtype, suggesting that a, non-EAAT 2 subtype may reside in a basal or perisynaptic area of cones, with a specialized ability to bind exocytosed glutamate from adjacent cones in dark. Furthermore, these results could be artificially replicated by dual-electrode recordings from two adjacent cones. When glutamate release was elicited from one cone, the TBOA-sensitive EAAT currents were observed from the other cone. Conclusions: Cones appear to act like a meshwork, synaptically connected via glutamate transporters. Light attenuates glutamate release and diminishes the cone-cone synaptic connections. This process may act as an important network mechanism for cone light adaptation.
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Date Issued
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2011
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PURL
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http://purl.flvc.org/FAU/3337186
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Subject Headings
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Synapses, Neural transmission, VIsual perception, Presynaptic receptors, Molecular neurobiology, Glutamic acid, Neural receptors, Cellular signal transduction, Retina, Cytology
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Format
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Document (PDF)
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Title
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Hypoxia-regulated glial cell-specific gene therapy to treat retinal neovascularization.
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Creator
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Biswal, Manas Ranjan., Charles E. Schmidt College of Science, Center for Complex Systems and Brain Sciences
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Abstract/Description
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Diabetic retinopathy is an ischemic retinal neovascular disease causing vision loss among adults. The studies presented involve the design and testing of a gene therapy vector to inhibit retinal revascularization, similar to that found in diabetic retinopathy. Gene therapy has proven to be an effective method to introduce therapeutic proteins to treat retinal diseases. Targeting a specific cell type and expression of therapeutic proteins according to the tissue microenvironment should have an...
Show moreDiabetic retinopathy is an ischemic retinal neovascular disease causing vision loss among adults. The studies presented involve the design and testing of a gene therapy vector to inhibit retinal revascularization, similar to that found in diabetic retinopathy. Gene therapy has proven to be an effective method to introduce therapeutic proteins to treat retinal diseases. Targeting a specific cell type and expression of therapeutic proteins according to the tissue microenvironment should have an advantage over traditional gene therapy by avoiding unwanted transgene expression. Hypoxia plays a significant role in the pathophysiology of many retinal ischemic diseases. Retinal Mèuller cells provide structural and functional support to retinal neurons, as well as playing a significant role in retinal neovascularization. Targeting Mèuller cells may be an effective strategy to prevent retinal neovascularization under pathological conditions. ... The hypoxia regulated, glial specific vector successfully reduced the abnormal neovascularization in the periphery by 93% and reduced the central vasobliterated area by 90%. A substantial amount of exogenous endostatin was produced in the retinas of P17 OIR mice. A significant increase in human endostatin protein and reduced vascular endothelial growth factor (VEGF) were identified by Western blot and ELISA, respectively. These findings suggest hypoxia-regulated, glial cell-specific scAAV mediated gene expression may be useful to prevent blindness found in devastating retinal diseases involving neovascularization.
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Date Issued
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2012
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PURL
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http://purl.flvc.org/FAU/3359290
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Subject Headings
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Diabetic retinopathy, Research, Methodology, Gene therapy, Retinal degeneration, Treatment, Neovascularization inhibitors, Mitochondrial pathology, Retina, Cytology, Gene mapping
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Format
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Document (PDF)