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Sample records for retina obtenidos con

  1. Infrared retina

    DOEpatents

    Krishna, Sanjay; Hayat, Majeed M.; Tyo, J. Scott; Jang, Woo-Yong

    2011-12-06

    Exemplary embodiments provide an infrared (IR) retinal system and method for making and using the IR retinal system. The IR retinal system can include adaptive sensor elements, whose properties including, e.g., spectral response, signal-to-noise ratio, polarization, or amplitude can be tailored at pixel level by changing the applied bias voltage across the detector. "Color" imagery can be obtained from the IR retinal system by using a single focal plane array. The IR sensor elements can be spectrally, spatially and temporally adaptive using quantum-confined transitions in nanoscale quantum dots. The IR sensor elements can be used as building blocks of an infrared retina, similar to cones of human retina, and can be designed to work in the long-wave infrared portion of the electromagnetic spectrum ranging from about 8 .mu.m to about 12 .mu.m as well as the mid-wave portion ranging from about 3 .mu.m to about 5 .mu.m.

  2. Cancers Affecting the Retina

    MedlinePlus

    ... or ARMD) Epiretinal Membrane Detachment of the Retina Retinitis Pigmentosa Blockage of Central Retinal Veins and Branch Retinal ... or ARMD) Epiretinal Membrane Detachment of the Retina Retinitis Pigmentosa Blockage of Central Retinal Veins and Branch Retinal ...

  3. CNTF AND RETINA

    PubMed Central

    Wen, Rong; Tao, Weng; Li, Yiwen; Sieving, Paul A.

    2011-01-01

    Ciliary neurotrophic factor (CNTF) is one of the most studied neurotrophic factors for neuroprotection of the retina. A large body of evidence demonstrates that CNTF promotes rod photoreceptor survival in almost all animal models. Recent studies indicate that CNTF also promotes cone photoreceptor survival and cone outer segment regeneration in the degenerating retina and improves cone function in dogs with congenital achromotopsia. In addition, CNTF is a neuroprotective factor and an axogenesis factor for retinal ganglion cells (RGCs). This review focuses on the effects of exogenous CNTF on photoreceptors and RGCs in the mammalian retina and the potential clinical application of CNTF for retinal degenerative diseases. PMID:22182585

  4. Retina and Omega-3

    PubMed Central

    Querques, Giuseppe; Forte, Raimondo; Souied, Eric H.

    2011-01-01

    Over the last decade, several epidemiological studies based on food frequency questionnaires suggest that omega-3 polyunsaturated fatty acids could have a protective role in reducing the onset and progression of retinal diseases. The retina has a high concentration of omega-3, particularly DHA, which optimizes fluidity of photoreceptor membranes, retinal integrity, and visual function. Furthermore, many studies demonstrated that DHA has a protective, for example antiapoptotic, role in the retina. From a nutritional point of view, it is known that western populations, particularly aged individuals, have a higher than optimal omega-6/omega-3 ratio and should enrich their diet with more fish consumption or have DHA supplementation. This paper underscores the potential beneficial effect of omega-3 fatty acids on retinal diseases. PMID:22175009

  5. Retinal Detachment: Torn or Detached Retina Diagnosis

    MedlinePlus

    ... Eye Health / Eye Health A-Z Detached or Torn Retina Sections Retinal Detachment: What Is a Torn ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment: Torn or Detached Retina Diagnosis Written by: Kierstan Boyd ...

  6. Retinal Detachment: Torn or Detached Retina Symptoms

    MedlinePlus

    ... Eye Health / Eye Health A-Z Detached or Torn Retina Sections Retinal Detachment: What Is a Torn ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment: Torn or Detached Retina Symptoms Written by: Kierstan Boyd ...

  7. Retina vascular network recognition

    NASA Astrophysics Data System (ADS)

    Tascini, Guido; Passerini, Giorgio; Puliti, Paolo; Zingaretti, Primo

    1993-09-01

    The analysis of morphological and structural modifications of the retina vascular network is an interesting investigation method in the study of diabetes and hypertension. Normally this analysis is carried out by qualitative evaluations, according to standardized criteria, though medical research attaches great importance to quantitative analysis of vessel color, shape and dimensions. The paper describes a system which automatically segments and recognizes the ocular fundus circulation and micro circulation network, and extracts a set of features related to morphometric aspects of vessels. For this class of images the classical segmentation methods seem weak. We propose a computer vision system in which segmentation and recognition phases are strictly connected. The system is hierarchically organized in four modules. Firstly the Image Enhancement Module (IEM) operates a set of custom image enhancements to remove blur and to prepare data for subsequent segmentation and recognition processes. Secondly the Papilla Border Analysis Module (PBAM) automatically recognizes number, position and local diameter of blood vessels departing from optical papilla. Then the Vessel Tracking Module (VTM) analyses vessels comparing the results of body and edge tracking and detects branches and crossings. Finally the Feature Extraction Module evaluates PBAM and VTM output data and extracts some numerical indexes. Used algorithms appear to be robust and have been successfully tested on various ocular fundus images.

  8. Benzodiazepine binding to bovine retina.

    PubMed

    Osborne, N N

    1980-02-01

    [3H]Diazepam binds to membrane preparations of the retina, suggesting that benzodiazepine receptors exist in this tissue. The binding characteristics are similar to those known to occur in the brain, with affinity constants in the same range. Unlike the finding in the brain, [3H]diazepam binding in the retina is not stimulated by GABA and other GABA agonists. These findings indicate that benzodiazepine receptors may have a more general function and not only be associated with anxiety or emotional behaviour. PMID:6302572

  9. Retinal Detachment: Torn or Detached Retina Treatment

    MedlinePlus

    ... of these procedures create a scar that helps seal the retina to the back of the eye. ... around the retinal tear. The scarring that results seals the retina to the underlying tissue, helping to ...

  10. A Computational Framework for Realistic Retina Modeling.

    PubMed

    Martínez-Cañada, Pablo; Morillas, Christian; Pino, Begoña; Ros, Eduardo; Pelayo, Francisco

    2016-11-01

    Computational simulations of the retina have led to valuable insights about the biophysics of its neuronal activity and processing principles. A great number of retina models have been proposed to reproduce the behavioral diversity of the different visual processing pathways. While many of these models share common computational stages, previous efforts have been more focused on fitting specific retina functions rather than generalizing them beyond a particular model. Here, we define a set of computational retinal microcircuits that can be used as basic building blocks for the modeling of different retina mechanisms. To validate the hypothesis that similar processing structures may be repeatedly found in different retina functions, we implemented a series of retina models simply by combining these computational retinal microcircuits. Accuracy of the retina models for capturing neural behavior was assessed by fitting published electrophysiological recordings that characterize some of the best-known phenomena observed in the retina: adaptation to the mean light intensity and temporal contrast, and differential motion sensitivity. The retinal microcircuits are part of a new software platform for efficient computational retina modeling from single-cell to large-scale levels. It includes an interface with spiking neural networks that allows simulation of the spiking response of ganglion cells and integration with models of higher visual areas. PMID:27354192

  11. Enkephalin in the goldfish retina

    SciTech Connect

    Su, Y.Y.; Fry, K.R.; Lam, D.M.; Watt, C.B.

    1986-12-01

    Enkephalin-like immunoreactive amacrine cells were visualized using the highly sensitive avidin-biotin method. The somas of these cells were situated in the inner nuclear and ganglion cell layers. Enkephalin-stained processes were observed in layers 1, 3, and 5 of the inner plexiform layer. The biosynthesis of sulfur-containing compounds in the goldfish retina was studied by means of a pulse-chase incubation with /sup 35/S-methionine. A /sup 35/S-labeled compound, which comigrated with authentic Met5-enkephalin on high-performance liquid chromatography (HPLC), was synthesized and was bound competitively by antibodies to enkephalin and by opiate receptors. This compound was tentatively identified as Met5-enkephalin. The newly synthesized /sup 35/S-Met5-enkephalin was released upon depolarization of the retina with a high K+ concentration. This K+-stimulated release was greatly suppressed by 5 mM Co/sup 2 +/, suggesting that the release was Ca/sup 2 +/ dependent. Using a double-label technique, enkephalin immunoreactivity and gamma-aminobutyric acid (GABA) uptake were colocalized to some amacrine cells, whereas others labeled only for enkephalin or GABA. The possible significance of enkephalin-GABA interactions is also discussed.

  12. The Functional Architecture of the Retina.

    ERIC Educational Resources Information Center

    Masland, Richard H.

    1986-01-01

    Examines research related to the retina's coding of visual input with emphasis on the organization of two kinds of ganglion cell receptive fields. Reviews current techniques for examining the shapes and arrangement in the retina of entire populations of nerve cells. (ML)

  13. Cytogenesis in the monkey retina

    SciTech Connect

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

    1991-07-01

    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.

  14. Glycogen metabolism in the rat retina.

    PubMed

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2004-02-01

    It has been reported that glycogen levels in retina vary with retinal vascularization. However, the electrical activity of isolated retina depends on glucose supply, suggesting that it does not contain energetic reserves. We determined glycogen levels and pyruvate and lactate production under various conditions in isolated retina. Ex vivo retinas from light- and dark-adapted rats showed values of 44 +/- 0.3 and 19.5 +/- 0.4 nmol glucosyl residues/mg protein, respectively. The glycogen content of retinas from light-adapted animals was reduced by 50% when they were transferred to darkness. Glycogen levels were low in retinas incubated in glucose-free media and increased in the presence of glucose. The highest glycogen values were found in media containing 20 mm of glucose. A rapid increase in lactate production was observed in the presence of glucose. Surprisingly, glycogen levels were the lowest and lactate production was also very low in the presence of 30 mm glucose. Our results suggest that glycogen can be used as an immediate accessible energy reserve in retina. We speculate on the possibility that gluconeogenesis may play a protective role by removal of lactic acid. PMID:14756809

  15. Trazando la materia oscura con cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

  16. Complex computation in the retina

    NASA Astrophysics Data System (ADS)

    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

  17. Imaging Single Cells in the Living Retina

    PubMed Central

    Williams, David R.

    2011-01-01

    A quarter century ago, we were limited to a macroscopic view of the retina inside the living eye. Since then, new imaging technologies, including confocal scanning laser ophthalmoscopy, optical coherence tomography, and adaptive optics fundus imaging, transformed the eye into a microscope in which individual cells can now be resolved noninvasively. These technologies have enabled a wide range of studies of the retina that were previously impossible. PMID:21596053

  18. Flipping coins in the fly retina.

    PubMed

    Mikeladze-Dvali, Tamara; Desplan, Claude; Pistillo, Daniela

    2005-01-01

    Color vision in Drosophila melanogaster relies on the presence of two different subtypes of ommatidia: the "green" and "blue." These two classes are distributed randomly throughout the retina. The decision of a given ommatidium to take on the "green" or "blue" fate seems to be based on a stochastic mechanism. Here we compare the stochastic choice of photoreceptors in the fly retina with other known examples of random choices in both sensory and other systems. PMID:16243594

  19. Spectral imaging of the retina

    PubMed Central

    Mordant, D J; Al-Abboud, I; Muyo, G; Gorman, A; Sallam, A; Ritchie, P; Harvey, A R; McNaught, A I

    2011-01-01

    Introduction The work described here involved the use of a modified fundus camera to obtain sequential hyperspectral images of the retina in 14 normal volunteers and in 1 illustrative patient with a retinal vascular occlusion. Methods The paper describes analysis techniques, which allow oximetry within retinal vessels; these results are presented as retinal oximetry maps. Results Using spectral images, with wavelengths between 556 and 650 nm, the mean oxygen saturation (OS) value in temporal retinal arterioles in normal volunteers was 104.3 (±16.7), and in normal temporal retinal venules was 34.8 (±17.8). These values are comparable to those quoted in the literature, although, the venular saturations are slightly lower than those values found by other authors; explanations are offered for these differences. Discussion The described imaging and analysis techniques produce a clinically useful map of retinal oximetric values. The results from normal volunteers and from one illustrative patient are presented. Further developments, including the recent development of a ‘snapshot' spectral camera, promises enhanced non-invasive retinal vessel oximetry mapping. PMID:21390065

  20. Radioadaptive Cytoprotective Pathways in the Mouse Retina

    NASA Technical Reports Server (NTRS)

    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.

  1. Neurotransmitter properties of the newborn human retina

    SciTech Connect

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

    1983-07-01

    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 /sup 3/H-glycine, /sup 3/H-dopamine, and /sup 3/H-GABA are present at birth. However, the number and distribution of cells labeled with each of these /sup 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 /sup 3/H-glutamate and /sup 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.

  2. Parallel processing in the mammalian retina.

    PubMed

    Wässle, Heinz

    2004-10-01

    Our eyes send different 'images' of the outside world to the brain - an image of contours (line drawing), a colour image (watercolour painting) or an image of moving objects (movie). This is commonly referred to as parallel processing, and starts as early as the first synapse of the retina, the cone pedicle. Here, the molecular composition of the transmitter receptors of the postsynaptic neurons defines which images are transferred to the inner retina. Within the second synaptic layer - the inner plexiform layer - circuits that involve complex inhibitory and excitatory interactions represent filters that select 'what the eye tells the brain'. PMID:15378035

  3. Eye formation in the absence of retina

    PubMed Central

    Swindell, Eric C.; Liu, Chaomei; Shah, Rina; Smith, April N.; Lang, Richard A.; Jamrich, Milan

    2008-01-01

    Eye development is a complex process that involves the formation of the retina and the lens, collectively called the eyeball, as well as the formation of auxiliary eye structures such as the eyelid, lacrimal gland, cornea and conjunctiva. The developmental requirements for the formation of each individual structure are only partially understood. We have shown previously that the homeobox-containing gene Rx is a key component in eye formation, as retinal structures do not develop and retina-specific gene expression is not observed in Rx-deficient mice. In addition, Rx−/− embryos do not develop any lens structure, despite the fact that Rx is not expressed in the lens. This demonstrates that during normal mammalian development, retina-specific gene expression is necessary for lens formation. In this paper we show that lens formation can be restored in Rx-deficient embryos experimentally, by the elimination of β-catenin expression in the head surface ectoderm. This suggests that β-catenin is involved in lens specification either through Wnt signaling or through its function in cell adhesion. In contrast to lens formation, we demonstrate that the development of auxiliary eye structures does not depend on retina-specific gene expression or retinal morphogenesis. These results point to the existence of two separate developmental processes involved in the formation of the eye and its associated structures. One involved in the formation of the eyeball and the second involved in the formation of the auxiliary eye structures. PMID:18675797

  4. Vascular tumors of the choroid and retina

    PubMed Central

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-01-01

    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed. PMID:25827544

  5. The Neurovascular Retina in Retinopathy of Prematurity

    PubMed Central

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

    2009-01-01

    The continuing worldwide epidemic of retinopathy of prematurity (ROP), a leading cause of childhood visual impairment, strongly motivates further research into mechanisms of the disease. Although the hallmark of ROP is abnormal retinal vasculature, a growing body of evidence supports a critical role for the neural retina in the ROP disease process. The age of onset of ROP coincides with the rapid developmental increase in rod photoreceptor outer segment length and rhodopsin content of the retina with escalation of energy demands. Using a combination of non-invasive electroretinographic (ERG), psychophysical, and image analysis procedures, the neural retina and its vasculature have been studied in prematurely born human subjects, both with and without ROP, and in rats that model the key vascular and neural parameters found in human ROP subjects. These data are compared to comprehensive numeric summaries of the neural and vascular features in normally developing human and rat retina. In rats, biochemical, anatomical, and molecular biological investigations are paired with the non-invasive assessments. ROP, even if mild, primarily and persistently alters the structure and function of photoreceptors. Post-receptor neurons and retinal vasculature, which are intimately related, are also affected by ROP; conspicuous neurovascular abnormalities disappear, but subtle structural anomalies and functional deficits may persist years after clinical ROP resolves. The data from human subjects and rat models identify photoreceptor and post-receptor targets for interventions that promise improved outcomes for children at risk for ROP. PMID:19563909

  6. Vascular Precursors in Developing Human Retina

    PubMed Central

    Hasegawa, Takuya; McLeod, D. Scott; Prow, Tarl; Merges, Carol; Grebe, Rhonda; Lutty, Gerard A.

    2016-01-01

    Purpose Prior investigation has demonstrated that angioblasts are present in the inner retinas of human embryos and fetuses and that they differentiate and organize to form the primordial retinal vasculature. The purpose of this study was to characterize these angioblasts further and examine ligands that might control their migration and differentiation. Methods Immunohistochemistry was used to localize stroma-derived factor-1 (SDF-1), its receptor CXCR4, stem cell factor (SCF), and its receptor c-Kit on sections obtained from human eyes at from 6 to 23 weeks’ gestation (WG). Coexpression of CD39 (marker for retinal angioblasts and endothelial cells) and CXCR4 or c-Kit was investigated by confocal microscopy. Results SDF-1 was prominent in inner retina with the greatest reaction product near the internal limiting membrane (ILM). SCF immunoreactivity was also confined to the inner retina and increased significantly between 7 and 12 WG. The level of both ligands declined by 22 WG. A layer of CXCR4+ and c-Kit+ precursors, some of which coexpressed CD39, existed in the inner retina from 7 to 12 WG. With migration, c-Kit was downregulated, whereas CD39+ cells continued to express CXCR4 as they formed cords. With canalization, CXCR4 expression was downregulated. Conclusions Embryonic human retina has a pool of precursors (CXCR4+ and c-Kit+) that enlarged centrifugally during fetal development. From this pool emerges angioblasts, which migrate anteriorly into the nerve fiber layer where SDF-1 and SCF levels are highest. c-Kit expression declines with apparent migration, and CXCR4 expression declines with canalization of new vessels. Both SCF and SDF-1 are associated with the differentiation of retinal precursors into angioblasts and their migration to sites of vessel assembly. PMID:18436851

  7. Computational adaptive optics of the human retina

    NASA Astrophysics Data System (ADS)

    South, Fredrick A.; Liu, Yuan-Zhi; Carney, P. Scott; Boppart, Stephen A.

    2016-03-01

    It is well known that patient-specific ocular aberrations limit imaging resolution in the human retina. Previously, hardware adaptive optics (HAO) has been employed to measure and correct these aberrations to acquire high-resolution images of various retinal structures. While the resulting aberration-corrected images are of great clinical importance, clinical use of HAO has not been widespread due to the cost and complexity of these systems. We present a technique termed computational adaptive optics (CAO) for aberration correction in the living human retina without the use of hardware adaptive optics components. In CAO, complex interferometric data acquired using optical coherence tomography (OCT) is manipulated in post-processing to adjust the phase of the optical wavefront. In this way, the aberrated wavefront can be corrected. We summarize recent results in this technology for retinal imaging, including aberration-corrected imaging in multiple retinal layers and practical considerations such as phase stability and image optimization.

  8. The Dept. of Energy Artificial Retina project

    SciTech Connect

    2009-08-10

    LLNL has assisted in the development of the first long-term retinal prosthesis - called an artificial retina - that can function for years inside the harsh biological environment of the eye. This work has been done in collaboration with four national laboratories (Argonne, Los Alamos, Oak Ridge and Sandia), four universities (the California Institute of Technology, the Doheny Eye Institute at USC, North Carolina State University and the University of California, Santa Cruz), an industrial partner (Second Sight® Medical Products Inc. of Sylmar, Calif.) and the U.S. Department of Energy. With this device, application-specific integrated circuits transform digital images from a camera into electric signals in the eye that the brain uses to create a visual image. In clinical trials, patients with vision loss were able to successfully identify objects, increase mobility and detect movement using the artificial retina.

  9. The Dept. of Energy Artificial Retina project

    ScienceCinema

    None

    2010-09-01

    LLNL has assisted in the development of the first long-term retinal prosthesis - called an artificial retina - that can function for years inside the harsh biological environment of the eye. This work has been done in collaboration with four national laboratories (Argonne, Los Alamos, Oak Ridge and Sandia), four universities (the California Institute of Technology, the Doheny Eye Institute at USC, North Carolina State University and the University of California, Santa Cruz), an industrial partner (Second Sight® Medical Products Inc. of Sylmar, Calif.) and the U.S. Department of Energy. With this device, application-specific integrated circuits transform digital images from a camera into electric signals in the eye that the brain uses to create a visual image. In clinical trials, patients with vision loss were able to successfully identify objects, increase mobility and detect movement using the artificial retina.

  10. TRPM3 Expression in Mouse Retina

    PubMed Central

    Brown, R. Lane; Xiong, Wei-Hong; Peters, James H.; Tekmen-Clark, Merve; Strycharska-Orczyk, Iwona; Reed, Brian T.; Morgans, Catherine W.; Duvoisin, Robert M.

    2015-01-01

    Transient receptor potential (TRP) channels constitute a large family of cation permeable ion channels that serve crucial functions in sensory systems by transducing environmental changes into cellular voltage and calcium signals. Within the retina, two closely related members of the melastatin TRP family, TRPM1 and TRPM3, are highly expressed. TRPM1 has been shown to be required for the depolarizing response to light of ON-bipolar cells, but the role of TRPM3 in the retina is unknown. Immunohistochemical staining of mouse retina with an antibody directed against the C-terminus of TRPM3 labeled the inner plexiform layer (IPL) and a subset of cells in the ganglion cell layer. Within the IPL, TRPM3 immunofluorescence was markedly stronger in the OFF sublamina than in the ON sublamina. Electroretinogram recordings showed that the scotopic and photopic a- and b-waves of TRPM3-/- mice are normal indicating that TRPM3 does not play a major role in visual processing in the outer retina. TRPM3 activity was measured by calcium imaging and patch-clamp recording of immunopurified retinal ganglion cells. Application of the TRPM3 agonist, pregnenolone sulfate (PS), stimulated increases in intracellular calcium in ~40% of cells from wild type and TRPM1‑/‑ mice, and the PS-stimulated increases in calcium were blocked by co-application of mefenamic acid, a TRPM3 antagonist. No PS-stimulated changes in fluorescence were observed in ganglion cells from TRPM3-/- mice. Similarly, PS-stimulated currents that could be blocked by mefenamic acid were recorded from wild type retinal ganglion cells but were absent in ganglion cells from TRPM3-/- mice. PMID:25679224

  11. The avian egg and the retina

    PubMed Central

    MALCOLM, J. E.

    1973-01-01

    A mathematical model for study of blood flow has been derived from the avian egg, utilizing the theories of crystallography and photosynthesis. The model is employed to explain the form of the eye and the function of the cells of the human retina, with special reference to colour vision and the pathology of migraine. ImagesFig. 1Fig. 4Fig. 5Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11 PMID:4736600

  12. Silicon retina for optical tracking systems

    NASA Technical Reports Server (NTRS)

    Strohbehn, K.; Jenkins, R. E.; Sun, X.; Andreou, A. G.

    1993-01-01

    There are a host of position sensors, such as quadcells and CCD's, which are candidates for detecting optical position errors and providing error signals for a mirror positioning loop. We are developing a novel, very high bandwidth, biologically inspired position sensor for optical position tracking systems. We present recent test results and design issues for the use of biologically inspired silicon retinas for spaceborne optical position tracking systems.

  13. Connecting the Retina to the Brain

    PubMed Central

    Herrera, Eloisa

    2014-01-01

    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. PMID:25504540

  14. Three-dimensional printing of the retina

    PubMed Central

    Lorber, Barbara; Hsiao, Wen-Kai; Martin, Keith R.

    2016-01-01

    Purpose of review Biological three-dimensional printing has received a lot of media attention over recent years with advances made in printing cellular structures, including skin and heart tissue for transplantation. Although limitations exist in creating functioning organs with this method, the hope has been raised that creating a functional retina to cure blindness is within reach. The present review provides an update on the advances made toward this goal. Recent findings It has recently been shown that two types of retinal cells, retinal ganglion cells and glial cells, can be successfully printed using a piezoelectric inkjet printer. Importantly, the cells remained viable and did not change certain phenotypic features as a result of the printing process. In addition, recent advances in the creation of complex and viable three-dimensional cellular structures have been made. Summary Some first promising steps toward the creation of a functional retina have been taken. It now needs to be investigated whether recent findings can be extended to other cells of the retina, including those derived from human tissue, and if a complex and viable retinal structure can be created through three-dimensional printing. PMID:27045545

  15. The mammalian retina as a clock

    NASA Technical Reports Server (NTRS)

    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. Connecting the retina to the brain.

    PubMed

    Erskine, Lynda; Herrera, Eloisa

    2014-01-01

    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. PMID:25504540

  17. Reactive gliosis in the adult zebrafish retina.

    PubMed

    Thomas, Jennifer L; Ranski, Alexandra H; Morgan, Gregory W; Thummel, Ryan

    2016-02-01

    In contrast to mammals, zebrafish posses the remarkable ability to regenerate retinal neurons. Damage to the zebrafish retina induces Müller glia to act as stem cells, generating retinal progenitors for regeneration. In contrast, injury in the mammalian retina results in Müller glial reactive gliosis, a characteristic gliotic response that is normally detrimental to vision. Understanding the signaling pathways that determine how Müller glia respond to injury is a critical step toward promoting regeneration in the mammalian retina. Here we report that zebrafish Müller glia exhibit signs of reactive gliosis even under normal regenerative conditions and that cell cycle inhibition increases this response. Persistently reactive Müller glia increase their neuroprotective functions, temporarily saving photoreceptors from a cytotoxic light lesion. However, the absence of a sustained proliferation response results in a significant inhibition of retinal regeneration. Interestingly, when cell cycle inhibition is released, a partial recovery of regeneration is observed. Together, these data demonstrate that zebrafish Müller glia possess both gliotic and regenerative potential. PMID:26492821

  18. Effect of diabetes on glycogen metabolism in rat retina.

    PubMed

    Sánchez-Chávez, Gustavo; Hernández-Berrones, Jethro; Luna-Ulloa, Luis Bernardo; Coffe, Víctor; Salceda, Rocío

    2008-07-01

    Glucose is the main fuel for energy metabolism in retina. The regulatory mechanisms that maintain glucose homeostasis in retina could include hormonal action. Retinopathy is one of the chemical manifestations of long-standing diabetes mellitus. In order to better understand the effect of hyperglycemia in retina, we studied glycogen content as well as glycogen synthase and phosphorylase activities in both normal and streptozotocin-induced diabetic rat retina and compared them with other tissues. Glycogen levels in normal rat retina are low (46 +/- 4.0 nmol glucosyl residues/mg protein). However, high specific activity of glycogen synthase was found in retina, indicating a substantial capacity for glycogen synthesis. In diabetic rats, glycogen synthase activity increased between 50% and 100% in retina, brain cortex and liver of diabetic rats, but only retina exhibited an increase in glycogen content. Although, total and phosphorylated glycogen synthase levels were similar in normal and diabetic retina, activation of glycogen synthase by glucose-6-P was remarkable increased. Glycogen phosphorylase activity decreased 50% in the liver of diabetic animals; it was not modified in the other tissues examined. We conclude that the increase in glycogen levels in diabetic retina was due to alterations in glycogen synthase regulation. PMID:18274898

  19. Insulin-like activity in the retina

    SciTech Connect

    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 /sup 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.

  20. Artificial Retina Project: Electromagnetic and Thermal Effects

    SciTech Connect

    Lazzi, Gianluca

    2014-08-29

    This award supported the investigation on electromagnetic and thermal effects associated with the artificial retina, designed in collaboration with national laboratories, universities, and private companies. Our work over the two years of support under this award has focused mainly on 1) Design of new telemetry coils for optimal power and data transfer between the implant and the external device while achieving a significant size reduction with respect to currently used coils; 2) feasibility study of the virtual electrode configuration 3) study the effect of pulse shape and duration on the stimulation efficacy.

  1. Modeling laser damage to the retina

    NASA Astrophysics Data System (ADS)

    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

  2. MicroRNAs in the Neural Retina

    PubMed Central

    Cooper, Nigel G. F.

    2014-01-01

    The health and function of the visual system rely on a collaborative interaction between diverse classes of molecular regulators. One of these classes consists of transcription factors, which are known to bind to DNA and control the transcription activities of their target genes. For a long time, it was thought that the transcription factors were the only regulators of gene expression. More recently, however, a novel class of regulators emerged. This class consists of a large number of small noncoding endogenous RNAs, namely, miRNAs. The miRNAs compose an essential component of posttranscriptional gene regulation, since they ultimately control the fate of gene transcripts. The retina, as a part of the central nervous system, is a well-established model for unraveling the molecular mechanisms underlying neuronal and glial functions. Numerous recent efforts have been made towards identification of miRNAs and their inferred roles in the visual pathway. In this review, we summarize the current state of our knowledge regarding the expression and function of miRNA in the neural retina and we discuss their potential uses as biomarkers for some retinal disorders. PMID:24745005

  3. Glycinergic pathways in the goldfish retina

    SciTech Connect

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

    1981-02-01

    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.

  4. Cell death in the developing vertebrate retina.

    PubMed

    Vecino, Elena; Hernández, María; García, Mónica

    2004-01-01

    Programmed cell death occurs naturally, as a physiological process, during the embryonic development of multicellular organisms. In the retina, which belongs to the central nervous system, at least two phases of cell death have been reported to occur during development. An early phase takes place concomitant with the processes of neurogenesis, cell migration and cell differentiation. A later phase affecting mainly neurons occurs when connections are established and synapses are formed, resulting in selective elimination of inappropriate connections. This pattern of cell death in the developing retina is common among different vertebrates. However, the timing and magnitude of retinal cell death varies among species. In addition, a precise regulation of apoptosis during retinal development has been described. Factors such as neurotrophins, among many others, and electrical activity influence the survival of retinal cells during the course of development. In this paper, we present a summary of these different aspects of programmed cell death during retinal development, and examine how these differ among different species. PMID:15558487

  5. Small field tritanopia in the peripheral retina.

    PubMed

    Volbrecht, Vicki J

    2016-07-01

    If stimuli are made sufficiently small, color-normal individuals report a loss in hue perception, in particular a decrease in the perception of green, in both the fovea and peripheral retina. This effect is referred to as small field tritanopia. It is not clear, however, how rod input may alter the dynamics of small field tritanopia in the peripheral retina. This paper looks at peripheral hue-naming data obtained for small stimuli at mesopic and photopic retinal illuminances under conditions that minimize (bleach) and maximize (no bleach) rod contribution. The data show that attenuation in the perception of green occurs with larger stimuli in the no-bleach condition than in the bleach condition. As retinal illuminance increases, the stimulus size that elicits small field tritanopia decreases, but the stimulus size is still larger under the no-bleach condition. Small field tritanopia in both the bleach and no-bleach conditions may be related to short-wavelength-sensitive (S) cone activity and its potential role in the mediation of the perception of green. The differences in stimulus size for small field tritanopia may be explained by rod input into the magnocellular and koniocellular pathways, which compromises the strength of the chromatic signals and creates a differential loss in the perception of green as compared to the other elemental hues. PMID:27409678

  6. Calcium-Permeable AMPA Receptors in the Retina

    PubMed Central

    Diamond, Jeffrey S.

    2011-01-01

    The retina transforms light entering the eye into a sophisticated neural representation of our visual world. Specialized synapses, cells, and circuits in the retina have evolved to encode luminance, contrast, motion, and other complex visual features. Although a great deal has been learned about the cellular morphology and circuitry that underlies this image processing, many of the synapses in the retina remain incompletely understood. For example, excitatory synapses in the retina feature the full panoply of glutamate receptors, but in most cases specific roles for different receptor subtypes are unclear. In this brief review, I will discuss recent progress toward understanding how Ca2+-permeable AMPA receptors (CP-GluARs) contribute to synaptic transmission and newly discovered forms of synaptic plasticity in the retina. PMID:21991245

  7. Adaptive optics imaging of the retina

    PubMed Central

    Battu, Rajani; Dabir, Supriya; Khanna, Anjani; Kumar, Anupama Kiran; Roy, Abhijit Sinha

    2014-01-01

    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. PMID:24492503

  8. Metabolic differentiation in the embryonic retina.

    PubMed

    Agathocleous, Michalis; Love, Nicola K; Randlett, Owen; Harris, Julia J; Liu, Jinyue; Murray, Andrew J; Harris, William A

    2012-08-01

    Unlike healthy adult tissues, cancers produce energy mainly by aerobic glycolysis instead of oxidative phosphorylation. This adaptation, called the Warburg effect, may be a feature of all dividing cells, both normal and cancerous, or it may be specific to cancers. It is not known whether, in a normally growing tissue during development, proliferating and postmitotic cells produce energy in fundamentally different ways. Here we show in the embryonic Xenopus retina in vivo, that dividing progenitor cells depend less on oxidative phosphorylation for ATP production than non-dividing differentiated cells, and instead use glycogen to fuel aerobic glycolysis. The transition from glycolysis to oxidative phosphorylation is connected to the cell differentiation process. Glycolysis is indispensable for progenitor proliferation and biosynthesis, even when it is not used for ATP production. These results suggest that the Warburg effect can be a feature of normal proliferation in vivo, and that the regulation of glycolysis and oxidative phosphorylation is critical for normal development. PMID:22750943

  9. Development of the Retina and Optic Pathway

    PubMed Central

    Reese, Benjamin E.

    2010-01-01

    Our understanding of the development of the retina and visual pathways has seen enormous advances during the past twenty-five years. New imaging technologies, coupled with advances in molecular biology, have permitted a fuller appreciation of the histotypical events associated with proliferation, fate determination, migration, differentiation, pathway navigation, target innervation, synaptogenesis and cell death, and in many instances, in understanding the genetic, molecular, cellular and activity-dependent mechanisms underlying those developmental changes. The present review considers those advances associated with the lineal relationships between retinal nerve cells, the production of retinal nerve cell diversity, the migration, patterning and differentiation of different types of retinal nerve cells, the determinants of the decussation pattern at the optic chiasm, the formation of the retinotopic map, and the establishment of ocular domains within the thalamus. PMID:20647017

  10. Infrared camera based on a curved retina.

    PubMed

    Dumas, Delphine; Fendler, Manuel; Berger, Frédéric; Cloix, Baptiste; Pornin, Cyrille; Baier, Nicolas; Druart, Guillaume; Primot, Jérôme; le Coarer, Etienne

    2012-02-15

    Design of miniature and light cameras requires an optical design breakthrough to achieve good optical performance. Solutions inspired by animals' eyes are the most promising. The curvature of the retina offers several advantages, such as uniform intensity and no field curvature, but this feature is not used. The work presented here is a solution to spherically bend monolithic IR detectors. Compared to state-of-the-art methods, a higher fill factor is obtained and the device fabrication process is not modified. We made an IR eye camera with a single lens and a curved IR bolometer. Images captured are well resolved and have good contrast, and the modulation transfer function shows better quality when comparing with planar systems. PMID:22344137

  11. Lateral interactions in the outer retina

    PubMed Central

    Thoreson, Wallace B.; Mangel, Stuart C.

    2012-01-01

    Lateral interactions in the outer retina, particularly negative feedback from horizontal cells to cones and direct feed-forward input from horizontal cells to bipolar cells, play a number of important roles in early visual processing, such as generating center-surround receptive fields that enhance spatial discrimination. These circuits may also contribute to post-receptoral light adaptation and the generation of color opponency. In this review, we examine the contributions of horizontal cell feedback and feed-forward pathways to early visual processing. We begin by reviewing the properties of bipolar cell receptive fields, especially with respect to modulation of the bipolar receptive field surround by the ambient light level and to the contribution of horizontal cells to the surround. We then review evidence for and against three proposed mechanisms for negative feedback from horizontal cells to cones: 1) GABA release by horizontal cells, 2) ephaptic modulation of the cone pedicle membrane potential generated by currents flowing through hemigap junctions in horizontal cell dendrites, and 3) modulation of cone calcium currents (ICa) by changes in synaptic cleft proton levels. We also consider evidence for the presence of direct horizontal cell feed-forward input to bipolar cells and discuss a possible role for GABA at this synapse. We summarize proposed functions of horizontal cell feedback and feed-forward pathways. Finally, we examine the mechanisms and functions of two other forms of lateral interaction in the outer retina: negative feedback from horizontal cells to rods and positive feedback from horizontal cells to cones. PMID:22580106

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

    SciTech Connect

    Walsh, C.; Polley, E.H.

    1985-03-01

    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 (/sup 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.

  13. Development of diabetes-induced acidosis in the rat retina.

    PubMed

    Dmitriev, Andrey V; Henderson, Desmond; Linsenmeier, Robert A

    2016-08-01

    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. PMID:27262608

  14. The acid mucopolysaccharides of cattle retina

    PubMed Central

    Berman, E. R.; Bach, G.

    1968-01-01

    1. Two polysaccharides were isolated from the interstitial matrix surrounding the photoreceptor cells of cattle retina. They were liberated from this region of the tissue in a soluble form after agitation of whole retinas in 0·9% sodium chloride. One, which comprises two-thirds of the polysaccharides present, is a hyaluronidase-sensitive `half-sulphated' chondroitin sulphate containing uronic acid, galactosamine and sulphate in the molar proportions 1·27:1·0:0·54. The other is a hyaluronidase-resistant non-sulphated heteropolysaccharide for which the name sialoglycan is proposed. It contains galactose, glucosamine and sialic acid in the molar proportions 2·4:1·0:0·4. Both polysaccharides contain only small amounts of nitrogen in excess of the amount calculated from their amino sugar and sialic acid content. 2. A similar combination of mucopolysaccharides is associated with the pigment epithelial-cell layer but in quantities only one-fifth of those present in the adjacent matrix area. 3. The ease with which they are released into aqueous media is consistent with the assumption that they are present in the extracellular spaces in both of these tissue layers. 4. The retinal residue left after removal of the two soluble polysaccharides is rich in amino sugar- and sialic acid-containing polymers, which appear to be firmly bound to the tissue fragments. 5. About one-third of the sialic acid and one-tenth of the amino sugar could be extracted with chloroform–methanol. The components in this fraction were tentatively identified as gangliosides. 6. Digestion of the chloroform–methanol-insoluble residue with Pronase yielded as the principal product a heteropolysaccharide containing 16·5% of glucosamine, 24·3% of neutral sugar (galactose plus fucose) and 18·1% of sialic acid. This substance has been classified as a sialoglycan of composition similar to (but not identical with) that of the soluble one isolated from the matrix area of the tissue. ImagesFig. 1

  15. Transplanted neurons integrate into adult retinas and respond to light.

    PubMed

    Venugopalan, Praseeda; Wang, Yan; Nguyen, Tu; Huang, Abigail; Muller, Kenneth J; Goldberg, Jeffrey L

    2016-01-01

    Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP(+) axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON-OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs. PMID:26843334

  16. Transplanted neurons integrate into adult retinas and respond to light

    PubMed Central

    Venugopalan, Praseeda; Wang, Yan; Nguyen, Tu; Huang, Abigail; Muller, Kenneth J.; Goldberg, Jeffrey L.

    2016-01-01

    Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP+ axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON–OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs. PMID:26843334

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

    ERIC Educational Resources Information Center

    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.

  18. Early functional neural networks in the developing retina

    NASA Astrophysics Data System (ADS)

    Wong, R. O. L.; Chernjavsky, A.; Smith, S. J.; Shatz, C. J.

    1995-04-01

    IN the adult mammalian retina, the principal direction of information flow is along a vertical pathway from photoreceptors to retinal interneurons to ganglion cells, the output neurons of the retina. We report here, however, that initially in development, at a time when the photoreceptors are not yet even present, there are already functionally defined networks within the retina. These networks are spontaneously active rather than visually driven, and they involve horizontal rather than vertical pathways. By means of optical recording using the calcium-sensitive dye Fura-2, we have found that sets of retinal ganglion cells and amacrine cells, a type of retinal interneuron, undergo synchronized oscillations in intracellular calcium concentration. These oscillations are highly correlated among subgroups of neighbouring cells, and spread in a wave-like fashion tangentially across the retina. Thus, in development of retinal circuitry, the initial patterning of neuronal function occurs in the horizontal domain before the adult pattern of vertical information transfer emerges.

  19. Light-evoked S-nitrosylation in the retina.

    PubMed

    Tooker, Ryan E; Vigh, Jozsef

    2015-10-01

    Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pretreatment with N-ethylmaleimide (NEM), which occludes S-nitrosylation, or with 1-(2-trifluromethylphenyl)imidazole (TRIM), an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant posttranslational modification affecting a wide range of proteins under physiological conditions. PMID:25823749

  20. Transformation of stimulus correlations by the retina

    NASA Astrophysics Data System (ADS)

    Prentice, Jason; Simmons, Kristina; Tkacik, Gasper; Homann, Jan; Yee, Heather; Palmer, Stephanie; Nelson, Phillip; Balasubramanian, Vijay

    2014-03-01

    Correlations in the responses of sensory neurons seem to waste neural resources, but can carry cues about structured stimuli and help the brain correct for response errors. To assess how the retina negotiates this tradeoff, we measured simultaneous responses from many retinal ganglion cells presented with natural and artificial stimuli that varied in correlation structure. Responding to spatio-temporally structured stimuli such as natural movies, pairs of ganglion cells were more correlated than in response to white noise checkerboards, but were much less correlated than predicted by a non-adapting functional model of retinal response. Meanwhile, responding to stimuli with purely spatial correlations, pairs of ganglion cells showed increased correlations consistent with a static, non-adapting receptive field and nonlinearity. We found that in response to spatio- temporally correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the pattern of correlations across stimuli.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Expression of myelin genes in the developing chick retina.

    PubMed

    Gotoh, Hitosh; Ueda, Takayuki; Uno, Aoi; Ohuchi, Hideyo; Ikenaka, Kazuhiro; Ono, Katsuhiko

    2011-12-01

    In submammalian animals including chicks, the retina contains oligodendrocytes (OLs), and axons in the optic fiber layer are wrapped with compact myelin within the retina; however, the expression of myelin genes in the chick retina has not been demonstrated yet. In the present study, we examined the expression of three myelin genes (proteolipid protein, PLP; myelin basic protein, MBP; cyclic nucleotide phosphodiesterase, CNP) and PLP in the developing chick retina, in comparison to the localization of Mueller cells. In situ hybridization demonstrated that all three myelin genes began to be expressed at E14 in the chick embryo retina. They are mostly restricted to the ganglion cell layer and the optic fiber layer, with a few exceptions in the inner nuclear layer where Mueller cells reside; however, PLP mRNA+ cells do not express glutamine synthetase, or vice versa. The present results elucidate that myelin genes are expressed only by OLs that are mostly localized in the innermost layer of the developing chick retina. PMID:21872683

  3. Gene Transcription Profile of the Detached Retina (An AOS Thesis)

    PubMed Central

    Zacks, David N.

    2009-01-01

    Purpose: Separation of the neurosensory retina from the retinal pigment epithelium (RPE) yields many morphologic and functional consequences, including death of the photoreceptor cells, Müller cell hypertrophy, and inner retinal rewiring. Many of these changes are due to the separation-induced activation of specific genes. In this work, we define the gene transcription profile within the retina as a function of time after detachment. We also define the early activation of kinases that might be responsible for the detachment-induced changes in gene transcription. Methods: Separation of the retina from the RPE was induced in Brown-Norway rats by the injection of 1% hyaluronic acid into the subretinal space. Retinas were harvested at 1, 7, and 28 days after separation. Gene transcription profiles for each time point were determined using the Affymetrix Rat 230A gene microarray chip. Transcription levels in detached retinas were compared to those of nondetached retinas with the BRB-ArrayTools Version 3.6.0 using a random variance analysis of variance (ANOVA) model. Confirmation of the significant transcriptional changes for a subset of the genes was performed using microfluidic quantitative real-time polymerase chain reaction (qRT-PCR) assays. Kinase activation was explored using Western blot analysis to look for early phosphorylation of any of the 3 main families of mitogen-activated protein kinases (MAPK): the p38 family, the Janus kinase family, and the p42/p44 family. Results: Retinas separated from the RPE showed extensive alterations in their gene transcription profile. Many of these changes were initiated as early as 1 day after separation, with significant increases by 7 days. ANOVA analysis defined 144 genes that had significantly altered transcription levels as a function of time after separation when setting a false discovery rate at ≤0.1. Confirmatory RT-PCR was performed on 51 of these 144 genes. Differential transcription detected on the microarray

  4. Characterization of glucagon-expressing neurons in the chicken retina

    PubMed Central

    Fischer, Andy J.; Skorupa, Dana; Schonberg, David L.; Walton, Nathaniel A.

    2008-01-01

    We have recently identified large glucagon-expressing neurons that densely ramify neurites in the peripheral edge of the retina and regulate the proliferation of progenitors in the circumferential marginal zone (CMZ) of the postnatal chicken eye (Fischer et al., 2005). However, nothing is known about the transmitters and proteins that are expressed by the glucagon-expressing neurons in the avian retina. We used antibodies to cell-distinguishing markers to better characterize the different types of glucagon-expressing neurons. We found that the large glucagon-expressing neurons were immunoreactive for substance P, neurofilament, Pax6, AP2α, HuD, calretinin, trkB and trkC. Colocalization of glucagon and substance P in the large glucagon-expressing neurons indicates that these cells are the “bullwhip cells” that have been briefly described by Ehrlich, Keyser and Karten (1987). Similar to the bullwhip cells, the conventional glucagon-expressing amacrine cells were immunoreactive for calretinin, HuD, Pax6, and AP2α. Unlike bullwhip cells, the conventional glucagon-expressing amacrine cells were immunoreactive for GABA. While glucagon-immunoreactive amacrine cells were negative for substance P in central regions of the retina, a subset of this type of amacrine cell was immunoreactive for substance P in far peripheral regions of the retina. An additional type of glucagon/substance P-expressing neuron, resembling the bullwhip cells, was found in far peripheral and dorsal regions of the retina. Based on morphology, distribution within the retina, and histological markers, we conclude that there may be 4 different types of glucagon-expressing neurons in the avian retina. PMID:16572462

  5. Intravitreal Injection of AAV2 Transduces Macaque Inner Retina

    PubMed Central

    Yin, Lu; Greenberg, Kenneth; Hunter, Jennifer J.; Dalkara, Deniz; Kolstad, Kathleen D.; Masella, Benjamin D.; Wolfe, Robert; Visel, Meike; Stone, Daniel; Libby, Richard T.; DiLoreto, David; Schaffer, David; Flannery, John; Williams, David R.

    2011-01-01

    Purpose. Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized morphology of the high-acuity human fovea. This was a study of inner retina transduction in the macaque, a primate with ocular characteristics most similar to that of humans. Methods. In vivo imaging and histology were used to examine GFP expression in the macaque inner retina after intravitreal injection of AAV vectors containing five distinct promoters. Results. AAV2 produced pronounced GFP expression in inner retinal cells of the fovea, no expression in the central retina beyond the fovea, and variable expression in the peripheral retina. AAV2 vector incorporating the neuronal promoter human connexin 36 (hCx36) transduced ganglion cells within a dense annulus around the fovea center, whereas AAV2 containing the ubiquitous promoter hybrid cytomegalovirus (CMV) enhancer/chicken-β-actin (CBA) transduced both Müller and ganglion cells in a dense circular disc centered on the fovea. With three shorter promoters—human synapsin (hSYN) and the shortened CBA and hCx36 promoters (smCBA and hCx36sh)—AAV2 produced visible transduction, as seen in fundus images, only when the retina was altered by ganglion cell loss or enzymatic vitreolysis. Conclusions. The results in the macaque suggest that intravitreal injection of AAV2 would produce high levels of gene expression at the human fovea, important in retinal gene therapy, but not in the central retina beyond the fovea. PMID:21310920

  6. Age-related changes in the tiger salamander retina.

    PubMed

    Townes-Anderson, E; Colantonio, A; St Jules, R S

    1998-05-01

    Tiger salamanders have been used in visual science because of the large size of their cells and the ease of preparation and maintenance of in vitro retinal preparations. We have found that salamanders over 27 cm in length show a variety of visual abnormalities. Compared to smaller animals (15-23 cm), large animals exhibited a decrease in visual responses determined by tests of the optomotor reflex. Small animals responded correctly an average of 84.5% of the time in visual testing at three light levels compared to an average of 68.4% for the large animals with the poorest visual performance at the lowest level of illumination. In addition, large animals contained (i) histological degeneration of the outer retina, in particular, loss and disruption of outer segments and abnormalities of the retinal pigmented epithelium, (ii) loss of cells, including photoreceptors, by apoptosis as evaluated with the TUNEL technique, and (iii) an increase in the number of macrophages and lymphocytes within the retina as determined by morphological examination. These histological changes were present in all large animals and all quadrants of their retinas. In contrast, small animals showed virtually no retinal degeneration, no TUNEL-positive cells, and few immune-like cells in the retina. Since large animals are also older animals. the visual changes are age-related. Loss of visual function and histological degeneration in the outer retina also typify aged human eyes. Thus, we propose that large salamanders serve as an animal model for age-related retinal degeneration. In addition to providing a source of aging retina that is readily accessible to experimental manipulation, the salamander provides a pigmented retina with a mixed (2:1, rod:cone) population of photoreceptors, similar to the degeneration-prone parafoveal region of the human eye. PMID:9631666

  7. Aberrant Activity in Degenerated Retinas Revealed by Electrical Imaging

    PubMed Central

    Zeck, Günther

    2016-01-01

    In this review, I present and discuss the current understanding of aberrant electrical activity found in the ganglion cell layer (GCL) of rod-degenerated (rd) mouse retinas. The reported electrophysiological properties revealed by electrical imaging using high-density microelectrode arrays can be subdivided between spiking activity originating from retinal ganglion cells (RGCs) and local field potentials (LFPs) reflecting strong trans-membrane currents within the GCL. RGCs in rd retinas show increased and rhythmic spiking compared to age-matched wild-type retinas. Fundamental spiking frequencies range from 5 to 15 Hz in various mouse models. The rhythmic RGC spiking is driven by a presynaptic network comprising AII amacrine and bipolar cells. In the healthy retina this rhythm-generating circuit is inhibited by photoreceptor input. A unique physiological feature of rd retinas is rhythmic LFP manifested as spatially-restricted low-frequency (5–15 Hz) voltage changes. Their spatiotemporal characterization revealed propagation and correlation with RGC spiking. LFPs rely on gap-junctional coupling and are shaped by glycinergic and by GABAergic transmission. The aberrant RGC spiking and LFPs provide a simple readout of the functionality of the remaining retinal circuitry which can be used in the development of improved vision restoration strategies. PMID:26903810

  8. Selective Gene Transfer to the Retina Using Intravitreal Ultrasound Irradiation

    PubMed Central

    Sonoda, Shozo; Tachibana, Katsuro; Yamashita, Toshifumi; Shirasawa, Makoto; Terasaki, Hiroto; Uchino, Eisuke; Suzuki, Ryo; Maruyama, Kazuo; Sakamoto, Taiji

    2012-01-01

    This paper aims to evaluate the efficacy of intravitreal ultrasound (US) irradiation for green fluorescent protein (GFP) plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 μL) and bubble liposomes (BLs; 50 μL) was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM) of GFP-positive cells (32 ± 4.9; n = 7; P < 0.01 ). No GFP-positive cells were observed in the control eyes (n = 7). Intravitreal retinal US irradiation can transfer the GFP plasmid into the retina without causing any apparent damage. This procedure could be used to transfer genes and drugs directly to the retina and therefore has potential therapeutic value. PMID:22518277

  9. Opsin expression in adult, developing, and regenerating newt retinas.

    PubMed

    Sakakibara, Shunsuke; Hiramatsu, Hidemasa; Takahashi, Yusuke; Hisatomi, Osamu; Kobayashi, Yuko; Sakami, Sanae; Saito, Takehiko; Tokunaga, Fumio

    2002-06-30

    Japanese common newts (Cynops pyrrhogaster) have an ability to regenerate their neural retina even as adults. Although extensive research has been carried out attempting to understand this retinal regeneration, the molecules characterized in newt retina are limited. We isolated cDNAs encoding three putative opsins (Cp-Rh, -LWS and -SWS1), in addition to Cp-SWS2 [Takahashi et al., FEBS Lett. 501 (2001) 151-155] from a cDNA library of adult newt retina. Our immunohistochemical and in situ hybridization studies demonstrated that Cp-Rh is selectively expressed in rods, whereas the other opsins are expressed in cones. The distribution of opsin mRNAs in normal and regenerated retinas is very similar. In both developing and regenerating retinas, Cp-Rh and its mRNA first appeared in immature rods at the beginning or just after the formation of plexiform layers. Cp-Rh was initially found isotropically in the plasma membrane, and then translocalized to the apical region along with the maturation of regenerating rods. This suggests that reorganization of the intracellular structure takes place during maturation of the regenerating newt photoreceptors. PMID:12106689

  10. Microgravity effects on neural retina regeneration in the newt

    NASA Astrophysics Data System (ADS)

    Grigoryan, E. N.; Anton, H. J.; Mitashov, V. I.

    Data on forelimb and eye lens regenerationin in urodeles under spaceflight conditions (SFC) have been obtained in our previous studies. Today, evidence is available that SFC stimulate regeneration in experimental animals rather than inhibit it. The results of control on-ground experiments with simulated microgravity suggest that the stimulatory effect of SFC is due largely to weightlessness. An original experimental model is proposed, which is convenient for comprehensively analyzing neural regeneration under SFC. The initial results described here concern regeneration of neural retina in Pleurodeles waltl newts exposed to microgravity simulated in radial clinostat. After clinorotation for seven days (until postoperation day 16), a positive effect of altered gravity on structural restoration of detached neural retina was confirmed by a number of criteria. Specifically, an increased number of Müllerian glial cells, an increased relative volume of the plexiform layers, reduced cell death, advanced redifferentiation of retinal pigment epithelium, and extended areas of neural retina reattachment were detected in experimental newts. Moreover, cell proliferation in the inner nuclear layer of neural retina increased as compared with control. Thus, low gravity appears to intensify natural cytological and molecular mechanisms of neural retina regeneration in lower vertebrates.

  11. The effect of accelerated argon ions on the retina.

    PubMed

    Krebs, W; Krebs, I; Merriam, G R; Worgul, B V

    1988-07-01

    It has been postulated that high energy heavy ions cause a unique form of damage in living tissue, which results from the high linear energy transfer of accelerated single particles. We have searched for these single-particle effects, so-called "microlesions," in composite electron micrographs of retinas of rats which had been irradiated with a dose of 1 Gy of 570 MeV/amu argon ions. The calculated rate of energy deposition of the radiation in the retina was about 100 keV/micron and the influence was four particles per 100 micron 2. Different areas of the irradiated retinas which combined would have been expected to be traversed by approximately 2400 particles were examined. We were unable to detect ultrastructural changes in the irradiated retinas distinct from those of controls. The spatial cellular densities of pigment epithelial and photoreceptor cells remained within the normal range when examined at 24 h and at 6 months after irradiation. These findings suggest that the retina is relatively resistant to heavy-ion irradiation and that under the experimental conditions the passage of high energy argon ions does not cause retinal microlesions that can be detected by ultrastructural analysis. PMID:3393633

  12. Synaptic mechanisms of adaptation and sensitization in the retina

    PubMed Central

    Nikolaev, Anton; Leung, Kin-Mei; Odermatt, Benjamin; Lagnado, Leon

    2014-01-01

    Sensory systems continually adjust the way stimuli are processed. What are the circuit mechanisms underlying this plasticity? We investigated how synapses in the retina of zebrafish adjust to changes in the temporal contrast of a visual stimulus by imaging activity in vivo. Following an increase in contrast, bipolar cell synapses with strong initial responses depressed, whereas synapses with weak initial responses facilitated. Depression and facilitation predominated in different strata of the inner retina, where bipolar cell output was anticorrelated with the activity of amacrine cell synapses providing inhibitory feedback. Pharmacological block of GABAergic feedback converted facilitating bipolar cell synapses into depressing ones. These results indicate that depression intrinsic to bipolar cell synapses causes adaptation of the ganglion cell response to contrast, whereas depression in amacrine cell synapses causes sensitization. Distinct microcircuits segregating to different layers of the retina can cause simultaneous increases or decreases in the gain of neural responses. PMID:23685718

  13. MEMS technologies for epiretinal stimulation of the retina

    NASA Astrophysics Data System (ADS)

    Mokwa, W.

    2004-09-01

    It has been shown that electrical stimulation of retinal ganglion cells yields visual sensations. Therefore, a retina implant for blind humans suffering from retinitis pigmentosa based on this concept seems to be feasible. In Germany, there are two projects funded by the government working on different approaches namely the subretinal and the epiretinal approaches. This paper describes the epiretinal approach for such a system. The extraocular part of this system records visual images. The images are transformed by a neural net into corresponding signals for stimulation of the retinal ganglion cells. These signals are transmitted to a receiver unit of an intraocular implant, the retina stimulator. Integrated circuitry of this unit decodes the signals and transfers the data to a stimulation circuitry that selects stimulation electrodes placed onto the retina and generates current pulses to the electrodes. By this, action potentials in retinal ganglion cells are evoked, causing a visual sensation. This paper concentrates on the MEMS part of this implant.

  14. Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina.

    PubMed

    Du, Jianhai; Rountree, Austin; Cleghorn, Whitney M; Contreras, Laura; Lindsay, Ken J; Sadilek, Martin; Gu, Haiwei; Djukovic, Danijel; Raftery, Dan; Satrústegui, Jorgina; Kanow, Mark; Chan, Lawrence; Tsang, Stephen H; Sweet, Ian R; Hurley, James B

    2016-02-26

    Production of energy in a cell must keep pace with demand. Photoreceptors use ATP to maintain ion gradients in darkness, whereas in light they use it to support phototransduction. Matching production with consumption can be accomplished by coupling production directly to consumption. Alternatively, production can be set by a signal that anticipates demand. In this report we investigate the hypothesis that signaling through phototransduction controls production of energy in mouse retinas. We found that respiration in mouse retinas is not coupled tightly to ATP consumption. By analyzing metabolic flux in mouse retinas, we also found that phototransduction slows metabolic flux through glycolysis and through intermediates of the citric acid cycle. We also evaluated the relative contributions of regulation of the activities of α-ketoglutarate dehydrogenase and the aspartate-glutamate carrier 1. In addition, a comprehensive analysis of the retinal metabolome showed that phototransduction also influences steady-state concentrations of 5'-GMP, ribose-5-phosphate, ketone bodies, and purines. PMID:26677218

  15. A Possible Role of Neuroglobin in the Retina After Optic Nerve Injury: A Comparative Study of Zebrafish and Mouse Retina.

    PubMed

    Sugitani, Kayo; Koriyama, Yoshiki; Ogai, Kazuhiro; Wakasugi, Keisuke; Kato, Satoru

    2016-01-01

    Neuroglobin (Ngb) is a new member of the family of heme proteins and is specifically expressed in neurons of the central and peripheral nervous systems in all vertebrates. In particular, the retina has a 100-fold higher concentration of Ngb than do other nervous tissues. The role of Ngb in the retina is yet to be clarified. Therefore, to understand the functional role of Ngb in the retina after optic nerve injury (ONI), we used two types of retina, from zebrafish and mice, which have permissible and non-permissible capacity for nerve regeneration after ONI, respectively. After ONI, the Ngb protein in zebrafish was upregulated in the amacrine cells within 3 days, whereas in the mouse retina, Ngb was downregulated in the retinal ganglion cells (RGCs) within 3 days. Zebrafish Ngb (z-Ngb) significantly enhanced neurite outgrowth in retinal explant culture. According to these results, we designed an overexpression experiment with the mouse Ngb (m-Ngb) gene in RGC-5 cells (retinal precursor cells). The excess of m-Ngb actually rescued RGC-5 cells under hypoxic conditions and significantly enhanced neurite outgrowth in cell culture. These data suggest that mammalian Ngb has positive neuroprotective and neuritogenic effects that induce nerve regeneration after ONI. PMID:26427474

  16. Retina-like sensor image coordinates transformation and display

    NASA Astrophysics Data System (ADS)

    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.

  17. Electrical coupling between cones in turtle retina.

    PubMed Central

    Detwiler, P B; Hodgkin, A L

    1979-01-01

    1. The electrical coupling between cones of known spectral sensitivity in the peripheral part of the turtle's retina was studied by passing current through a micro-electrode inserted into one cone and recording with a second micro-electrode inserted into a neighbouring cone. 2. Spatial sensitivity profiles were determined by recording flash responses to a long narrow strip of light which was moved across the impaled cones in orthogonal directions. These measurements gave both the length constant lambda of electrical spread in the cone network and the separation of the two cones. 3. The cone separation determined from the spatial profiles agreed closely with that measured directly by injecting a fluorescent dye into two cones. 4. The length constant lambda varied from 18 to 39 micron with a mean of 25 micron for red-sensitive cones and 26 micron for green-sensitive cones. 5. The majority of cone pairs studied were electrically coupled provided they had the same spectral sensitivity and were separated by less than 60 micron: thirty-two out of thirty-six red-red pairs, two out of two green-green pairs, none out of eight red-green pairs: no blue cones were observed. 6. The strength of electrical coupling was expressed as a mutual resistance defined as the voltage in one cell divided by the current flowing into the other. Mutual resistances decreased from a maximum value of about 30 M omega at separations close to zero to 0.2 M omega, the lower limit of detectable coupling at separations of about 60 micron. Mutual resistances were always positive and were independent of which cell was directly polarized. The coupling seemed to be ohmic and any rectification or non-linearity probably arose in the cone membranes rather than in the coupling resistances. 7. The results were analysed in terms of the Lamb & Simon (1977) theories of square and hexagonal lattices, which approximate to the continuous sheet model except in the case of the cone to which current is applied. 8. The

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

    PubMed Central

    Bedore, Jake; Martyn, Amanda C.; Li, Anson K. C.; Dolinar, Eric A.; McDonald, Ian S.; Coupland, Stuart G.; Prado, Vania F.; Prado, Marco A.; Hill, Kathleen A.

    2015-01-01

    Background 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. Methods & Results 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. Significance 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. PMID:26226617

  19. Ganglion Cell Regeneration Following Whole-Retina Destruction in Zebrafish

    PubMed Central

    Sherpa, Tshering; Fimbel, Shane M.; Mallory, Dianne E.; Maaswinkel, Hans; Spritzer, Scott D.; Sand, Jordan A.; Li, L.; Hyde, David R.; Stenkamp, Deborah L.

    2008-01-01

    The retinas of adult teleost fish can regenerate neurons following injury. The current study provides the first documentation of functional whole retina regeneration in the zebrafish, Danio rerio, following intraocular injection of the cytotoxin, ouabain. Loss and replacement of laminated retinal tissue was monitored by analysis of cell death and cell proliferation, and by analysis of retina-specific gene expression patterns. The spatiotemporal process of retinal ganglion cell (RGC) regeneration was followed through the use of selective markers, and was found to largely recapitulate the spatiotemporal process of embryonic ganglion cell neurogenesis, over a more protracted time frame. However, the re-expression of some ganglion cell markers was not observed. The growth and pathfinding of ganglion cell axons was evaluated by measurement of the optic nerve head (ONH), and the restoration of normal ONH size was found to correspond to the time of recovery of two visually-mediated behaviors. However, some abnormalities were noted, including overproduction of RGCs, and progressive and excessive growth of the ONH at longer recovery times. This model system for whole-retina regeneration has provided an informative view of the regenerative process. PMID:18000816

  20. Fluorescence spectroscopy of the retina from scrapie-infected mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, we have proposed that the fluorescence spectra of sheep retina can be well correlated to the presence or absence of scrapie. Scrapie is the most widespread TSE (transmissible spongiform encephalopathy) affecting sheep and goats worldwide. Mice eyes have been previously reported as a model ...

  1. Assessment of Glial Function in the In Vivo Retina

    PubMed Central

    Srienc, Anja I.; Kornfield, Tess E.; Mishra, Anusha; Burian, Michael A.; Newman, Eric A.

    2013-01-01

    Glial cells, traditionally viewed as passive elements in the CNS, are now known to have many essential functions. Many of these functions have been revealed by work on retinal glial cells. This work has been conducted almost exclusively on ex vivo preparations and it is essential that retinal glial cell functions be characterized in vivo as well. To this end, we describe an in vivo rat preparation to assess the functions of retinal glial cells. The retina of anesthetized, paralyzed rats is viewed with confocal microscopy and laser speckle flowmetry to monitor glial cell responses and retinal blood flow. Retinal glial cells are labeled with the Ca2+ indicator dye Oregon Green 488 BAPTA-1 and the caged Ca2+ compound NP-EGTA by injection of the compounds into the vitreous humor. Glial cells are stimulated by photolysis of caged Ca2+ and the activation state of the cells assessed by monitoring Ca2+ indicator dye fluorescence. We find that, as in the ex vivo retina, retinal glial cells in vivo generate both spontaneous and evoked intercellular Ca2+ waves. We also find that stimulation of glial cells leads to the dilation of neighboring retinal arterioles, supporting the hypothesis that glial cells regulate blood flow in the retina. This in vivo preparation holds great promise for assessing glial cell function in the healthy and pathological retina. PMID:22144328

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

    EPA Science Inventory

    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...

  3. Glaucoma related Proteomic Alterations in Human Retina Samples

    PubMed Central

    Funke, Sebastian; Perumal, Natarajan; Beck, Sabine; Gabel-Scheurich, Silke; Schmelter, Carsten; Teister, Julia; Gerbig, Claudia; Gramlich, Oliver W.; Pfeiffer, Norbert; Grus, Franz H.

    2016-01-01

    Glaucoma related proteomic changes have been documented in cell and animal models. However, proteomic studies investigating on human retina samples are still rare. In the present work, retina samples of glaucoma and non-glaucoma control donors have been examined by a state-of-the-art mass spectrometry (MS) workflow to uncover glaucoma related proteomic changes. More than 600 proteins could be identified with high confidence (FDR < 1%) in human retina samples. Distinct proteomic changes have been observed in 10% of proteins encircling mitochondrial and nucleus species. Numerous proteins showed a significant glaucoma related level change (p < 0.05) or distinct tendency of alteration (p < 0.1). Candidates were documented to be involved in cellular development, stress and cell death. Increase of stress related proteins and decrease of new glaucoma related candidates, ADP/ATP translocase 3 (ANT3), PC4 and SRFS1-interacting protein 1 (DFS70) and methyl-CpG-binding protein 2 (MeCp2) could be documented by MS. Moreover, candidates could be validated by Accurate Inclusion Mass Screening (AIMS) and immunostaining and supported for the retinal ganglion cell layer (GCL) by laser capture microdissection (LCM) in porcine and human eye cryosections. The workflow allowed a detailed view into the human retina proteome highlighting new molecular players ANT3, DFS70 and MeCp2 associated to glaucoma. PMID:27425789

  4. Müller glia cell reprogramming and retina regeneration

    PubMed Central

    Goldman, Daniel

    2014-01-01

    Müller glia are the major glial component of the retina. They are one of the last retinal cell types to be born during development and they function to maintain retinal homeostasis and integrity. In mammals, Müller glia respond to retinal injury in a variety of ways that can be either protective or detrimental to retinal function. Although under special circumstances these cells can be coaxed to proliferate and generate neurons, these responses are meager and insufficient for repairing a damaged retina. By contrast, in teleost fish (such as zebrafish) the response of Müller glia to retinal injury involves a reprogramming event that imparts retinal stem cell characteristics and allows them to produce a proliferating population of progenitors that can regenerate all major retinal cell types and restore vision. Recent studies have revealed a number of important mechanisms underlying Müller glia reprogramming and retina regeneration in fish that may lead to new strategies for stimulating retina regeneration in mammals. PMID:24894585

  5. Functional Architecture of the Retina: Development and Disease

    PubMed Central

    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

  6. The Virtual Retina: Is Good Educational Technology Always Strategic?

    ERIC Educational Resources Information Center

    Dowie, Sandra

    Educational technology units must continually monitor their strategic plans to ensure that they are aligned with the realities of their institutions. Strategic dissonance occurs when previously successful strategies are no longer achieving the same positive outcomes. The Virtual Retina CD-ROM project is used in this paper as an example of…

  7. Distribution of cone photoreceptors in the mammalian retina.

    PubMed

    Szél, A; Röhlich, P; Caffé, A R; van Veen, T

    1996-12-15

    The retina of mammals contains various amounts of cone photoreceptors that are relatively evenly distributed and display a radially or horizontally oriented area of peak density. In most mammalian species two spectrally different classes of cone can be distinguished with various histochemical and physiological methods. These cone classes occur in a relatively constant ratio, middle-to-longwave sensitive cones being predominant over short-wave cones. Recent observations do not support the idea that each cone subpopulation is uniformly distributed across the retina. With appropriate type-specific markers, unexpected patterns of colour cone topography have been revealed in certain species. In the mouse and the rabbit, the "standard" uniform pattern was found to be confined exclusively to the dorsal retina. In a ventral zone of variable width all cones express short-wave pigment, a phenomenon whose biological significance is not known yet. Dorso-ventral asymmetries have been described in lower vertebrates, matching the spectral distribution of light reaching the retina from various sectors of the visual field. It is not clear, however, whether the retinal cone fields in mammals carry out a function similar to that of their counterparts in fish and amphibians. Since in a number of mammalian species short-wave cones are the first to differentiate, and the expression of the short-wave pigment seems to be the default pathway of cone differentiation, we suggest that the short-wave sensitive cone fields are rudimentary areas conserving an ancestral stage of the photopigment evolution. PMID:9016448

  8. New spectral imaging techniques for blood oximetry in the retina

    NASA Astrophysics Data System (ADS)

    Alabboud, Ied; Muyo, Gonzalo; Gorman, Alistair; Mordant, David; McNaught, Andrew; Petres, Clement; Petillot, Yvan R.; Harvey, Andrew R.

    2007-07-01

    Hyperspectral imaging of the retina presents a unique opportunity for direct and quantitative mapping of retinal biochemistry - particularly of the vasculature where blood oximetry is enabled by the strong variation of absorption spectra with oxygenation. This is particularly pertinent both to research and to clinical investigation and diagnosis of retinal diseases such as diabetes, glaucoma and age-related macular degeneration. The optimal exploitation of hyperspectral imaging however, presents a set of challenging problems, including; the poorly characterised and controlled optical environment of structures within the retina to be imaged; the erratic motion of the eye ball; and the compounding effects of the optical sensitivity of the retina and the low numerical aperture of the eye. We have developed two spectral imaging techniques to address these issues. We describe first a system in which a liquid crystal tuneable filter is integrated into the illumination system of a conventional fundus camera to enable time-sequential, random access recording of narrow-band spectral images. Image processing techniques are described to eradicate the artefacts that may be introduced by time-sequential imaging. In addition we describe a unique snapshot spectral imaging technique dubbed IRIS that employs polarising interferometry and Wollaston prism beam splitters to simultaneously replicate and spectrally filter images of the retina into multiple spectral bands onto a single detector array. Results of early clinical trials acquired with these two techniques together with a physical model which enables oximetry map are reported.

  9. In vivo Electroporation of Morpholinos into the Adult Zebrafish Retina

    PubMed Central

    Thummel, Ryan; Bailey, Travis J.; Hyde, David R.

    2011-01-01

    Many devastating inherited eye diseases result in progressive and irreversible blindness because humans cannot regenerate dying or diseased retinal neurons. In contrast, the adult zebrafish retina possesses the robust ability to spontaneously regenerate any neuronal class that is lost in a variety of different retinal damage models, including retinal puncture, chemical ablation, concentrated high temperature, and intense light treatment 1-8. Our lab extensively characterized regeneration of photoreceptors following constant intense light treatment and inner retinal neurons after intravitreal ouabain injection 2, 5, 9. In all cases, resident Müller glia re-enter the cell cycle to produce neuronal progenitors, which continue to proliferate and migrate to the proper retinal layer, where they differentiate into the deficient neurons. We characterized five different stages during regeneration of the light-damaged retina that were highlighted by specific cellular responses. We identified several differentially expressed genes at each stage of retinal regeneration by mRNA microarray analysis 10. Many of these genes are also critical for ocular development. To test the role of each candidate gene/protein during retinal regeneration, we needed to develop a method to conditionally limit the expression of a candidate protein only at times during regeneration of the adult retina. Morpholino oligos are widely used to study loss of function of specific proteins during the development of zebrafish, Xenopus, chick, mouse, and tumors in human xenografts 11-14. These modified oligos basepair with complementary RNA sequence to either block the splicing or translation of the target RNA. Morpholinos are stable in the cell and can eliminate or "knockdown" protein expression for three to five days 12. Here, we describe a method to efficiently knockdown target protein expression in the adult zebrafish retina. This method employs lissamine-tagged antisense morpholinos that are injected

  10. Impact of bronchopulmonary dysplasia on brain and retina.

    PubMed

    Poon, Annie Wing Hoi; Ma, Emilie Xiao Hang; Vadivel, Arul; Jung, Suna; Khoja, Zehra; Stephens, Laurel; Thébaud, Bernard; Wintermark, Pia

    2016-01-01

    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. PMID:26988760

  11. Impact of bronchopulmonary dysplasia on brain and retina

    PubMed Central

    Poon, Annie Wing Hoi; Ma, Emilie Xiao Hang; Vadivel, Arul; Jung, Suna; Khoja, Zehra; Stephens, Laurel; Thébaud, Bernard; Wintermark, Pia

    2016-01-01

    ABSTRACT 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. PMID:26988760

  12. Vibratome Sectioning Mouse Retina to Prepare Photoreceptor Cultures

    PubMed Central

    Clérin, Emmanuelle; Yang, Ying; Forster, Valérie; Fontaine, Valérie; Sahel, José-Alain; Léveillard, Thierry

    2014-01-01

    The retina is a part of the central nervous system that has organized architecture, with neurons in layers from the photoreceptors, both rods and cones in contact with the retinal pigmented epithelium in the most distant part on the retina considering the direction of light, and the ganglion cells in the most proximal distance. This architecture allows the isolation of the photoreceptor layer by vibratome sectioning. The dissected neural retina of a mouse aged 8 days is flat-embedded in 4% gelatin on top of a slice of 20% gelatin photoreceptor layer facing down. Using a vibratome and a double edged razor blade, the 100 µm thick inner retina is sectioned. This section contains the ganglion cells and the inner layer with notably the bipolar cells. An intermediary section of 15 µm is discarded before 200 µm of the outer retina containing the photoreceptors is recovered. The gelatin is removed by heating at 37 °C. Pieces of outer layer are incubated in 500 µl of Ringer's solution with 2 units of activated papain for 20 min at 37 °C. The reaction is stopped by adding 500 µl 10% fetal calf serum (FCS) in Dulbecco's Modified Eagle Medium (DMEM), then 25 units of DNAse I is added before centrifugation at RT, washed several times to remove serum and the cells are resuspended in 500 µl of DMEM and seeded at 1 x 105 cells/cm2. The cells are grown to 5 days in vitro and their viability scored using live/dead assay. The purity of the culture is first determined by microscopic observation during the experiment. The purity is then validated by seeding and fixing cells on a histological slide and analyzing using a rabbit polyclonal anti-SAG, a photoreceptor marker and mouse monoclonal anti-RHO, a rod photoreceptor specific marker. Alternatively, the photoreceptor layer (97% rods) can be used for gene or protein expression analysis and for transplantation. PMID:25548881

  13. Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia.

    PubMed Central

    Hayreh, S. S.; Weingeist, T. A.

    1980-01-01

    Ophthalmoscopic, fluorescein angiographic, electrophysiological, and morphological studies on 63 eyes of rhesus monkeys with acute transient experimental occlusion of the central artery of the retina (OCAR) showed that the retina suffered irreparable damage after ischaemia of 105 minutes but recovered well after ischaemia of 97-98 minutes. The tolerance time of the brain to acute transient ischaemia is many times shorter than that of the retina. The metabolism of ischaemic neurones (in the retina and brain) is discussed with a view to explaining this difference, and also the various factors possibly responsible for the retina's longer tolerance to ischaemia, as compared to the brain. PMID:7426553

  14. Artificial retina: the multichannel processing of the mammalian retina achieved with a neuromorphic asynchronous light acquisition device.

    PubMed

    Lorach, Henri; Benosman, Ryad; Marre, Olivier; Ieng, Sio-Hoi; Sahel, José A; Picaud, Serge

    2012-12-01

    Objective. Accurate modeling of retinal information processing remains a major challenge in retinal physiology with applications in visual rehabilitation and prosthetics. Most of the current artificial retinas are fed with static frame-based information, losing thereby the fundamental asynchronous features of biological vision. The objective of this work is to reproduce the spatial and temporal properties of the majority of ganglion cell (GC) types in the mammalian retina. Approach. Here, we combined an asynchronous event-based light sensor with a model pulling nonlinear subunits to reproduce the parallel filtering and temporal coding occurring in the retina. We fitted our model to physiological data and were able to reconstruct the spatio-temporal responses of the majority of GC types previously described in the mammalian retina (Roska et al 2006 J. Neurophysiol. 95 3810-22). Main results. Fitting of the temporal and spatial components of the response was achieved with high coefficients of determination (median R(2) = 0.972 and R(2) = 0.903, respectively). Our model provides an accurate temporal precision with a reliability of only few milliseconds-peak of the distribution at 5 ms-similar to biological retinas (Berry et al 1997 Proc. Natl Acad. Sci. USA 94 5411-16; Gollisch and Meister 2008 Science 319 1108-11). The spiking statistics of the model also followed physiological measurements (Fano factor: 0.331). Significance. This new asynchronous retinal model therefore opens new perspectives in the development of artificial visual systems and visual prosthetic devices. PMID:23075696

  15. Diosmin Protects Rat Retina from Ischemia/Reperfusion Injury

    PubMed Central

    Tong, Nianting; Zhang, Zhenzhen; Gong, Yuanyuan; Yin, Lili

    2012-01-01

    Abstract Objective Diosmin, a natural flavone glycoside, possesses antioxidant activity and has been used to alleviate ischemia/reperfusion (I/R) injury. The aim of this study was to clarify whether the administration of diosmin has a protective effect against I/R injury induced using the high intraocular pressure (IOP) model in rat retina, and to determine the possible antioxidant mechanisms involved. Methods Retinal I/R injury was induced in the rats by elevating the IOP to 110 mmHg for 60 min. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. The levels of malondialdehyde (MDA) and the activities of total-superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the retinal tissues were determined 24 h after I/R injury. At 7 days post-I/R injury, electroretinograms (ERGs) were recorded, and the density of surviving retinal ganglion cells (RGCs) was estimated by counting retrograde tracer-labeled cells in whole-mounted retinas. Retinal histological changes were also examined and quantified using light microscopy. Results Diosmin significantly decreased the MDA levels and increased the activities of T-SOD, GSH-Px, and CAT in the retina of rats compared with the ischemia group (P<0.05), and suppressed the I/R-induced reduction in the a- and b-wave amplitudes of the ERG (P<0.05). The thickness of the entire retina, inner nuclear layer, inner plexiform layer, and outer retinal layer and the number of cells in the ganglion cell layer were significantly less after I/R injury (P<0.05), and diosmin remarkably ameliorated these changes on retinal morphology. Diosmin also attenuated the I/R-induced loss of RGCs of the rat retina (P<0.05). Conclusion Diosmin protected the retina from I/R injury, possibly via a mechanism involving the regulation of oxidative parameters. PMID:22509733

  16. Optical Coherence Tomography and Raman Spectroscopy of the retina

    SciTech Connect

    Evans, J W; Zawadzki, R J; Liu, R; Chan, J; Lane, S; Werner, J S

    2009-01-16

    Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to combining these imaging modalities. We present an ex vivo OCT microscope combined with Raman spectroscopy capable of collecting morphological and molecular information about a sample simultaneously. The combined instrument will be used to investigate remaining technical challenges to combine these imaging modalities, such as the laser power levels needed to achieve a Raman signal above the noise level without damaging the sample.

  17. Numerical computational of fluid flow through a detached retina

    NASA Astrophysics Data System (ADS)

    Jiann, Lim Yeou; Ismail, Zuhaila; Shafie, Sharidan; Fitt, Alistair

    2015-02-01

    In this paper, a phenomenon of fluid flow through a detached retina is studied. Rhegmatogeneous retinal detachment happens when vitreous humour flow through a detached retina. The exact mechanism of Rhegmatogeneous retinal detachment is complex and remains incomplete. To understand the fluid flow, a paradigm mathematical model is developed and is approximated by the lubrication theory. The numerical results of the velocity profile and pressure distribution are computed by using Finite Element Method. The effects of fluid mechanical on the retinal detachment is discussed and analyzed. Based on the analysis, it is found that the retinal detachment deformation affects the pressure distribution. It is important to comprehend the development of the retinal detachment so that a new treatment method can be developed.

  18. A polyaxonal amacrine cell population in the primate retina.

    PubMed

    Greschner, Martin; Field, Greg D; Li, Peter H; Schiff, Max L; Gauthier, Jeffrey L; Ahn, Daniel; Sher, Alexander; Litke, Alan M; Chichilnisky, E J

    2014-03-01

    Amacrine cells are the most diverse and least understood cell class in the retina. Polyaxonal amacrine cells (PACs) are a unique subset identified by multiple long axonal processes. To explore their functional properties, populations of PACs were identified by their distinctive radially propagating spikes in large-scale high-density multielectrode recordings of isolated macaque retina. One group of PACs exhibited stereotyped functional properties and receptive field mosaic organization similar to that of parasol ganglion cells. These PACs had receptive fields coincident with their dendritic fields, but much larger axonal fields, and slow radial spike propagation. They also exhibited ON-OFF light responses, transient response kinetics, sparse and coordinated firing during image transitions, receptive fields with antagonistic surrounds and fine spatial structure, nonlinear spatial summation, and strong homotypic neighbor electrical coupling. These findings reveal the functional organization and collective visual signaling by a distinctive, high-density amacrine cell population. PMID:24599459

  19. Recovery of the rabbit retina after light damage (preliminary observations).

    PubMed

    McKechnie, N M; Foulds, W S

    1980-01-01

    The retinae of anaesthetised Dutch rabbits were exposed to one of two intensities of white light for a period of 1 h. After exposure the animals were allowed to recover for various periods up to 4 weeks. The animals were then killed, and retinal and choroidal tissue was taken for investigation by both light and electron microscopy. Exposure to the lower intensity produced disruption of the visual cell outer segments and distension of the pigment epithelium. Recovery from this insult was rapid although disturbances in rod disc stacking and a loss of cone cell outer segments were evident 4 weeks after exposure. Exposure to the higher intensity resulted in necrosis of visual cells and pigment epithelial cells. Non-native phagocytic cells were active in the removal of cellular debris. Recovery from this insult was not observed. Four weeks after exposure much of the previously illuminated retina was reduced to disorganised Müller cells and occasional macrophages. PMID:6906139

  20. Transcriptomic analyses of Onecut1 and Onecut2 deficient retinas.

    PubMed

    Goetz, Jillian J; Trimarchi, Jeffrey M

    2015-06-01

    In this article, we further explore the data generated for the research article "Onecut1 and Onecut2 play critical roles in the development of the mouse retina". To better understand the functionality of the Onecut family of transcription factors in retinogenesis, we investigated the retinal transcriptomes of developing and mature mice to identify genes with differential expression. This data article reports the full transcriptomes resulting from these experiments and provides tables detailing the differentially expressed genes between wildtype and Onecut1 or 2 deficient retinas. The raw array data of our transcriptomes as generated using Affymetrix microarrays are available on the NCBI Gene Expression Omnibus (GEO) browser (Reference number GSE57917 and GSE57918GSE57917GSE57918). PMID:26484186

  1. Modeling and Simulation of Microelectrode-Retina Interactions

    SciTech Connect

    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.

  2. Inhibition of HDAC2 Protects the Retina From Ischemic Injury

    PubMed Central

    Fan, Jie; Alsarraf, Oday; Dahrouj, Mohammad; Platt, Kenneth A.; Chou, C. James; Rice, Dennis S.; Crosson, Craig E.

    2013-01-01

    Purpose. Protein acetylation is an essential mechanism in regulating transcriptional and inflammatory events. Studies have shown that nonselective histone deacetylase (HDAC) inhibitors can protect the retina from ischemic injury in rats. However, the role of specific HDAC isoforms in retinal degenerative processes remains obscure. The purpose of this study was to investigate the role of HDAC2 isoform in a mouse model of ischemic retinal injury. Methods. Localization of HDAC2 in mice retinas was evaluated by immunohistochemical analyses. To investigate whether selective reduction in HDAC2 activity can protect the retina from ischemic injury, Hdac2+/− mice were utilized. Electroretinographic (ERG) and morphometric analyses were used to assess retinal function and morphology. Results. Our results demonstrated that HDAC2 is primarily localized in nuclei in inner nuclear and retinal ganglion cell layers, and HDAC2 activity accounted for approximately 35% of the total activities of HDAC1, 2, 3, and 6 in the retina. In wild-type mice, ERG a- and b-waves from ischemic eyes were significantly reduced when compared to pre-ischemia baseline values. Morphometric examination of these eyes revealed significant degeneration of inner retinal layers. In Hdac2+/− mice, ERG a- and b-waves from ischemic eyes were significantly greater than those measured in ischemic eyes from wild-type mice. Morphologic measurements demonstrated that Hdac2+/− mice exhibit significantly less retinal degeneration than wild-type mice. Conclusions. This study demonstrated that suppressing HDAC2 expression can effectively reduce ischemic retinal injury. Our results support the idea that the development of selective HDAC2 inhibitors may provide an efficacious treatment for ischemic retinal injury. PMID:23696608

  3. Photovoltage of Rods and Cones in the Macaque Retina

    NASA Astrophysics Data System (ADS)

    Schneeweis, David M.; Schnapf, Julie L.

    1995-05-01

    The kinetics, gain, and reliability of light responses of rod and cone photoreceptors are important determinants of overall visual sensitivity. In voltage recordings from photoreceptors in an intact primate retina, rods were found to be functionally isolated from each other, unlike the tightly coupled rods of cold-blooded vertebrates. Cones were observed to receive excitatory input from rods, which indicates that the cone pathway also processes rod signals. This input might be expected to degrade the spatial resolution of mesopic vision.

  4. Effects and Responses to Spaceflight in the Mouse Retina

    NASA Technical Reports Server (NTRS)

    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

  5. Immunohistochemical and Calcium Imaging Methods in Wholemount Rat Retina

    PubMed Central

    Sargoy, Allison; Barnes, Steven; Brecha, Nicholas C.; De Sevilla Müller, Luis Pérez

    2015-01-01

    In this paper we describe the tools, reagents, and the practical steps that are needed for: 1) successful preparation of wholemount retinas for immunohistochemistry and, 2) calcium imaging for the study of voltage gated calcium channel (VGCC) mediated calcium signaling in retinal ganglion cells. The calcium imaging method we describe circumvents issues concerning non-specific loading of displaced amacrine cells in the ganglion cell layer. PMID:25349920

  6. The Retina and Other Light-sensitive Ocular Clocks.

    PubMed

    Besharse, Joseph C; McMahon, Douglas G

    2016-06-01

    Ocular clocks, first identified in the retina, are also found in the retinal pigment epithelium (RPE), cornea, and ciliary body. The retina is a complex tissue of many cell types and considerable effort has gone into determining which cell types exhibit clock properties. Current data suggest that photoreceptors as well as inner retinal neurons exhibit clock properties with photoreceptors dominating in nonmammalian vertebrates and inner retinal neurons dominating in mice. However, these differences may in part reflect the choice of circadian output, and it is likely that clock properties are widely dispersed among many retinal cell types. The phase of the retinal clock can be set directly by light. In nonmammalian vertebrates, direct light sensitivity is commonplace among body clocks, but in mice only the retina and cornea retain direct light-dependent phase regulation. This distinguishes the retina and possibly other ocular clocks from peripheral oscillators whose phase depends on the pace-making properties of the hypothalamic central brain clock, the suprachiasmatic nuclei (SCN). However, in mice, retinal circadian oscillations dampen quickly in isolation due to weak coupling of its individual cell-autonomous oscillators, and there is no evidence that retinal clocks are directly controlled through input from other oscillators. Retinal circadian regulation in both mammals and nonmammalian vertebrates uses melatonin and dopamine as dark- and light-adaptive neuromodulators, respectively, and light can regulate circadian phase indirectly through dopamine signaling. The melatonin/dopamine system appears to have evolved among nonmammalian vertebrates and retained with modification in mammals. Circadian clocks in the eye are critical for optimum visual function where they play a role fine tuning visual sensitivity, and their disruption can affect diseases such as glaucoma or retinal degeneration syndromes. PMID:27095816

  7. Maximizing contrast resolution in the outer retina of mammals

    PubMed Central

    Smith, Robert G.; Taylor, W. Rowland

    2010-01-01

    The outer retina removes the first-order correlation, the background light level, and thus more efficiently transmits contrast. This removal is accomplished by negative feedback from horizontal cell to photoreceptors. However, the optimal feedback gain to maximize the contrast sensitivity and spatial resolution is not known. The objective of this study was to determine, from the known structure of the outer retina, the synaptic gains that optimize the response to spatial and temporal contrast within natural images. We modeled the outer retina as a continuous 2D extension of the discrete 1D model of Yagi et al. (Proc Int Joint Conf Neural Netw 1: 787–789, 1989). We determined the spatio-temporal impulse response of the model using small-signal analysis, assuming that the stimulus did not perturb the resting state of the feedback system. In order to maximize the efficiency of the feedback system, we derived the relationships between time constants, space constants, and synaptic gains that give the fastest temporal adaptation and the highest spatial resolution of the photoreceptor input to bipolar cells. We found that feedback which directly modulated photoreceptor calcium channel activation, as opposed to changing photoreceptor voltage, provides faster adaptation to light onset and higher spatial resolution. The optimal solution suggests that the feedback gain from horizontal cells to photoreceptors should be ~0.5. The model can be extended to retinas that have two or more horizontal cell networks with different space constants. The theoretical predictions closely match experimental observations of outer retinal function. PMID:20361204

  8. Plastic retina: image enhancement using polymer grid triode arrays

    NASA Astrophysics Data System (ADS)

    Heeger, Alan J.; Heeger, David J.; Langan, John D.; Yang, Yang

    1996-02-01

    An array of polymer grid triodes (PGTs) connected through a common grid functions as a 'plastic retina' which provides local contrast gain control for image enhancement. This device, made from layers of conducting polymers, functions as an active resistive network that performs center-surround filtering. The PGT array with common grid is a continuous analog of the discrete approach of Mead, with a variety of fabrication advantages and with a significant saving of 'real estate' within the unit cell of each pixel.

  9. Photoreceptor types and distributions in the retinae of insectivores.

    PubMed

    Peichl, L; Künzle, H; Vogel, P

    2000-01-01

    The retinae of insectivores have been rarely studied, and their photoreceptor arrangements and expression patterns of visual pigments are largely unknown. We have determined the presence and distribution of cones in three species of shrews (common shrew Sorex araneus, greater white-toothed shrew Crocidura russula, dark forest shrew Crocidura poensis; Soricidae) and in the lesser hedgehog tenrec Echinops telfairi (Tenrecidae). Special cone types were identified and quantified in flattened whole retinae by antisera/antibodies recognizing the middle-to-long-wavelength-sensitive (M/L-)cone opsin and the short-wavelength-sensitive (S-)cone opsin, respectively. A combination of immunocytochemistry with conventional histology was used to assess rod densities and cone/rod ratios. In all four species the rods dominate at densities of about 230,000-260,000/mm2. M/L- and S-cones are present, comprising between 2% of the photoreceptors in the nocturnal Echinops telfairi and 13% in Sorex araneus that has equal diurnal and nocturnal activity phases. This suggests dichromatic color vision like in many other mammals. A striking feature in all four species are dramatically higher S-cone proportions in ventral than in dorsal retina (0.5% vs. 2.5-12% in Sorex, 5-15% vs. 30-45% in Crocidura poensis, 3-12% vs. 20-50% in Crocidura russula, 10-30% vs. 40-70% in Echinops). The functional and comparative aspects of these structural findings are discussed. PMID:11193110

  10. Parallel information processing channels created in the retina

    PubMed Central

    Schiller, Peter H.

    2010-01-01

    In the retina, several parallel channels originate that extract different attributes from the visual scene. This review describes how these channels arise and what their functions are. Following the introduction four sections deal with these channels. The first discusses the “ON” and “OFF” channels that have arisen for the purpose of rapidly processing images in the visual scene that become visible by virtue of either light increment or light decrement; the ON channel processes images that become visible by virtue of light increment and the OFF channel processes images that become visible by virtue of light decrement. The second section examines the midget and parasol channels. The midget channel processes fine detail, wavelength information, and stereoscopic depth cues; the parasol channel plays a central role in processing motion and flicker as well as motion parallax cues for depth perception. Both these channels have ON and OFF subdivisions. The third section describes the accessory optic system that receives input from the retinal ganglion cells of Dogiel; these cells play a central role, in concert with the vestibular system, in stabilizing images on the retina to prevent the blurring of images that would otherwise occur when an organism is in motion. The last section provides a brief overview of several additional channels that originate in the retina. PMID:20876118

  11. In vivo intrinsic optical signal imaging of mouse retinas

    NASA Astrophysics Data System (ADS)

    Wang, Benquan; Yao, Xincheng

    2016-03-01

    Intrinsic optical signal (IOS) imaging is a promising noninvasive method for advanced study and diagnosis of eye diseases. Before pursuing clinical applications, more IOS studies employing animal models are necessary to establish the relationship between IOS distortions and eye diseases. Ample mouse models are available for investigating the relationship between IOS distortions and eye diseases. However, in vivo IOS imaging of mouse retinas is challenging due to the small ocular lens (compared to frog eyes) and inevitable eye movements. We report here in vivo IOS imaging of mouse retinas using a custom-designed functional OCT. The OCT system provided high resolution (3 μm) and high speed (up to 500 frames/s) imaging of mouse retinas. An animal holder equipped with a custom designed ear bar and bite bar was used to minimize eye movement due to breathing and heartbeats. Residual eye movement in OCT images was further compensated by accurate image registration. Dynamic OCT imaging revealed rapid IOSs from photoreceptor outer segments immediately (<10 ms) after the stimulation delivery, and unambiguous IOS changes were also observed from inner retinal layers with delayed time courses compared to that of photoreceptor IOSs.

  12. Light pollution: the possible consequences of excessive illumination on retina.

    PubMed

    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. PMID:26541085

  13. The major cell populations of the mouse retina.

    PubMed

    Jeon, C J; Strettoi, E; Masland, R H

    1998-11-01

    We report a quantitative analysis of the major populations of cells present in the retina of the C57 mouse. Rod and cone photoreceptors were counted using differential interference contrast microscopy in retinal whole mounts. Horizontal, bipolar, amacrine, and Müller cells were identified in serial section electron micrographs assembled into serial montages. Ganglion cells and displaced amacrine cells were counted by subtracting the number of axons in the optic nerve, learned from electron microscopy, from the total neurons of the ganglion cell layer. The results provide a base of reference for future work on genetically altered animals and put into perspective certain recent studies. Comparable data are now available for the retinas of the rabbit and the monkey. With the exception of the monkey fovea, the inner nuclear layers of the three species contain populations of cells that are, overall, quite similar. This contradicts the previous belief that the retinas of lower mammals are "amacrine-dominated", and therefore more complex, than those of higher mammals. PMID:9786999

  14. Targeted microinjection into cells and retina using optoporation

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Mohanty, Samarendra K.

    2011-12-01

    The laser microbeam has enabled highly precise noncontact delivery of exogenous materials into targeted cells without compromising cell viability, which has been a highly challenging task for traditional methods. Here, we report targeted delivery of impermeable substances into mammalian cells and goldfish retinal explants subsequent to ultrafast laser microbeam assisted injection. Introduction of impermeable dye into the cell through localized pore formation was confirmed by distinct fluorescence at the site of pore formation on the membrane and its spatiotemporal diffusion pattern through the nucleus. Indirect optoporation by bubble formation, external to cell, led to a similar spatial diffusion pattern but with a larger time constant for injection. Using optimized laser intensity, exposure, and a spatial irradiation pattern, desired spatial transfection patterns in goldfish retina explants were achieved as confirmed by the expression of injected plasmids encoded for light-activable channelrhodopsin-2 ion-channel, tagged with fluorescent protein. Laser assisted delivery of exogenous material into a specific area of three-dimensional neuronal tissue, such as the retina, will help to understand the functioning of neuronal circuitry of normal and degenerated retina.

  15. Statistics of Optical Coherence Tomography Data From Human Retina

    PubMed Central

    de Juan, Joaquín; Ferrone, Claudia; Giannini, Daniela; Huang, David; Koch, Giorgio; Russo, Valentina; Tan, Ou; Bruni, Carlo

    2010-01-01

    Optical coherence tomography (OCT) has recently become one of the primary methods for noninvasive probing of the human retina. The pseudoimage formed by OCT (the so-called B-scan) varies probabilistically across pixels due to complexities in the measurement technique. Hence, sensitive automatic procedures of diagnosis using OCT may exploit statistical analysis of the spatial distribution of reflectance. In this paper, we perform a statistical study of retinal OCT data. We find that the stretched exponential probability density function can model well the distribution of intensities in OCT pseudoimages. Moreover, we show a small, but significant correlation between neighbor pixels when measuring OCT intensities with pixels of about 5 µm. We then develop a simple joint probability model for the OCT data consistent with known retinal features. This model fits well the stretched exponential distribution of intensities and their spatial correlation. In normal retinas, fit parameters of this model are relatively constant along retinal layers, but varies across layers. However, in retinas with diabetic retinopathy, large spikes of parameter modulation interrupt the constancy within layers, exactly where pathologies are visible. We argue that these results give hope for improvement in statistical pathology-detection methods even when the disease is in its early stages. PMID:20304733

  16. Anti-excitotoxic activity of trimetazidine in the retina.

    PubMed

    Payet, Olivier; D'Aldin, Christine; Maurin, Laurence; Bonne, Claude; Muller, Agnès

    2004-02-01

    The purpose of this study was to investigate the mechanism of the neuroprotective activity of trimetazidine in animal retina stressed by ischemia or kainate. Flash electroretinograms were recorded in guinea pigs after ischemia, induced by an acute increase in the intraocular pressure (IOP), or after an intravitreal injection of kainate. Treatment with trimetazidine per os afforded a significant protection of the electroretinogram against the ischemic as well as the excitotoxic insult as an antioxidant (dimethylthiourea) and a nitric oxide synthase inhibitor (nitroarginine) did. The effect of the drug on the extracellular accumulation of glutamate induced by chemical ischemia was studied by incubating rat retina in vitro. Trimetazidine was able to inhibit the extracellular glutamate accumulation, which represents the first step of the excitotoxic phenomenon. Then the compound activity on the glial uptake of glutamate was studied in a rat Müller cell line (rMC-1) in culture. Chemical ischemia inhibited the active 3H-glutamate transport, an effect that was reversed by trimetazidine, at micromolar concentrations. These results demonstrate that trimetazidine which is recognized as an efficient drug against ischemic injuries, is also capable of protecting the retina against excitotoxicity by reducing ischemia-induced accumulation of glutamate due in particular to glial transporter inhibition. PMID:15006162

  17. A Crystallin Gene Network in the Mouse Retina

    PubMed Central

    Templeton, Justin P.; Wang, XiangDi; Freeman, Natalie E.; Ma, Zhiwei; Lu, Anna; Hejtmancik, Fielding; Geisert, Eldon E.

    2013-01-01

    The present study was designed to examine the regulation of crystallin genes and protein in the mouse retina using the BXD recombinant inbred (RI) strains. Illumina Sentrix BeadChip Arrays (MouseWG-6v2) were used to analyze mRNA levels in 75 BXD RI strains along with the parental strains (C57Bl/6J and DBA/2J), and the reciprocal crosses in the Hamilton Eye Institute (HEI) Retina Dataset (www.genenetwork.org). Protein levels were investigated using immunoblots to quantify levels of proteins and indirect immunohistochemistry to define the distribution of protein. Algorithms in the Genomatix program were used to identify transcription factor binding sites common to the regulatory sequences in the 5′ regions of co-regulated set of crystallin and other genes as compared to a set of control genes. As subset of genes, including many encoding lens crystallins is part of a tightly co-regulated network that is active in the retina. Expression of this crystallin network appears to be binary in nature, being expressed either at relatively low levels or being highly upregulated. Relative to a control set of genes, the 5′ regulatory sequences of the crystallin network genes show an increased frequency of a set of common transcription factor-binding sites, the most common being those of the Maf family. Chromatin immunoprecipitation of human lens epithelial cells (HLEC) and rat retinal ganglion cells (RGC) confirmed the functionality of these sites, showing that MafA binds the predicted sites of CRYGA and CRYGD in HLE and CRYAB, CRYGA, CRYBA1, and CRYBB3 in RGC cells. In the retina there is a highly correlated group of genes containing many members of the α- β- and γ-crystallin families. These genes can be dramatically upregulated in the retina. One transcription factor that appears to be involved in this coordinated expression is the MAF family transcription of factors associated with both lens and extralenticular expression of crystallin genes. PMID:23978599

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

    NASA Astrophysics Data System (ADS)

    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.

  19. [A complication in gas surgery: injection of gas beneath the retina in a pseudophakic eye].

    PubMed

    Lincoff, H; Kreissig, I; Jakobiec, F

    1987-02-01

    Report on an inadvertent injection of gas beneath the retina in a pseudophakic eye. The gas was injected through the pupil to tamponade a retinal break. Instead, however, it found its way under the retina, increasing the extent of the detachment. A thick, transparent membrane posterior to the intraocular lens prevented the gas from entering the vitreous space and diverted it laterally behind the iris to the ciliary body, where it penetrated between layers of the ciliary epithelium and entered the subretinal space. The gas became visible under the retina. The bullous redetachment had a mother-of-pearl-like opalescence characteristic of gas beneath the retina. PMID:3573664

  20. Seeing double: visual physiology of double-retina eye ontogeny in stomatopod crustaceans.

    PubMed

    Feller, Kathryn D; Cohen, Jonathan H; Cronin, Thomas W

    2015-03-01

    Stomatopod eye development is unusual among crustaceans. Just prior to metamorphosis, an adult retina and associated neuro-processing structures emerge adjacent to the existing material in the larval compound eye. Depending on the species, the duration of this double-retina eye can range from a few hours to several days. Although this developmental process occurs in all stomatopod species observed to date, the retinal physiology and extent to which each retina contributes to the animal's visual sensitivity during this transition phase is unknown. We investigated the visual physiology of stomatopod double retinas using microspectrophotometry and electroretinogram recordings from different developmental stages of the Western Atlantic species Squilla empusa. Though microspectrophotometry data were inconclusive, we found robust ERG responses in both larval and adult retinas at all sampled time points indicating that the adult retina responds to light from the very onset of its emergence. We also found evidence of an increase in the response dynamics with ontogeny as well as an increase in sensitivity of retinal tissue during the double-retina phase relative to single retinas. These data provide an initial investigation into the ontogeny of vision during stomatopod double-retina eye development. PMID:25471793

  1. MicroRNA Expression in the Glaucomatous Retina

    PubMed Central

    Jayaram, Hari; Cepurna, William O.; Johnson, Elaine C.; Morrison, John C.

    2015-01-01

    Purpose MicroRNAs are small, endogenous noncoding RNAs that modulate posttranscriptional gene expression. Although the contribution of microRNAs to the pathogenesis of glaucomatous damage is unknown, supporting evidence from central nervous system (CNS) research suggests they may play a role. It was therefore hypothesized that microRNAs known to be altered in CNS injury are also altered in experimental glaucoma. Methods Intraocular pressure (IOP) was elevated in rats by unilateral injection of hypertonic saline and IOP monitored for 5 weeks. After rats were killed, retrobulbar optic nerve sections were graded for damage. MicroRNA was extracted from whole retinae of eyes with advanced nerve damage (n = 8) and from normal, noninjected control eyes (n = 8). Quantitative PCRs were performed using a panel of 17 microRNAs, reported from CNS research to be implicated in mechanisms also linked to glaucomatous damage. Computationally and experimentally derived gene targets were identified for the differentially expressed microRNAs. These were then integrated with existing gene array data. Functional interpretation was performed using the Molecular Signatures Database and DAVID Functional Annotation Clustering. Results Eight microRNAs were significantly downregulated in glaucomatous retinae compared with controls (miR-181c, miR-497, miR-204, let-7a, miR-29b, miR-16, miR106b, and miR-25); miR-27a was significantly upregulated. Enrichment of targets associated with extracellular matrix/cell proliferation, immune system, and regulation of apoptosis were observed. Cholesterol homeostasis and mTORC-1 pathways showed reduced expression. Conclusions MicroRNAs are differentially expressed in retinae of eyes with advanced glaucomatous damage compared with normal controls. Integrating microRNA with gene expression data may improve understanding of the complex biological responses produced by chronically elevated IOP. PMID:26720444

  2. Measuring In Vivo Free Radical Production by the Outer Retina

    PubMed Central

    Berkowitz, Bruce A.; Bredell, Bryce X.; Davis, Christopher; Samardzija, Marijana; Grimm, Christian; Roberts, Robin

    2015-01-01

    Purpose Excessive and continuously produced free radicals in the outer retina are implicated in retinal aging and the pathogenesis of sight-threatening retinopathies, yet measuring outer retinal oxidative stress in vivo remains a challenge. Here, we test the hypothesis that continuously produced paramagnetic free radicals from the outer retina can be measured in vivo using high-resolution (22-μm axial resolution) 1/T1magnetic resonance imaging (MRI) without and with a confirmatory quench (quench-assisted MRI). Methods Low-dose sodium iodate–treated and diabetic C57Bl6/J mice (and their controls), and rod-dominated (129S6) or cone-only R91W;Nrl−/− mice were studied. In dark-adapted groups, 1/T1 was mapped transretinally in vivo without or with (1) the antioxidant combination of methylene blue (MB) and α-lipoic acid (LPA), or (2) light exposure; in subgroups, retinal superoxide production was measured ex vivo (lucigenin). Results In the sodium iodate model, retinal superoxide production and outer retina-specific 1/T1 values were both significantly greater than normal and corrected to baseline with MB+LPA therapy. Nondiabetic mice at two ages and 1.2-month diabetic mice (before the appearance of oxidative stress) had similar transretinal 1/T1 profiles. By 2.3 months of diabetes, only outer retinal 1/T1 values were significantly greater than normal and were corrected to baseline with MB+LPA therapy. In mice with healthy photoreceptors, a light quench caused 1/T1 of rods, but not cones, to significantly decrease from their values in the dark. Conclusions Quench-assisted MRI is a feasible method for noninvasively measuring normal and pathologic production of free radicals in photoreceptors/RPE in vivo. PMID:26670830

  3. Protective and Antioxidant Effects of PPARα in the Ischemic Retina

    PubMed Central

    Moran, Elizabeth; Ding, Lexi; Wang, Zhongxiao; Cheng, Rui; Chen, Qian; Moore, Robert; Takahashi, Yusuke; Ma, Jian-xing

    2014-01-01

    Purpose. Previous studies have demonstrated that peroxisome proliferator-activated receptor-alpha (PPARα) agonists have therapeutic effects in diabetic retinopathy, although the mechanism of action remains incompletely understood. The purpose of this study was to evaluate PPARα's protective effects in the ischemic retina, and to delineate its molecular mechanism of action. Methods. For the oxygen-induced retinopathy (OIR) model, wild-type (WT), and PPARα knockout (PPARα−/−) mice were exposed to 75% O2 from postnatal day 7 (P7) to P12 and treated with the PPARα agonist fenofibric acid (Feno-FA) from P12 to P16. At P17, the effects of Feno-FA on retinal glial fibrillary acidic protein (GFAP) expression, apoptotic DNA cleavage, and TUNEL labeling were analyzed. Cultured retinal cells were exposed to CoCl2 to induce hypoxia, and TUNEL staining and 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein dye were used to measure apoptosis and reactive oxygen species (ROS) generation. Western blotting was used to measure GFAP levels and cell signaling. Results. Feno-FA decreased retinal apoptosis and oxidative stress in WT but not PPARα−/− OIR mice. Peroxisome proliferator-activated receptor-alpha knockout OIR mice showed increased retinal cell death and glial activation in comparison to WT OIR mice. Feno-FA treatment and PPARα overexpression protected cultured retinal cells from hypoxic cell death and decreased ROS levels. Nuclear hypoxia-inducible factor-α (HIF-1α) and nicotine adenine dinucleotide phosphate oxidase-4 (Nox 4) were increased in OIR retinas and downregulated by Feno-FA in WT but not in PPARα−/− mice. Conclusions. Peroxisome proliferator-activated receptor-alpha has a potent antiapoptotic effect in the ischemic retina. This protective effect may be mediated in part through downregulation of HIF-1α/Nox 4 and consequently alleviation of oxidative stress. PMID:24825105

  4. Cadmium effects on the retina of adult Danio rerio.

    PubMed

    Avallone, Bice; Crispino, Roberta; Cerciello, Raimondo; Simoniello, Palma; Panzuto, Raffaele; Maria Motta, Chiara

    2015-01-01

    The aim of this work is to describe the effects of cadmium pollution on the vision of adult zebrafish, Danio rerio. Retinal morpho-cytological alterations were investigated by light and electron microscopy, while the functionality of cadmium-exposed retinae was assessed by re-illumination behavioral tests with white or colored light. Our results demonstrate that cadmium toxicity causes significant degeneration and loss of organization at both macro and microscopic levels. These alterations impair functional responses particularly through an increase in light sensitivity. Metallothioneins were not seen to be up-regulated, while the recovery of visual acuity is due to a regenerative process by Müller cells. PMID:25528674

  5. Specifying and controlling the optical image on the human retina.

    PubMed

    Westheimer, Gerald

    2006-01-01

    A review covering the trends that led to the current state of knowledge in the areas of: (a) schematic models of the eye, and the definition of the retinal image in terms of first-order optics; (b) the description of the actual image on the retina and methods for accessing and characterizing it; (c) available procedures for controlling the quality of the retinal image in defined situations; and (d) intra-receptoral optical effects that cause differences between the light distribution on the retinal surface and at the level of interaction with photopigment molecules. PMID:16099192

  6. Third harmonic generation microscopy of a mouse retina

    PubMed Central

    Lei, Tim C.; Domingue, Scott R.; Kahook, Malik Y.; Bartels, Randy A.; Ammar, David A.

    2015-01-01

    Purpose To demonstrate lipid-specific imaging of the retina through the use of third harmonic generation (THG), a multiphoton microscopic technique in which tissue contrast is generated from optical inhomogeneities. Methods A custom fiber laser and multiphoton microscope was constructed and optimized for simultaneous two-photon autofluorescence (TPAF) and THG retinal imaging. Imaging was performed using fixed-frozen sections of mouse eyes without the use of exogenous fluorescent dyes. In parallel experiments, a fluorescent nuclear stain was used to verify the location of the retinal cell nuclei. Results Simultaneous THG and TPAF images revealed all retinal layers with subcellular resolution. In BALB/c strains, the THG signal stems from the lipidic organelles of the cellular and nuclear membranes. In the C57BL/6 strain, the THG signal from the RPE cells originates from the pigmented granules. Conclusions THG microscopy can be used to image structures of the mouse retina using contrast inherent to the tissue and without the use of a fluorescent dye or exogenously expressed recombinant protein. PMID:25999681

  7. Survey of intravitreal injection techniques among retina specialists in Israel

    PubMed Central

    Segal, Ori; Segal-Trivitz, Yael; Nemet, Arie Y; Geffen, Noa; Nesher, Ronit; Mimouni, Michael

    2016-01-01

    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 that combine safety and efficacy while causing as little discomfort to the patients as possible. PMID:27366050

  8. Multipurpose semistatic shift registers for digital programmable retinas

    NASA Astrophysics Data System (ADS)

    Bernard, Thierry M.

    2000-05-01

    A digital programmable retina is a functional extension of a CMOS imager, in which every pixel is fitted with a tiny digital programmable processor. We actually call it a PAR, standing for Programmable Artificial Retina. From an architectural viewpoint, a PAR is a SIMD array processor with local optical input. A PAR is aimed at processing images on-site (where they are sensed) until they can be output from the array under concentrated form. The overall goal is to get compact, fast and inexpensive vision systems, e.g. for robotics applications. PAR design is subject to harsh constraints resulting from small pixel area and sensing/processing cohabitation. Meeting these constraints leads to using peculiar architectural and circuit technique solutions. In the last three generations of PARs we have designed, semi-static shift registers have played a crucial role in the maximization of computational power versus silicon area. In particular, the latter have been used to store, shift and--through some slight modifications--to perform local computations on images. Here, we show their abilities to support asynchronous propagation in order to implement `geodesic reconstruction', an extremely useful computational operator, in particular for image segmentation and then for object selection and manipulation purposes.

  9. A new approach towards a minimal invasive retina implant

    NASA Astrophysics Data System (ADS)

    Gerding, H.

    2007-03-01

    The possibility of using retina implants ('retinal prostheses') for the restoration of basic orientation in blind patients suffering from distal retinal diseases is presently under investigation by at least 18 independent project groups worldwide. It is a common feature of all implants to bypass degenerated retinal layers and to transfer visual information into the retinal network either by direct electrical stimulation or by neurotransmitter release. Contemporary implant designs are differing in the position of stimulating electrodes (epiretinal, subretinal, external) and the anatomical arrangement of implant components (intraocular, extraocular). The latter is of high relevance with regard to possible implant-tissue interactions and biological reactions. During the last few years new types of implants appeared that reduce intraocular components which are now deposited on the outer scleral surface or even in extraorbital position. The extreme of this trend are completely extraocular implants with transchoroidal or extraocular stimulation of the retina. The new type of implant presented in this paper combines the principle of direct retinal stimulation and minimal invasive implantation in a way that stimulating electrodes are the only implant component penetrating the eye via sclera, choroid and retinal pigment epithelium. All other device elements are positioned in extraocular position. The new concept necessitates a paradigmatic change about surgical handling of the choroid and multiple penetrations of the eye. Successful data about this type of retinal prosthesis are already available from long-term observation in non-human primates.

  10. TRP channel gene expression in the mouse retina.

    PubMed

    Gilliam, Jared C; Wensel, Theodore G

    2011-12-01

    In order to identify candidate cation channels important for retinal physiology, 28 TRP channel genes were surveyed for expression in the mouse retina. Transcripts for all TRP channels were detected by RT-PCR and sequencing. Northern blotting revealed that mRNAs for 12 TRP channel genes are enriched in the retina. The strongest signals were observed for TRPC1, TRPC3, TRPM1, TRPM3, and TRPML1, and clear signals were obtained for TRPC4, TRPM7, TRPP2, TRPV2, and TRPV4. In situ hybridization and immunofluorescence revealed widespread expression throughout multiple retinal layers for TRPC1, TRPC3, TRPC4, TRPML1, PKD1, and TRPP2. Striking localization of enhanced mRNA expression was observed for TRPC1 in the photoreceptor inner segment layer, for TRPM1 in the inner nuclear layer (INL), for TRPM3 in the INL, and for TRPML1 in the outer plexiform and nuclear layers. Strong immunofluorescence signal in cone outer segments was observed for TRPM7 and TRPP2. TRPC5 immunostaining was largely confined to INL cells immediately adjacent to the inner plexiform layer. TRPV2 antibodies stained photoreceptor axons in the outer plexiform layer. Expression of TRPM1 splice variants was strong in the ciliary body, whereas TRPM3 was strongly expressed in the retinal pigmented epithelium. PMID:22037305

  11. A Retina Inspired Model for Enhancing Visibility of Hazy Images

    PubMed Central

    Zhang, Xian-Shi; Gao, Shao-Bing; Li, Chao-Yi; Li, Yong-Jie

    2015-01-01

    The mammalian retina seems far smarter than scientists have believed so far. Inspired by the visual processing mechanisms in the retina, from the layer of photoreceptors to the layer of retinal ganglion cells (RGCs), we propose a computational model for haze removal from a single input image, which is an important issue in the field of image enhancement. In particular, the bipolar cells serve to roughly remove the low-frequency of haze, and the amacrine cells modulate the output of cone bipolar cells to compensate the loss of details by increasing the image contrast. Then the RGCs with disinhibitory receptive field surround refine the local haze removal as well as the image detail enhancement. Results on a variety of real-world and synthetic hazy images show that the proposed model yields results comparative to or even better than the state-of-the-art methods, having the advantage of simultaneous dehazing and enhancing of single hazy image with simple and straightforward implementation. PMID:26733857

  12. Developmental expression of dysbindin in Muller cells of rat retina.

    PubMed

    Matteucci, Andrea; Gaddini, Lucia; Macchia, Gianfranco; Varano, Monica; Petrucci, Tamara C; Macioce, Pompeo; Malchiodi-Albedi, Fiorella; Ceccarini, Marina

    2013-11-01

    Dysbindin, the product of the DTNBP1 gene, was identified by yeast two hybrid assay as a binding partner of dystrobrevin, a cytosolic component of the dystrophin protein complex. Although its functional role has not yet been completely elucidated, the finding that dysbindin assembles into the biogenesis of lysosome related organelles complex 1 (BLOC-1) suggests that it participates in intracellular trafficking and biogenesis of organelles and vesicles. Dysbindin is ubiquitous and in brain is expressed primarily in neurons. Variations at the dysbindin gene have been associated with increased risk for schizophrenia. As anomalies in retinal function have been reported in patients suffering from neuropsychiatric disorders, we investigated the expression of dysbindin in the retina. Our results show that differentially regulated dysbindin isoforms are expressed in rat retina during postnatal maturation. Interestingly, we found that dysbindin is mainly localized in Müller cells. The identification of dysbindin in glial cells may open new perspectives for a better understanding of the functional involvement of this protein in visual alterations associated to neuropsychiatric disorders. PMID:23954924

  13. Types of bipolar cells in the mouse retina.

    PubMed

    Ghosh, Krishna K; Bujan, Sascha; Haverkamp, Silke; Feigenspan, Andreas; Wässle, Heinz

    2004-01-26

    We studied the morphology of bipolar cells in fixed vertical tissue sections (slices) of the mouse retina by injecting the cells with Lucifer Yellow and Neurobiotin. Nine different cone bipolar cell types and one rod bipolar cell type were distinguished. The major criteria for classifying the cells were the branching pattern and stratification level of their axon terminals in the inner plexiform layer (IPL). To assess this, the IPL was subdivided into five strata of equal width. The slices were immunostained for calretinin, which labels three horizontal bands serving as a standard measure for the precise localization of the axon terminals. Immunostaining the retina with antibodies against the G-protein Ggamma13, a marker for ON-bipolar cells, made it possible to separate OFF- and ON-bipolar cells. At least two OFF-cone bipolar cells (Types 1 and 2) were immunolabeled with antibodies against the neurokinin 3 receptors (NK3R). A further OFF- and an ON-cone bipolar cell (Types 3 and 5) were immunostained with antibodies against the calcium-binding protein CaB5. The bipolar cell types described here were compared with previous schemes of rat and primate bipolar cells. Homologous types between the three species are discussed. PMID:14689473

  14. Ischemia-induced spreading depolarization in the retina.

    PubMed

    Srienc, Anja I; Biesecker, Kyle R; Shimoda, Angela M; Kur, Joanna; Newman, Eric A

    2016-09-01

    Cortical spreading depolarization is a metabolically costly phenomenon that affects the brain in both health and disease. Following severe stroke, subarachnoid hemorrhage, or traumatic brain injury, cortical spreading depolarization exacerbates tissue damage and enlarges infarct volumes. It is not known, however, whether spreading depolarization also occurs in the retina in vivo. We report now that spreading depolarization episodes are generated in the in vivo rat retina following retinal vessel occlusion produced by photothrombosis. The properties of retinal spreading depolarization are similar to those of cortical spreading depolarization. Retinal spreading depolarization waves propagate at a velocity of 3.0 ± 0.1 mm/min and are associated with a negative shift in direct current potential, a transient cessation of neuronal spiking, arteriole constriction, and a decrease in tissue O2 tension. The frequency of retinal spreading depolarization generation in vivo is reduced by administration of the NMDA antagonist MK-801 and the 5-HT(1D) agonist sumatriptan. Branch retinal vein occlusion is a leading cause of vision loss from vascular disease. Our results suggest that retinal spreading depolarization could contribute to retinal damage in acute retinal ischemia and demonstrate that pharmacological agents can reduce retinal spreading depolarization frequency after retinal vessel occlusion. Blocking retinal spreading depolarization generation may represent a therapeutic strategy for preserving vision in branch retinal vein occlusion patients. PMID:27389181

  15. Sector mapping method for 3D detached retina visualization.

    PubMed

    Zhai, Yi-Ran; Zhao, Yong; Zhong, Jie; Li, Ke; Lu, Cui-Xin; Zhang, Bing

    2016-10-01

    A new sphere-mapping algorithm called sector mapping is introduced to map sector images to the sphere of an eyeball. The proposed sector-mapping algorithm is evaluated and compared with the plane-mapping algorithm adopted in previous work. A simulation that maps an image of concentric circles to the sphere of the eyeball and an analysis of the difference in distance between neighboring points in a plane and sector were used to compare the two mapping algorithms. A three-dimensional model of a whole retina with clear retinal detachment was generated using the Visualization Toolkit software. A comparison of the mapping results shows that the central part of the retina near the optic disc is stretched and its edges are compressed when the plane-mapping algorithm is used. A better mapping result is obtained by the sector-mapping algorithm than by the plane-mapping algorithm in both the simulation results and real clinical retinal detachment three-dimensional reconstruction. PMID:27480739

  16. Crossover Inhibition Generates Sustained Visual Responses in the Inner Retina

    PubMed Central

    Rosa, Juliana M.; Ruehle, Sabine; Ding, Huayu; Lagnado, Leon

    2016-01-01

    Summary In daylight, the input to the retinal circuit is provided primarily by cone photoreceptors acting as band-pass filters, but the retinal output also contains neuronal populations transmitting sustained signals. Using in vivo imaging of genetically encoded calcium reporters, we investigated the circuits that generate these sustained channels within the inner retina of zebrafish. In OFF bipolar cells, sustained transmission was found to depend on crossover inhibition from the ON pathway through GABAergic amacrine cells. In ON bipolar cells, the amplitude of low-frequency signals was regulated by glycinergic amacrine cells, while GABAergic inhibition regulated the gain of band-pass signals. We also provide the first functional description of a subset of sustained ON bipolar cells in which synaptic activity was suppressed by fluctuations at frequencies above ∼0.2 Hz. These results map out the basic circuitry by which the inner retina generates sustained visual signals and describes a new function of crossover inhibition. PMID:27068790

  17. Histotypic differentiation of neonatal mouse retina in organ culture.

    PubMed

    Caffé, A R; Visser, H; Jansen, H G; Sanyal, S

    1989-10-01

    Retinae from neonatal mice were explanted in toto, with or without the retinal pigment epithelium (RPE) and adjoining mesenchymal cells, and maintained in organ culture for up to 3 weeks. The explants remained flat, rosette formation was minimal and histogenetic changes followed in the normal sequence. After 11, 14 and 21 days in vitro the three cellular layers--the outer nuclear layer including well differentiated rod and cone perikarya, the inner nuclear layer and the ganglion cell layer--with the intervening plexiform layers were comparable to those of the in vivo eyes. Electron microscopic analysis revealed that in the explants without RPE the nuclear layers developed as in vivo, but receptor outer segments (ROS) were not formed. When the RPE was present, receptor inner segments appeared normal and ROS including profuse disc structures were developed. Presence of synaptic elements was also recognized. Mesenchymal cells, when present differentiated into choroidal and scleral tissues and appeared to play a supportive role for the RPE cells. The system is described in detail and its suitability for the analysis of various cellular and metabolic factors in the development of the retina is discussed. PMID:2612197

  18. Pharmacological Analysis of Intrinsic Neuronal Oscillations in rd10 Retina

    PubMed Central

    Biswas, Sonia; Haselier, Christine; Mataruga, Anja; Thumann, Gabriele; Walter, Peter; Müller, Frank

    2014-01-01

    In the widely used mouse model of retinal degeneration, rd1, the loss of photoreceptors leads to rhythmic electrical activity of around 10–16 Hz in the remaining retinal network. Recent studies suggest that this oscillation is formed within the electrically coupled network of AII amacrine cells and ON-bipolar cells. A second mouse model, rd10, displays a delayed onset and slower progression of degeneration, making this mouse strain a better model for human retinitis pigmentosa. In rd10, oscillations occur at a frequency of 3–7 Hz, raising the question whether oscillations have the same origin in the two mouse models. As rd10 is increasingly being used as a model to develop experimental therapies, it is important to understand the mechanisms underlying the spontaneous rhythmic activity. To study the properties of oscillations in rd10 retina we combined multi electrode recordings with pharmacological manipulation of the retinal network. Oscillations were abolished by blockers for ionotropic glutamate receptors and gap junctions. Frequency and amplitude of oscillations were modulated strongly by blockers of inhibitory receptors and to a lesser extent by blockers of HCN channels. In summary, although we found certain differences in the pharmacological modulation of rhythmic activity in rd10 compared to rd1, the overall pattern looked similar. This suggests that the generation of rhythmic activity may underlie similar mechanisms in rd1 and rd10 retina. PMID:24918437

  19. In vivo cellular visualization of the human retina using optical coherence tomography and adaptive optics

    SciTech Connect

    Olivier, S S; Jones, S M; Chen, D C; Zawadzki, R J; Choi, S S; Laut, S P; Werner, J S

    2006-01-05

    Optical coherence tomography (OCT) sees the human retina sharply with adaptive optics. In vivo cellular visualization of the human retina at micrometer-scale resolution is possible by enhancing Fourier-domain optical-coherence tomography with adaptive optics, which compensate for the eye's optical aberrations.

  20. DEVELOPMENTAL CHANGES IN CARBACHOL-STIMULATED INOSITOLPHOSPHATE RELEASE IN PIGMENTED RAT RETINA

    EPA Science Inventory

    Muscarinic stimulation of inositolphosphate (IP) release in the albino rat retina changes during development. ittle is known, however, about the developmental profile of receptor-stimulated IP release in pigmented rat retina. arbachol-stimulated EP release was studied in the whol...

  1. A Comparison of Some Organizational Characteristics of the Mouse Central Retina and the Human Macula

    PubMed Central

    Hoo, Juyea; Yee, Claudine; Williams, David S.

    2015-01-01

    Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch’s membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch’s membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident. PMID:25923208

  2. Selenium dependent glutathione-peroxidase (GSH-Px) activity in the retina of preterm human infants

    SciTech Connect

    Lane, H.; Hittner, H.; Barron, S.; Mehta, R.; Kretzer, F.

    1986-03-01

    GSH-Px activity was determined in the retina of 15 preterm human neonates with gestational ages of 17-28 weeks and birth weights of 120 to 960 g. GSH-Px activity was measured using the coupled assay. The infants survived from 0.5 to 9 hours after parturition. The retinas were removed within 3 hours of autopsy. Through electronmicroscopy, there was verification that the entire retina was removed and no contamination of other eye tissues occurred. After removal, the retinas were immediately dissolved in phosphate buffered pH 7.0 saline for assay of GSH-Px activity. The mean GSH-Px activity was 19.44 +/- 6.44 with a range of 11.1 to 32.8 units NAPH/sub 2/ oxidized/min/g protein. There was a negative correlation between birth weight and GSH-Px activity (r = -0.86) and between week of gestation and GSH-Px activity (r = -0.91). The neonatal retina GSH-Px activity was 2 to 15 times higher than found in adult retinas. Thus, this research demonstrates that selenium dependent GSH-Px activity is elevated in the preterm neonate's retina which indicates that retina GSH-Px activity may be an important antioxidation system in the premature neonate.

  3. In vivo volumetric imaging of chicken retina with ultrahigh-resolution spectral domain optical coherence tomography

    PubMed Central

    Moayed, Alireza Akhlagh; Hariri, Sepideh; Song, Eun Sun; Choh, Vivian; Bizheva, Kostadinka

    2011-01-01

    The chicken retina is an established animal model for myopia and light-associated growth studies. It has a unique morphology: it is afoveate and avascular; oxygen and nutrition to the inner retina is delivered by a vascular tissue (pecten) that protrudes into the vitreous. Here we present, to the best of our knowledge, the first in vivo, volumetric high-resolution images of the chicken retina. Images were acquired with an ultrahigh-resolution optical coherence tomography (UHROCT) system with 3.5 µm axial resolution in the retina, at the rate of 47,000 A-scans/s. Spatial variations in the thickness of the nerve fiber and ganglion cell layers were mapped by segmenting and measuring the layer thickness with a semi-automatic segmentation algorithm. Volumetric visualization of the morphology and morphometric analysis of the chicken retina could aid significantly studies with chicken retinal models of ophthalmic diseases. PMID:21559138

  4. Compact high-speed line scanning quasi-confocal ophthalmoscope and retina imaging experiments

    NASA Astrophysics Data System (ADS)

    He, Yi; Wang, Zhibin; Wei, Ling; Li, Xiqi; Shi, Guohua; Zhang, Yudong

    2014-09-01

    A compact, high-speed line scanning quasi-confocal ophthalmoscope (LSO) for retina imaging is presented in this paper. By using a line beam to illuminate the retina, meanwhile a linear array sensor is used for imaging the retina, the LSO system significantly reduces the size, complexity, and cost comparing to a conventional confocal scanning laser ophthalmoscope (CSLO). With only one moving scanner to provide raster scanning of the line beam of the retina, the imaging frequency achieves 160 Hz and the lateral resolution is nearly 10 μm for 1024×330 pixels imaging mode. Preliminary experiments are performed for imaging the macula, the optic nerve head and other targets, providing high resolution and high speed videos of human retina.

  5. Distribution of Cones in Human and Monkey Retina: Individual Variability and Radial Asymmetry

    NASA Astrophysics Data System (ADS)

    Curcio, Christine A.; Sloan, Kenneth R.; Packer, Orin; Hendrickson, Anita E.; Kalina, Robert E.

    1987-05-01

    The distribution of photoreceptors is known for only one complete human retina and for the cardinal meridians only in the macaque monkey retina. Cones can be mapped in computer-reconstructed whole mounts of human and monkey retina. A 2.9-fold range in maximum cone density in the foveas of young adult human eyes may contribute to individual differences in acuity. Cone distribution is radially asymmetrical about the fovea in both species, as previously described for the distribution of retinal ganglion cells and for lines of visual isosensitivity. Cone density was greater in the nasal than in the temporal peripheral retina, and this nasotemporal asymmetry was more pronounced in monkey than in human retina.

  6. Effects of Aging and Anatomic Location on Gene Expression in Human Retina

    PubMed Central

    Cai, Hui; Fields, Mark A.; Hoshino, Risa; Priore, Lucian V. Del

    2012-01-01

    Objective: To determine the effects of age and topographic location on gene expression in human neural retina. Methods: Macular and peripheral neural retina RNA was isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses. Results: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula, and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young, or old retina were identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10, and SFRP2) which are preferably expressed in the periphery. Conclusion: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases. PMID:22666212

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

    NASA Astrophysics Data System (ADS)

    Vörösházi, Zsolt; Nagy, Zoltán; Szolgay, Péter

    2009-12-01

    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.

  8. Rhythmic Ganglion Cell Activity in Bleached and Blind Adult Mouse Retinas

    PubMed Central

    Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

    2014-01-01

    In retinitis pigmentosa – a degenerative disease which often leads to incurable blindness- the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor’s dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance <200 µm) reveals synchrony among homologous RGC types and a constant phase shift (∼70 msec) among heterologous cell types (ON versus OFF). The rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the

  9. Gene Delivery to the Retina: From Mouse to Man

    PubMed Central

    Bennett, Jean; Chung, Daniel C.; Maguire, Albert

    2013-01-01

    With the recent progress in identifying disease-causing genes in humans and in animal models, there are more and more opportunities for using retinal gene transfer to learn more about retinal physiology and also to develop therapies for blinding disorders. Success in preclinical studies for one form of inherited blindness have led to testing in human clinical trials. This paves the way to consider a number of other retinal diseases as ultimate gene therapy targets in human studies. The information presented here is designed to assist scientists and clinicians to use gene transfer to probe the biology of the retina and/or to move appropriate gene-based treatment studies from the bench to the clinic. PMID:22365778

  10. A test of metabolically efficient coding in the retina.

    PubMed

    Balasubramanian, Vijay; Berry, Michael J

    2002-11-01

    We tested the hypothesis that aspects of the neural code of retinal ganglion cells are optimized to transmit visual information at minimal metabolic cost. Under a broad ensemble of light patterns, ganglion cell spike trains consisted of sparse, precise bursts of spikes. These bursts were viewed as independent neural symbols. The noise in each burst was measured via repeated presentation of the visual stimulus, and the energy cost was estimated from the total charge flow during ganglion cell spiking. Given these costs and noise, the theory of efficient codes predicts an optimal distribution of symbol usage. Symbols that are either noisy or costly occur less frequently in this optimal code. We found good qualitative and quantitative agreement with the measured distribution of burst sizes for ganglion cells in the tiger salamander retina. PMID:12463343

  11. Wavefront optimized nonlinear microscopy of ex vivo human retinas

    NASA Astrophysics Data System (ADS)

    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.

  12. Binding of amaranthin in photoreceptors of monkey retina.

    PubMed

    Uehara, F; Ohba, N; Sameshima, M; Unoki, K; Okubo, A; Yanagita, T; Sugata, M; Iwakiri, N; Nakagawa, S

    1994-01-01

    The binding of amaranthin, specific for the Gal beta 1,3 GalNAc and NeuAc alpha 2,3 Gal beta 1,3 GalNAc sequences, to the photoreceptors of the monkey retina was investigated using the avidin-biotinylated peroxidase method. Amaranthin bound to the surfaces of both cone and rod photoreceptors. This and previous lectin histochemical studies show that O-glycoside-linked glycoconjugates are present on the surfaces of both cones and rods: Gal beta 1,3 GalNAc and NeuAc alpha 2,3 Gal beta 1,3 GalNAc are the terminal sugars of the glycoconjugates around cones and rods, respectively. PMID:7723202

  13. Using Stem Cells to Model Diseases of the Outer Retina

    PubMed Central

    Yvon, Camille; Ramsden, Conor M.; Lane, Amelia; Powner, Michael B.; da Cruz, Lyndon; Coffey, Peter J.; Carr, Amanda-Jayne F.

    2015-01-01

    Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE). It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC)-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP), Usher syndrome (USH), Leber congenital amaurosis (LCA), gyrate atrophy (GA), juvenile neuronal ceroid lipofuscinosis (NCL), Best vitelliform macular dystrophy (BVMD) and age related macular degeneration (AMD). PMID:26106463

  14. Resonant imaging of carotenoid pigments in the human retina

    NASA Astrophysics Data System (ADS)

    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.

  15. Label-free nonlinear optical imaging of mouse retina

    PubMed Central

    He, Sicong; Ye, Cong; Sun, Qiqi; Leung, Christopher K.S.; Qu, Jianan Y.

    2015-01-01

    A nonlinear optical (NLO) microscopy system integrating stimulated Raman scattering (SRS), two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) was developed to image fresh mouse retinas. The morphological and functional details of various retinal layers were revealed by the endogenous NLO signals. Particularly, high resolution label-free imaging of retinal neurons and nerve fibers in the ganglion cell and nerve fiber layers was achieved by capturing endogenous SRS and TPEF signals. In addition, the spectral and temporal analysis of TPEF images allowed visualization of different fluorescent components in the retinal pigment epithelium (RPE). Fluorophores with short TPEF lifetime, such as A2E, can be differentiated from other long-lifetime components in the RPE. The NLO imaging method would provide important information for investigation of retinal ganglion cell degeneration and holds the potential to study the biochemical processes of visual cycle in the RPE. PMID:25798325

  16. Neuronal cell types and connectivity: lessons from the retina

    PubMed Central

    Seung, H. Sebastian; Sümbül, Uygar

    2014-01-01

    We describe recent progress towards defining neuronal cell types in the mouse retina, and attempt to extract lessons that may be generally useful in the mammalian brain. Achieving a comprehensive catalog of retinal cell types now appears within reach, because researchers have achieved consensus concerning two fundamental challenges. The first is accuracy—defining pure cell types rather than settling for neuronal classes that are mixtures of types. The second is completeness—developing methods guaranteed to eventually identify all cell types, as well as criteria for determining when all types have been found. Case studies illustrate how these two challenges are handled by combining state-of-the-art molecular, anatomical and physiological techniques. Progress is also being made in observing and modeling connectivity between cell types. Scaling up to larger brain regions, such as the cortex, will require not only technical advances but careful consideration of the challenges of accuracy and completeness. PMID:25233310

  17. Electroanatomy of a unique amacrine cell in the rabbit retina.

    PubMed Central

    Miller, R F; Bloomfield, S A

    1983-01-01

    Intracellular electrophysiological recordings were obtained from a specialized class of "starburst" amacrine cells by using an isolated superperfused retina-eyecup preparation of the rabbit. These cells were injected intracellularly with horseradish peroxidase and identified with light microscopy. A computer-controlled image-processing system was used to map and display the three-dimensional dendritic organization and provide information on length and sublaminar distribution of dendritic processes. Starburst amacrines show an unusual dendritic architecture that includes thin intermediate dendritic segments. Analysis with steady-state cable equations suggests that these thin segments may provide electrical isolation of distal processes, raising the possibility that a single dendrite, which lies beyond the thin segment, may constitute a functional subunit of the cell. Images PMID:6574470

  18. MARCKS in advanced stages of neural retina histogenesis.

    PubMed

    Zolessi, Flavio R; Arruti, Cristina

    2004-01-01

    Myristoylated alanine-rich kinase C substrate (MARCKS), an actin-binding protein, is involved in several signal transduction pathways. It is susceptible to be phosphorylated by protein kinases as protein kinase C and some proline-directed kinases. These phosphorylations differently modulate its functions. We previously showed that a phosphorylation at its Ser25 (S25p-MARCKS) in chickens is a signature of this ubiquitous protein in neuron differentiation. To gain insight into the possible involvement of MARCKS in late retinal histogenesis, we compared the developmental expression patterns of the total protein and its S25p variants. Here we show that the most outstanding modifications occur at the outer retina, where S25p disappears at the end of embryonic development and where MARCKS is missing in adults. These results suggest diverse functional specializations in the different retinal layers. PMID:15855766

  19. Advances in color science: from retina to behavior

    PubMed Central

    Chatterjee, Soumya; Field, Greg D.; Horwitz, Gregory D.; Johnson, Elizabeth N.; Koida, Kowa; Mancuso, Katherine

    2010-01-01

    Color has become a premier model system for understanding how information is processed by neural circuits, and for investigating the relationships among genes, neural circuits and perception. Both the physical stimulus for color and the perceptual output experienced as color are quite well characterized, but the neural mechanisms that underlie the transformation from stimulus to perception are incompletely understood. The past several years have seen important scientific and technical advances that are changing our understanding of these mechanisms. Here, and in the accompanying minisymposium, we review the latest findings and hypotheses regarding color computations in the retina, primary visual cortex and higher-order visual areas, focusing on non-human primates, a model of human color vision. PMID:21068298

  20. The developing and evolving retina: using time to organize form.

    PubMed

    Finlay, Barbara L

    2008-02-01

    Evolutionary and other functional accounts of the retina and its normal development highlight different aspects of control of its growth and form than genomic and mechanistic accounts. Discussing examples from opsin expression, developmental regulation of the eye's size and optical quality, regulation of eye size with respect to brain and body size, and the development of the fovea, these different aspects of control are contrasted. Contributions of mouse models, particularly with regard to relative timing of events in different species are reviewed, introducing a Web-based utility for exploration of timing issues (www.translatingtime.net). Variation at the individual level, in early experience, and also across species is an essential source of information to understand normal development and its pathologies. PMID:17692298

  1. Raman spectroscopy using 1550 nm (retina-safe) laser excitation.

    PubMed

    Brouillette, Carl; Huang, Hermes; Smith, Wayne; Farquharson, Stuart

    2011-05-01

    During the past decade, the use of portable Raman analyzers for field measurements has grown dramatically. However, most analyzers use 785 nm excitation lasers that can cause permanent eye damage. To overcome this safety concern, we have built a portable Fourier transform (FT) Raman analyzer using a 1550 nm retina-safe excitation laser and have compared its performance to our 1064 nm FT-Raman analyzer, which uses the same optical design. Raman theory predicts approximately five times lower peak intensities at 1550 nm. Although we found that intensities were as much as 20 times less intense, the analyzer is still capable of measuring spectra of sufficient quality to identify and differentiate chemicals. PMID:21513601

  2. Suppression of Acid Sphingomyelinase Protects the Retina from Ischemic Injury

    PubMed Central

    Fan, Jie; Wu, Bill X.; Crosson, Craig E.

    2016-01-01

    Purpose Acid sphingomyelinase (ASMase) catalyzes the hydrolysis of sphingomyelin to ceramide and mediates multiple responses involved in inflammatory and apoptotic signaling. However, the role ASMase plays in ischemic retinal injury has not been investigated. The purpose of this study was to investigate how reduced ASMase expression impacts retinal ischemic injury. Methods Changes in ceramide levels and ASMase activity were determined by high performance liquid chromatography-tandem mass spectrometry analysis and ASMase activity. Retinal function and morphology were assessed by electroretinography (ERG) and morphometric analyses. Levels of TNF-α were determined by ELISA. Activation of p38 MAP kinase was assessed by Western blot analysis. Results In wild-type mice, ischemia produced a significant increase in retinal ASMase activity and ceramide levels. These increases were associated with functional deficits as measured by ERG analysis and significant structural degeneration in most retinal layers. In ASMase+/− mice, retinal ischemia did not significantly alter ASMase activity, and the rise in ceramide levels were significantly reduced compared to levels in retinas from wild-type mice. In ASMase+/− mice, functional and morphometric analyses of ischemic eyes revealed significantly less retinal degeneration than in injured retinas from wild-type mice. The ischemia-induced increase in retinal TNF-α levels was suppressed by the administration of the ASMase inhibitor desipramine, or by reducing ASMase expression. Conclusions Our results demonstrate that reducing ASMase expression provides partial protection from ischemic injury. Hence, the production of ceramide and subsequent mediators plays a role in the development of ischemic retinal injury. Modulating ASMase may present new opportunities for adjunctive therapies when treating retinal ischemic disorders. PMID:27571014

  3. Fragile X Mental Retardation Protein expression in the retina is regulated by light.

    PubMed

    Guimarães-Souza, E M; Perche, O; Morgans, C W; Duvoisin, R M; Calaza, K C

    2016-05-01

    Fragile X Mental Retardation Protein (FMRP) is a RNA-binding protein that modulates protein synthesis at the synapse and its function is regulated by glutamate. The retina is the first structure that participates in vision, and uses glutamate to transduce electromagnetic signals from light to electrochemical signals to neurons. FMRP has been previously detected in the retina, but its localization has not been studied yet. In this work, our objectives were to describe the localization of FMRP in the retina, to determine whether different exposure to dark or light stimulus alters FMRP expression in the retina, and to compare the pattern in two different species, the mouse and chick. We found that both FMRP mRNA and protein are expressed in the retina. By immunohistochemistry analysis we found that both mouse and chick present similar FMRP expression localized mainly in both plexiform layers and the inner retina. It was also observed that FMRP is down-regulated by 24 h dark adaptation compared to its expression in the retina of animals that were exposed to light for 1 h after 24 h in the dark. We conclude that FMRP is likely to participate in retinal physiology, since its expression changes with light exposure. In addition, the expression pattern and regulation by light of FMRP seems well conserved since it was similar in both mouse and chick. PMID:26719241

  4. Pixel arrangement design of retina-like sensor based on forward motion imaging visual task

    NASA Astrophysics Data System (ADS)

    Wang, Fan; Cao, Fengmei; Bai, Tingzhu; Luo, Zhihu; Su, Yulu

    2014-11-01

    Retina-like sensor is a kind of anthropomorphic visual sensor, which mimic the distribution of photoreceptors in the human retina. They are applied in fields of machine vision and target tracking. However, there are few reports on retina-like sensor used for forward-motion imaging. During forward-motion imaging, as the objects being imaged move along the optical axis direction during the integration time, image quality becomes worse towards the border of the image. In order to get clearer image, retina-like sensor are trying to be designed based on the feature of forward-motion imaging. In this paper, firstly, the degraded law of rectilinear sensor used for forward-motion imaging is analyzed, the retina-like sensor model based on the feature of forward-motion imaging are proposed. Secondly, the output image of retina-like sensor and rectilinear sensor used during the forward-motion imaging for different scenes at different degeneration degrees are simulated, respectively. Thirdly, the simulated images of both two sensors are assessed by four different image quality assessment methods including visual information fidelity (VIF), complex wavelet structural similarity index (CW-SSIM), Gabor filtered image contrast similarity (GFCS) and peak signal to noise ratio (PSNR), besides, the data amount of two sensors are compared. Four image quality assessments all demonstrate that image quality of retina-like sensor based on the feature of forward motion imaging is superior to that of rectilinear sensor.

  5. Early Divergence of Central and Peripheral Neural Retina Precursors During Vertebrate Eye Development

    PubMed Central

    Venters, Sara J.; Mikawa, Takashi; Hyer, Jeanette

    2015-01-01

    During development of the vertebrate eye, optic tissue is progressively compartmentalized into functionally distinct tissues. From the central to the peripheral optic cup, the original optic neuroepithelial tissue compartmentalizes, forming retina, ciliary body and iris. The retina can be further sub-divided into peripheral and central compartments, where the central domain is specialized for higher visual acuity, having a higher ratio and density of cone photoreceptors in most species. Classically, models depict a segregation of the early optic cup into only two domains, neural and non-neural. Recent studies, however, uncovered discrete precursors for central and peripheral retina in the optic vesicle, indicating that the neural retina cannot be considered as a single unit with homogeneous specification and development. Instead, central and peripheral retina may be subject to distinct developmental pathways that underlie their specialization. This review focuses on lineage relationships in the retina and revisits the historical context for segregation of central and peripheral retina precursors before overt eye morphogenesis. PMID:25329498

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

    SciTech Connect

    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. Semiconductor Nanorod–Carbon Nanotube Biomimetic Films for Wire-Free Photostimulation of Blind Retinas

    PubMed Central

    2014-01-01

    We report the development of a semiconductor nanorod-carbon nanotube based platform for wire-free, light induced retina stimulation. A plasma polymerized acrylic acid midlayer was used to achieve covalent conjugation of semiconductor nanorods directly onto neuro-adhesive, three-dimensional carbon nanotube surfaces. Photocurrent, photovoltage, and fluorescence lifetime measurements validate efficient charge transfer between the nanorods and the carbon nanotube films. Successful stimulation of a light-insensitive chick retina suggests the potential use of this novel platform in future artificial retina applications. PMID:25350365

  8. Evaluation of Electrical Stimulus Current Applied to Retina Cells for Retinal Prosthesis

    NASA Astrophysics Data System (ADS)

    Motonami, Keita; Watanabe, Taiichiro; Deguchi, Jun; Fukushima, Takafumi; Tomita, Hiroshi; Sugano, Eriko; Sato, Manami; Kurino, Hiroyuki; Tamai, Makoto; Koyanagi, Mitsumasa

    2006-04-01

    We have proposed a novel multilayer stacked retinal prosthesis chip based on three-dimensional integration technology. Implantable stimulus electrode arrays in polyimide flexible cables were fabricated for the electrical stimulation of the retina. To evaluate optimal retinal stimulus current, electrically evoked potential (EEP) was recorded in animal experiments using Japanese white rabbits. The EEP waveform was compared with visually evoked potential (VEP) waveform. The amplitude of the recorded EEP increased with stimulus current. The EEP waveform shows a similar behavior to the VEP waveform, indicating that the electrical stimulation of the retina can be exploited for the blind to perceive incident light to the retina.

  9. Effect of CW YAG and argon green lasers on experimentally detached retinas.

    PubMed

    Peyman, G A; Conway, M D; House, B J

    1984-06-01

    We evaluated the effects of argon-green (514.5 nm) and CW neodymium YAG (1060 nm) wavelengths on experimentally detached retinas of primates. Neither laser produced damage to the sensory retina of the fovea. The argon green wavelength, which was absorbed by haemoglobin in the vessel or by extravasated red blood cells, created vasospasm and nerve fiber layer damage. The beam of the CW YAG was not absorbed by haemoglobin; therefore, no vasospasm could be produced on experimentally detached retinas. PMID:6547800

  10. Mass spectrometric identification and quantification of 5-methoxytryptophol in quail retina

    SciTech Connect

    Tsang, C.W.; Chan, S.F.; Lee, P.P.; Pang, S.F. )

    1989-12-29

    The occurrence of 5-methoxytryptophol (5-MTL) in the quail retina was investigated by capillary column gas chromatography/mass spectrometry/selected ion monitoring using a deuterated internal standard. Based on ion intensity ratios in the mass spectra of pentafluoropropionyl and heptafluorobutyryl derivatives of 5-MTL and deuterated 5-MTL, 5-MTL was unequivocally identified in the quail retina. Similar to the circadian rhythm of retinal melatonin, retinal 5-MTL also exhibited a diurnal variation with high levels at mid-dark. However, no significant correlation between the diurnal levels of 5-MTL and melatonin was observed in the quail retina at mid-light or mid-dark.

  11. Transplantation of ocular stem cells: the role of injury in incorporation and differentiation of grafted cells in the retina.

    PubMed

    Chacko, David M; Das, Ani V; Zhao, Xing; James, Jackson; Bhattacharya, Sumitra; Ahmad, Iqbal

    2003-04-01

    The incorporation of transplanted cells into the host retina is one of the prerequisites for successful cell replacement therapy to treat retinal degeneration. To test the hypothesis that injury promotes cell incorporation, stem cells/progenitors were isolated from the retina, ciliary epithelium or limbal epithelium and transplanted into the eyes of rats with retinal injury. Different stem cell/progenitor populations incorporated into traumatized or diseased retina but not into the normal retina. The proportion of cells incorporated into the inner retina was consistently higher than in the outer retina. The transplanted cells expressed markers specific to cells of the lamina into which they were incorporated suggesting that cues for specific differentiation are localized within the inner and outer retina. These findings demonstrate that injury-induced cues play a significant role in promoting the incorporation of ocular stem cells/progenitors regardless of their origin or their differentiation along specific retinal sublineage. PMID:12668063

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

    PubMed Central

    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

  13. Ubiquitous presence of gluconeogenic regulatory enzyme, fructose-1,6-bisphosphatase, within layers of rat retina

    PubMed Central

    Mamczur, Piotr; Mazurek, Jakub

    2010-01-01

    To shed some light on gluconeogenesis in mammalian retina, we have focused on fructose-1,6-bisphosphatase (FBPase), a regulatory enzyme of the process. The abundance of the enzyme within the layers of the rat retina suggests that, in mammals in contrast to amphibia, gluconeogenesis is not restricted to one specific cell of the retina. We propose that FBPase, in addition to its gluconeogenic role, participates in the protection of the retina against reactive oxygen species. Additionally, the nuclear localization of FBPase and of its binding partner, aldolase, in the retinal cells expressing the proliferation marker Ki-67 indicates that these two gluconeogenic enzymes are involved in non-enzymatic nuclear processes. Electronic supplementary material The online version of this article (doi:10.1007/s00441-010-1008-2) contains supplementary material, which is available to authorized users. PMID:20614135

  14. Illumination-invariant face recognition with a contrast sensitive silicon retina

    SciTech Connect

    Buhmann, J.M.; Lades, M.; Eeckman, F.

    1993-11-29

    Changes in lighting conditions strongly effect the performance and reliability of computer vision systems. We report face recognition results under drastically changing lighting conditions for a computer vision system which concurrently uses a contrast sensitive silicon retina and a conventional, gain controlled CCD camera. For both input devices the face recognition system employs an elastic matching algorithm with wavelet based features to classify unknown faces. To assess the effect of analog on-chip preprocessing by the silicon retina the CCD images have been digitally preprocessed with a bandpass filter to adjust the power spectrum. The silicon retina with its ability to adjust sensitivity increases the recognition rate up to 50 percent. These comparative experiments demonstrate that preprocessing with an analog VLSI silicon retina generates image data enriched with object-constant features.

  15. FENTHION PRODUCES PERSISTENT DECREASES IN MUSCARINIC RECEPTOR FUNCTION IN THE ADULT RAT RETINA

    EPA Science Inventory

    reports have suggested that exposure to organophosphate pesticides damages the visual system. he Prolonged effects of an acute dose of fenthion (dimethyl 3-methyl-4-methylthiophenyl phosphorothionate) were studied on the cholinergic system in the rat retina. enthion was administe...

  16. Retina-on-a-chip: a microfluidic platform for point access signaling studies.

    PubMed

    Dodson, Kirsten H; Echevarria, Franklin D; Li, Deyu; Sappington, Rebecca M; Edd, Jon F

    2015-12-01

    We report on a microfluidic platform for culture of whole organs or tissue slices with the capability of point access reagent delivery to probe the transport of signaling events. Whole mice retina were maintained for multiple days with negative pressure applied to tightly but gently bind the bottom of the retina to a thin poly-(dimethylsiloxane) membrane, through which twelve 100 μm diameter through-holes served as fluidic access points. Staining with toluidine blue, transport of locally applied cholera toxin beta, and transient response to lipopolysaccharide in the retina demonstrated the capability of the microfluidic platform. The point access fluidic delivery capability could enable new assays in the study of various kinds of excised tissues, including retina. PMID:26559199

  17. Retina-on-a-chip: a microfluidic platform for point access signaling studies

    PubMed Central

    Dodson, Kirsten H.; Echevarria, Franklin D.; Li, Deyu; Sappington, Rebecca M.; Edd, Jon F.

    2016-01-01

    We report on a microfluidic platform for culture of whole organs or tissue slices with the capability of point access reagent delivery to probe the transport of signaling events. Whole mice retina were maintained for multiple days with negative pressure applied to tightly but gently bind the bottom of the retina to a thin poly-(dimethylsiloxane) membrane, through which twelve 100 μm diameter through-holes served as fluidic access points. Staining with toluidine blue, transport of locally applied cholera toxin beta, and transient response to lipopolysaccharide in the retina demonstrated the capability of the microfluidic platform. The point access fluidic delivery capability could enable new assays in the study of various kinds of excised tissues, including retina. PMID:26559199

  18. [CHARACTERISTICS OF THE RETINA IN CHRONIC STRESS IN LABORATORY RATS OF DIFFERENT AGE GROUPS].

    PubMed

    Nesterova, A A; Yermilov, V V; Tiurenkov, I N; Smirnov, A V; Grigoriyeva, N V; Zagrebin, V L; Rogova, L N; Antoshkin, O N; Dovgalyov, A O

    2016-01-01

    The retina was studied in albino laboratory male rats of two age groups (12 and 24 months), 10 animals in each subjected to chronic combined stress. The stress was caused in animals by simultaneous exposure to pulsed light, loud sound, swinging and restriction of mobility for 7 days, 30 mm daily. The retina of intact rats of the corresponding age groups (n = 20) served as control. Enucleated eyes of stressed and control animals were processed with standard histological technique and stained with Nissl's method and hematoxylin-eosin. The retina of the stressed animals of both age groups showed the decrease in the number of cells and the disarrangement of its layers, most pronounced in the layers of photoreceptor neurons and ganglion cells. The comparative morphometric analysis demonstrated a reduction of the layer thickness and cell numerical density in the retina of stressed animals, both young (12 months) and old (24 months), as compared to that of control animals. PMID:27487662

  19. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

    NASA Astrophysics Data System (ADS)

    Ooto, Sotaro; Akagi, Tadamichi; Kageyama, Ryoichiro; Akita, Joe; Mandai, Michiko; Honda, Yoshihito; Takahashi, Masayo

    2004-09-01

    It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.

  20. Frequency spectrum might act as communication code between retina and visual cortex I

    PubMed Central

    Yang, Xu; Gong, Bo; Lu, Jian-Wei

    2015-01-01

    AIM To explore changes and possible communication relationship of local potential signals recorded simultaneously from retina and visual cortex I (V1). METHODS Fourteen C57BL/6J mice were measured with pattern electroretinogram (PERG) and pattern visually evoked potential (PVEP) and fast Fourier transform has been used to analyze the frequency components of those signals. RESULTS The amplitude of PERG and PVEP was measured at about 36.7 µV and 112.5 µV respectively and the dominant frequency of PERG and PVEP, however, stay unchanged and both signals do not have second, or otherwise, harmonic generation. CONCLUSION The results suggested that retina encodes visual information in the way of frequency spectrum and then transfers it to primary visual cortex. The primary visual cortex accepts and deciphers the input visual information coded from retina. Frequency spectrum may act as communication code between retina and V1. PMID:26682156

  1. Immunohistochemical localization of glycogen synthase and GSK3β: control of glycogen content in retina.

    PubMed

    Pérezleón, Jorge Alberto; Osorio-Paz, Ixchel; Francois, Liliana; Salceda, Rocío

    2013-05-01

    Glycogen has an important role in energy handling in several brain regions. In the brain, glycogen is localized in astrocytes and its role in several normal and pathological processes has been described, whereas in the retina, glycogen metabolism has been scarcely investigated. The enzyme glycogen phosphorylase has been located in retinal Müller cells; however the cellular location of glycogen synthase (GS) and its regulatory partner, glycogen synthase kinase 3β (GSK3β), has not been investigated. Our aim was to localize these enzymes in the rat retina by immunofluorescence techniques. We found both GS and GSK3β in Müller cells in the synaptic layers, and within the inner segments of photoreceptor cells. The presence of these enzymes in Müller cells suggests that glycogen could be regulated within the retina as in other tissues. Indeed, we showed that glycogen content in the whole retina in vitro was increased by high glucose concentrations, glutamate, and insulin. In contrast, retina glycogen levels were not modified by norepinephrine nor by depolarization with high KCl concentrations. Insulin also induced an increase in glycogen content in cultured Müller cells. The effect of insulin in both, whole retina and cultured Müller cells was blocked by inhibitors of phosphatidyl-inositol 3-kinase, strongly suggesting that glycogen content in retina is modulated by the insulin signaling pathway. The expression of GS and GSK3β in the synaptic layers and photoreceptor cells suggests an important role of GSK3β regulating glycogen synthase in neurons, which opens multiple feasible roles of insulin within the retina. PMID:23512644

  2. Transcriptome networks in the mouse retina: An exon level BXD RI database

    PubMed Central

    King, Rebecca; Lu, Lu; Williams, Robert W.

    2015-01-01

    Purpose Differences in gene expression provide diverse retina phenotypes and may also contribute to susceptibility to injury and disease. The present study defines the transcriptome of the retina in the BXD RI strain set, using the Affymetrix Mouse Gene 2.0 ST array to investigate all exons of traditional protein coding genes, non-coding RNAs, and microRNAs. These data are presented in a highly interactive database on the GeneNetwork website. Methods In the Normal Retina Database, the mRNA levels of the transcriptome from retinas was quantified using the Affymetrix Mouse Gene 2.0 ST array. This database consists of data from male and female mice. The data set includes a total of 52 BXD RI strains, the parental strains (C57BL/6J and DBA/2J), and a reciprocal cross. Results In combination with GeneNetwork, the Department of Defense (DoD) Congressionally Directed Medical Research Programs (CDMRP) Normal Retina Database provides a large resource for mapping, graphing, analyzing, and testing complex genetic networks. Protein-coding and non-coding RNAs can be used to map quantitative trait loci (QTLs) that contribute to expression differences among the BXD strains and to establish links between classical ocular phenotypes associated with differences in the genomic sequence. Using this resource, we extracted transcriptome signatures for retinal cells and defined genetic networks associated with the maintenance of the normal retina. Furthermore, we examined differentially expressed exons within a single gene. Conclusions The high level of variation in mRNA levels found among the BXD RI strains makes it possible to identify expression networks that underline differences in retina structure and function. Ultimately, we will use this database to define changes that occur following blast injury to the retina. PMID:26604663

  3. Electrooptical model of the first retina layers of a visual analyzer

    NASA Technical Reports Server (NTRS)

    Chibalashvili, Y. L.; Riabinin, A. D.; Svechnikov, S. V.; Chibalashvili, Y. L.; Shkvar, A. M.

    1979-01-01

    An electrooptical principle of converting and transmitting optical signals is proposed and used as the basis for constructing a model of the upper layers of the retina of the visual analyzer of animals. An evaluation of multichannel fibrous optical systems, in which the conversion of optical signals is based on the electrooptical principle, to model the upper retina layers is presented. The symbolic circuit of the model and its algorithm are discussed.

  4. Electrophysiological fingerprints of OFF bipolar cells in rat retina.

    PubMed

    Vielma, Alex H; Schmachtenberg, Oliver

    2016-01-01

    Retinal bipolar cells (BCs) divide photoreceptor output into different channels for the parallel extraction of temporal and chromatic stimulus properties. In rodents, five types of OFF BCs have been differentiated, based on morphological and functional criteria, but their electrophysiological characterization remains incomplete. This study analyzed OFF BCs with the patch clamp technique in acute slices of rat retina. Their specific voltage-dependent currents and glutamate responses are shown to represent individual fingerprints which define the signal processing and filtering properties of each cell type and allow their unequivocal identification. Two additions to the rat BC repertoire are presented: OFF BC-2', a variation of BC-2 with wider axonal arbours and prominent Na(+) currents, is described for the first time in rodents, and OFF BC-3b, previously identified in mouse, is electrophysiologically characterized in rat. Moreover, the glutamate responses of rat OFF BCs are shown to be differentially sensitive to AMPA- and kainate-receptor blockers and to modulation by nitric oxide (NO) through a cGMP-dependent mechanism. These results contribute to our understanding of the diversity and function of bipolar cells in mammals. PMID:27457753

  5. Microcystic macular edema detection in retina OCT images

    NASA Astrophysics Data System (ADS)

    Swingle, Emily K.; Lang, Andrew; Carass, Aaron; Ying, Howard S.; Calabresi, Peter A.; Prince, Jerry L.

    2014-03-01

    Optical coherence tomography (OCT) is a powerful imaging tool that is particularly useful for exploring retinal abnormalities in ophthalmological diseases. Recently, it has been used to track changes in the eye associated with neurological diseases such as multiple sclerosis (MS) where certain tissue layer thicknesses have been associated with disease progression. A small percentage of MS patients also exhibit what has been called microcystic macular edema (MME), where uid collections that are thought to be pseudocysts appear in the inner nuclear layer. Very little is known about the cause of this condition so it is important to be able to identify precisely where these pseudocysts occur within the retina. This identi cation would be an important rst step towards furthering our understanding. In this work, we present a detection algorithm to nd these pseudocysts and to report on their spatial distribution. Our approach uses a random forest classi er trained on manual segmentation data to classify each voxel as pseudocyst or not. Despite having a small sample size of ve subjects, the algorithm correctly identi es 84.6% of pseudocysts as compared to manual delineation. Finally, using our method, we show that the spatial distribution of pseudocysts within the macula are generally contained within an annulus around the fovea.

  6. Development of asymmetric inhibition underlying direction selectivity in the retina

    PubMed Central

    Wei, Wei; Hamby, Aaron M.; Zhou, Kaili; Feller, Marla B.

    2014-01-01

    Establishing precise synaptic connections is crucial to the development of functional neural circuits. The direction-selective circuit in the retina relies upon highly selective wiring of inhibitory inputs from starburst amacrine cells1 (SACs) onto four subtypes of on–off direction-selective ganglion cell (DSGC), each preferring motion in one of four cardinal directions2. It has been reported in rabbit that the SACs on the ‘null’ sides of DSGCs form functional GABA (γ-aminobutyric acid)-mediated synapses, whereas those on the preferred sides do not3. However, it is not known how the asymmetric wiring between SACs and DSGCs is established during development. Here we report that in transgenic mice with cell-type-specific labelling, the synaptic connections from SACs to DSGCs were of equal strength during the first postnatal week, regardless of whether the SAC was located on the preferred or null side of the DSGC. However, by the end of the second postnatal week, the strength of the synapses made from SACs on the null side of a DSGC significantly increased whereas those made from SACs located on the preferred side remained constant. Blocking retinal activity by intraocular injections of muscimol or gabazine during this period did not alter the development of direction selectivity. Hence, the asymmetric inhibition between the SACs and DSGCs is achieved by a developmental program that specifically strengthens the GABA-mediated inputs from SACs located on the null side, in a manner not dependent on neural activity. PMID:21131947

  7. High resolution confocal polarimeter for the living human retina

    NASA Astrophysics Data System (ADS)

    Lara, D.; Paterson, C.

    2011-09-01

    There is strong evidence that the living human retina has polarization signatures that could be linked to the presence of Glaucoma, an ocular disease that is the second cause of blindness in the western world. In a polarization sensitive ophthalmoscope, the amount of light that can be used is limited for the safety of the subject, and the return is typically a small fraction of the light used for illumination, of the order of 10-6. Furthermore, the acquisition rates have to be sufficiently fast to avoid eye-movement artifacts. The light-budget available to produce a polarization image with a scanning laser ophthalmoscope is typically in the order of 10 nW, and pixel acquisition sampling rates are of several MHz. We are currently developing an imaging instrument for vision research and clinical vision applications and aim to introduce it to the medical and clinical environment using objective methods of image quality assessment. Here we discuss the stringent imaging requirements, polarimeter design, and show high resolution polarization retinal images.

  8. Electrophysiological fingerprints of OFF bipolar cells in rat retina

    PubMed Central

    Vielma, Alex H.; Schmachtenberg, Oliver

    2016-01-01

    Retinal bipolar cells (BCs) divide photoreceptor output into different channels for the parallel extraction of temporal and chromatic stimulus properties. In rodents, five types of OFF BCs have been differentiated, based on morphological and functional criteria, but their electrophysiological characterization remains incomplete. This study analyzed OFF BCs with the patch clamp technique in acute slices of rat retina. Their specific voltage-dependent currents and glutamate responses are shown to represent individual fingerprints which define the signal processing and filtering properties of each cell type and allow their unequivocal identification. Two additions to the rat BC repertoire are presented: OFF BC-2′, a variation of BC-2 with wider axonal arbours and prominent Na+ currents, is described for the first time in rodents, and OFF BC-3b, previously identified in mouse, is electrophysiologically characterized in rat. Moreover, the glutamate responses of rat OFF BCs are shown to be differentially sensitive to AMPA- and kainate-receptor blockers and to modulation by nitric oxide (NO) through a cGMP-dependent mechanism. These results contribute to our understanding of the diversity and function of bipolar cells in mammals. PMID:27457753

  9. Spare the rods and spoil the retina: revisited.

    PubMed

    Sivaprasad, S; Arden, G

    2016-02-01

    Visual function improves with oxygen inhalation in people with diabetes even in the absence of visible retinopathy. Rods consume the most oxygen in the retina due to the high metabolic activity required to maintain the dark current. Therefore, Arden hypothesized that in diabetes where oxygen supply may also be affected due to the changes in retinal vasculature, prevention of dark adaptation may be a viable option to prevent or decrease the rate of progression of diabetic retinopathy. Animal experiments have proven that the absence of rods decreases the development of retinal neovascularisation. The same principle applies to panretinal photocoagulation, an established treatment for proliferative diabetic retinopathy. Recently, a few clinical studies have also shown that preventing dark adaptation by suppressing rods with 500-nm light source at night decreases the rate of progression of early diabetic retinopathy and maculopathy in the short-term. We await the results of a large two-year multi-centre trial (CLEOPATRA trial) to evaluate the long-term effects of decreasing dark adaptation by applying a 500nm light source as a mask over eyes with non-central diabetic macular oedema. PMID:26656085

  10. Optimal Prediction in the Retina and Natural Motion Statistics

    NASA Astrophysics Data System (ADS)

    Salisbury, Jared M.; Palmer, Stephanie E.

    2016-03-01

    Almost all behaviors involve making predictions. Whether an organism is trying to catch prey, avoid predators, or simply move through a complex environment, the organism uses the data it collects through its senses to guide its actions by extracting from these data information about the future state of the world. A key aspect of the prediction problem is that not all features of the past sensory input have predictive power, and representing all features of the external sensory world is prohibitively costly both due to space and metabolic constraints. This leads to the hypothesis that neural systems are optimized for prediction. Here we describe theoretical and computational efforts to define and quantify the efficient representation of the predictive information by the brain. Another important feature of the prediction problem is that the physics of the world is diverse enough to contain a wide range of possible statistical ensembles, yet not all inputs are probable. Thus, the brain might not be a generalized predictive machine; it might have evolved to specifically solve the prediction problems most common in the natural environment. This paper summarizes recent results on predictive coding and optimal predictive information in the retina and suggests approaches for quantifying prediction in response to natural motion. Basic statistics of natural movies reveal that general patterns of spatiotemporal correlation are present across a wide range of scenes, though individual differences in motion type may be important for optimal processing of motion in a given ecological niche.

  11. Cholesterol in the retina: the best is yet to come

    PubMed Central

    Pikuleva, Irina A.; Curcio, Christine A.

    2014-01-01

    Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes’ roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. PMID:24704580

  12. Surrogate electroretinographic markers for assessing therapeutic efficacy in the retina.

    PubMed

    Birch, David G

    2004-09-01

    Visual acuity remains the primary surrogate marker for clinical trials in ophthalmology (and the primary outcome for most US Food and Drug Administration applications) due to its long history, ease of measurement and clear relationship to clinically meaningful characteristics of daily life. However, treatment trials are being planned for diseases that are currently untreatable where visual acuity may not be the most appropriate outcome measure. Specialized electroretinographic tests can be powerful surrogate markers in such trials. The selection of outcome measures and surrogate markers depends in part on whether the goal is to preserve remaining vision in a progressive retinal degeneration or to improve vision in an eye that has already undergone extensive degeneration. Among the electroretinographic tests available are those involving the whole retina (full-field electroretinographic), the posterior pole (pattern electroretinographic) or focal areas within the macula (multifocal electroretinographic). The advantages and disadvantages of each will be discussed along with selected applications of each test to a specific category of disease. PMID:15347262

  13. Speeding rod recovery improves temporal resolution in the retina

    PubMed Central

    Fortenbach, Christopher R.; Kessler, Christopher; Peinado, Gabriel; Burns, Marie E.

    2015-01-01

    The temporal resolution of the visual system progressively increases with light intensity. Under scotopic conditions, temporal resolution is relatively poor, and may be limited by both retinal and cortical processes. Rod photoresponses themselves are quite slow because of the slowly deactivating biochemical cascade needed for light transduction. Here, we have used a transgenic mouse line with faster than normal rod phototransduction deactivation (RGS9-overexpressors) to test whether rod signaling to second-order retinal neurons is rate-limited by phototransduction or by other mechanisms. We compared electrical responses of individual wild-type and RGS9-overexpressing (RGS9-ox) rods to steady illumination and found that RGS9-ox rods required 2-fold brighter light for comparable activation, owing to faster G-protein deactivation. When presented with flickering stimuli, RGS9-ox rods showed greater magnitude fluctuations around a given steady-state current amplitude. Likewise, in vivo electroretinography (ERG) and whole-cell recording from OFF-bipolar, rod bipolar, and horizontal cells of RGS9-ox mice displayed larger than normal magnitude flicker responses, demonstrating an improved ability to transmit frequency information across the rod synapse. Slow phototransduction recovery therefore limits synaptic transmission of increments and decrements of light intensity across the first retinal synapse in normal retinas, apparently sacrificing temporal responsiveness for greater overall sensitivity in ambient light. PMID:25748270

  14. Tgfbi/Bigh3 silencing activates ERK in mouse retina.

    PubMed

    Allaman-Pillet, Nathalie; Oberson, Anne; Bustamante, Mauro; Tasinato, Andrea; Hummler, Edith; Schorderet, Daniel F

    2015-11-01

    BIGH3 is a secreted protein, part of the extracellular matrix where it interacts with collagen and integrins on the cell surface. BIGH3 can play opposing roles in cancer, acting as either tumor suppressor or promoter, and its mutations lead to different forms of corneal dystrophy. Although many studies have been carried out, little is known about the physiological role of BIGH3. Using the cre-loxP system, we generated a mouse model with disruption of the Bigh3 genomic locus. Bigh3 silencing did not result in any apparent phenotype modifications, the mice remained viable and fertile. We were able to determine the presence of BIGH3 in the retinal pigment epithelium (RPE). In the absence of BIGH3, a transient decrease in the apoptotic process involved in retina maturation was observed, leading to a transient increase in the INL thickness at P15. This phenomenon was accompanied by an increased activity of the pro-survival ERK pathway. PMID:26387839

  15. Mouse Embryonic Retina Delivers Information Controlling Cortical Neurogenesis

    PubMed Central

    Bonetti, Ciro; Surace, Enrico Maria

    2010-01-01

    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 [1]. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded [2], 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. PMID:21170332

  16. Network Analysis and Visualization of Mouse Retina Connectivity Data

    PubMed Central

    2016-01-01

    The largest available cellular level connectivity map, of a 0.1 mm sample of the mouse retina Inner Plexiform Layer, was analysed using network models and visualized using spectral graph layouts and observed cell coordinates. This allows key nodes in the network to be identified with retinal neurons. Their strongest synaptic links can trace pathways in the network, elucidating possible circuits. Modular decomposition of the network, by sampling signal flows over nodes and links using the InfoMap method, shows discrete modules of cone bipolar cells that form a tiled mosaic in the retinal plane. The highest flow nodes, calculated by InfoMap, proved to be the most useful landmarks for elucidating possible circuits. Their dominant links to high flow amacrine cells reveal possible circuits linking bipolar through to ganglion cells and show an Off-On discrimination between the Left-Right sections of the sample. Circuits suggested by this analysis confirm known roles for some cells and point to roles for others. PMID:27414405

  17. Transcriptome profiling of the rat retina after optic nerve transection

    PubMed Central

    Yasuda, Masayuki; Tanaka, Yuji; Omodaka, Kazuko; Nishiguchi, Koji M.; Nakamura, Orie; Tsuda, Satoru; Nakazawa, Toru

    2016-01-01

    Glaucoma is a group of eye diseases characterized by alterations in the contour of the optic nerve head (ONH), with corresponding visual field defects and progressive loss of retinal ganglion cells (RGCs). This progressive RGC death is considered to originate in axonal injury caused by compression of the axon bundles in the ONH. However, the molecular pathomechanisms of axonal injury-induced RGC death are not yet well understood. Here, we used RNA sequencing (RNA-seq) to examine transcriptome changes in rat retinas 2 days after optic nerve transection (ONT), and then used computational techniques to predict the resulting alterations in the transcriptional regulatory network. RNA-seq revealed 267 differentially expressed genes after ONT, 218 of which were annotated and 49 unannotated. We also identified differentially expressed transcripts, including potentially novel isoforms. An in silico pathway analysis predicted that CREB1 was the most significant upstream regulator. Thus, this study identified genes and pathways that may be involved in the pathomechanisms of axonal injury. We believe that our data should serve as a valuable resource to understand the molecular processes that define axonal injury-driven RGC death and to discover novel therapeutic targets for glaucoma. PMID:27353354

  18. Phenotypic and functional characterization of Bst+/− mouse retina

    PubMed Central

    Riazifar, Hamidreza; Sun, Guoli; Wang, Xinjian; Rupp, Alan; Vemaraju, Shruti; Ross-Cisneros, Fred N.; Lang, Richard A.; Sadun, Alfredo A.; Hattar, Samer; Guan, Min-Xin; Huang, Taosheng

    2015-01-01

    ABSTRACT The belly spot and tail (Bst+/−) mouse phenotype is caused by mutations of the ribosomal protein L24 (Rpl24). Among various phenotypes in Bst+/− mice, the most interesting are its retinal abnormalities, consisting of delayed closure of choroid fissures, decreased ganglion cells and subretinal vascularization. We further characterized the Bst+/− mouse and investigated the underlying molecular mechanisms to assess the feasibility of using this strain as a model for stem cell therapy of retinal degenerative diseases due to retinal ganglion cell (RGC) loss. We found that, although RGCs are significantly reduced in retinal ganglion cell layer in Bst+/− mouse, melanopsin+ RGCs, also called ipRGCs, appear to be unchanged. Pupillary light reflex was completely absent in Bst+/− mice but they had a normal circadian rhythm. In order to examine the pathological abnormalities in Bst+/− mice, we performed electron microscopy in RGC and found that mitochondria morphology was deformed, having irregular borders and lacking cristae. The complex activities of the mitochondrial electron transport chain were significantly decreased. Finally, for subretinal vascularization, we also found that angiogenesis is delayed in Bst+/− associated with delayed hyaloid regression. Characterization of Bst+/− retina suggests that the Bst+/− mouse strain could be a useful murine model. It might be used to explore further the pathogenesis and strategy of treatment of retinal degenerative diseases by employing stem cell technology. PMID:26035379

  19. Neuroprotective role of erythropoietin by antiapoptosis in the retina.

    PubMed

    Chung, Hyewon; Lee, Hyunju; Lamoke, Folami; Hrushesky, William J M; Wood, Patricia A; Jahng, Wan Jin

    2009-08-01

    Erythropoietin (EPO) stimulates red blood cell production, in part by inhibiting apoptosis of the red blood cell precursors. The erythropoietic effects of EPO are circadian stage dependent. Retinal injury due to light occurs through oxidative mechanisms and is manifest by retinal and retinal pigment epithelium (RPE) cells apoptosis. The visual cycle might be circadian coordinated as a means of effectively protecting the retina from the detrimental effects of light-induced, oxygen-dependent, free radical-mediated damage, especially at the times of day when light is more intense. We show that the retinal expression of EPO and its receptor (EPOR), as well as subsequent Janus kinase 2 (Jak2) phosphorylations, are each tightly linked to a specific time after oxidative stress and in anticipation of daily light onset. This is consistent with physiological protection against daily light-induced, oxidatively mediated retinal apoptosis. In vitro, we verify that EPO protects RPE cells from light, hyperoxia, and hydrogen peroxide-induced retinal cell apoptosis, and that these stimuli increase EPO and EPOR expression in cultured RPE cells. Together, these data support the premise that EPO and its EPOR interactions represent an important retinal shield from physiologic and pathologic light-induced oxidative injury. PMID:19301424

  20. Adaptation of the Central Retina for High Acuity Vision: Cones, the Fovea and the Avascular Zone

    PubMed Central

    Provis, Jan M; Dubis, Adam M; Maddess, Ted; Carroll, Joseph

    2013-01-01

    Presence of a fovea centralis is directly linked to molecular specification of an avascular area in central retina, before the fovea (or `pit') begins to form. Modeling suggests that mechanical forces, generated within the eye, initiate formation of a pit within the avascular area, and its later remodeling in the postnatal period. Within the avascular area the retina is dominated by `midget' circuitry, in which signals are transferred from a single cone to a single bipolar cell, then a single ganglion cell. Thus in inner, central retina there are relatively few lateral connections between neurons. This renders the region adaptable to tangential forces, that translocate of ganglion cells laterally / centrifugally, to form the fovea. Optical coherence tomography enables live imaging of the retina, and shows that there is greater variation in the morphology of foveae in humans than previously thought. This variation is associated with differences in size of the avascular area and appears to be genetically based, but can be modified by environmental factors, including prematurity. Even when the fovea is absent (foveal hypoplasia), cones in central retina adopt an elongated and narrow morphology, enabling them to pack more densely to increase the sampling rate, and to act as more effective waveguides. Given these findings, what then is the adaptive advantage of a fovea? We suggest that the advantages of having a pit in central retina are relatively few, and minor, but together work to enhance acuity. PMID:23500068

  1. Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina?

    PubMed Central

    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 retinal disease. Macular xanthophylls are thought to combat light-induced damage mediated by reactive oxygen species by absorbing the most damaging incoming wavelength of light prior to the formation of reactive oxygen species (a function expected of carotenoids in nerve fibers) and by chemically and physically quenching reactive oxygen species once they are formed (a function expected of carotenoids in photoreceptor outer segments). There are two major hypotheses about the precise location of macular xanthophylls in the nerve fiber layer of photoreceptor axons and in photoreceptor outer segments. According to the first, macular xanthophylls transversely incorporate in the lipid-bilayer portion of membranes of the human retina. According to the second, macular xanthophylls are protein-bound by membrane-associated, xanthophyll-binding proteins. In this review we indicate specific properties of macular xanthophylls that could help explain their selective accumulation in the primate retina with special attention paid to xanthophyll-membrane interactions. PMID:24883226

  2. Morphometric analysis of the retina from horses infected with the Borna disease virus.

    PubMed

    Dietzel, J; Kuhrt, H; Stahl, T; Kacza, J; Seeger, J; Weber, M; Uhlig, A; Reichenbach, A; Grosche, A; Pannicke, T

    2007-01-01

    Borna disease (BD) is a fatal disorder of horses, often characterized by blindness. Although degeneration of retinal neurons has been demonstrated in a rat model, there are controversial data concerning whether a similar degeneration occurs in the retina of infected horses. To investigate whether BD may cause degeneration of photoreceptors and possibly of other neuronal cells at least at later stages of the disease, we performed a detailed quantitative morphologic study of retinal tissue from Borna-diseased horses. BD was diagnosed by detection of pathognomonic Joest-Degen inclusion bodies in the postmortem brains. Paraffin sections of paraformaldehyde-fixed retinae were used for histologic and immunohistochemical stainings. Numbers of neurons and Müller glial cells were counted, and neuron-to-Müller cell ratios were calculated. Among tissues from 9 horses with BD, we found retinae with strongly altered histologic appearance as well as retinae with only minor changes. The neuron-to-Müller cell ratio for the whole retina was significantly smaller in diseased animals (8.5 +/- 0.4; P < .01) as compared with controls (17.6 +/- 0.8). It can be concluded that BD in horses causes alterations of the retinal histology of a variable degree. The study provides new data about the pathogenesis of BD concerning the retina and demonstrates that a loss of photoreceptors may explain the observed blindness in infected horses. PMID:17197624

  3. Blood supply to the retina and the lens in the gerbil (Meriones unguiculatus).

    PubMed

    Imada, Hideki; Isomura, Genzoh; Miyachi, Ei-ichi

    2003-03-01

    The blood supply to the retina and the lens in 32 gerbils (Meriones unguiculatus) of both sexes from infancy to maturity was studied under light and stereoscopic microscopes, and a scanning electron microscope. Mercox (CL-2R; Dai Nippon Ink, Tokyo, Japan) was injected into the left ventricle of 30 animals in order to visualize the blood supply to the retina and the lens from the ophthalmic artery. The central retinal artery arises from the ophthalmic artery, passes through the papilla of the optic nerve together with the central retinal vein and penetrates the vitreous space (cavity of the eye) between the lens and the internal limiting membrane of the retina, where it divides into the central branches covering the lens and the parietal branches to supply the retina. The former passes through the hyaloid space after branching several arterioles and then covers the lens like a network from its medial and marginal sides. Different from small experimental animals, the parietal branches, just after separating from the central one, divides into the nasal, dorsal and temporal branches in the vitreous space, each of which then subdivides to distribute across the retina on the inner limiting membrane, then delineates the membrana vasculosa retinae. This basal pattern of vasculization 1 day after birth continues to death. Both the central and parietal branches of the central retinal artery correspond to the branches of the hyaloid artery in embryo and the latter is preserved in adult gerbils. PMID:12680468

  4. Cholesterol in mouse retina originates primarily from in situ de novo biosynthesis.

    PubMed

    Lin, Joseph B; Mast, Natalia; Bederman, Ilya R; Li, Yong; Brunengraber, Henri; Björkhem, Ingemar; Pikuleva, Irina A

    2016-02-01

    The retina, a thin tissue in the back of the eye, has two apparent sources of cholesterol: in situ biosynthesis and cholesterol available from the systemic circulation. The quantitative contributions of these two cholesterol sources to the retinal cholesterol pool are unknown and have been determined in the present work. A new methodology was used. Mice were given separately deuterium-labeled drinking water and chow containing 0.3% deuterium-labeled cholesterol. In the retina, the rate of total cholesterol input was 21 μg of cholesterol/g retina • day, of which 15 μg of cholesterol/g retina • day was provided by local biosynthesis and 6 μg of cholesterol/g retina • day was uptaken from the systemic circulation. Thus, local cholesterol biosynthesis accounts for the majority (72%) of retinal cholesterol input. We also quantified cholesterol input to mouse brain, the organ sharing important similarities with the retina. The rate of total cerebral cholesterol input was 121 μg of cholesterol/g brain • day with local biosynthesis providing 97% of total cholesterol input. Our work addresses a long-standing question in eye research and adds new knowledge to the potential use of statins (drugs that inhibit cholesterol biosynthesis) as therapeutics for age-related macular degeneration, a common blinding disease. PMID:26630912

  5. Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina

    NASA Technical Reports Server (NTRS)

    Rachel, Rivka A.; Dolen, Gul; Hayes, Nancy L.; Lu, Alice; Erskine, Lynda; Nowakowski, Richard S.; Mason, Carol A.

    2002-01-01

    In albino mammals, lack of pigment in the retinal pigment epithelium is associated with retinal defects, including poor visual acuity from a photoreceptor deficit in the central retina and poor depth perception from a decrease in ipsilaterally projecting retinal fibers. Possible contributors to these abnormalities are reported delays in neuronogenesis (Ilia and Jeffery, 1996) and retinal maturation (Webster and Rowe, 1991). To further determine possible perturbations in neuronogenesis and/or differentiation, we used cell-specific markers and refined birth dating methods to examine these events during retinal ganglion cell (RGC) genesis in albino and pigmented mice from embryonic day 11 (E11) to E18. Our data indicate that relative to pigmented mice, more ganglion cells are born in the early stages of neuronogenesis in the albino retina, although the initiation of RGC genesis in the albino is unchanged. The cellular organization of the albino retina is perturbed as early as E12. In addition, cell cycle kinetics and output along the nasotemporal axis differ in retinas of albino and pigmented mice, both absolutely, with the temporal aspect of the retina expanded in albino, and relative to the position of the optic nerve head. Finally, blocking melanin synthesis in pigmented eyecups in culture leads to an increase in RGC differentiation, consistent with a role for melanin formation in regulating RGC neuronogenesis. These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype.

  6. A Comparative Analysis of the Endocannabinoid System in the Retina of Mice, Tree Shrews, and Monkeys.

    PubMed

    Bouskila, Joseph; Javadi, Pasha; Elkrief, Laurent; Casanova, Christian; Bouchard, Jean-François; Ptito, Maurice

    2016-01-01

    The endocannabinoid (eCB) system is widely expressed in various parts of the central nervous system, including the retina. The localization of the key eCB receptors, particularly CB1R and CB2R, has been recently reported in rodent and primate retinas with striking interspecies differences. Little is known about the distribution of the enzymes involved in the synthesis and degradation of these eCBs. We therefore examined the expression and localization of the main components of the eCB system in the retina of mice, tree shrews, and monkeys. We found that CB1R and FAAH distributions are well-preserved among these species. However, expression of NAPE-PLD is circumscribed to the photoreceptor layer only in monkeys. In contrast, CB2R expression is variable across these species; in mice, CB2R is found in retinal neurons but not in glial cells; in tree shrews, CB2R is expressed in Müller cell processes of the outer retina and in retinal neurons of the inner retina; in monkeys, CB2R is restricted to Müller cells. Finally, the expression patterns of MAGL and DAGLα are differently expressed across species. Overall, these results provide evidence that the eCB system is differently expressed in the retina of these mammals and suggest a distinctive role of eCBs in visual processing. PMID:26977322

  7. A Comparative Analysis of the Endocannabinoid System in the Retina of Mice, Tree Shrews, and Monkeys

    PubMed Central

    Bouskila, Joseph; Javadi, Pasha; Elkrief, Laurent; Casanova, Christian; Bouchard, Jean-François; Ptito, Maurice

    2016-01-01

    The endocannabinoid (eCB) system is widely expressed in various parts of the central nervous system, including the retina. The localization of the key eCB receptors, particularly CB1R and CB2R, has been recently reported in rodent and primate retinas with striking interspecies differences. Little is known about the distribution of the enzymes involved in the synthesis and degradation of these eCBs. We therefore examined the expression and localization of the main components of the eCB system in the retina of mice, tree shrews, and monkeys. We found that CB1R and FAAH distributions are well-preserved among these species. However, expression of NAPE-PLD is circumscribed to the photoreceptor layer only in monkeys. In contrast, CB2R expression is variable across these species; in mice, CB2R is found in retinal neurons but not in glial cells; in tree shrews, CB2R is expressed in Müller cell processes of the outer retina and in retinal neurons of the inner retina; in monkeys, CB2R is restricted to Müller cells. Finally, the expression patterns of MAGL and DAGLα are differently expressed across species. Overall, these results provide evidence that the eCB system is differently expressed in the retina of these mammals and suggest a distinctive role of eCBs in visual processing. PMID:26977322

  8. Generating 3D anatomically detailed models of the retina from OCT data sets: implications for computational modelling

    NASA Astrophysics Data System (ADS)

    Shalbaf, Farzaneh; Dokos, Socrates; Lovell, Nigel H.; Turuwhenua, Jason; Vaghefi, Ehsan

    2015-12-01

    Retinal prosthesis has been proposed to restore vision for those suffering from the retinal pathologies that mainly affect the photoreceptors layer but keep the inner retina intact. Prior to costly risky experimental studies computational modelling of the retina will help to optimize the device parameters and enhance the outcomes. Here, we developed an anatomically detailed computational model of the retina based on OCT data sets. The consecutive OCT images of individual were subsequently segmented to provide a 3D representation of retina in the form of finite elements. Thereafter, the electrical properties of the retina were modelled by implementing partial differential equation on the 3D mesh. Different electrode configurations, that is bipolar and hexapolar configurations, were implemented and the results were compared with the previous computational and experimental studies. Furthermore, the possible effects of the curvature of retinal layers on the current steering through the retina were proposed and linked to the clinical observations.

  9. Nonvisual photoreceptors of the deep brain, pineal organs and retina.

    PubMed

    Vigh, B; Manzano, M J; Zádori, A; Frank, C L; Lukáts, A; Röhlich, P; Szél, A; Dávid, C

    2002-04-01

    The role of the nonvisual photoreception is to synchronise periodic functions of living organisms to the environmental light periods in order to help survival of various species in different biotopes. In vertebrates, the so-called deep brain (septal and hypothalamic) photoreceptors, the pineal organs (pineal- and parapineal organs, frontal- and parietal eye) and the retina (of the "lateral" eye) are involved in the light-based entrain of endogenous circadian clocks present in various organs. In humans, photoperiodicity was studied in connection with sleep disturbances in shift work, seasonal depression, and in jet-lag of transmeridional travellers. In the present review, experimental and molecular aspects are discussed, focusing on the histological and histochemical basis of the function of nonvisual photoreceptors. We also offer a view about functional changes of these photoreceptors during pre- and postnatal development as well as about its possible evolution. Our scope in some points is different from the generally accepted views on the nonvisual photoreceptive systems. The deep brain photoreceptors are hypothalamic and septal nuclei of the periventricular cerebrospinal fluid (CSF)-contacting neuronal system. Already present in the lancelet and representing the most ancient type of vertebrate nerve cells ("protoneurons"), CSF-contacting neurons are sensory-type cells sitting in the wall of the brain ventricles that send a ciliated dendritic process into the CSF. Various opsins and other members of the phototransduction cascade have been demonstrated in telencephalic and hypothalamic groups of these neurons. In all species examined so far, deep brain photoreceptors play a role in the circadian and circannual regulation of periodic functions. Mainly called pineal "glands" in the last decades, the pineal organs actually represent a differentiated form of encephalic photoreceptors. Supposed to be intra- and extracranially outgrown groups of deep brain photoreceptors

  10. Endoscopic device for functional imaging of the retina

    NASA Astrophysics Data System (ADS)

    Barriga, Simon; Lohani, Sweyta; Martell, Bret; Soliz, Peter; Ts'o, Dan

    2011-03-01

    Non-invasive imaging of retinal function based on the recording of spatially distributed reflectance changes evoked by visual stimuli has to-date been performed primarily using modified commercial fundus cameras. We have constructed a prototype retinal functional imager, using a commercial endoscope (Storz) for the frontend optics, and a low-cost back-end that includes the needed dichroic beam splitter to separate the stimulus path from the imaging path. This device has been tested to demonstrate its performance for the delivery of adequate near infrared (NIR) illumination, intensity of the visual stimulus and reflectance return in the imaging path. The current device was found to be capable of imaging reflectance changes of 0.1%, similar to that observable using the modified commercial fundus camera approach. The visual stimulus (a 505nm spot of 0.5secs) was used with an interrogation illumination of 780nm, and a sequence of imaged captured. At each pixel, the imaged signal was subtracted and normalized by the baseline reflectance, so that the measurement was ΔR/R. The typical retinal activity signal observed had a ΔR/R of 0.3-1.0%. The noise levels were measured when no stimulus was applied and found to vary between +/- 0.05%. Functional imaging has been suggested as a means to provide objective information on retina function that may be a preclinical indicator of ocular diseases, such as age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. The endoscopic approach promises to yield a significantly more economical retinal functional imaging device that would be clinically important.

  11. A Novel Type of Complex Ganglion Cell in Rabbit Retina

    PubMed Central

    Sivyer, Benjamin; Venkataramani, Sowmya; Taylor, W. Rowland; Vaney, David I.

    2012-01-01

    The 15–20 physiological types of retinal ganglion cells (RGCs) can be grouped according to whether they fire to increased illumination in the receptive-field center (ON cells), decreased illumination (OFF cells), or both (ON-OFF cells). The diversity of RGCs has been best described in the rabbit retina, which has three types of ON-OFF RGCs with complex receptive-field properties: the ON-OFF direction-selective ganglion cells (DSGCs), the local edge detectors, and the uniformity detectors. Here we describe a novel type of bistratified ON-OFF RGC that has not been described in either physiological or morphological studies of rabbit RGCs. These cells stratify in the ON and OFF sublaminae of the inner plexiform layer, branching at about 30% and 60% depth, between the ON and OFF arbors of the bistratified DSGCs. Similar to the ON-OFF DSGCs, these cells respond with transient firing to both bright and dark spots flashed in the receptive field but, unlike the DSGCs, they show no directional preference for moving stimuli. We have termed these cells “transient ON-OFF” RGCs. Area-response measurements show that both the ON and the OFF spike responses have an antagonistic receptive-field organization, but with different spatial extents. Voltage-clamp recordings reveal transient excitatory inputs at light ON and light OFF; this excitation is strongly suppressed by surround stimulation, which also elicits direct inhibitory inputs to the cells at light ON and light OFF. Thus the receptive-field organization is mediated both within the presynaptic circuitry and by direct feed-forward inhibition. PMID:21800303

  12. Electrical responses of rods in the retina of Bufo marinus

    PubMed Central

    Cervetto, L.; Pasino, E.; Torre, V.

    1977-01-01

    1. Intracellular responses to flashes and steps of light have been recorded from the outer segment and the cell body of rods in the retina of the Bufo marinus. The identification of the origin of recorded responses has been confirmed by intracellular marking. 2. Responses to flashes delivered in darkness or superimposed on a background were analysed. Responses recorded from outer segments conform to the principle of `spectral univariance'. The shape of the response is not affected by enlarging the spot diameter from 150 to 1000 μm. 3. The membrane potential measured in darkness at the outer segments varied from -15 to -25 mV. Injection of steady hyperpolarizing currents increases the size of the response to light; depolarizing currents reduce the response. The mean value of the input resistance is 97 ± 30 MΩ in darkness and increases by 20-30% during illumination. 4. The responses obtained from the cell body of rods have the same shape, time course and spectral sensitivity of those recorded at the outer segment. Injection of steady current at the cell body produces different effects than at the outer segment: hyperpolarizing currents reduce the amplitude of the response to light; depolarizing currents increase the response. 5. The experimental data are fitted according to a model similar to that used to describe the responses of turtle cones (Baylor & Hodgkin, 1974; Baylor, Hodgkin & Lamb, 1974a, b). 6. The model reproduces the electrical responses of the rod outer segment to a variety of stimuli: (a) brief flashes and steps of light in dark adapted conditions; (b) bright flashes superimposed on background illuminations; (c) pairs of flashes delivered at different time intervals. Responses to hyperpolarizing steps of current are also reproduced by the model. ImagesABCD PMID:406383

  13. Adenovirus vectors targeting distinct cell types in the retina.

    PubMed

    Sweigard, J Harry; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2010-04-01

    Purpose. Gene therapy for a number of retinal diseases necessitates efficient transduction of photoreceptor cells. Whereas adenovirus (Ad) serotype 5 (Ad5) does not transduce photoreceptors efficiently, previous studies have demonstrated improved photoreceptor transduction by Ad5 pseudotyped with Ad35 (Ad5/F35) or Ad37 (Ad5/F37) fiber or by the deletion of the RGD domain in the Ad5 penton base (Ad5DeltaRGD). However, each of these constructs contained a different transgene cassette, preventing the evaluation of the relative performance of these vectors, an important consideration before the use of these vectors in the clinic. The aim of this study was to evaluate these vectors in the retina and to attempt photoreceptor-specific transgene expression. Methods. Three Ad5-based vectors containing the same expression cassette were generated and injected into the subretinal space of adult mice. Eyes were analyzed for green fluorescence protein expression in flat-mounts, cross-sections, quantitative RT-PCR, and a modified stereological technique. A 257-bp fragment derived from the mouse opsin promoter was analyzed in the context of photoreceptor-specific transgene expression. Results. Each virus tested efficiently transduced the retinal pigment epithelium. The authors found no evidence that Ad5/F35 or Ad5/F37 transduced photoreceptors. Instead, they found that Ad5/F37 transduced Müller cells. Robust photoreceptor transduction by Ad5DeltaRGD was detected. Photoreceptor-specific transgene expression from the 257-bp mouse opsin promoter in the context of Ad5DeltaRGD vectors was found. Conclusions. Adenovirus vectors may be designed with tropism to distinct cell populations. Robust photoreceptor-specific transgene expression can be achieved in the context of Ad5DeltaRGD vectors. PMID:19892875

  14. Endocannabinoids in the Retina: From Marijuana to Neuroprotection

    PubMed Central

    Yazulla, Stephen

    2008-01-01

    The active component of the marijuana plant Cannabis sativa, Δ9-tetrahydrocannabinol (THC), produces numerous beneficial effects, including analgesia, appetite stimulation and nausea reduction, in addition to its psychotropic effects. THC mimics the action of endogenous fatty acid derivatives, referred to as endocannabinoids. The effects of THC and the endocannabinoids are mediated largely by metabotropic receptors that are distributed throughout the nervous and peripheral organ systems. There is great interest in endocannabinoids for their role in neuroplasticity as well as for therapeutic use in numerous conditions, including pain, stroke, cancer, obesity, osteoporosis, fertility, neurodegenerative diseases, multiple sclerosis, glaucoma and inflammatory diseases, among others. However, there has been relatively far less research on this topic in the eye and retina compared with the brain and other organ systems. The purpose of this review is to introduce the “cannabinergic” field to the retinal community. All of the fundamental work on cannabinoids has been performed in non-retinal preparations, necessitating extensive dependence on this literature for background. Happily, the retinal cannabinoid system has much in common with other regions of the central nervous system. For example, there is general agreement that cannabinoids suppress dopamine release and presynaptically reduce transmitter release from cones and bipolar cells. How these effects relate to light and dark adaptation, receptive field formation, temporal properties of ganglion cells or visual perception are unknown. The presence of multiple endocannabinoids, degradative enzymes with their bioactive metabolites, and receptors provides a broad spectrum of opportunities for basic research and to identify targets for therapeutic application to retinal diseases. PMID:18725316

  15. Crizotinib-Induced Abnormal Signal Processing in the Retina

    PubMed Central

    Ishii, Toshiyuki; Iwasawa, Shunichiro; Kurimoto, Ryota; Maeda, Akemi; Takiguchi, Yuichi; Kaneda, Makoto

    2015-01-01

    Molecular target therapy for cancer is characterized by unique adverse effects that are not usually observed with cytotoxic chemotherapy. For example, the anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor crizotinib causes characteristic visual disturbances, whereas such effects are rare when another ALK-tyrosine kinase inhibitor, alectinib, is used. To elucidate the mechanism responsible for these visual disturbances, the responses to light exhibited by retinal ganglion cells treated with these agents were evaluated using a C57BL6 mouse ex vivo model. Both crizotinib and alectinib changed the firing rate of ON and OFF type retinal ganglion cells. However, the ratio of alectinib-affected cells (15.7%) was significantly lower than that of crizotinib-affected cells (38.6%). Furthermore, these drugs changed the response properties to light stimuli of retinal ganglion cells in some of the affected cells, i.e., OFF cells responded to both ON and OFF stimuli, etc. Finally, the expressions of ALK (a target receptor of both crizotinib and alectinib) and of MET and ROS1 (additional target receptors of crizotinib) were observed at the mRNA level in the retina. Our findings suggest that these drugs might target retinal ganglion cells and that the potency of the drug actions on the light responses of retinal ganglion cells might be responsible for the difference in the frequencies of visual disturbances observed between patients treated with crizotinib and those treated with alectinib. The present experimental system might be useful for screening new molecular target agents prior to their use in clinical trials. PMID:26271036

  16. mfERG Response Dynamics of the Aging Retina

    PubMed Central

    Gerth, Christina; Sutter, Erich E.; Werner, John S.

    2008-01-01

    Purpose To determine age-related changes in retinal response dynamics derived from multifocal electroretinograms (mfERGs). Methods MfERG data were obtained from 70 subjects with normal phakic eyes, age 9 to 80 years. Whereas the first- and higher-order kernels resulting from the mfERG contain detailed information regarding the nonlinear response dynamics of the retina, they do not lend themselves directly to an easy and intuitive interpretation. To achieve a better appreciation of fast adaptive mechanisms and their changes with aging, regional averages of the kernel series were translated at different retinal eccentricities (0°−5°, 5°−15°, and 15°−25°) into responses generated in different contexts. Specifically, the effect of aging on responses to stimuli presented in isolation was compared with the effect on responses adapted by preceding stimuli (“forward” effect). The interference of the immediately following stimuli with the response generation (“backward effect”) was also considered. Results Age-related changes were found in the isolated flash response as well as in the backward and forward interactions between consecutive flash responses. Larger fractional changes with age were found in response density than in implicit time, and the rate of change with age was larger for responses to isolated flashes than for responses adapted by preceding flashes. Conclusions Senescent changes in the isolated flash response and in consecutive flash interactions derived from the binary kernel series indicate an aging process at an early stage in the visual system. Mechanisms of retinal adaptation may partially compensate for age-related reductions in the isolated flash response. PMID:14507891

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

    PubMed Central

    Contartese, Daniela S.; Rolón, Federico; Sarotto, Anibal; Dorfman, Veronica B.; Loidl, Cesar F.; Martínez, Alfredo

    2016-01-01

    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. PMID:27556928

  18. Optical imaging of retina in response to grating stimuli in cats.

    PubMed

    Hirohara, Y; Mihashi, T; Kanda, H; Morimoto, T; Miyoshi, T; Wolffsohn, J S; Fujikado, T

    2013-04-01

    We examined the intrinsic signals in response to grating stimuli in order to determine whether the light-evoked intrinsic signals of the retina are due to changes in the photoreceptor activities induced by the image projected on to the retina or are due to neural activities of the inner retina. The retinas of the left eye of 12 cats under general anesthesia were examined by a functional imaging fundus camera. Near infrared light was used to monitor the reflectance changes (RCs) of the retina. Vertical grating were used to stimulate the retina at 4 Hz. The spatial frequencies of the gratings were 0.05, 0.11, 0.22, 0.43, 0.86, 1.73, and 3.46 cycles/degree (cpd). Ten images were averaged and used to analyze the RCs to obtain the peak value (PV) of a two dimensional fast Fourier transfer of the RCs. The wavefront aberrations (WA) were measured with a compact wavefront aberrometer and the spatial modulation transfer function (MTF) of the eye was calculated. The retinal reflectance image had a grating pattern. The PV of the spatial sensitivity curve was highest at low spatial frequencies (0.05 and 0.11 cpd), and the sensitivity decreased steeply with an increase in the spatial frequency. RCs were not detectable at 3.46 cpd. The MTF decreased gradually with increases in the spatial frequencies and was 0.68 at 3.46 cpd. The reflectance pattern of the retinal intrinsic signal elicited by grating stimuli of different spatial frequencies was different from that of the MTF. This suggests that the intrinsic signal represents not only the response of the photoreceptors but also other neuronal or vascular changes in the retina. PMID:23353892

  19. Ionotropic purinergic receptors P2X in frog and turtle retina: glial and neuronal localization.

    PubMed

    Vitanova, Lily Alexandrova; Kupenova, Petia Nikolova

    2014-06-01

    Purinergic signaling is represented in both the peripheral and central nervous system (CNS), and in particular in the retina, which may be regarded as a part of the CNS. While purigenic signaling is relatively well studied in mammalian retinas, little is known about it in retinas of lower vertebrates. The aim of present study was to investigate, using immunocytochemistry, the distribution of purinoreceptors P2X in retinas of frog and turtle, which are appropriate models of the brain neuron-to-glia interactions. The results showed widespread expression of all seven ionotropic purinoreceptors (P2X1-P2X7) in both frog and turtle retinas. They were predominantly expressed in Müller cells, the principal glial cells in the retina. All structures typical of Müller cells: the outer and the inner limiting membranes, the cells bodies in the inner nuclear layer, the radial processes in the inner plexiform layer (IPL), and the so called endfeet (frog) or the orthogonal arrays of particles (turtle) in the ganglion cells layer were immunostained. Colocalizations between P2X1-P2X7 and the glial cell marker Vimentin proved that the immunostaining was in the Müller cells. In addition to the glial staining, neuronal staining was also seen as fine puncta in the inner plexiform layer and by small dots and patches in the outer plexiform layer. Some cell bodies of horizontal, amacrine and ganglion cells were also stained. The results obtained imply that the purinergic P2X receptors may significantly contribute to the neuron-to-glia signaling in retinas of the lower vertebrates. PMID:24461518

  20. Neural retina identity is specified by lens-derived BMP signals.

    PubMed

    Pandit, Tanushree; Jidigam, Vijay K; Patthey, Cedric; Gunhaga, Lena

    2015-05-15

    The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity. PMID:25968316

  1. Optical imaging of the retina in response to the electrical stimulation

    NASA Astrophysics Data System (ADS)

    Fujikado, Takashi; Okawa, Yoshitaka; Miyoshi, Tomomitsu; Hirohara, Yoko; Mihashi, Toshifumi; Tano, Yasuo

    2008-02-01

    Purposes: To determine if reflectance changes of the retina can be detected following electrical stimulation to the retina using a newly developed optical-imaging fundus camera. Methods: Eyes of cats were examined after pupil dilation. Retina was stimulated either focally by a ball-type electrode (BE) placed on the fenestrated sclera or diffusely using a ring-type electrode (RE) placed on the corneoscleral limbus. Electrical stimulation by biphasic pulse trains was applied for 4 seconds. Fundus images with near-infrared (800-880 nm) light were obtained between 2 seconds before and 20 seconds after the electrical stimulation (ES). A two-dimensional map of the reflectance changes (RCs) was constructed. The effect of Tetrodotoxin (TTX) was also investigated on RCs by ES using RE. Results: RCs were observed around the retinal locus where the stimulating electrodes were positioned (BE) or in the retina of the posterior pole (RE), in which the latency was about 0.5 to 1.0 sec and the peak time about 2 to 5 sec after the onset of ES. The intensity of the RCs increased with the increase of the stimulus current in both cases. RCs were completely suppressed after the injection of TTX. Conclusions: The functional changes of the retina either by focal or diffuse electrical stimulation were successfully detected by optical imaging of the retina. The contribution of retinal ganglion cells on RCs by ES was confirmed by TTX experiment. This method may be applied to the objective evaluation of the artificial retina.

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

    PubMed

    Larrayoz, Ignacio M; Rey-Funes, Manuel; Contartese, Daniela S; Rolón, Federico; Sarotto, Anibal; Dorfman, Veronica B; Loidl, Cesar F; Martínez, Alfredo

    2016-01-01

    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. PMID:27556928

  3. Expression of Inducible Nitric Oxide Synthase (iNOS) in Microglia of the Developing Quail Retina

    PubMed Central

    Sierra, Ana; Navascués, Julio; Cuadros, Miguel A.; Calvente, Ruth; Martín-Oliva, David; Ferrer-Martín, Rosa M.; Martín-Estebané, María; Carrasco, María-Carmen; Marín-Teva, José L.

    2014-01-01

    Inducible nitric oxide synthase (iNOS), which produce large amounts of nitric oxide (NO), is induced in macrophages and microglia in response to inflammatory mediators such as LPS and cytokines. Although iNOS is mainly expressed by microglia that become activated in different pathological and experimental situations, it was recently reported that undifferentiated amoeboid microglia can also express iNOS during normal development. The aim of this study was to investigate the pattern of iNOS expression in microglial cells during normal development and after their activation with LPS by using the quail retina as model. iNOS expression was analyzed by iNOS immunolabeling, western-blot, and RT-PCR. NO production was determined by using DAR-4M AM, a reliable fluorescent indicator of subcellular NO production by iNOS. Embryonic, postnatal, and adult in situ quail retinas were used to analyze the pattern of iNOS expression in microglial cells during normal development. iNOS expression and NO production in LPS-treated microglial cells were investigated by an in vitro approach based on organotypic cultures of E8 retinas, in which microglial cell behavior is similar to that of the in situ retina, as previously demonstrated in our laboratory. We show here that amoeboid microglia in the quail retina express iNOS during normal development. This expression is stronger in microglial cells migrating tangentially in the vitreal part of the retina and is downregulated, albeit maintained, when microglia differentiate and become ramified. LPS treatment of retina explants also induces changes in the morphology of amoeboid microglia compatible with their activation, increasing their lysosomal compartment and upregulating iNOS expression with a concomitant production of NO. Taken together, our findings demonstrate that immature microglial cells express iNOS during normal development, suggesting a certain degree of activation. Furthermore, LPS treatment induces overactivation of amoeboid

  4. Oxytocin Expression and Function in the Posterior Retina: A Novel Signaling Pathway

    PubMed Central

    Halbach, Patrick; Pillers, De-Ann M.; York, Nathaniel; Asuma, Matti P.; Chiu, Michelle A.; Luo, Wenxiang; Tokarz, Sara; Bird, Ian M.; Pattnaik, Bikash R.

    2015-01-01

    Purpose. Oxytocin (OXT) is recognized as an ubiquitously acting nonapeptide hormone that is involved in processes ranging from parturition to neural development. Its effects are mediated by cell signaling that occurs as a result of oxytocin receptor (OXTR) activation. We sought to determine whether the OXT-OXTR signaling pathway is also expressed within the retina. Methods. Immunohistochemistry using cell-specific markers was used to localize OXT within the rhesus retina. Reverse transcriptase PCR and immunohistochemistry were used to assess the expression of OXTR in both human and rhesus retina. Single-cell RT-PCR and Western blot analyses were used to determine the expression of OXTR in cultured human fetal RPE (hfRPE) cells. Human fetal RPE cells loaded with FURA-2 AM were studied by ratiometric Ca2+ imaging to assess transient mobilization of intracellular Ca2+ ([Ca2+]i). Results. Oxytocin was expressed in the cone photoreceptor extracellular matrix of the rhesus retina. Oxytocin mRNA and protein were expressed in the human and rhesus RPE. Oxytocin mRNA and protein expression were observed in cultured hfRPE cells, and exposure of these cells to 100 nM OXT induced a transient 79 ± 1.5 nM increase of [Ca2+]i. Conclusions. Oxytocin and OXTR are present in the posterior retina, and OXT induces an increase in hfRPE [Ca2+]i. These results suggest that the OXT-OXTR signaling pathway is active in the retina. We propose that OXT activation of the OXTR occurs in the posterior retina and that this may serve as a paracrine signaling pathway that contributes to communication between the cone photoreceptor and the RPE. PMID:25593022

  5. Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration.

    PubMed

    Haynes, Tracy; Luz-Madrigal, Agustin; Reis, Edimara S; Echeverri Ruiz, Nancy P; Grajales-Esquivel, Erika; Tzekou, Apostolia; Tsonis, Panagiotis A; Lambris, John D; Del Rio-Tsonis, Katia

    2013-01-01

    Identifying the initiation signals for tissue regeneration in vertebrates is one of the major challenges in regenerative biology. Much of the research thus far has indicated that certain growth factors have key roles. Here we show that complement fragment C3a is sufficient to induce complete regeneration of the embryonic chick retina from stem/progenitor cells present in the eye, independent of fibroblast growth factor receptor signaling. Instead, C3a induces retina regeneration via STAT3 activation, which in turn activates the injury- and inflammation-responsive factors, IL-6, IL-8 and TNF-α. This activation sets forth regulation of Wnt2b, Six3 and Sox2, genes associated with retina stem and progenitor cells. Thus, our results establish a mechanism for retina regeneration based on injury and inflammation signals. Furthermore, our results indicate a unique function for complement anaphylatoxins that implicate these molecules in the induction and complete regeneration of the retina, opening new avenues of experimentation in the field. PMID:23942241

  6. Mathematical and computational models of the retina in health, development and disease.

    PubMed

    Roberts, Paul A; Gaffney, Eamonn A; Luthert, Philip J; Foss, Alexander J E; Byrne, Helen M

    2016-07-01

    The retina confers upon us the gift of vision, enabling us to perceive the world in a manner unparalleled by any other tissue. Experimental and clinical studies have provided great insight into the physiology and biochemistry of the retina; however, there are questions which cannot be answered using these methods alone. Mathematical and computational techniques can provide complementary insight into this inherently complex and nonlinear system. They allow us to characterise and predict the behaviour of the retina, as well as to test hypotheses which are experimentally intractable. In this review, we survey some of the key theoretical models of the retina in the healthy, developmental and diseased states. The main insights derived from each of these modelling studies are highlighted, as are model predictions which have yet to be tested, and data which need to be gathered to inform future modelling work. Possible directions for future research are also discussed. Whilst the present modelling studies have achieved great success in unravelling the workings of the retina, they have yet to achieve their full potential. For this to happen, greater involvement with the modelling community is required, and stronger collaborations forged between experimentalists, clinicians and theoreticians. It is hoped that, in addition to bringing the fruits of current modelling studies to the attention of the ophthalmological community, this review will encourage many such future collaborations. PMID:27063291

  7. Optical imaging of fast light-evoked fast neural activation in amphibian retina

    NASA Astrophysics Data System (ADS)

    Yao, Xin-Cheng; George, John S.

    2006-02-01

    High performance functional imaging is needed for dynamic measurements of neural processing in retina. Emerging techniques of visual prosthesis also require advanced methodology for reliable validation of electromagnetic stimulation of the retina. Imaging of fast intrinsic optical responses associated with neural activation promises a variety of technical advantages over traditional single and multi-channel electrophysiological techniques for these purposes, but the application of fast optical signals for neural imaging has been limited by low signal to noise ratio and high background light intensity. However, using optimized near infrared probe light and improved optical systems, we have improved the optical signals substantially, allowing single pass measurements. Fast photodiode measurements typically disclose dynamic transmitted light changes of whole retina at the level of 10 -4 dI/I, where dI is the dynamic optical change and I is the baseline light intensity. Using a fast high performance CCD, we imaged fast intrinsic optical responses from isolated retina activated by a visible light flash. Fast, high resolution imaging disclosed larger local optical responses, and showed evidence of multiple response components with both negative- and positive-going signals, on different timescales. Darkfield imaging techniques further enhanced the sensitivity of optical measurements. At single cell resolution, brightfield imaging disclosed maxima of optical responses ~5% dI/I, while darkfield imaging showed maxima of optical responses exceeding 10% dI/I. In comparison with simultaneous electrophysiological recording, optical imaging provided much better localized patterns of response over the activated area of the retina.

  8. New developments in eye models with retina tissue phantoms for ophthalmic optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Rowe, T. Scott; Zawadzki, Robert J.

    2012-03-01

    We document our latest work in developing eye models with solid-state retinal tissue phantoms designed for demonstrating, validating and comparing ophthalmic Optical Coherence Tomography (OCT) instruments. Eye models with retina tissue phantoms can serve a variety of purposes, including demonstrating OCT functionality and performance in both the clinic and exhibit hall, validating retina layer thickness measurements from different commercial OCT instruments and as an aide for the R&D engineer and field service technician in the development and repair of instruments, respectively. The ideal eye model for OCT, the optical cross-sectional imaging modality, would have a volumetric morphology and scattering and absorption properties similar to that of normal human retina. These include a multi-layered structure of equivalent thickness to nominal human retina layers, a foveal pit that can be used to orient the image, and a RPE/OS and choroid like layers to demonstrate the depth penetration of the OCT system. A solid state tissue phantom relieves the user of constant cleaning and maintenance associated with the more common water bath model eyes. Novel processes12 have been developed to create retinal layers model that closely mimic the reflectance and scattering coefficients of the real layers of the retina, as imaged by spectral bandwidth of OCT.

  9. Expression of hermes gene is restricted to the ganglion cells in the retina.

    PubMed

    Piri, Natik; Kwong, Jacky M K; Song, Min; Caprioli, Joseph

    2006-09-11

    The RNA binding protein with multiple splicing 2, or hermes, is a member of the RRM (RNA recognition motif) family of RNA-binding proteins. In this study, we show that the hermes gene is expressed in the rat retina, and its expression is restricted to the ganglion cell layer. Double in situ hybridization with riboprobes corresponding to the hermes gene and Thy-1, the RGC marker in the retina, showed that the majority of the Thy-1 positive cells in the ganglion cell layer were also hermes positive. This was also shown by co-localization of the hermes in situ hybridization signals with the retrogradely labeled RGCs. Our observations suggest that hermes is expressed in the majority, if not all, of RGCs and is not restricted to only certain RGC types. Hermes in situ hybridization signals were not detected in the retinal sections of optic nerve transected animals, which are characterized by rapid and specific RGC degeneration. The dramatic reduction of the hermes mRNA level in axotomized retinas was also observed by semi-quantitative RT-PCR. The specific expression of hermes in retinal ganglion cells qualifies this gene as a potential RGC marker in the retina. Outside the retina, hermes is expressed in the heart, liver, and kidney, and to a lesser degree in the cerebellum, cortex, lung, and small intestine. PMID:16870336

  10. [Guanidinoacetate-N-methyltransferase: location in mammalian retina and rat Harderian gland].

    PubMed

    Mardashchev, S R

    1975-01-01

    Homogenates of retinal external segments of rat, rabbit, beef and hen and of rat Harderian gland were found to possess a considerable activity of guanidineacetate-N-methyltransferase (GAMT, E.C. 2.1.1.2), comparable with the enzyme activity in liver, pancreas and testis. Permanent UV-illumination of rats (from 1 day to 1 week) resulted in the decrease of GAMT activity in retina and especially in Harderian gland. Caffeine (10(-4) M) and papaverine (10(-7) M) activated GAMT in retina and rat Harderian gland, while cycloheximide, a protein synthesis inhibitor (0.5-2 mkg/ml), eliminated caffeine-stimulated GAMT activity. Histamine (0.3 mkg/ml) inhibited GAMT activity both in retina and Harderian gland. A decrease of GAMT activity in retina, liver and testis of rat and an increase of the enzyme activity in rat pancreas and Harderian gland were observed in the presence of Mg2+ (5 mM). Physiological importance of GAMT and creatine in mammalian retina and rat Harderian gland is discussed. PMID:1203355

  11. Correlation of diacylglycerol level and protein kinase C activity in rat retina to retinal circulation.

    PubMed

    Shiba, T; Inoguchi, T; Sportsman, J R; Heath, W F; Bursell, S; King, G L

    1993-11-01

    The increases in diacylglycerol (DAG) level and protein kinase C (PKC) activity have been characterized biochemically and functionally in the retina and the brain of diabetic rats as well as in cultured vascular cells. PKC specific activities were increased in the membraneous fraction of retina from streptozotocin (STZ)-induced diabetic rats and the genetically determined diabetic BB rats, respectively, after 1 or 2 wk of diabetes, compared with control. The ratio of total PKC activities from membraneous and cytosol fractions was also increased in the retina of diabetic rats. With diabetes, all the isoenzymes and the total DAG level were increased in the rat retina, whereas no changes were found in the rat brain. Insulin treatment normalized plasma glucose levels and partially prevented the increases in the membraneous PKC activity and all the isoenzymes in the retina. In the retinal endothelial cells, the total DAG level and PKC specific activities are increased by 36 and 22%, respectively, in the membraneous pool when the glucose levels are changed from 5.5 to 22 mM. Activation of PKC activity and isoform beta II by the vitreal injection of phorbol dibutyrate mimicked the abnormal retinal blood circulation observed in diabetic rats (2.22 +/- 0.24 vs. 1.83 +/- 0.40 s). Thus diabetes and elevated glucose levels will increase DAG level and PKC activities and its isoenzyme specifically in vascular cells and may affect retinal hemodynamics. PMID:8238505

  12. Mouse retina explants after long-term culture in serum free medium.

    PubMed

    Caffé, A R; Ahuja, P; Holmqvist, B; Azadi, S; Forsell, J; Holmqvist, I; Söderpalm, A K; van Veen, T

    2001-11-01

    The neonatal mouse retina remains viable as an explant in serum-supplemented growth media for more than 4 weeks. Interpretation of drug effects on this tissue is compromised by the enigmatic composition of the serum. We sought to remove this ambiguity by culturing neonatal as well as late postnatal mouse retina in serum-free nutrient medium. In this study three important observations were made, (1) there is histotypic development of neonatal as well as preservation of late postnatal mouse retinal structure during long-term culture in serum-free medium, although the late postnatal tissue tends to show some loss of cells in the outer nuclear layer. (2) Protein expression in explant photoreceptor cells was similar to that in the litter-matched ones, except for green cone opsin and interphotoreceptor retinoid-binding protein, although mRNA of the latter is present at similar amounts as in age-matched in vivo controls. (3) Cells of the inner retina stained by antibodies to calcium-binding proteins display some novel sprouting of processes. The results show that the mouse retina can be cultured as an explant for more than 4 weeks in a serum-free medium. This represents an important step forward because, (1) the possibility of interference of drug effects by unknown serum factors has been eliminated; and (2) the spent culture medium can be analyzed to investigate biomolecules released by the retina in vitro. PMID:11719023

  13. Experimental measurement of modulation transfer function of a retina-like sensor

    NASA Astrophysics Data System (ADS)

    Wang, Fan; Cao, Fengmei; Bai, Tingzhu; Cao, Nan; Liu, Changju; Deng, Guangping

    2014-11-01

    The retina-like sensor is a kind of anthropomorphic visual sensor. It plays an important role in both biological and machine vision due to its advantages of high resolution in the fovea, a wide field-of-view, and minimum pixel count. The space-variant property of the sensor makes it difficult to directly measure its modulation transfer function (MTF). The MTF of a retina-like sensor is measured with the bar-target pattern method. According to the pixel arrangement, the sensor is divided into rings and the MTF of each ring is measured using spoke targets with different periods. Comparison between the measured MTF and the theoretical MTF of the sensor showed that they coincide. The differences between them are also analyzed and discussed. The measured MTF helps to analyze the performance of an imaging system containing a retina-like sensor.

  14. A robust face recognition algorithm under varying illumination using adaptive retina modeling

    NASA Astrophysics Data System (ADS)

    Cheong, Yuen Kiat; Yap, Vooi Voon; Nisar, Humaira

    2013-10-01

    Variation in illumination has a drastic effect on the appearance of a face image. This may hinder the automatic face recognition process. This paper presents a novel approach for face recognition under varying lighting conditions. The proposed algorithm uses adaptive retina modeling based illumination normalization. In the proposed approach, retina modeling is employed along with histogram remapping following normal distribution. Retina modeling is an approach that combines two adaptive nonlinear equations and a difference of Gaussians filter. Two databases: extended Yale B database and CMU PIE database are used to verify the proposed algorithm. For face recognition Gabor Kernel Fisher Analysis method is used. Experimental results show that the recognition rate for the face images with different illumination conditions has improved by the proposed approach. Average recognition rate for Extended Yale B database is 99.16%. Whereas, the recognition rate for CMU-PIE database is 99.64%.

  15. Alterations in glutamate cysteine ligase content in the retina of two retinitis pigmentosa animal models.

    PubMed

    Sánchez-Vallejo, Violeta; Benlloch-Navarro, Soledad; Trachsel-Moncho, Laura; López-Pedrajas, Rosa; Almansa, Inmaculada; Romero, Francisco Javier; Miranda, María

    2016-07-01

    Retinitis Pigmentosa (RP) comprises a group of rare genetic retinal disorders in which one of several different mutations induces photoreceptor death. Oxidative stress and glutathione (GSH) alterations may be related to the pathogenesis of RP. GSH has been shown to be present in high concentrations in the retina. In addition, the retina has the capability to synthesize GSH. In this study, we tested whether the two subunits of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis, and the concentrations of retinal GSH, oxidized glutathione (GSSG), cysteine (Cys) and glutamate are altered in the retina of two different RP mice models. Retinas from C3H and rd1 mice at different postnatal days (P7, P11, P15, P19, P21 and P28) and from C57BL/6 and rd10 mice at P21 were obtained. Western blot analysis was performed to determine the protein content of catalytic and modulatory subunits from glutamate cysteine ligase (GCLC and GCLM, respectively). In another set of experiments, control and rd1 mice were administered buthinine sulfoximine, a glutathione synthase inhibitor, or paraquat. GSH, GSSG, glutamate and Cys concentrations were determined, by HPLC. A decrease in retinal GCLC content was observed in C3H and rd1 mice with age, nevertheless, there was an increase in retinal GCLC in rd1 mice compared to control retinas at P19. No modifications in GCLM content with age and no difference between GCLM content in rd1 and control retinas were observed. The GSH concentration decreased in the rd1 retinas compared with control ones at P15, it increased at P19, and was again similar at P21 and P28. No changes in GSSG concentration in control retinas with age were observed; the GSSG levels in rd1 retinas were similar from P7 to P19 and then increased significantly at P21 and P28. Glutamate concentration was increased in the rd1 retinas compared to control mice from P7 to P15 and were comparable at P21 and P28. The Cys concentrations was measured in control and rd1

  16. Wiring patterns in the mouse retina: collecting evidence across the connectome, physiology and light microscopy

    PubMed Central

    Dunn, Felice A; Wong, Rachel O L

    2014-01-01

    The visual system has often been thought of as a parallel processor because distinct regions of the brain process different features of visual information. However, increasing evidence for convergence and divergence of circuit connections, even at the level of the retina where visual information is first processed, chips away at a model of dedicated and distinct pathways for parallel information flow. Instead, our current understanding is that parallel channels may emerge, not from exclusive microcircuits for each channel, but from unique combinations of microcircuits. This review depicts diagrammatically the current knowledge and remaining puzzles about the retinal circuit with a focus on the mouse retina. Advances in techniques for labelling cells and genetic manipulations have popularized the use of transgenic mice. We summarize evidence gained from serial electron microscopy, electrophysiology and light microscopy to illustrate the wiring patterns in mouse retina. We emphasize the need to explore proposed retinal connectivity using multiple methods to verify circuits both structurally and functionally. PMID:25172948

  17. Review: Tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain?

    PubMed Central

    Ho, Wing-Lau; Leung, Yen; Tsang, Andrea Wing-Ting; So, Kwok-Fai; Chiu, Kin

    2012-01-01

    Tau protein’s versatility lies in its functions within the central nervous system, including protein scaffolding and intracellular signaling. Tauopathy has been one of the most extensively studied neuropathologies among the neurodegenerative diseases. Because the retina and optic nerve are parts of the central nervous system, we hypothesize that tauopathy also plays a role in various eye diseases. However, little is known about tauopathy in the retina and optic nerve. Here, we summarize the findings from histopathological studies on animal models and human specimens with distinct neurodegenerative diseases. Similar pathological changes of tau protein can be found in Alzheimer’s disease, frontotemporal lobe dementia, and glaucoma. In view of the important roles of tauopathy in the brain, it is hoped that this review can stimulate research on eye diseases of the retina and optic nerve. PMID:23170062

  18. Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis.

    PubMed

    Horstmann, Lioba; Kuehn, Sandra; Pedreiturria, Xiomara; Haak, Kathrin; Pfarrer, Christiane; Dick, H Burkhard; Kleiter, Ingo; Joachim, Stephanie C

    2016-09-15

    Experimental autoimmune encephalomyelitis (EAE) is a common rodent model for multiple sclerosis (MS). Yet, the long-term consequences for retina and optic nerve (ON) are unknown. C57BL/6 mice were immunized with an encephalitogenic peptide (MOG35-55) and the controls received the carriers or PBS. Clinical symptoms started at day 8, peaked at day 14, and were prevalent until day 60. They correlated with infiltration and demyelination of the ON. In MOG-immunized animals more microglia cells in the ONs and retinas were detected at day 60. Additionally, retinal ganglion cell (RGC) loss was combined with an increased macroglia response. At this late stage, an increased number of microglia was associated with axonal damage in the ON and in the retina with RGC loss. Whether glial activation contributes to repair mechanisms or adversely affects the number of RGCs is currently unclear. PMID:27609273

  19. Ontogenic changes of kynurenine aminotransferase I activity and its expression in the chicken retina.

    PubMed

    Rejdak, Robert; Zielinska, Elzbieta; Shenk, Yana; Turski, Waldemar A; Okuno, Etsuo; Zarnowski, Tomasz; Zagorski, Zbigniew; Zrenner, Eberhart; Kohler, Konrad

    2003-06-01

    Kynurenine aminotransferases are key enzymes for the synthesis of kynurenic acid (KYNA), an endogenous glutamate receptor antagonist. The study described here examined ontogenic changes of kynurenine aminotransferase I (KAT I) activity and its expression in the chicken retina. KAT I activity measured on embryonic day 16 (E16) was significantly higher than at all other stages (E12, P0 and P7). Double labeling with antibodies against glutamine synthetase showed that on P7 KAT I was expressed in Müller cell endfeet and their processes in the inner retina. Since KAT I activity is high in the late embryonic stages, it is conceivable that it plays a neuromodulatory role in the retina during the late phase of embryogenesis. PMID:12782065

  20. The sarcoglycan-sarcospan complex localization in mouse retina is independent from dystrophins

    PubMed Central

    Fort, Patrice; Estrada, Francisco-Javier; Bordais, Agnès; Mornet, Dominique; Sahel, José-Alain; Picaud, Serge; Vargas, Haydeé Rosas; Coral-Vázquez, Ramón M.; Rendon, Alvaro

    2005-01-01

    The sarcoglycan–sarcospan (SG–SSPN) complex is part of the dystrophin-glycoprotein complex that has been extensively characterized in muscle. To establish the framework for functional studies of sarcoglycans in retina here, we quantified sarcoglycans mRNA levels with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and performed immunohistochemistry to determine their cellular and subcellular distribution. We showed that the β-, δ-, γ-, ε-sarcoglycans and sarcospan are expressed in mouse retina. They are localized predominantly in the outer and the inner limiting membranes, probably in the Müller cells and also in the ganglion cells axons where the expression of dystrophins have never been reported. We also investigated the status of the sarcoglycans in the retina of mdx3cv mutant mice for all Duchene Muscular Dystrophy (DMD) gene products. The absence of dystrophin did not produce any change in the sarcoglycan–sarcospan components expression and distribution. PMID:15993965

  1. An ultra-low power CMOS oscillating pixel array for retina implantation

    NASA Astrophysics Data System (ADS)

    Sun, Kang-Ming; Yuan, Xiang-Hui; Meng, Li-Ya; Rao, Cheng

    2010-07-01

    A light-controlled oscillating array for retina prosthesis is presented. The unique advantage of the circuit is that it has a lower voltage and ultra-low power consumption. And it has some other features as below: it is applicable to the natural light illumination and each pixel is an independent oscillator whose frequency is proportional to the intensity of the incident light. The fundamental characteristics of the circuit are analyzed. It is fabricated with a standard 0.6 μm CMOS technology. The experimental results indicate that the proposed circuit can be used for retina implantation, taking the place of the suffered photoreceptor in the retina of the blind and partially recovering the blind’s eyesight.

  2. Flow of energy in the outer retina in darkness and in light.

    PubMed

    Linton, Jonathan D; Holzhausen, Lars C; Babai, Norbert; Song, Hongman; Miyagishima, Kiyoharu J; Stearns, George W; Lindsay, Ken; Wei, Junhua; Chertov, Andrei O; Peters, Theo A; Caffe, Romeo; Pluk, Helma; Seeliger, Mathias W; Tanimoto, Naoyuki; Fong, Kimberly; Bolton, Laura; Kuok, Denise L T; Sweet, Ian R; Bartoletti, Theodore M; Radu, Roxana A; Travis, Gabriel H; Zagotta, Willam N; Townes-Anderson, Ellen; Parker, Ed; Van der Zee, Catharina E E M; Sampath, Alapakkam P; Sokolov, Maxim; Thoreson, Wallace B; Hurley, James B

    2010-05-11

    Structural features of neurons create challenges for effective production and distribution of essential metabolic energy. We investigated how metabolic energy is distributed between cellular compartments in photoreceptors. In avascular retinas, aerobic production of energy occurs only in mitochondria that are located centrally within the photoreceptor. Our findings indicate that metabolic energy flows from these central mitochondria as phosphocreatine toward the photoreceptor's synaptic terminal in darkness. In light, it flows in the opposite direction as ATP toward the outer segment. Consistent with this model, inhibition of creatine kinase in avascular retinas blocks synaptic transmission without influencing outer segment activity. Our findings also reveal how vascularization of neuronal tissue can influence the strategies neurons use for energy management. In vascularized retinas, mitochondria in the synaptic terminals of photoreceptors make neurotransmission less dependent on creatine kinase. Thus, vasculature of the tissue and the intracellular distribution of mitochondria can play key roles in setting the strategy for energy distribution in neurons. PMID:20445106

  3. Flow of energy in the outer retina in darkness and in light

    PubMed Central

    Linton, Jonathan D.; Holzhausen, Lars C.; Babai, Norbert; Song, Hongman; Miyagishima, Kiyoharu J.; Stearns, George W.; Lindsay, Ken; Wei, Junhua; Chertov, Andrei O.; Peters, Theo A.; Caffe, Romeo; Pluk, Helma; Seeliger, Mathias W.; Tanimoto, Naoyuki; Fong, Kimberly; Bolton, Laura; Kuok, Denise L. T.; Sweet, Ian R.; Bartoletti, Theodore M.; Radu, Roxana A.; Travis, Gabriel H.; Zagotta, Willam N.; Townes-Anderson, Ellen; Parker, Ed; Van der Zee, Catharina E. E. M.; Sampath, Alapakkam P.; Sokolov, Maxim; Thoreson, Wallace B.; Hurley, James B.

    2010-01-01

    Structural features of neurons create challenges for effective production and distribution of essential metabolic energy. We investigated how metabolic energy is distributed between cellular compartments in photoreceptors. In avascular retinas, aerobic production of energy occurs only in mitochondria that are located centrally within the photoreceptor. Our findings indicate that metabolic energy flows from these central mitochondria as phosphocreatine toward the photoreceptor’s synaptic terminal in darkness. In light, it flows in the opposite direction as ATP toward the outer segment. Consistent with this model, inhibition of creatine kinase in avascular retinas blocks synaptic transmission without influencing outer segment activity. Our findings also reveal how vascularization of neuronal tissue can influence the strategies neurons use for energy management. In vascularized retinas, mitochondria in the synaptic terminals of photoreceptors make neurotransmission less dependent on creatine kinase. Thus, vasculature of the tissue and the intracellular distribution of mitochondria can play key roles in setting the strategy for energy distribution in neurons. PMID:20445106

  4. Hazardous effects of fried potato chips on the development of retina in albino rats

    PubMed Central

    El-Sayyad, Hassan I; Sakr, Saber A; Badawy, Gamal M; Afify, Hanaa S

    2011-01-01

    Objective To evaluate the hazardous effects of fried potato chips upon the retina of two developmental stages of the albino rats aged 7 and 14 days from parturition. Methods Pregnant rats were arranged into two groups: control pregnant rats and consequently their delivered newborns until reaching 7 and 14 days old from parturition and fried potato chips group in which pregnant rats at the 6th day of gestation maintained on diet formed of fried potato chips supplied from the market mixed with standard diet at a concentration of 50% per each till 7 and 14 post-partum. Three fold integrated approaches were adopted, namely, histological, ultrastructural and proteomic analysis. Results Histological examination of the retina of the experimental offsprings revealed many histopathological changes, including massive degeneration, vacuolization and cell loss in the ganglion cell layer, as well as general reduction in retinal size. At the ultrastructural level, the retina of experimental offsprings exhibited number of deformities, including ill differentiated and degenerated nuclear layer, malformed and vacuolated pigment epithelium with vesiculated and fragmented rough endoplasmic reticulum, degenerated outer segment of photoreceptors, as well as swollen choriocapillaris and loss of neuronal cells. Proteomic analysis of retina of the two experimental developmental stages showed variations in the expressed proteins as a result of intoxication which illustrated the adverse toxic effects of fried potato chips upon the retina. Conclusions It can be concluded that the effect of fried potato chips on the development of retina in rats may be due to the presence of acrylamide or its metabolite. PMID:23569770

  5. A full reference image quality assessment method for retina-like sensor

    NASA Astrophysics Data System (ADS)

    Luo, Zhihu; Cao, Fengmei

    2013-12-01

    Retina_like sensor is characterized by a space-variant resolution mimicking the distribution of photoreceptors in the human retina. It is devided into two areas-the central area and the peripheral area. Density of pixels is highest in the center and decreases monotonically toward the periphery area. Such space-varant image allows high-resolution tasks using the central region while maintaining a lower resolution part providing relevant information about the background. In high speed forward motion field, because the image system is approaching or leaving the object in a high speed, the recorded image will be blurred radially. However, this kind of radial blur can be reduced by changing the pixel layout of retina_like sensor. So image quality assessment studies carried out on the different structures of the retina_like sensor output image can provide theoretical guidance for the establishment of the optimal layout of the retina_like sensor. This paper first analyzes the distortion process of the retina_like sensor output image in high-speed forward motion and find that such a distortion of the image including under-sampled distortion and radial blur distortion. Based on the characteristics of the distorted image, the author puts forward a full reference image quality assessment method, named Qretina, for such images. The method is according to the distortion process. Do under-sampling evaluation and radial fuzzy evaluation firstly, then weigh the two parts to get the final image quality evaluation results. The experimental results show that Qretina has better performance than the SSIM.

  6. Dynamic coupling of pattern formation and morphogenesis in the developing vertebrate retina.

    PubMed

    Picker, Alexander; Cavodeassi, Florencia; Machate, Anja; Bernauer, Sabine; Hans, Stefan; Abe, Gembu; Kawakami, Koichi; Wilson, Stephen W; Brand, Michael

    2009-10-01

    During embryonic development, pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements. In the vertebrate retina, patterning along the dorsal-ventral and nasal-temporal (anterior-posterior) axes is required for correct spatial representation in the retinotectal map. However, it is unknown how specification of axial cell positions in the retina occurs during the complex process of early eye morphogenesis. Studying zebrafish embryos, we show that morphogenetic tissue rearrangements during eye evagination result in progenitor cells in the nasal half of the retina primordium being brought into proximity to the sources of three fibroblast growth factors, Fgf8/3/24, outside the eye. Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. Surprisingly, nasal-temporal axis specification occurs very early along the dorsal-ventral axis of the evaginating eye. By in vivo imaging GFP-tagged retinal progenitor cells, we find that subsequent eye morphogenesis requires gradual tissue compaction in the nasal half and directed cell movements into the temporal half of the retina. Balancing these processes drives the progressive alignment of the nasal-temporal retina axis with the anterior-posterior body axis and is controlled by a feed-forward effect of Fgf signaling on Foxg1-mediated cell cohesion. Thus, the mechanistic coupling and dynamic synchronization of tissue patterning with morphogenetic cell behavior through Fgf signaling leads to the graded allocation of cell positional identity in the eye, underlying retinotectal map formation. PMID:19823566

  7. Transducin Duplicates in the Zebrafish Retina and Pineal Complex: Differential Specialisation after the Teleost Tetraploidisation

    PubMed Central

    Lagman, David; Callado-Pérez, Amalia; Franzén, Ilkin E.

    2015-01-01

    Gene duplications provide raw materials that can be selected for functional adaptations by evolutionary mechanisms. We describe here the results of 350 million years of evolution of three functionally related gene families: the alpha, beta and gamma subunits of transducins, the G protein involved in vision. Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones. The teleost-specific tetraploidisation generated additional duplicates for gnb1, gnb3 and gngt2. We report here that the duplicates have undergone several types of subfunctionalisation or neofunctionalisation in the zebrafish. We have found that gnb1a and gnb1b are co-expressed at different levels in rods; gnb3a and gnb3b have undergone compartmentalisation restricting gnb3b to the dorsal and medial retina, however, gnb3a expression was detected only at very low levels in both larvae and adult retina; gngt2b expression is restricted to the dorsal and medial retina, whereas gngt2a is expressed ventrally. This dorsoventral distinction could be an adaptation to protect the lower part of the retina from intense light damage. The ontogenetic analysis shows earlier onset of expression in the pineal complex than in the retina, in accordance with its earlier maturation. Additionally, gnb1a but not gnb1b is expressed in the pineal complex, and gnb3b and gngt2b are transiently expressed in the pineal during ontogeny, thus showing partial temporal subfunctionalisation. These retina-pineal distinctions presumably reflect their distinct functional roles in vision and circadian rhythmicity. In summary, this study describes several functional differences between transducin gene duplicates resulting from the teleost-specific tetraploidisation. PMID:25806532

  8. Transducin duplicates in the zebrafish retina and pineal complex: differential specialisation after the teleost tetraploidisation.

    PubMed

    Lagman, David; Callado-Pérez, Amalia; Franzén, Ilkin E; Larhammar, Dan; Abalo, Xesús M

    2015-01-01

    Gene duplications provide raw materials that can be selected for functional adaptations by evolutionary mechanisms. We describe here the results of 350 million years of evolution of three functionally related gene families: the alpha, beta and gamma subunits of transducins, the G protein involved in vision. Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones. The teleost-specific tetraploidisation generated additional duplicates for gnb1, gnb3 and gngt2. We report here that the duplicates have undergone several types of subfunctionalisation or neofunctionalisation in the zebrafish. We have found that gnb1a and gnb1b are co-expressed at different levels in rods; gnb3a and gnb3b have undergone compartmentalisation restricting gnb3b to the dorsal and medial retina, however, gnb3a expression was detected only at very low levels in both larvae and adult retina; gngt2b expression is restricted to the dorsal and medial retina, whereas gngt2a is expressed ventrally. This dorsoventral distinction could be an adaptation to protect the lower part of the retina from intense light damage. The ontogenetic analysis shows earlier onset of expression in the pineal complex than in the retina, in accordance with its earlier maturation. Additionally, gnb1a but not gnb1b is expressed in the pineal complex, and gnb3b and gngt2b are transiently expressed in the pineal during ontogeny, thus showing partial temporal subfunctionalisation. These retina-pineal distinctions presumably reflect their distinct functional roles in vision and circadian rhythmicity. In summary, this study describes several functional differences between transducin gene duplicates resulting from the teleost-specific tetraploidisation. PMID:25806532

  9. Characterization of a novel C-kinesin (KIFC3) abundantly expressed in vertebrate retina and RPE.

    PubMed

    Hoang, E; Bost-Usinger, L; Burnside, B

    1999-07-01

    Many forms of intracellular transport are mediated by microtubule-dependent motors of the kinesin superfamily (KIFs). To identify kinesins expressed in human retina and RPE, we used degenerate primer RT-PCR to amplify a approximately 440 bp kinesin motor domain fragment from human retinal and RPE messenger RNAs. Four distinct kinesins were detected: one C-kinesin (HsKIFC3); one kinesin from the unc104/KIF1 family [HsKIF1A]; and the ubiquitous and neuronal forms of conventional kinesin heavy chain [HsuKHC and HsnKHC]. The C-kinesin HsKIFC3 comprised 33.3% of the retinal clones and was 60% identical to FKIF2, the most abundant kinesin detected in a previous screen of fish retina and 95% identical to a fragment of MmKifC3 recently amplified from mouse brain. Elsewhere we have reported the sequence of HsKIFC3 and shown that it maps to the same locus on chromosome 16q13-q21 as Bardet-Biedl syndrome Type II, a hereditary retinal degeneration. We describe here the kinesin PCR screen of human retina and RPE and examine the tissue and subcellular distribution of KIFC3 in both fish and human retina using an antibody raised against a peptide conserved between FKIF2 and HsKIFC3. This peptide antibody identified a single approximately 80 kDa band in Western blots of fish and human retina and RPE. In both fish and human retina this antibody strongly labeled photoreceptor terminals in the outer plexiform layer, suggesting that FKIF2/KIFC3 may play some role in the photoreceptor synapse. PMID:10375449

  10. Dynamic Coupling of Pattern Formation and Morphogenesis in the Developing Vertebrate Retina

    PubMed Central

    Picker, Alexander; Cavodeassi, Florencia; Machate, Anja; Bernauer, Sabine; Hans, Stefan; Abe, Gembu; Kawakami, Koichi; Wilson, Stephen W.; Brand, Michael

    2009-01-01

    During embryonic development, pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements. In the vertebrate retina, patterning along the dorsal-ventral and nasal-temporal (anterior-posterior) axes is required for correct spatial representation in the retinotectal map. However, it is unknown how specification of axial cell positions in the retina occurs during the complex process of early eye morphogenesis. Studying zebrafish embryos, we show that morphogenetic tissue rearrangements during eye evagination result in progenitor cells in the nasal half of the retina primordium being brought into proximity to the sources of three fibroblast growth factors, Fgf8/3/24, outside the eye. Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. Surprisingly, nasal-temporal axis specification occurs very early along the dorsal-ventral axis of the evaginating eye. By in vivo imaging GFP-tagged retinal progenitor cells, we find that subsequent eye morphogenesis requires gradual tissue compaction in the nasal half and directed cell movements into the temporal half of the retina. Balancing these processes drives the progressive alignment of the nasal-temporal retina axis with the anterior-posterior body axis and is controlled by a feed-forward effect of Fgf signaling on Foxg1-mediated cell cohesion. Thus, the mechanistic coupling and dynamic synchronization of tissue patterning with morphogenetic cell behavior through Fgf signaling leads to the graded allocation of cell positional identity in the eye, underlying retinotectal map formation. PMID:19823566

  11. Rod Photoreceptors Express GPR55 in the Adult Vervet Monkey Retina

    PubMed Central

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian; Ptito, Maurice; Bouchard, Jean-François

    2013-01-01

    Cannabinoids exert their actions mainly through two receptors, the cannabinoid CB1 receptor (CB1R) and cannabinoid CB2 receptor (CB2R). In recent years, the G-protein coupled receptor 55 (GPR55) was suggested as a cannabinoid receptor based on its activation by anandamide and tetrahydrocannabinol. Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its neural (cone photoreceptor, horizontal, bipolar, amacrine and ganglion cells) and CB2R in glial components (Müller cells). The aim of this study was to determine the expression pattern of GPR55 in the monkey retina by using confocal microscopy. Our results show that GPR55 is strictly localized in the photoreceptor layer of the extrafoveal portion of the retina. Co-immunolabeling of GPR55 with rhodopsin, the photosensitive pigment in rods, revealed a clear overlap of expression throughout the rod structure with most prominent staining in the inner segments. Additionally, double-label of GPR55 with calbindin, a specific marker for cone photoreceptors in the primate retina, allowed us to exclude expression of GPR55 in cones. The labeling of GPR55 in rods was further assessed with a 3D visualization in the XZ and YZ planes thus confirming its exclusive expression in rods. These results provide data on the distribution of GPR55 in the monkey retina, different than CB1R and CB2R. The presence of GPR55 in rods suggests a function of this receptor in scotopic vision that needs to be demonstrated. PMID:24244730

  12. Unique topographic separation of two spectral classes of cones in the mouse retina.

    PubMed

    Szél, A; Röhlich, P; Caffé, A R; Juliusson, B; Aguirre, G; Van Veen, T

    1992-11-15

    We have found two immunologically distinguishable cone types in the retina of the mouse, each localized to two opposite halves of the eye. One cone type was labelled by the monoclonal antibody COS-1 specific to the middle-to-long wave sensitive visual pigment of the mammals, while the other type was stained by the shortwave-specific monoclonal antibody (OS-2). These results were confirmed with other antibodies directed against specific sequences of the visual pigments. As a result of the uneven distribution of the two cone types the mouse retina is divided into two fields separated by an oblique meridional line. The middlewave sensitive cones were present exclusively in the dorsal half of the mouse retina (M-field). The overwhelming majority of the shortwave sensitive cones occupied the ventral half (S-field), and only a small number was scattered among the middlewave sensitive cones in the dorsal retina. The ratio of the two cone types in the M-field corresponds to what has been found in the retina of other mammals, including rodents such as the gerbil and the rat. The S-field represents an entirely unique area with the unusually great number of shortwave sensitive cones and with the complete lack of the middlewave sensitive ones. The present study provides the structural basis for dichromacy in a rodent species considered for a long time to be monochromat. In addition, it shows that the ventral retina, containing exclusively S-cones in a relatively high density, is a unique retinal field not present in other mammalian species studied so far. PMID:1447405

  13. Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina

    PubMed Central

    Yang, Xiangjun; Hondur, Gözde; Li, Ming; Cai, Jian; Klein, Jon B.; Kuehn, Markus H.; Tezel, Gülgün

    2015-01-01

    Purpose To better understand ocular hypertension–induced early molecular alterations that may determine the initiation of neurodegeneration in human glaucoma, this study analyzed retinal proteomic alterations in the ocular hypertensive human retina. Methods Retina samples were obtained from six human donors with ocular hypertension (without glaucomatous injury) and six age- and sex-matched normotensive controls. Retinal proteins were analyzed by two-dimensional LC-MS/MS (liquid chromatography and linear ion trap mass spectrometry) using oxygen isotope labeling for relative quantification of protein expression. Proteomics data were validated by Western blot and immunohistochemical analyses of selected proteins. Results Out of over 2000 retinal proteins quantified, hundreds exhibited over 2-fold increased or decreased expression in ocular hypertensive samples relative to normotensive controls. Bioinformatics linked the proteomics datasets to various pathways important for maintenance of cellular homeostasis in the ocular hypertensive retina. Upregulated proteins included various heat shock proteins, ubiquitin proteasome pathway components, antioxidants, and DNA repair enzymes, while many proteins involved in mitochondrial oxidative phosphorylation exhibited downregulation in the ocular hypertensive retina. Despite the altered protein expression reflecting intrinsic adaptive/protective responses against mitochondrial energy failure, oxidative stress, and unfolded proteins, no alterations suggestive of an ongoing cell death process or neuroinflammation were detectable. Conclusions This study provides information about ocular hypertension–related molecular risk factors for glaucoma development. Molecular alterations detected in the ocular hypertensive human retina as opposed to previously detected alterations in human donor retinas with clinically manifest glaucoma suggest that proteome alterations determine the individual threshold to tolerate the ocular

  14. Dynamic response of the human retina to pulsed optical and electrical stimulation

    NASA Astrophysics Data System (ADS)

    Akchurin, Garif G.; Bakutkin, Valery V.; Kamenskih, Tatyana G.; Zemskova, Tatyana M.; Ahuja, Poonam

    2000-04-01

    Transcutaneous millisecond stimulation of the retina by electric pulses is used for diagnosis, determination of the extent of optic nerve damage, and also partial restoration of visual function in patients with glaucoma, myopia and different types of optic nerve atrophy. Correlation between the threshold of phosphen formation and duration of the stimulating electric pulses was determined experimentally in normal eyes and in eyes with various pathologies. Comparison of optical and electrical scintillating frequency gives information about the dynamic processes in the normal and pathological retina.

  15. Analysis of the optical field on the human retina from wavefront aberration data.

    PubMed

    Barbero, Sergio; Marcos, Susana

    2008-09-01

    Wave aberrations in the human eye are usually known with respect to the ideal spherical wavefront in the exit pupil. Using Kirchhoff's diffraction theory, we have derived a diffraction integral to compute the optical field on the retina from the wave aberration data. We have proposed a numerical algorithm based on the Stamnes-Spjelkavik-Pedersen (SSP) method to solve that integral. We have shown which approximations are admissible to reduce the complexity of the diffraction integral. In addition, we have compared our results with those of the conventional procedure used to compute intensities on the retina. We have found significant differences between our results and the conventional ones. PMID:18758554

  16. Design and realization of retina-like three-dimensional imaging based on a MOEMS mirror

    NASA Astrophysics Data System (ADS)

    Cao, Jie; Hao, Qun; Xia, Wenze; Peng, Yuxin; Cheng, Yang; Mu, Jiaxing; Wang, Peng

    2016-07-01

    To balance conflicts for high-resolution, large-field-of-view and real-time imaging, a retina-like imaging method based on time-of flight (TOF) is proposed. Mathematical models of 3D imaging based on MOEMS are developed. Based on this method, we perform simulations of retina-like scanning properties, including compression of redundant information and rotation and scaling invariance. To validate the theory, we develop a prototype and conduct relevant experiments. The preliminary results agree well with the simulations.

  17. Ganglion cell topography of the retina in the bottlenosed dolphin, Tursiops truncatus.

    PubMed

    Mass, A M; Supin AYa

    1995-01-01

    The distribution and size of ganglion cells in the retina of the bottlenosed dolphin are described. Ganglion cells concentrate at two spots of the highest density in the nasal and temporal quadrants, 15 to 16 mm (50 to 55 degrees) from the optic disk. The mean peak cell density in both spots is about 670 cells/mm2. With a posterior nodal distance of 14.5 mm (under water), this corresponds to 43 cells/deg2, which provides a retinal resolution of about 9' in water and 12' in air. Mean cell size was from 26 to 31 microns in various parts of the retina. PMID:7620874

  18. Short Wavelength Cone Opsin Is Not Expressed in the Retina of Arboreal African Pangolin (Manis tricuspis)

    PubMed Central

    Adekanmbi, Adejoke J.; Adekanmbi, Adefisayo A.; Akinola, Oluwole B.

    2016-01-01

    This paper reports a study of cone photoreceptors present in the retina of Manis tricuspis. Specifically, the LWS (L-) opsin expressed in longwave-sensitive cones and SWS1 (S-) opsin shortwave-sensitive cones were targeted. Vertical sections revealed reactivity to a cone marker, peanut agglutinin (PNA), and to an LWS antibody, but not to an SWS1 antibody. This suggests that the Manis tricuspis visual system is not able to discriminate shorter wavelengths from longer wavelengths because the short wavelength cones are not expressed in their retina. PMID:27242946

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Short Wavelength Cone Opsin Is Not Expressed in the Retina of Arboreal African Pangolin (Manis tricuspis).

    PubMed

    Adekanmbi, Adejoke J; Adekanmbi, Adefisayo A; Akinola, Oluwole B

    2016-01-01

    This paper reports a study of cone photoreceptors present in the retina of Manis tricuspis. Specifically, the LWS (L-) opsin expressed in longwave-sensitive cones and SWS1 (S-) opsin shortwave-sensitive cones were targeted. Vertical sections revealed reactivity to a cone marker, peanut agglutinin (PNA), and to an LWS antibody, but not to an SWS1 antibody. This suggests that the Manis tricuspis visual system is not able to discriminate shorter wavelengths from longer wavelengths because the short wavelength cones are not expressed in their retina. PMID:27242946

  1. Raman spectroscopy reveals spectroscopic changes in histologically normal retinas in a mouse model of alpha-synucleinopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The retina is an extension of the nervous system and is accessible for in vivo assessments. We have previously demonstrated changes in retinal function and pathology associated with scrapie, TME and BSE. The purpose of this work was to determine the utility of the retina to identify early CNS change...

  2. [Regeneration of the retina using pigment epithelial cell transplantation].

    PubMed

    Abe, Toshiaki

    2002-12-01

    At has been reported that transplantation of appropriate cells, growth factors, and/or extracellular matrix may help the regeneration of damaged tissues or organs. Some growth factors, such as basic fibroblast growth factor(bFGF), have been successfully transferred to patients with ischemic heart disease. Embryonic dopamine neurons were also transplanted into the brains of patients with Parkinson's disease successfully. We have also performed cultured auto iris pigment epithelial cell (IPE) transplantation into the subretinal space after removal of choroidal neovascularization in patients with age-related macular degeneration (AMD). Here, we report the results of auto IPE transplantation in 35 patients, who could be followed for more than 6 months. We also tried to apply cell transplantation to other retinal diseases by managing the transplanted cells as introduced growth factor genes. Auto IPE transplantation was performed after removal of choroidal neovascular membranes (CNV). Visual acuity wes improved by more than 0.2 log MAR in 18 of 35 patients (51.5%), it was unchanged in 11 patients (31.5%), and it was worsened in 6 patients (17%). No significant difference was observed in comparison to patients who underwent CNV removal only. However, unlike the previous reports, we found no patients showing rejection. We also found that the cultured transplanted cells never showed proliferation under the retina or in the vitreous cavity and concluded that cultured auto IPE transplantation can be performed safely without complications. Next, we examined whether cell transplantation can be expanded to other degenerative retinal diseases. One of our results showed that host RPE may play an important role against the transplanted cells in the subretinal regions. When we introduced bFGF gene into the cells, we found synexpression cluster of the genes in the cells. One of the most prominent movements among the genes was lysyl oxidase like-1 gene, which plays an important role

  3. Cellular and physiological mechanisms underlying blood flow regulation in the retina choroid in health disease

    PubMed Central

    Kur, Joanna; Newman, Eric A.; Chan-Ling, Tailoi

    2012-01-01

    We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored. PMID:22580107

  4. Reduction of Scattered Light by M"uller Cells in the Human Retina

    NASA Astrophysics Data System (ADS)

    Bendix, Oliver; Fleischmann, Ragnar; Geisel, Theo

    2012-02-01

    It is a long standing question why in the mammalian eye photoreceptors are positioned at the back of the retina, forcing photons to travel through various neuronal layers of the retina before the light-sensitive rods and cones can detect them. Recent studies suggest that certain retinal glial cells--called M"uller cells (MCs)--play an important role in answering that question. It has been experimentally shown that MCs extracted from the retina can act as optical fibers [1]. To understand the light guiding properties of the MC in the natural fluctuating optical environment, we developed a model to analyze the light reflection and transmission of MCs embedded in a random medium neuronal tissue. With these quantities and a simplified geometrical eye model we study how light is scattered in the eye. We found that MCs can lead to a substantial increase of the signal-to-noise ratio (SNR), the ratio of the intensity of direct incident light at a photoreceptor to the intensity of back-scattered light from other areas of the retina. The SNR is most pronounced in the vicinity of the fovea and can be more than an order of magnitude.[4pt] [1] Franze et. al., Proc Natl Acad Sci USA, 2007, 104, 8287-8292.

  5. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species.

    PubMed

    Amann, Barbara; Kleinwort, Kristina J H; Hirmer, Sieglinde; Sekundo, Walter; Kremmer, Elisabeth; Hauck, Stefanie M; Deeg, Cornelia A

    2016-01-01

    Aquaporins (AQPs) are small integral membrane proteins with 13 members in mammals and are essential for water transport across membranes. They are found in many different tissues and cells. Currently, there are conflicting results regarding retinal aquaporin expression and subcellular localization between genome and protein analyses and among various species. AQP4, 7, 9 and 11 were described in the retina of men; whereas AQP6, 8 and 10 were earlier identified in rat retinas and AQP4, 5 and 11 in horses. Since there is a lack of knowledge regarding AQP expression on protein level in retinas of different animal models, we decided to analyze retinal cellular expression of AQP4, 5 and 11 in situ with immunohistochemistry. AQP4 was detected in all 15 explored species, AQP5 and AQP11 in 14 out of 15. Interestingly, AQP4 was unambiguously expressed in Muller glial cells, whereas AQP5 was differentially allocated among the species analyzed. AQP11 expression was Muller glial cell-specific in 50% of the animals, whereas in the others, AQP11 was detected in ganglion cell layer and at photoreceptor outer segments. Our data indicate a disparity in aquaporin distribution in retinas of various animals, especially for AQP5 and 11. PMID:27438827

  6. Linear information processing in the retina: a study of horizontal cell responses.

    PubMed Central

    Tranchina, D; Gordon, J; Shapley, R; Toyoda, J

    1981-01-01

    A basic question about visual perception is whether the retina produces a faithful or a distorted neural representation of the visual image. It is now well known that in some retinal pathways there are significant nonlinear transductions which distort the neural image. The next natural question is, What are the locations of the nonlinear stages within the retinal network? We report here on an investigation of linearity and nonlinearity of responses of horizontal cells in the turtle retina as an assay of the degree of nonlinearity in the outer plexiform layer of the retina. The visual stimuli were sinusoidal gratings; these patterns were modulated by contrast reversal with a sinusoidal time course. The conclusion from our experiments is that the turtle's horizontal cell responses show evidence only of linear spatial summation even at moderately high contrasts on moderately high background levels. Our work thus indicates that there is no significant distortion of the visual image by the photoreceptors or by the neural summation of photoreceptor signals by horizontal cells under normal physiological conditions. These results are consistent with the view that the major nonlinearities of the retina are proximal to the outer plexiform layer. PMID:6947242

  7. Effects of Radiation on Rat Retina after 18 days of Space Flight

    NASA Technical Reports Server (NTRS)

    Philpott, D.; Corbett, R.; Turnbill, C.; Black, S.; Dayhoff, D.; McGourty, J.; Lee, R.; Harrison, G.; Savick, L.

    1978-01-01

    Although cumulative effects an retina from low-dose radiation during prolonged spaceflight are not known, ary impairment of vision could set limits for spaceflight duration. Cosmic rays are now considered to be the cause of the "light flashes" seen during spaceflight by activating retina cells as they pass through the photoreceptors. Previous studies have also shown retinal cellular alterations and cell necrosis from high-energy, particle (HZE) radiation. Ten rats, 5 centrifuged during flight (FC) to simulate gravity and 5 in-flight stationary (FS) experiencing hypogravity, orbited Earth for 18.5 days on Cosmos 936. The animals were sacrificed 25 days post-recovery and the eyes flown to Ames Res. Ctr. The pattern of cell necrosis in the retinas from the FC group showed the same response to radiation as the FS. This would indicate that hypogravity was not a factor in the observed results. Also the cellular response in the retinas exposed in the Berkeley accelerator again matched both the FC and FS eyes. Thus all three conditions provide comparable changes and indicate HZE particles as the possible cause of the cellular alterations, channels, and breakdown.

  8. A model microfluidics-based system for the human and mouse retina.

    PubMed

    Mishra, Shawn; Thakur, Ankush; Redenti, Stephen; Vazquez, Maribel

    2015-12-01

    The application of microfluidics technologies to the study of retinal function and response holds great promise for development of new and improved treatments for patients with degenerative retinal diseases. Restoration of vision via retinal transplantation therapy has been severely limited by the low numbers of motile cells observed post transplantation. Using modern soft lithographic techniques, we have developed the μRetina, a novel and convenient biomimetic microfluidics device capable of examing the migratory behavior of retinal lineage cells within biomimetic geometries of the human and mouse retina. Coupled computer simulations and experimental validations were used to characterize and confirm the formation of chemical concentration gradients within the μRetina, while real-time images within the device captured radial and theta cell migration in response to concentration gradients of stromal derived factor (SDF-1), a known chemoattractant. Our data underscore how the μRetina can be used to examine the concentration-dependent migration of retinal progenitors in order to enhance current therapies, as well as develop novel migration-targeted treatments. PMID:26475458

  9. Optical Recording of Retinal and Visual Cortical Responses Evoked by Electrical Stimulation on the Retina

    NASA Astrophysics Data System (ADS)

    Osanai, Makoto; Sakaehara, Haruko; Sawai, Hajime; Song, Wen-Jie; Yagi, Tetsuya

    To develop a retinal prosthesis for blind patients using an implanted multielectrode array, it is important to study the response properties of retinal ganglion cells and of the visual cortex to localized retinal electrical stimulation. Optical imaging can reveal the spatio-temporal properties of neuronal activity. Therefore, we conducted a calcium imaging study to investigate response properties to local current stimulation in frog retinas, and a membrane potential imaging study to explore the visual cortical responses to retinal stimulation in guinea pigs. In the retina, local current stimuli evoked transient responses in the ganglion cells located near the stimulus electrode. The spatial pattern of the responding area was altered by changing the location of the stimulation. Local electrical stimulation to the retina also caused transient responses in the visual cortex. The responding cortical areas in the primary visual cortex were localized. A spatially different cortical response was observed to stimulation of a different position on the retina. These results suggest that the imaging study has great potential in revealing the spatio-temporal properties of the neuronal response for the retinal prosthesis.

  10. An atlas of gene expression and gene co-regulation in the human retina.

    PubMed

    Pinelli, Michele; Carissimo, Annamaria; Cutillo, Luisa; Lai, Ching-Hung; Mutarelli, Margherita; Moretti, Maria Nicoletta; Singh, Marwah Veer; Karali, Marianthi; Carrella, Diego; Pizzo, Mariateresa; Russo, Francesco; Ferrari, Stefano; Ponzin, Diego; Angelini, Claudia; Banfi, Sandro; di Bernardo, Diego

    2016-07-01

    The human retina is a specialized tissue involved in light stimulus transduction. Despite its unique biology, an accurate reference transcriptome is still missing. Here, we performed gene expression analysis (RNA-seq) of 50 retinal samples from non-visually impaired post-mortem donors. We identified novel transcripts with high confidence (Observed Transcriptome (ObsT)) and quantified the expression level of known transcripts (Reference Transcriptome (RefT)). The ObsT included 77 623 transcripts (23 960 genes) covering 137 Mb (35 Mb new transcribed genome). Most of the transcripts (92%) were multi-exonic: 81% with known isoforms, 16% with new isoforms and 3% belonging to new genes. The RefT included 13 792 genes across 94 521 known transcripts. Mitochondrial genes were among the most highly expressed, accounting for about 10% of the reads. Of all the protein-coding genes in Gencode, 65% are expressed in the retina. We exploited inter-individual variability in gene expression to infer a gene co-expression network and to identify genes specifically expressed in photoreceptor cells. We experimentally validated the photoreceptors localization of three genes in human retina that had not been previously reported. RNA-seq data and the gene co-expression network are available online (http://retina.tigem.it). PMID:27235414

  11. NR2C and NR2D subunits of NMDA receptors in frog and turtle retina.

    PubMed

    Vitanova, Lily Alexandrova

    2012-12-01

    Glutamate NMDA (N-methyl-D-aspartate) receptors are widely distributed in the central nervous system where they are involved in cognitive processes, motor control and many other functions. They are also well studied in the retina, which may be regarded as a biological model of the nervous system. However, little is known about NR2C and NR2D subunits of NMDA receptors, which have some specific features as compared to other subunits. Consequently the aim of the present study was to investigate their distribution in frog (Rana ridibunda) and turtle (Emys orbicularis) retinas which possess mixed and cone types of retina respectively. The experiments were performed using an indirect immunofluorescence method. Four antibodies directed to NR2C and NR2D subunits of NMDA receptor, as well as three antibodies directed to different splice variants of NR1 subunit, which is known to be obligatory for proper functioning of the receptor, were applied. All antibodies caused well expressed labeling in frog and turtle retinas. The NR2C and NR2D subunits were localized in glial Müller cells, while the NR1 subunit had both neuronal and glial localization. Our results show that glial NMDA receptors differ from neuronal ones in their subunit composition. The functional significance of the NMDA receptors and their NR2C and NR2D subunits, in particular for the neuron-glia interactions, is discussed. PMID:22386206

  12. Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain

    PubMed Central

    Casanova, Christian

    2016-01-01

    Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system. Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function. In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing. The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far. It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells. The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases. PMID:26839718

  13. Glutamatergic Monopolar Interneurons Provide a Novel Pathway of Excitation in the Mouse Retina.

    PubMed

    Della Santina, Luca; Kuo, Sidney P; Yoshimatsu, Takeshi; Okawa, Haruhisa; Suzuki, Sachihiro C; Hoon, Mrinalini; Tsuboyama, Kotaro; Rieke, Fred; Wong, Rachel O L

    2016-08-01

    Excitatory and inhibitory neurons in the CNS are distinguished by several features, including morphology, transmitter content, and synapse architecture [1]. Such distinctions are exemplified in the vertebrate retina. Retinal bipolar cells are polarized glutamatergic neurons receiving direct photoreceptor input, whereas amacrine cells are usually monopolar inhibitory interneurons with synapses almost exclusively in the inner retina [2]. Bipolar but not amacrine cell synapses have presynaptic ribbon-like structures at their transmitter release sites. We identified a monopolar interneuron in the mouse retina that resembles amacrine cells morphologically but is glutamatergic and, unexpectedly, makes ribbon synapses. These glutamatergic monopolar interneurons (GluMIs) do not receive direct photoreceptor input, and their light responses are strongly shaped by both ON and OFF pathway-derived inhibitory input. GluMIs contact and make almost as many synapses as type 2 OFF bipolar cells onto OFF-sustained A-type (AOFF-S) retinal ganglion cells (RGCs). However, GluMIs and type 2 OFF bipolar cells possess functionally distinct light-driven responses and may therefore mediate separate components of the excitatory synaptic input to AOFF-S RGCs. The identification of GluMIs thus unveils a novel cellular component of excitatory circuits in the vertebrate retina, underscoring the complexity in defining cell types even in this well-characterized region of the CNS. PMID:27426514

  14. Mapping the Time Line of Development in Each Layer of Human Foetal Retina

    PubMed Central

    Kapoor, Kanchan; Sahni, Daisy; Singh, Balbir

    2016-01-01

    Introduction There is need to elucidate the histological developmental stages of various layers of retina, to understand the process better and provide clinically significant insights. Aim To study the details and chronology of in utero development of different layers of retina. Materials and Methods To study time of appearance, differentiation and organization of all layers of central retina in different gestational age groups. Retina was studied histologically in 27 foetuses from18th to 34th weeks of gestation. Results We found the period of mid gestation (19th -21st week of gestation) to be the defining time for retinal layers: The bruch’s membrane was fully formed at 20th week of gestation; the photoreceptor layer became well defined at 21st week of gestation; both the nuclear layers and both the plexiform layers and the ganglion cell layer became distinct at 19th week of gestation. Before the 19th week, outer and inner neuroblastic zones separated by the neuropil were seen. Well defined nerve fibre layer and inner limiting membrane was present at 18th week. The outer limiting membrane was first appreciated at 32nd week of gestation. Foetal retinal pigment epithelium was cuboidal and filled with melanin granules while no trace of lipofuscin pigment was found under fluorescent microscope. Conclusion Detailed data on retinal histogenesis and its timeline might aid in directed differentiation of retinal cell types from stem cells for therapeutic purposes. PMID:27134848

  15. IL-33 amplifies an innate immune response in the degenerating retina

    PubMed Central

    Xi, Hongkang; Katschke, Kenneth J.; Li, Yun; Truong, Tom; Lee, Wyne P.; Diehl, Lauri; Rangell, Linda; Tao, Jianhua; Arceo, Rommel; Eastham-Anderson, Jeffrey; Hackney, Jason A.; Iglesias, Antonio; Cote-Sierra, Javier; Elstrott, Justin; Weimer, Robby M.

    2016-01-01

    Age-related macular degeneration (AMD), a leading cause of vision impairment in the ageing population, is characterized by irreversible loss of retinal pigment epithelial (RPE) cells and photoreceptors and can be associated with choroidal neovascularization. Mononuclear phagocytes are often present in AMD lesions, but the processes that direct myeloid cell recruitment remain unclear. Here, we identify IL-33 as a key regulator of inflammation and photoreceptor degeneration after retina stress or injury. IL-33+ Müller cells were more abundant and IL-33 cytokine was elevated in advanced AMD cases compared with age-matched controls with no AMD. In rodents, retina stress resulted in release of bioactive IL-33 that in turn increased inflammatory chemokine and cytokine expression in activated Müller cells. Deletion of ST2, the IL-33 receptor α chain, or treatment with a soluble IL-33 decoy receptor significantly reduced release of inflammatory mediators from Müller cells, inhibited accumulation of mononuclear phagocytes in the outer retina, and protected photoreceptor rods and cones after a retina insult. This study demonstrates a central role for IL-33 in regulating mononuclear phagocyte recruitment to the photoreceptor layer and positions IL-33 signaling as a potential therapeutic target in macular degenerative diseases. PMID:26755704

  16. Lgr5+ amacrine cells possess regenerative potential in the retina of adult mice

    PubMed Central

    Chen, Mengfei; Tian, Shenghe; Glasgow, Nathan G; Gibson, Gregory; Yang, Xiaoling; Shiber, Christen E; Funderburgh, James; Watkins, Simon; Johnson, Jon W; Schuman, Joel S; Liu, Hongjun

    2015-01-01

    Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5+ cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5+ amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5+ amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5+ amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases. PMID:25990970

  17. DSCAM Promotes Refinement in the Mouse Retina through Cell Death and Restriction of Exploring Dendrites

    PubMed Central

    Li, Shuai; Sukeena, Joshua M.; Simmons, Aaron B.; Hansen, Ethan J.; Nuhn, Renee E.; Samuels, Ivy S.

    2015-01-01

    In this study we develop and use a gain-of-function mouse allele of the Down syndrome cell adhesion molecule (Dscam) to complement loss-of-function models. We assay the role of Dscam in promoting cell death, spacing, and laminar targeting of neurons in the developing mouse retina. We find that ectopic or overexpression of Dscam is sufficient to drive cell death. Gain-of-function studies indicate that Dscam is not sufficient to increase spatial organization, prevent cell-to-cell pairing, or promote active avoidance in the mouse retina, despite the similarity of the Dscam loss-of-function phenotype in the mouse retina to phenotypes observed in Drosophila Dscam1 mutants. Both gain- and loss-of-function studies support a role for Dscam in targeting neurites; DSCAM is necessary for precise dendrite lamination, and is sufficient to retarget neurites of outer retinal cells after ectopic expression. We further demonstrate that DSCAM guides dendrite targeting in type 2 dopaminergic amacrine cells, by restricting the stratum in which exploring retinal dendrites stabilize, in a Dscam dosage-dependent manner. Based on these results we propose a single model to account for the numerous Dscam gain- and loss-of-function phenotypes reported in the mouse retina whereby DSCAM eliminates inappropriately placed cells and connections. PMID:25855178

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

    PubMed Central

    Yan, Shu; Zheng, Cui; Chen, Zhi-qi; Liu, Rong; Li, Gui-gang; Hu, Wei-kun; Pei, Han; Li, Bin

    2012-01-01

    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. PMID:21904541

  19. An atlas of gene expression and gene co-regulation in the human retina

    PubMed Central

    Pinelli, Michele; Carissimo, Annamaria; Cutillo, Luisa; Lai, Ching-Hung; Mutarelli, Margherita; Moretti, Maria Nicoletta; Singh, Marwah Veer; Karali, Marianthi; Carrella, Diego; Pizzo, Mariateresa; Russo, Francesco; Ferrari, Stefano; Ponzin, Diego; Angelini, Claudia; Banfi, Sandro; di Bernardo, Diego

    2016-01-01

    The human retina is a specialized tissue involved in light stimulus transduction. Despite its unique biology, an accurate reference transcriptome is still missing. Here, we performed gene expression analysis (RNA-seq) of 50 retinal samples from non-visually impaired post-mortem donors. We identified novel transcripts with high confidence (Observed Transcriptome (ObsT)) and quantified the expression level of known transcripts (Reference Transcriptome (RefT)). The ObsT included 77 623 transcripts (23 960 genes) covering 137 Mb (35 Mb new transcribed genome). Most of the transcripts (92%) were multi-exonic: 81% with known isoforms, 16% with new isoforms and 3% belonging to new genes. The RefT included 13 792 genes across 94 521 known transcripts. Mitochondrial genes were among the most highly expressed, accounting for about 10% of the reads. Of all the protein-coding genes in Gencode, 65% are expressed in the retina. We exploited inter-individual variability in gene expression to infer a gene co-expression network and to identify genes specifically expressed in photoreceptor cells. We experimentally validated the photoreceptors localization of three genes in human retina that had not been previously reported. RNA-seq data and the gene co-expression network are available online (http://retina.tigem.it). PMID:27235414

  20. A preparation for studying electrical stimulation of the retina in vivo in rat

    NASA Astrophysics Data System (ADS)

    Baig-Silva, M. S.; Hathcock, C. D.; Hetling, J. R.

    2005-03-01

    A remaining challenge to the development of electronic prostheses for vision is improving the effectiveness of retinal stimulation. Electrode design and stimulus parameters need to be optimized such that the neural output from the retina conveys information to the mind's eye that aids the patient in interpreting his or her environment. This optimization will require a detailed understanding of the response of the retina to electrical stimulation. The identity and response characteristics of the cellular targets of stimulation need to be defined and evaluated. Described here is an in vivo preparation for studying electrical stimulation of the retina in rat at the cellular level. The use of rat makes available a number of well-described models of retinal disease that motivate prosthesis development. Artificial stimulation can be investigated by adapting techniques traditionally employed to study the response of the retina to photic stimuli, such as recording at the cornea, single-cell recording, and pharmacological dissection of the response. Pilot studies include amplitude-intensity response data for subretinal and transretinal stimulation paradigms recorded in wild-type rats and a transgenic rat model of autosomal dominant retinitis pigmentosa. The ability to record single-unit ganglion cell activity in vivo is also demonstrated.

  1. Antioxidant drug therapy approaches for neuroprotection in chronic diseases of the retina.

    PubMed

    Payne, Andrew J; Kaja, Simon; Naumchuk, Yuliya; Kunjukunju, Nancy; Koulen, Peter

    2014-01-01

    The molecular pathways contributing to visual signal transduction in the retina generate a high energy demand that has functional and structural consequences such as vascularization and high metabolic rates contributing to oxidative stress. Multiple signaling cascades are involved to actively regulate the redox state of the retina. Age-related processes increase the oxidative load, resulting in chronically elevated levels of oxidative stress and reactive oxygen species, which in the retina ultimately result in pathologies such as glaucoma or age-related macular degeneration, as well as the neuropathic complications of diabetes in the eye. Specifically, oxidative stress results in deleterious changes to the retina through dysregulation of its intracellular physiology, ultimately leading to neurodegenerative and potentially also vascular dysfunction. Herein we will review the evidence for oxidative stress-induced contributions to each of the three major ocular pathologies, glaucoma, age-related macular degeneration, and diabetic retinopathy. The premise for neuroprotective strategies for these ocular disorders will be discussed in the context of recent clinical and preclinical research pursuing novel therapy development approaches. PMID:24473138

  2. Simultaneous ex vivo Functional Testing of Two Retinas by in vivo Electroretinogram System

    PubMed Central

    Vinberg, Frans; Kefalov, Vladimir

    2015-01-01

    An In vivo electroretinogram (ERG) signal is composed of several overlapping components originating from different retinal cell types, as well as noise from extra-retinal sources. Ex vivo ERG provides an efficient method to dissect the function of retinal cells directly from an intact isolated retina of animals or donor eyes. In addition, ex vivo ERG can be used to test the efficacy and safety of potential therapeutic agents on retina tissue from animals or humans. We show here how commercially available in vivo ERG systems can be used to conduct ex vivo ERG recordings from isolated mouse retinas. We combine the light stimulation, electronic and heating units of a standard in vivo system with custom-designed specimen holder, gravity-controlled perfusion system and electromagnetic noise shielding to record low-noise ex vivo ERG signals simultaneously from two retinas with the acquisition software included in commercial in vivo systems. Further, we demonstrate how to use this method in combination with pharmacological treatments that remove specific ERG components in order to dissect the function of certain retinal cell types. PMID:25992809

  3. THE PROTEASOME IS A TARGET OF OXIDATIVE DAMAGE IN HUMAN RETINA PIGMENT EPITHELIAL CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Dysfunction of the ubiquitin-proteasome pathway (UPP) is associated with several age-related degenerative diseases. The objective of this study is to investigate the effect of oxidative stress on the UPP in retina pigment epithelial cells. Methods: To mimic physiological oxidative stress...

  4. IL-33 amplifies an innate immune response in the degenerating retina.

    PubMed

    Xi, Hongkang; Katschke, Kenneth J; Li, Yun; Truong, Tom; Lee, Wyne P; Diehl, Lauri; Rangell, Linda; Tao, Jianhua; Arceo, Rommel; Eastham-Anderson, Jeffrey; Hackney, Jason A; Iglesias, Antonio; Cote-Sierra, Javier; Elstrott, Justin; Weimer, Robby M; van Lookeren Campagne, Menno

    2016-02-01

    Age-related macular degeneration (AMD), a leading cause of vision impairment in the ageing population, is characterized by irreversible loss of retinal pigment epithelial (RPE) cells and photoreceptors and can be associated with choroidal neovascularization. Mononuclear phagocytes are often present in AMD lesions, but the processes that direct myeloid cell recruitment remain unclear. Here, we identify IL-33 as a key regulator of inflammation and photoreceptor degeneration after retina stress or injury. IL-33(+) Müller cells were more abundant and IL-33 cytokine was elevated in advanced AMD cases compared with age-matched controls with no AMD. In rodents, retina stress resulted in release of bioactive IL-33 that in turn increased inflammatory chemokine and cytokine expression in activated Müller cells. Deletion of ST2, the IL-33 receptor α chain, or treatment with a soluble IL-33 decoy receptor significantly reduced release of inflammatory mediators from Müller cells, inhibited accumulation of mononuclear phagocytes in the outer retina, and protected photoreceptor rods and cones after a retina insult. This study demonstrates a central role for IL-33 in regulating mononuclear phagocyte recruitment to the photoreceptor layer and positions IL-33 signaling as a potential therapeutic target in macular degenerative diseases. PMID:26755704

  5. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species

    PubMed Central

    Amann, Barbara; Kleinwort, Kristina J. H.; Hirmer, Sieglinde; Sekundo, Walter; Kremmer, Elisabeth; Hauck, Stefanie M.; Deeg, Cornelia A.

    2016-01-01

    Aquaporins (AQPs) are small integral membrane proteins with 13 members in mammals and are essential for water transport across membranes. They are found in many different tissues and cells. Currently, there are conflicting results regarding retinal aquaporin expression and subcellular localization between genome and protein analyses and among various species. AQP4, 7, 9 and 11 were described in the retina of men; whereas AQP6, 8 and 10 were earlier identified in rat retinas and AQP4, 5 and 11 in horses. Since there is a lack of knowledge regarding AQP expression on protein level in retinas of different animal models, we decided to analyze retinal cellular expression of AQP4, 5 and 11 in situ with immunohistochemistry. AQP4 was detected in all 15 explored species, AQP5 and AQP11 in 14 out of 15. Interestingly, AQP4 was unambiguously expressed in Muller glial cells, whereas AQP5 was differentially allocated among the species analyzed. AQP11 expression was Muller glial cell-specific in 50% of the animals, whereas in the others, AQP11 was detected in ganglion cell layer and at photoreceptor outer segments. Our data indicate a disparity in aquaporin distribution in retinas of various animals, especially for AQP5 and 11. PMID:27438827

  6. Species-specific wiring for direction selectivity in the mammalian retina.

    PubMed

    Ding, Huayu; Smith, Robert G; Poleg-Polsky, Alon; Diamond, Jeffrey S; Briggman, Kevin L

    2016-07-01

    Directionally tuned signalling in starburst amacrine cell (SAC) dendrites lies at the heart of the circuit that detects the direction of moving stimuli in the mammalian retina. The relative contributions of intrinsic cellular properties and network connectivity to SAC direction selectivity remain unclear. Here we present a detailed connectomic reconstruction of SAC circuitry in mouse retina and describe two previously unknown features of synapse distributions along SAC dendrites: input and output synapses are segregated, with inputs restricted to proximal dendrites; and the distribution of inhibitory inputs is fundamentally different from that observed in rabbit retina. An anatomically constrained SAC network model suggests that SAC–SAC wiring differences between mouse and rabbit retina underlie distinct contributions of synaptic inhibition to velocity and contrast tuning and receptive field structure. In particular, the model indicates that mouse connectivity enables SACs to encode lower linear velocities that account for smaller eye diameter, thereby conserving angular velocity tuning. These predictions are confirmed with calcium imaging of mouse SAC dendrites responding to directional stimuli. PMID:27350241

  7. Imaging the primate retina using polarization-sensitve optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Marsack, Jason D.; Ducros, Mathieu G.; Parekh, Sapun H.; Thomsen, Sharon L.; Rylander, Henry G., III; Milner, Thomas E.

    2001-06-01

    We report results of a study using polarization sensitive optical coherence tomography (PSOCT) to measure physical properties of the retina and to create images of retinal microstructure. Our instrument incorporates a mode-locked Ti:Al2O3 laser and achromatic polarization optics to record high resolution images. High-resolution B scans (two-dimensional images) of the in-vivo rhesus monkey retina have been recorded in the optic disk, peripapillary area and macula. Images of the peripapillary area allow measurement of the retinal nerve fiber layer (RNFL) thickness and calculation of the Stokes parameters of light back-scattered from the retina. Results of our study indicate: 1) PSOCT may be utilized to measure RNFL thickness; 2) PSOCT may be used to measure areas of birefringent tissue in the retina; and 3) selection of a scan pattern surrounding the optic nerve should account for the relatively large radial RNFL thickness gradient. Moreover, since glaucoma manifests in a destruction of the RNFL, PSOCT may be useful as a screening and diagnostic modality.

  8. Synthesis and secretion of interstitial retinol-binding protein by the human retina

    SciTech Connect

    Hollyfield, J.G.; Fliesler, S.J.; Rayborn, M.E.; Fong, S.L.; Landers, R.A.; Bridges, C.D.

    1985-01-01

    Interstitial retinol-binding protein (IRBP) is a soluble glycoprotein present between the retina and pigmented epithelium, which may function to shuttle vitamin A derivatives between these tissues. While previous studies have shown that the retina is solely responsible for IRBP synthesis, the specific retinal cell(s) in which this occurs has not been established. Since the carbohydrate moiety of IRBP contains fucose, the authors have analyzed the sites of incorporation of /sup 3/H-fucose in the human retina in vitro, using autoradiography. Following a 30-min pulse incubation, all retinal layers exhibited incorporation of label; however, the rod photoreceptor inner segments contained one- to two-fold more radioactivity than was present in any other retinal compartment. In autoradiographs of retinas recovered following a 4 hr chase incubation, all retinal layers retained similar levels of radioactivity with the exception of the rod photoreceptors, cone photoreceptors and cells in the inner nuclear layer, which lost 75, 11, and 14 percent, respectively of the radioactivity present immediately following the 30-min pulse. Proteins present in the chase incubation medium were analyzed by polyacrylamide gel electrophoresis and fluorography. The principal labeled component in the chase medium was identified as IRBP by immunoprecipitation with antibovine-IRBP immunoglobulins.

  9. The Wellcome Prize Lecture. Visual signals in the retina: from photons to synapses.

    PubMed

    Lagnado, L

    2000-01-01

    The ability to see the world around us is an immediate and striking example of the abilities of the nervous system, and perhaps for this reason, vision is one of the most intensively studied aspects of brain function (Hubel, 1995). This paper examines some of the earliest steps in vision occurring in the retina (Dowling, 1987; Rodieck, 1998). PMID:10662887

  10. Celsr3 is required for normal development of GABA circuits in the inner retina.

    PubMed

    Lewis, Alaron; Wilson, Neil; Stearns, George; Johnson, Nicolas; Nelson, Ralph; Brockerhoff, Susan E

    2011-08-01

    The identity of the specific molecules required for the process of retinal circuitry formation is largely unknown. Here we report a newly identified zebrafish mutant in which the absence of the atypical cadherin, Celsr3, leads to a specific defect in the development of GABAergic signaling in the inner retina. This mutant lacks an optokinetic response (OKR), the ability to visually track rotating illuminated stripes, and develops a super-normal b-wave in the electroretinogram (ERG). We find that celsr3 mRNA is abundant in the amacrine and ganglion cells of the retina, however its loss does not affect synaptic lamination within the inner plexiform layer (IPL) or amacrine cell number. We localize the ERG defect pharmacologically to a late-stage disruption in GABAergic modulation of ON-bipolar cell pathway and find that the DNQX-sensitive fast b1 component of the ERG is specifically affected in this mutant. Consistently, we find an increase in GABA receptors on mutant ON-bipolar terminals, providing a direct link between the observed physiological changes and alterations in GABA signaling components. Finally, using blastula transplantation, we show that the lack of an OKR is due, at least partially, to Celsr3-mediated defects within the brain. These findings support the previously postulated inner retina origin for the b1 component and reveal a new role for Celsr3 in the normal development of ON visual pathway circuitry in the inner retina. PMID:21852962

  11. In vivo imaging of raptor retina with ultra high resolution spectral domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ruggeri, Marco; Major, James C., Jr.; McKeown, Craig; Wehbe, Hassan; Jiao, Shuliang; Puliafito, Carmen A.

    2008-02-01

    Among birds, raptors are well known for their exceptional eyesight, which is partly due to the unique structure of their retina. Because the raptor retina is the most advanced of any animal species, in vivo examination of its structure would be remarkable. Furthermore, a noticeable percentage of traumatic ocular injuries are identified in birds of prey presented to rehabilitation facilities. Injuries affecting the posterior segment have been considered as a major impact on raptor vision. Hence, in vivo examination of the structure of the posterior segment of the raptors would be helpful for the diagnosis of traumatized birds. The purpose of this study is to demonstrate the application of ultrahigh-resolution Spectral Domain Optical Coherence Tomography (SD-OCT) for non contact in vivo imaging of the retina of birds of prey, which to the best of our knowledge has never been attempted. For the first time we present high quality OCT images of the retina of two species of bird of prey, one diurnal hawk and one nocturnal owl.

  12. Effects of moderate-intensity light on vitamin A-deficient rat retinas

    SciTech Connect

    Carter-Dawson, L.; Kuwabara, T.; Bieri, J.G.

    1981-05-01

    The effects of moderate-intensity light (150 to 200 ft-cd) on retinal structure were compared between retinol-adequate and retinol-deficient rats after 1 to 6 days of light exposure during the 12 hr light phase of the cycle. Both damage to the outer segments and loss of photoreceptor cells were accelerated in retinol-adequate rats. Outer segments in retinas of retinol-adequate rats showed an abnormal staining pattern and disruption of disc structure in the distal portion about 2 days before those of retinol-deficient rats. After 4 days of exposure 24% of the photoreceptor cells had degenerated in the retinol-adequate retinas, but only 6% in the retinol-deficient retinas. By 6 days 65% and 41% of the photoreceptors had degenerated in the retinol-adequate and retinol-deficient retinas, respectively. Thus light exposure induced more rapid degeneration of photoreceptor cells in rats receiving adequate retinol than in those deficient in this vitamin.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Adaptive Colour Contrast Coding in the Salamander Retina Efficiently Matches Natural Scene Statistics

    PubMed Central

    Vasserman, Genadiy; Schneidman, Elad; Segev, Ronen

    2013-01-01

    The visual system continually adjusts its sensitivity to the statistical properties of the environment through an adaptation process that starts in the retina. Colour perception and processing is commonly thought to occur mainly in high visual areas, and indeed most evidence for chromatic colour contrast adaptation comes from cortical studies. We show that colour contrast adaptation starts in the retina where ganglion cells adjust their responses to the spectral properties of the environment. We demonstrate that the ganglion cells match their responses to red-blue stimulus combinations according to the relative contrast of each of the input channels by rotating their functional response properties in colour space. Using measurements of the chromatic statistics of natural environments, we show that the retina balances inputs from the two (red and blue) stimulated colour channels, as would be expected from theoretical optimal behaviour. Our results suggest that colour is encoded in the retina based on the efficient processing of spectral information that matches spectral combinations in natural scenes on the colour processing level. PMID:24205373

  15. Transplantation of cultured rabbit retinal epithelium to rabbit retina using a closed-eye method.

    PubMed

    Lopez, R; Gouras, P; Brittis, M; Kjeldbye, H

    1987-07-01

    We have developed a closed-eye technique for transplanting cultured rabbit retinal epithelial cells to Bruch's membrane of the rabbit. A glass micropipette containing a suspension of 3H-thymidine-labeled, cultured retinal pigment epithelial (RPE) cells is inserted through a pars plana incision and positioned adjacent to the neural retina. A jet stream from the pipette is used to make a small retinal hole and bleb detachment. Patches of host retinal epithelium lift off with the neural retina, creating areas of bare Bruch's membrane. The cell suspension is injected into the subretinal space, and labeled cells can be seen attached to Bruch's membrane as early as 1 hr later. The neural retina spontaneously reattaches within 24 to 48 hr, bringing photoreceptor outer segments in direct contact with the transplanted cells. Phagocytosis of outer segment material by transplanted cells can be seen as early as 24 hr after surgery. This closed-eye technique offers an advantage over the open-sky method used previously in that it allows for reattachment of the neural retina and at least a partial return of function in the transplanted retinal epithelium. PMID:3596991

  16. Features of Cutaneous Malignant Melanoma Metastatic to the Retina and Vitreous

    PubMed Central

    Breazzano, Mark P.; Barker-Griffith, Ann E.

    2015-01-01

    Background/Aims To report a case of cutaneous malignant melanoma with cerebral metastasis found to have vitreoretinal metastasis upon referral for neovascular glaucoma. Methods The clinical history and ocular examination findings, including histologic, cytologic, genetic, and immunohistochemical features of the vitreoretinal metastatic tumor, were reviewed. Additionally, the histologic and immunohistochemical features of the primary skin tumor and brain metastasis were also assessed. Results A 62-year-old woman with cutaneous malignant melanoma metastatic to the right frontal lobe (BRAF V600E negative) was evaluated for blurred vision in the right eye. Neovascular glaucoma, iritis, and posterior synechiae with no view of the retina or vitreous were evident on examination. Vitreoretinal biopsy and enucleation specimen both showed widespread neoplastic involvement of the retina and residual vitreous strands after vitrectomy. Choroid, trabeculum, and other intraocular structures were devoid of tumor burden. Diagnosis of cutaneous malignant melanoma metastatic to the retina and vitreous was confirmed, and the patient expired shortly thereafter. Conclusion Cutaneous malignant melanoma metastatic to the eye has a relatively greater preference for the retina and frequently presents with uveitis and glaucoma. Neovascular glaucoma in these cases may likely be attributable to unusually increased vascular endothelial growth factor production by the intraocular melanoma tumor cells. PMID:27172390

  17. Spatiotemporal Pattern of Doublecortin Expression in the Retina of the Sea Lamprey

    PubMed Central

    Fernández-López, Blanca; Romaus-Sanjurjo, Daniel; Senra-Martínez, Pablo; Anadón, Ramón; Barreiro-Iglesias, Antón; Rodicio, María Celina

    2016-01-01

    Despite the importance of doublecortin (DCX) for the development of the nervous system, its expression in the retina of most vertebrates is still unknown. The key phylogenetic position of lampreys, together with their complex life cycle, with a long blind larval stage and an active predator adult stage, makes them an interesting model to study retinal development. Here, we studied the spatiotemporal pattern of expression of DCX in the retina of the sea lamprey. In order to characterize the DCX expressing structures, the expression of acetylated α-tubulin (a neuronal marker) and cytokeratins (glial marker) was also analyzed. Tract-tracing methods were used to label ganglion cells. DCX immunoreactivity appeared initially in photoreceptors, ganglion cells and in fibers of the prolarval retina. In larvae smaller than 100 mm, DCX expression was observed in photoreceptors, in cells located in the inner nuclear and inner plexiform layers (IPLs) and in fibers coursing in the nuclear and IPLs, and in the optic nerve (ON). In retinas of premetamorphic and metamorphic larvae, DCX immunoreactivity was also observed in radially oriented cells and fibers and in a layer of cells located in the outer part of the inner neuroblastic layer (INbL) of the lateral retina. Photoreceptors and fibers ending in the outer limitans membrane (OLM) showed DCX expression in adults. Some retinal pigment epithelium cells were also DCX immunoreactive. Immunofluorescence for α-tubulin in premetamorphic larvae showed coexpression in most of the DCX immunoreactive structures. No cells/fibers were found showing DCX and cytokeratins colocalization. The perikaryon of mature ganglion cells is DCX negative. The expression of DCX in sea lamprey retinas suggests that it could play roles in the migration of cells that differentiate in the metamorphosis, in the establishment of connections of ganglion cells and in the development of photoreceptors. Our results also suggest that the radial glia and retinal

  18. Expression of Quaking RNA-Binding Protein in the Adult and Developing Mouse Retina

    PubMed Central

    Aono, Kentaro; Kawashima, Togo; Inoue, Kiyoshi; Ku, Li; Feng, Yue; Koike, Chieko

    2016-01-01

    Quaking (QKI), which belongs to the STAR family of KH domain-containing RNA-binding proteins, functions in pre-mRNA splicing, microRNA regulation, and formation of circular RNA. QKI plays critical roles in myelinogenesis in the central and peripheral nervous systems and has been implicated neuron-glia fate decision in the brain; however, neither the expression nor function of QKI in the neural retina is known. Here we report the expression of QKI RNA-binding protein in the developing and mature mouse retina. QKI was strongly expressed by Müller glial cells in both the developing and adult retina. Intriguingly, during development, QKI was expressed in early differentiating neurons, such as the horizontal and amacrine cells, and subsequently in later differentiating bipolar cells, but not in photoreceptors. Neuronal expression was uniformly weak in the adult. Among QKI isoforms (5, 6, and 7), QKI-5 was the predominantly expressed isoform in the adult retina. To study the function of QKI in the mouse retina, we examined quakingviable(qkv) mice, which have a dysmyelination phenotype that results from deficiency of QKI expression and reduced numbers of mature oligodendrocytes. In homozygous qkv mutant mice (qkv/qkv), the optic nerve expression levels of QKI-6 and 7, but not QKI-5 were reduced. In the retina of the mutant homozygote, QKI-5 levels were unchanged, and QKI-6 and 7 levels, already low, were also unaffected. We conclude that QKI is expressed in developing and adult Müller glia. QKI is additionally expressed in progenitors and in differentiating neurons during retinal development, but expression weakened or diminished during maturation. Among QKI isoforms, we found that QKI-5 predominated in the adult mouse retina. Since Müller glial cells are thought to share properties with retinal progenitor cells, our data suggest that QKI may contribute to maintaining retinal progenitors prior to differentiation into neurons. On the other hand, the expression of QKI in

  19. Spatiotemporal Pattern of Doublecortin Expression in the Retina of the Sea Lamprey.

    PubMed

    Fernández-López, Blanca; Romaus-Sanjurjo, Daniel; Senra-Martínez, Pablo; Anadón, Ramón; Barreiro-Iglesias, Antón; Rodicio, María Celina

    2016-01-01

    Despite the importance of doublecortin (DCX) for the development of the nervous system, its expression in the retina of most vertebrates is still unknown. The key phylogenetic position of lampreys, together with their complex life cycle, with a long blind larval stage and an active predator adult stage, makes them an interesting model to study retinal development. Here, we studied the spatiotemporal pattern of expression of DCX in the retina of the sea lamprey. In order to characterize the DCX expressing structures, the expression of acetylated α-tubulin (a neuronal marker) and cytokeratins (glial marker) was also analyzed. Tract-tracing methods were used to label ganglion cells. DCX immunoreactivity appeared initially in photoreceptors, ganglion cells and in fibers of the prolarval retina. In larvae smaller than 100 mm, DCX expression was observed in photoreceptors, in cells located in the inner nuclear and inner plexiform layers (IPLs) and in fibers coursing in the nuclear and IPLs, and in the optic nerve (ON). In retinas of premetamorphic and metamorphic larvae, DCX immunoreactivity was also observed in radially oriented cells and fibers and in a layer of cells located in the outer part of the inner neuroblastic layer (INbL) of the lateral retina. Photoreceptors and fibers ending in the outer limitans membrane (OLM) showed DCX expression in adults. Some retinal pigment epithelium cells were also DCX immunoreactive. Immunofluorescence for α-tubulin in premetamorphic larvae showed coexpression in most of the DCX immunoreactive structures. No cells/fibers were found showing DCX and cytokeratins colocalization. The perikaryon of mature ganglion cells is DCX negative. The expression of DCX in sea lamprey retinas suggests that it could play roles in the migration of cells that differentiate in the metamorphosis, in the establishment of connections of ganglion cells and in the development of photoreceptors. Our results also suggest that the radial glia and retinal

  20. Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina

    PubMed Central

    Lahouaoui, Hasna; Coutanson, Christine; Cooper, Howard M.; Bennis, Mohamed

    2016-01-01

    Purpose Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock. Methods To quantify circadian expression of clock and clock-controlled genes, retinas and suprachiasmatic nucleus (SCN) from the same animals were collected every 4 h in circadian conditions, 12 weeks post-diabetes. Induction of Per1, Per2, and c-fos mRNAs was quantified in the retina after the administration of a pulse of monochromatic light (480 nm, 1.17×1014 photons/cm2/s, 15 min) at circadian time 16. Gene expression was assessed with real-time reverse transcription PCR (RT–PCR). Pooled retinas from the control and STZ-diabetic mice were collected 2 h after light ON and light OFF (Zeitgeber time (ZT)2 and ZT14), and DA and its metabolite were analyzed with high-performance liquid chromatography (HPLC). Results We found variable effects of diabetes on the expression of clock genes in the retina and only slight differences in phase and/or amplitude in the SCN. c-fos and Per1 induction by a 480 nm light pulse was abolished in diabetic animals at 12 weeks post-induction of diabetes in comparison with the control mice, suggesting a deficit in light-induced neuronal activation of the retinal clock. Finally, we quantified a 56% reduction in the total number of tyrosine hydroxylase (TH) immunopositive cells, associated with a decrease in DA levels during the subjective day (ZT2

  1. Plasmalemmal and Vesicular γ-Aminobutyric Acid Transporter Expression in the Developing Mouse Retina

    PubMed Central

    GUO, CHENYING; STELLA, SALVATORE L.; HIRANO, ARLENE A.; BRECHA, NICHOLAS C.

    2009-01-01

    Plasmalemmal and vesicular γ-aminobutyric acid (GABA) transporters influence neurotransmission by regulating high-affinity GABA uptake and GABA release into the synaptic cleft and extracellular space. Postnatal expression of the plasmalemmal GABA transporter-1 (GAT-1), GAT-3, and the vesicular GABA/glycine transporter (VGAT) were evaluated in the developing mouse retina by using immunohistochemistry with affinity-purified antibodies. Weak transporter immunoreactivity was observed in the inner retina at postnatal day 0 (P0). GAT-1 immunostaining at P0 and at older ages was in amacrine and displaced amacrine cells in the inner nuclear layer (INL) and ganglion cell layer (GCL), respectively, and in their processes in the inner plexiform layer (IPL). At P10, weak GAT-1 immunostaining was in Müller cell processes. GAT-3 immunostaining at P0 and older ages was in amacrine cells and their processes, as well as in Müller cells and their processes that extended radially across the retina. At P10, Müller cell somata were observed in the middle of the INL. VGAT immunostaining was present at P0 and older ages in amacrine cells in the INL as well as processes in the IPL. At P5, weak VGAT immunostaining was also observed in horizontal cell somata and processes. By P15, the GAT and VGAT immunostaining patterns appear similar to the adult immunostaining patterns; they reached adult levels by about P20. These findings demonstrate that GABA uptake and release are initially established in the inner retina during the first postnatal week and that these systems subsequently mature in the outer retina during the second postnatal week. PMID:18975268

  2. Alzheimer’s Disease-Related Protein Expression in the Retina of Octodon degus

    PubMed Central

    Du, Lucia Y.; Chang, Lily Y-L.; Ardiles, Alvaro O.; Tapia-Rojas, Cheril; Araya, Joaquin; Inestrosa, Nibaldo C.

    2015-01-01

    New studies show that the retina also undergoes pathological changes during the development of Alzheimer’s disease (AD). While transgenic mouse models used in these previous studies have offered insight into this phenomenon, they do not model human sporadic AD, which is the most common form. Recently, the Octodon degus has been established as a sporadic model of AD. Degus display age-related cognitive impairment associated with Aβ aggregates and phosphorylated tau in the brain. Our aim for this study was to examine the expression of AD-related proteins in young, adult and old degus retina using enzyme-linked or fluorescence immunohistochemistry and to quantify the expression using slot blot and western blot assays. Aβ4G8 and Aβ6E10 detected Aβ peptides in some of the young animals but the expression was higher in the adults. Aβ peptides were observed in the inner and outer segment of the photoreceptors, the nerve fiber layer (NFL) and ganglion cell layer (GCL). Expression was higher in the central retinal region than in the retinal periphery. Using an anti-oligomer antibody we detected Aβ oligomer expression in the young, adult and old retina. Immunohistochemical labeling showed small discrete labeling of oligomers in the GCL that did not resemble plaques. Congo red staining did not result in green birefringence in any of the animals analyzed except for one old (84 months) animal. We also investigated expression of tau and phosphorylated tau. Expression was seen at all ages studied and in adults it was more consistently observed in the NFL-GCL. Hyperphosphorylated tau detected with AT8 antibody was significantly higher in the adult retina and it was localized to the GCL. We confirm for the first time that Aβ peptides and phosphorylated tau are expressed in the retina of degus. This is consistent with the proposal that AD biomarkers are present in the eye. PMID:26267479

  3. Wavelength-Dependent Change of Retinal Nerve Fiber Layer Reflectance in Glaucomatous Retinas

    PubMed Central

    Huang, Xiang-Run; Zhou, Ye; Knighton, Robert W.; Kong, Wei; Feuer, William J.

    2012-01-01

    Purpose. Retinal nerve fiber layer (RNFL) reflectance is often used in optical methods for RNFL assessment in clinical diagnosis of glaucoma, yet little is known about the reflectance property of the RNFL under the development of glaucoma. This study measured the changes in RNFL reflectance spectra that occurred in retinal nerve fiber bundles with different degrees of glaucomatous damage. Methods. A rat model of glaucoma with laser photocoagulation of trabecular meshwork was used. Reflectance of the RNFL in an isolated retina was measured at wavelengths of 400–830 nm. Cytostructural distribution of the bundles measured optically was evaluated by confocal imaging of immunohistochemistry staining of cytoskeletal components, F-actin, microtubules, and neurofilaments. RNFL reflectance spectra were studied in bundles with normal-looking appearance, early F-actin distortion, and apparent damage of all cytoskeletal components. Changes of RNFL reflectance spectra were studied at different radii (0.22, 0.33, and 0.44 mm) from the optic nerve head (ONH). Results. Bundles in 30 control retinas and 41 glaucomatous retinas were examined. In normal retinas, reflectance spectra were similar along the same bundles. In glaucomatous retinas, reflectance spectra changed along bundles with the spectra becoming flatter as bundle areas approached the ONH. Conclusions. Elevation of intraocular pressure (IOP) causes nonuniform changes in RNFL reflectance across wavelengths. Changes of reflectance spectra occur early in bundles near the ONH and prior to apparent cytoskeletal distortion. Using the ratio of RNFL reflectance measured at different wavelengths can provide early and sensitive detection of glaucomatous damage. PMID:22836775

  4. Increased Oxidative and Nitrative Stress Accelerates Aging of the Retinal Vasculature in the Diabetic Retina

    PubMed Central

    Lamoke, Folami; Shaw, Sean; Yuan, Jianghe; Ananth, Sudha; Duncan, Michael; Martin, Pamela; Bartoli, Manuela

    2015-01-01

    Hyperglycemia-induced retinal oxidative and nitrative stress can accelerate vascular cell aging, which may lead to vascular dysfunction as seen in diabetes. There is no information on whether this may contribute to the progression of diabetic retinopathy (DR). In this study, we have assessed the occurrence of senescence-associated markers in retinas of streptozotocin-induced diabetic rats at 8 and 12 weeks of hyperglycemia as compared to normoglycemic aging (12 and 14 months) and adult (4.5 months) rat retinas. We have found that in the diabetic retinas there was an up-regulation of senescence-associated markers SA-β-Gal, p16INK4a and miR34a, which correlated with decreased expression of SIRT1, a target of miR34a. Expression of senescence-associated factors primarily found in retinal microvasculature of diabetic rats exceeded levels measured in adult and aging rat retinas. In aging rats, retinal expression of senescence associated-factors was mainly localized at the level of the retinal pigmented epithelium and only minimally in the retinal microvasculature. The expression of oxidative/nitrative stress markers such as 4-hydroxynonenal and nitrotyrosine was more pronounced in the retinal vasculature of diabetic rats as compared to normoglycemic aging and adult rat retinas. Treatments of STZ-rats with the anti-nitrating drug FeTPPS (10mg/Kg/day) significantly reduced the appearance of senescence markers in the retinal microvasculature. Our results demonstrate that hyperglycemia accelerates retinal microvascular cell aging whereas physiological aging affects primarily cells of the retinal pigmented epithelium. In conclusion, hyperglycemia-induced retinal vessel dysfunction and DR progression involve vascular cell senescence due to increased oxidative/nitrative stress. PMID:26466127

  5. Two-Photon Autofluorescence Imaging Reveals Cellular Structures Throughout the Retina of the Living Primate Eye

    PubMed Central

    Sharma, Robin; Williams, David R.; Palczewska, Grazyna; Palczewski, Krzysztof; Hunter, Jennifer J.

    2016-01-01

    Purpose Although extrinsic fluorophores can be introduced to label specific cell types in the retina, endogenous fluorophores, such as NAD(P)H, FAD, collagen, and others, are present in all retinal layers. These molecules are a potential source of optical contrast and can enable noninvasive visualization of all cellular layers. We used a two-photon fluorescence adaptive optics scanning light ophthalmoscope (TPF-AOSLO) to explore the native autofluorescence of various cell classes spanning several layers in the unlabeled retina of a living primate eye. Methods Three macaques were imaged on separate occasions using a custom TPF-AOSLO. Two-photon fluorescence was evoked by pulsed light at 730 and 920 nm excitation wavelengths, while fluorescence emission was collected in the visible range from several retinal layers and different locations. Backscattered light was recorded simultaneously in confocal modality and images were postprocessed to remove eye motion. Results All retinal layers yielded two-photon signals and the heterogeneous distribution of fluorophores provided optical contrast. Several structural features were observed, such as autofluorescence from vessel walls, Müller cell processes in the nerve fibers, mosaics of cells in the ganglion cell and other nuclear layers of the inner retina, as well as photoreceptor and RPE layers in the outer retina. Conclusions This in vivo survey of two-photon autofluorescence throughout the primate retina demonstrates a wider variety of structural detail in the living eye than is available through conventional imaging methods, and broadens the use of two-photon imaging of normal and diseased eyes. PMID:26903224

  6. Cerebral malaria in children: using the retina to study the brain

    PubMed Central

    Beare, Nicholas A. V.; Taylor, Terrie E.; Barrera, Valentina; White, Valerie A.; Hiscott, Paul; Molyneux, Malcolm E.; Dhillon, Baljean; Harding, Simon P.

    2014-01-01

    Cerebral malaria is a dangerous complication of Plasmodium falciparum infection, which takes a devastating toll on children in sub-Saharan Africa. Although autopsy studies have improved understanding of cerebral malaria pathology in fatal cases, information about in vivo neurovascular pathogenesis is scarce because brain tissue is inaccessible in life. Surrogate markers may provide insight into pathogenesis and thereby facilitate clinical studies with the ultimate aim of improving the treatment and prognosis of cerebral malaria. The retina is an attractive source of potential surrogate markers for paediatric cerebral malaria because, in this condition, the retina seems to sustain microvascular damage similar to that of the brain. In paediatric cerebral malaria a combination of retinal signs correlates, in fatal cases, with the severity of brain pathology, and has diagnostic and prognostic significance. Unlike the brain, the retina is accessible to high-resolution, non-invasive imaging. We aimed to determine the extent to which paediatric malarial retinopathy reflects cerebrovascular damage by reviewing the literature to compare retinal and cerebral manifestations of retinopathy-positive paediatric cerebral malaria. We then compared retina and brain in terms of anatomical and physiological features that could help to account for similarities and differences in vascular pathology. These comparisons address the question of whether it is biologically plausible to draw conclusions about unseen cerebral vascular pathogenesis from the visible retinal vasculature in retinopathy-positive paediatric cerebral malaria. Our work addresses an important cause of death and neurodisability in sub-Saharan Africa. We critically appraise evidence for associations between retina and brain neurovasculature in health and disease, and in the process we develop new hypotheses about why these vascular beds are susceptible to sequestration of parasitized erythrocytes. PMID:24578549

  7. Step-by-step instructions for retina recordings with perforated multi electrode arrays.

    PubMed

    Reinhard, Katja; Tikidji-Hamburyan, Alexandra; Seitter, Hartwig; Idrees, Saad; Mutter, Marion; Benkner, Boris; Münch, Thomas A

    2014-01-01

    Multi-electrode arrays are a state-of-the-art tool in electrophysiology, also in retina research. The output cells of the retina, the retinal ganglion cells, form a monolayer in many species and are well accessible due to their proximity to the inner retinal surface. This structure has allowed the use of multi-electrode arrays for high-throughput, parallel recordings of retinal responses to presented visual stimuli, and has led to significant new insights into retinal organization and function. However, using conventional arrays where electrodes are embedded into a glass or ceramic plate can be associated with three main problems: (1) low signal-to-noise ratio due to poor contact between electrodes and tissue, especially in the case of strongly curved retinas from small animals, e.g. rodents; (2) insufficient oxygen and nutrient supply to cells located on the bottom of the recording chamber; and (3) displacement of the tissue during recordings. Perforated multi-electrode arrays (pMEAs) have been found to alleviate all three issues in brain slice recordings. Over the last years, we have been using such perforated arrays to study light evoked activity in the retinas of various species including mouse, pig, and human. In this article, we provide detailed step-by-step instructions for the use of perforated MEAs to record visual responses from the retina, including spike recordings from retinal ganglion cells and in vitro electroretinograms (ERG). In addition, we provide in-depth technical and methodological troubleshooting information, and show example recordings of good quality as well as examples for the various problems which might be encountered. While our description is based on the specific equipment we use in our own lab, it may also prove useful when establishing retinal MEA recordings with other equipment. PMID:25165854

  8. Evolutionary loss of cone photoreception in balaenid whales reveals circuit stability in the mammalian retina.

    PubMed

    Schweikert, Lorian E; Fasick, Jeffry I; Grace, Michael S

    2016-10-01

    The classical understanding of mammalian vision is that it occurs through "duplex" retinae containing both rod and cone photoreceptors, the signals from which are processed through rod- and/or cone-specific signaling pathways. The recent discovery of rod monochromacy in some cetacean lineages provides a novel opportunity to investigate the effects of an evolutionary loss of cone photoreception on retinal organization. Sequence analysis of right whale (Eubalaena glacialis; family Balaenidae) cDNA derived from long-wavelength sensitive (LWS) cone opsin mRNA identified several mutations in the opsin coding sequence, suggesting the loss of cone cell function, but maintenance of non-photosensitive, cone opsin mRNA-expressing cells in the retina. Subsequently, we investigated the retina of the closely related bowhead whale (Balaena mysticetus; family Balaenidae) to determine how the loss of cone-mediated photoreception affects light signaling pathways in the retina. Anti-opsin immunofluorescence demonstrated the total loss of cone opsin expression in B. mysticetus, whereas light microscopy, transmission electron microscopy, and bipolar cell (protein kinase C-α [PKC-α] and recoverin) immunofluorescence revealed the maintenance of cone soma, putative cone pedicles, and both rod and cone bipolar cell types. These findings represent the first immunological and anatomical evidence of a naturally occurring rod-monochromatic mammalian retina, and suggest that despite the loss of cone-mediated photoreception, the associated cone signaling structures (i.e., cone synapses and cone bipolar cells) may be maintained for multichannel rod-based signaling in balaenid whales. J. Comp. Neurol. 524:2873-2885, 2016. © 2016 Wiley Periodicals, Inc. PMID:26972896

  9. Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress.

    PubMed

    Simón, María Victoria; Agnolazza, Daniela L; German, Olga Lorena; Garelli, Andrés; Politi, Luis E; Agbaga, Martin-Paul; Anderson, Robert E; Rotstein, Nora P

    2016-03-01

    Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here, we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat and hydrogen peroxide (H2 O2 ). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in retina photoreceptors, and its precursor, eicosapentaenoic acid (EPA) have multiple beneficial effects. Here, we show that retina neurons in vitro express the desaturase FADS2 and can synthesize DHA from EPA. Moreover, addition of EPA to these cultures protects photoreceptors from oxidative stress and promotes their differentiation through its metabolization to DHA. PMID:26662863

  10. Automatic Counting of Microglial Cells in Healthy and Glaucomatous Mouse Retinas

    PubMed Central

    Rojas, Blanca; Ramírez, Ana I.; de Hoz, Rosa; Salazar, Juan J.; Triviño, Alberto; Ramírez, José M.

    2015-01-01

    Proliferation of microglial cells has been considered a sign of glial activation and a hallmark of ongoing neurodegenerative diseases. Microglia activation is analyzed in animal models of different eye diseases. Numerous retinal samples are required for each of these studies to obtain relevant data of statistical significance. Because manual quantification of microglial cells is time consuming, the aim of this study was develop an algorithm for automatic identification of retinal microglia. Two groups of adult male Swiss mice were used: age-matched controls (naïve, n = 6) and mice subjected to unilateral laser-induced ocular hypertension (lasered; n = 9). In the latter group, both hypertensive eyes and contralateral untreated retinas were analyzed. Retinal whole mounts were immunostained with anti Iba-1 for detecting microglial cell populations. A new algorithm was developed in MATLAB for microglial quantification; it enabled the quantification of microglial cells in the inner and outer plexiform layers and evaluates the area of the retina occupied by Iba-1+ microglia in the nerve fiber-ganglion cell layer. The automatic method was applied to a set of 6,000 images. To validate the algorithm, mouse retinas were evaluated both manually and computationally; the program correctly assessed the number of cells (Pearson correlation R = 0.94 and R = 0.98 for the inner and outer plexiform layers respectively). Statistically significant differences in glial cell number were found between naïve, lasered eyes and contralateral eyes (P<0.05, naïve versus contralateral eyes; P<0.001, naïve versus lasered eyes and contralateral versus lasered eyes). The algorithm developed is a reliable and fast tool that can evaluate the number of microglial cells in naïve mouse retinas and in retinas exhibiting proliferation. The implementation of this new automatic method can enable faster quantification of microglial cells in retinal pathologies. PMID:26580208

  11. Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

    PubMed Central

    Widomska, Justyna; Zareba, Mariusz; Subczynski, Witold Karol

    2016-01-01

    Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene) and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin). Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases. PMID:27030822

  12. Effects of ascorbic acid on UV light-mediated photoreceptor damage in isolated rat retina

    PubMed Central

    Tokuda, Kazuhiro; Zorumski, Charles F.; Izumi, Yukitoshi

    2007-01-01

    Concerns have been raised about whether operating microscopes and endoillumination used during ophthalmic surgeries contribute to retinal damage. Despite the recognition that ascorbic acid (vitamin C) helps to protect the eye from light and the abundance of vitamin C in the retina, artificial aqueous humors used during surgery only contain the antioxidant glutathione. To test whether inclusion of antioxidants other than glutathione in surgical solutions might help to preserve retinal integrity, we studied the effects of vitamin C on acute toxicity in isolated rat retinas. Male Sprague-Dawley rats (PND 30 ± 2) were sacrificed for retinal isolation. In the presence or absence of vitamin C (1 or 3 mM), retinas were exposed to 302 nm ultraviolet B (UVB) light for 1 hour and were incubated for a total of 5 hours at 30°C. Retinal damage was assessed by morphological examination and biochemical assay measuring the amount of lactate dehydrogenase (LDH) released from injured cells. In control retinas, LDH release was significantly increased after UVB exposure. The presence of 1 mM vitamin C in the incubation media significantly reduced LDH release during the post-incubation period following UV exposure. No difference was found between 1 mM and 3 mM vitamin C. Microscopic examination revealed that disorganization in the outer nuclear layer after UVB exposure was markedly attenuated by administration of 1 mM vitamin C. One mM vitamin C, a concentration found in the anterior chamber in humans, but not glutathione, prevented phototoxic injury following UV exposure. Although vitamin C itself cannot be used in intraocular irrigating solutions because of adverse interactions with iron released during bleeding, inclusion of antioxidants equivalent to vitamin C should be considered to help protect the retina from intraoperative light toxicity. PMID:17222826

  13. Vesicular expression and release of ATP from dopaminergic neurons of the mouse retina and midbrain

    PubMed Central

    Ho, Tracy; Jobling, Andrew I.; Greferath, Ursula; Chuang, Trinette; Ramesh, Archana; Fletcher, Erica L.; Vessey, Kirstan A.

    2015-01-01

    Vesicular nucleotide transporter (VNUT) is required for active accumulation of adenosine tri-phosphate (ATP) into vesicles for purinergic neurotransmission, however, the cell types that express VNUT in the central nervous system remain unknown. This study characterized VNUT expression within the mammalian retina and brain and assessed a possible functional role in purinergic signaling. Two native isoforms of VNUT were detected in mouse retina and brain based on RNA transcript and protein analysis. Using immunohistochemistry, VNUT was found to co-localize with tyrosine hydroxylase (TH) positive, dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, however, VNUT expression in extranigral non-DA neurons was also observed. In the retina, VNUT labeling was found to co-localize solely with TH-positive DA-cells. In the outer retina, VNUT-positive interplexiform cell processes were in close contact with horizontal cells and cone photoreceptor terminals, which are known to express P2 purinergic-receptors. In order to assess function, dissociated retinal neurons were loaded with fluorescent ATP markers (Quinacrine or Mant-ATP) and the DA marker FFN102, co-labeled with a VNUT antibody and imaged in real time. Fluorescent ATP markers and FFN102 puncta were found to co-localize in VNUT positive neurons and upon stimulation with high potassium, ATP marker fluorescence at the cell membrane was reduced. This response was blocked in the presence of cadmium. These data suggest DA neurons co-release ATP via calcium dependent exocytosis and in the retina this may modulate the visual response by activating purine receptors on closely associated neurons. PMID:26500494

  14. Vesicular expression and release of ATP from dopaminergic neurons of the mouse retina and midbrain.

    PubMed

    Ho, Tracy; Jobling, Andrew I; Greferath, Ursula; Chuang, Trinette; Ramesh, Archana; Fletcher, Erica L; Vessey, Kirstan A

    2015-01-01

    Vesicular nucleotide transporter (VNUT) is required for active accumulation of adenosine tri-phosphate (ATP) into vesicles for purinergic neurotransmission, however, the cell types that express VNUT in the central nervous system remain unknown. This study characterized VNUT expression within the mammalian retina and brain and assessed a possible functional role in purinergic signaling. Two native isoforms of VNUT were detected in mouse retina and brain based on RNA transcript and protein analysis. Using immunohistochemistry, VNUT was found to co-localize with tyrosine hydroxylase (TH) positive, dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, however, VNUT expression in extranigral non-DA neurons was also observed. In the retina, VNUT labeling was found to co-localize solely with TH-positive DA-cells. In the outer retina, VNUT-positive interplexiform cell processes were in close contact with horizontal cells and cone photoreceptor terminals, which are known to express P2 purinergic-receptors. In order to assess function, dissociated retinal neurons were loaded with fluorescent ATP markers (Quinacrine or Mant-ATP) and the DA marker FFN102, co-labeled with a VNUT antibody and imaged in real time. Fluorescent ATP markers and FFN102 puncta were found to co-localize in VNUT positive neurons and upon stimulation with high potassium, ATP marker fluorescence at the cell membrane was reduced. This response was blocked in the presence of cadmium. These data suggest DA neurons co-release ATP via calcium dependent exocytosis and in the retina this may modulate the visual response by activating purine receptors on closely associated neurons. PMID:26500494

  15. Circadian organization of the mammalian retina: from gene regulation to physiology and diseases.

    PubMed

    McMahon, Douglas G; Iuvone, P Michael; Tosini, Gianluca

    2014-03-01

    The retinal circadian system represents a unique structure. It contains a complete circadian system and thus the retina represents an ideal model to study fundamental questions of how neural circadian systems are organized and what signaling pathways are used to maintain synchrony of the different structures in the system. In addition, several studies have shown that multiple sites within the retina are capable of generating circadian oscillations. The strength of circadian clock gene expression and the emphasis of rhythmic expression are divergent across vertebrate retinas, with photoreceptors as the primary locus of rhythm generation in amphibians, while in mammals clock activity is most robust in the inner nuclear layer. Melatonin and dopamine serve as signaling molecules to entrain circadian rhythms in the retina and also in other ocular structures. Recent studies have also suggested GABA as an important component of the system that regulates retinal circadian rhythms. These transmitter-driven influences on clock molecules apparently reinforce the autonomous transcription-translation cycling of clock genes. The molecular organization of the retinal clock is similar to what has been reported for the SCN although inter-neural communication among retinal neurons that form the circadian network is apparently weaker than those present in the SCN, and it is more sensitive to genetic disruption than the central brain clock. The melatonin-dopamine system is the signaling pathway that allows the retinal circadian clock to reconfigure retinal circuits to enhance light-adapted cone-mediated visual function during the day and dark-adapted rod-mediated visual signaling at night. Additionally, the retinal circadian clock also controls circadian rhythms in disk shedding and phagocytosis, and possibly intraocular pressure. Emerging experimental data also indicate that circadian clock is also implicated in the pathogenesis of eye disease and compelling experimental data

  16. Immunocytochemical description of five bipolar cell types of the mouse retina.

    PubMed

    Haverkamp, Silke; Ghosh, Krishna K; Hirano, Arlene A; Wässle, Heinz

    2003-01-20

    With the ever-growing number of transgenic mice being used in vision research, a precise knowledge of the cellular organization of the mouse retina is required. As with the cat, rabbit, rat, and primate retinae, as many as 10 cone bipolar types and one rod bipolar type can be expected to exist in the mouse retina; however, they still have to be defined. In the current study, several immunocytochemical markers were applied to sections of mouse retina, and the labeling of bipolar cells was studied using confocal microscopy and electron microscopy. By using antibodies against the neurokinin-3 receptor NK3R; the plasma membrane calcium ATPase1 (PMCA1); and the calcium (Ca)-binding proteins CaB1, CaB5, caldendrin, and recoverin, three different OFF-cone bipolar cells could be identified. One type of ON-cone bipolar cell was identified through its immunoreactivity for CaB5 and PMCA1. Rod bipolar cells, comparable in morphology to those of other mammalian retinae, expressed protein kinase Calpha and CaB5. It was also shown that putative OFF-cone bipolar cells receive light signals through flat contacts at the cone pedicle base, whereas ON-cone bipolar signaling involves invaginating contacts. The distribution of the kainate receptor subunit GluR5 was studied by confocal and electron microscopy. GluR5 was expressed at flat bipolar cell contacts; however, it appears to be involved with only certain types of OFF-cone bipolar cells. This suggests that different bipolar cell types receive their light signals through different sets of glutamate receptors. PMID:12508320

  17. Dysregulation of neuroendocrine crossroads: depression, circadian rhythms and the retina--a hypothesis.

    PubMed

    Steiner, M; Werstiuk, E S; Seggie, J

    1987-01-01

    The pathophysiology of depression and the mechanism of action of lithium and other antidepressant drugs involve alterations in circadian rhythms. These include changes in both the intrinsic rhythm of circadian oscillators and in the sensitivity of the retina to LIGHT. The retina in humans is the only photoreceptor for circadian entrainment. The retinal-hypothalamic-pineal axis is the essential pathway for neuronal entrainment of rhythms which use light as a phase cue. A common substance throughout this axis in many species is MELATONIN. Retinal melatonin has been implicated in regulation of the sensitivity of the retina to light. The hypothalamus, at THE NEUROENDOCRINE CROSSROADS, has a central role in the integration of neurotransmitters and hormones in circadian rhythms. DYSREGULATION of the hypothalamic-pituitary-adrenal, as well as -gonadal, axes has been documented in depressed patients. Abnormalities in circulating melatonin have also been found in patients with affective disorders. It is speculated that the availability of melatonin along the retinal-hypothalamic-pineal axis may have important implications in the genesis of affective disorders. More specifically--is there a latent biochemical defect which causes a phase shift and change in circadian rhythms of melatonin and/or other neurotransmitters in the retina which then alters the sensitivity of the retina to light (for the visible spectrum) which in turn desynchronizes all other biological rhythms thus disrupting mental well-being? We suggest that variations of retinal photosensitivity in humans can be measured by using a visual testing system, and that depressed patients might show changes in photosensitivity which could be corrected when treated with lithium and/or antidepressants. It is our working hypothesis that the primary defect in depression may be a change in retinal function, and that behavioural and neuroendocrine concomitants of this disorder are secondary events. PMID:2888161

  18. Primary blast injury-induced lesions in the retina of adult rats

    PubMed Central

    2013-01-01

    Background The effect of primary blast exposure on the brain is widely reported but its effects on the eye remains unclear. Here, we aim to examine the effects of primary blast exposure on the retina. Methods Adult male Sprague–Dawley rats were exposed to primary blast high and low injury and sacrificed at 24 h, 72 h, and 2 weeks post injury. The retina was subjected to western analysis for vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4), glutamine synthethase (GS), inducible nitric oxide synthase (NOS), endothelial NOS, neuronal NOS and nestin expression; ELISA analysis for cytokines and chemokines; and immunofluorescence for glial fibrillary acidic protein (GFAP)/VEGF, GFAP/AQP4, GFAP/nestin, GS/AQP4, lectin/iNOS, and TUNEL. Results The retina showed a blast severity-dependent increase in VEGF, iNOS, eNOS, nNOS, and nestin expression with corresponding increases in inflammatory cytokines and chemokines. There was also increased AQP4 expression and retinal thickness after primary blast exposure that was severity-dependent. Finally, a significant increase in TUNEL+ and Caspase-3+ cells was observed. These changes were observed at 24 h post-injury and sustained up to 2 weeks post injury. Conclusions Primary blast resulted in severity-dependent pathological changes in the retina, manifested by the increased expression of a variety of proteins involved in inflammation, edema, and apoptosis. These changes were observed immediately after blast exposure and sustained up to 2 weeks suggesting acute and chronic injury mechanisms. These changes were most obvious in the astrocytes and Müller cells and suggest important roles for these cells in retina pathophysiology after blast. PMID:23819902

  19. Formación estelar en NGC 6357: viendo a través del polvo con Gemini

    NASA Astrophysics Data System (ADS)

    Bosch, G.; Morrell, N.; Barbá, R.

    Presentamos aquí los primeros resultados de fotometría JHKs obtenidos con Flamingos I en el telescopio Gemini Sur. El mosaico comprendido por tres posiciones adyacentes tomadas a lo largo de varios semestres nos permite caracterizar la población estelar en la zona que presenta una interacción más importante entre las estrellas masivas y la nube molecular que les dió origen. Los diagramas color-magnitud nos permiten identificar numerosas fuentes con exceso infrarrojo, la mayoría de ellas imposible de detectarse en el rango óptico debido a la fuerte absorción del polvo presente en la región. Es altamente probable que la mayoría de estas fuentes con exceso sean protoestrellas, aunque es necesario realizar espectroscopía infrarroja de las mismas para confirmar su naturaleza.

  20. Using the Electroretinogram to Assess Function in the Rodent Retina and the Protective Effects of Remote Limb Ischemic Preconditioning.

    PubMed

    Brandli, Alice; Stone, Jonathan

    2015-01-01

    The ERG is the sum of all retinal activity. The ERG is usually recorded from the cornea, which acts as an antenna that collects and sums signals from the retina. The ERG is a sensitive measure of changes in retinal function that are pan-retinal, but is less effective for detecting damage confined to a small area of retina. In the present work we describe how to record the 'flash' ERG, which is the potential generated when the retina is exposed to a brief light flash. We describe methods of anaesthesia, mydriasis and corneal management during recording; how to keep the retina dark adapted; electrode materials and placement; the range and calibration of stimulus energy; recording parameters and the extraction of data. We also describe a method of inducing ischemia in one limb, and how to use the ERG to assess the effects of this remote-from-the-retina ischemia on retinal function after light damage. A two-flash protocol is described which allows isolation of the cone-driven component of the dark-adapted ERG, and thereby the separation of the rod and cone components. Because it can be recorded with techniques that are minimally invasive, the ERG has been widely used in studies of the physiology, pharmacology and toxicology of the retina. We describe one example of this usefulness, in which the ERG is used to assess the function of the light-damaged retina, with and without a neuroprotective intervention; preconditioning by remote ischemia. PMID:26131649

  1. Spectral-Domain Optical Coherence Tomography as a Noninvasive Method to Assess Damaged and Regenerating Adult Zebrafish Retinas

    PubMed Central

    Bailey, Travis J.; Davis, Darin H.; Vance, Joseph E.; Hyde, David R.

    2012-01-01

    Purpose. These experiments assessed the ability of spectral-domain optical coherence tomography (SD-OCT) to accurately represent the structural organization of the adult zebrafish retina and reveal the dynamic morphologic changes during either light-induced damage and regeneration of photoreceptors or ouabain-induced inner retinal damage. Methods. Retinas of control dark-adapted adult albino zebrafish were compared with retinas subjected to 24 hours of constant intense light and recovered for up to 8 weeks or ouabain-damaged retinas that recovered for up to 3 weeks. Images were captured and the measurements of retinal morphology were made by SD-OCT, and then compared with those obtained by histology of the same eyes. Results. Measurements between SD-OCT and histology were very similar for the undamaged, damaged, and regenerating retinas. Axial measurements of SD-OCT also revealed vitreal morphology that was not readily visualized by histology. Conclusions. SD-OCT accurately represented retinal lamination and photoreceptor loss and recovery during light-induced damage and subsequent regeneration. SD-OCT was less accurate at detecting the inner nuclear layer in ouabain-damaged retinas, but accurately detected the undamaged outer nuclear layer. Thus, SD-OCT provides a noninvasive and quantitative method to assess the morphology and the extent of damage and repair in the zebrafish retina. PMID:22499984

  2. Immuno-Histochemical Analysis of Rod and Cone Reaction to RPE65 Deficiency in the Inferior and Superior Canine Retina

    PubMed Central

    Klein, Daniela; Mendes-Madeira, Alexandra; Schlegel, Patrice; Rolling, Fabienne; Lorenz, Birgit; Haverkamp, Silke; Stieger, Knut

    2014-01-01

    Mutations in the RPE65 gene are associated with autosomal recessive early onset severe retinal dystrophy. Morphological and functional studies indicate early and dramatic loss of rod photoreceptors and early loss of S-cone function, while L and M cones remain initially functional. The Swedish Briard dog is a naturally occurring animal model for this disease. Detailed information about rod and cone reaction to RPE65 deficiency in this model with regard to their location within the retina remains limited. The aim of this study was to analyze morphological parameters of cone and rod viability in young adult RPE65 deficient dogs in different parts of the retina in order to shed light on local disparities in this disease. In retinae of affected dogs, sprouting of rod bipolar cell dendrites and horizontal cell processes was dramatically increased in the inferior peripheral part of affected retinae, while central inferior and both superior parts did not display significantly increased sprouting. This observation was correlated with photoreceptor cell layer thickness. Interestingly, while L/M cone opsin expression was uniformly reduced both in the superior and inferior part of the retina, S-cone opsin expression loss was less severe in the inferior part of the retina. In summary, in retinae of young adult RPE65 deficient dogs, the degree of rod bipolar and horizontal cell sprouting as well as of S-cone opsin expression depends on the location. As the human retinal pigment epithelium (RPE) is pigmented similar to the RPE in the inferior part of the canine retina, and the kinetics of photoreceptor degeneration in humans seems to be similar to what has been observed in the inferior peripheral retina in dogs, this area should be studied in future gene therapy experiments in this model. PMID:24466015

  3. Morphology of bipolar cells and their participation in spatial organization of the inner plexiform layer of jack mackerel retina.

    PubMed

    Podugolnikova, T A

    1985-01-01

    Morphology of bipolar cells in the jack mackerel retina [Trachurus mediterraneus ponticus (Aleev)] was investigated by the Golgi method. Eight types of bipolar cells are described. It is the first time that cells with an unbranched main dendrite are found in fish retina. It is shown that the inner plexiform layer of the jack mackerel retina contains regular lattices, located at 5 levels and conserted in a characteristic way with the cone mosaic. These lattices are formed by swellings of bipolar cell axons. It is shown that only bipolar cells with small dendritic aborizations (less than or equal to 14 micron dia) take part in this organization. PMID:3832608

  4. Relative permeability of retina and retinal pigment epithelium to the diffusion of tritiated water from vitreous to choroid

    SciTech Connect

    Orr, G.; Goodnight, R.; Lean, J.S.

    1986-11-01

    The movement of intravitreally injected tritiated water from the vitreous to the choroid was accelerated by the removal of intervening retina. Both rate of transfer and peak choroidal levels of the tracer were increased, but the proportion of the intravitreal dose recovered was unaltered. In contrast, the movement of tritiated water after diffuse damage to the retinal pigment epithelium by sodium iodate was similar to that of control eyes. The main resistance to the diffusion of this tracer from the vitreous to the choroid is the retina. The differential permeability of the retina and the retinal pigment epithelium may have a role in normal retinal adhesion.

  5. Expression and distribution of the class III ubiquitin-conjugating enzymes in the retina

    PubMed Central

    Mirza, Saima; Plafker, Kendra S.; Aston, Christopher

    2010-01-01

    Purpose Mounting evidence implicates chronic oxidative stress as a significant pathogenic factor in the development and progression of retinopathies, including age-related macular degeneration (AMD). The age-dependent toxic accumulation of oxidatively damaged proteins, lipids, and DNA in susceptible cells of the retina arises, at least in part, from a decreased capacity to eliminate these damaged biomolecules. The goal of this study was to determine the expression patterns and function of class III ubiquitin-conjugating enzymes (UbcM3, UBE2E2, and UbcM2) in the retina. These enzymes have been implicated in the ubiquitin-dependent degradation of oxidatively damaged and misfolded proteins. Methods Complementary western blotting and immunohistochemistry was performed with specific antibodies to determine the retinal cell expression pattern of each enzyme. Additional analyses using antibodies raised against UbcM2 were performed to determine the relative levels of the enzyme in lysates derived from various mouse organs as compared to the retina. An established light-damage model of oxidative stress-induced retinal degeneration was used to determine alterations in the susceptibility of mice harboring a single intact allele of UbcM2. Ubiquitin charging and auto-ubiquitylation assays were done to assess the catalytic state of UbcM2 following photo-oxidative stress. Results Expression of the class III ubiquitin-conjugating enzymes in the retina, from highest to lowest, is UbcM2>UbcM3>UBE2E2. In addition to being the most robustly expressed, UbcM2 is further distinguished by its expression in photoreceptors and retinal pigment epithelial cells. UbcM2 is expressed in most mouse tissues analyzed and is most abundant in the retina. Studies using a bright-light-damage model of acute oxidative stress in mice harboring a single disrupted allele of UbcM2 revealed that a 58% reduction in enzyme levels did not increase the susceptibility of photoreceptors to acute photo

  6. The active transport of fluorescein by the retinal vessels and the retina

    PubMed Central

    Cunha-Vaz, J. G.; Maurice, D. M.

    1967-01-01

    1. The movement of fluorescein across the retinal surface of the rabbit's eye was estimated by measuring the concentration gradient of the dye in the vitreous body. These measurements were made in vivo by means of a slit-lamp fluorophotometer, or were taken from frozen sections of enucleated eyes. 2. In the normal eye, fluorescein does not pass from the blood to the vitreous body across any part of the retina. When injected into the vitreous body it passes rapidly out across the entire retinal surface, even against a very large concentration gradient. 3. A variety of metabolic and competitive inhibitors, effective in blocking organic anion transport in the kidney and liver, tend to abolish this unidirectional movement of fluorescein across the retina. 4. The region occupied by the retinal vessels is more sensitive to inhibition than other areas of the retina. Occlusion of the vessels by diathermy prevents the exchange of fluorescein in this region. 5. It appears, then, that there is an active transport of organic anions out of the vitreous body, both by the retinal capillaries and by the retina itself. The latter system is probably located in the pigment epithelium and seems to be carried forward to the rear surface of the iris. 6. Since the walls of the retinal vessels of the rabbit are freely in contact with the vitreous body, the active transport must take place across the capillary endothelial cells themselves. These vessels have structural and permeability characteristics found only in the central nervous system and it is to be presumed that the anion transport system is shared by the capillaries of the brain. 7. The function of the transport in the retina may be to protect the nervous tissue from toxic materials by preventing their entry from the blood or by removing products of metabolism conjugated as organic anions. Alternatively, the mechanism may be concerned in maintaining the normal adhesion of the retina to the choroid, since retinal detachment was

  7. Highly Efficient Delivery of Adeno-Associated Viral Vectors to the Primate Retina.

    PubMed

    Boye, Shannon E; Alexander, John J; Witherspoon, C Douglas; Boye, Sanford L; Peterson, James J; Clark, Mark E; Sandefer, Kristen J; Girkin, Chris A; Hauswirth, William W; Gamlin, Paul D

    2016-08-01

    Adeno-associated virus (AAV) has emerged as the preferred vector for targeting gene expression to the retina. Subretinally injected AAV can efficiently transduce retinal pigment epithelium and photoreceptors in primate retina. Inner and middle primate retina can be transduced by intravitreally delivered AAV, but with low efficiency. This is due to dilution of vector, potential neutralization of capsid because it is not confined to the immune-privileged retinal compartment, and the presence of the inner limiting membrane (ILM), a barrier separating the vitreous from the neural retina. We here describe a novel "subILM" injection method that addresses all three issues. Specifically, vector is placed in a surgically induced, hydrodissected space between the ILM and neural retina. In an initial experiment, we injected viscoelastic (Healon(®)), a substance we confirmed was biocompatible with AAV, to create a subILM bleb and subsequently injected AAV2-GFP into the bleb after irrigation with basic salt solution. For later experiments, we used a Healon-AAV mixture to place single, subILM injections. In all cases, subILM delivery of AAV was well tolerated-no inflammation or gross structural changes were observed by ophthalmological examination or optical coherence tomography. In-life fluorescence imaging revealed profound transgene expression within the area of the subILM injection bleb that persisted for the study duration. Uniform and extensive transduction of retinal ganglion cells (RGCs) was achieved in the areas beneath the subILM bleb. Transduction of Müller glia, ON bipolar cells, and photoreceptors was also observed. Robust central labeling from green fluorescent protein-expressing RGCs confirmed their continued survival, and was observed in the lateral geniculate nucleus, the superior colliculus, and the pretectum. Our results confirm that the ILM is a major barrier to transduction by AAV in primate retina and that, when it is circumvented, the efficiency and

  8. Doublecortin is widely expressed in the developing and adult retina of sharks.

    PubMed

    Sánchez-Farías, Nuria; Candal, Eva

    2015-05-01

    Doublecortin (DCX) is a microtubule-associated protein that has been considered a marker for neuronal precursors and young migrating neurons during the development of the central nervous system and in adult neurogenic niches. The retina of fishes represents an accessible, continuously growing and highly structured (layered) part of the central nervous system and, therefore, offers an exceptional model to extend our knowledge on the possible role of DCX in promoting neurogenesis and migration to appropriate layers. We have analyzed the distribution of DCX in the embryonic and postembryonic retina of a small shark, the lesser spotted dogfish Scyliorhinus canicula, by means of immunohistochemistry. We investigated the relationship between DCX expression and the neurogenic state of DCX-labeled cells by exploring its co-localization with the proliferation marker PCNA (proliferating cell nuclear antigen) and the marker of neuronal differentiation HuC/D. Since radially migrating neurons use radial glial fibers as substrate, we explored the possible correlation between DCX expression and cell migration along radial glia by comparing its expression with that of the glial marker GFAP (glial fibrillary acidic protein). Additionally, we characterized DCX-expressing cells by double immunocytochemistry using antibodies against Calbindin (a marker for mature bipolar and horizontal cells in this species) and Pax6, which has been proposed as a regulator of cell proliferation, cell differentiation, and neuron diversification in the neural retina of sharks. Strong DCX immunoreactivity was observed in immature cells and cell processes, at a time when retinal cells were not yet organized into different laminae. DCX was also found in subsets of mature ganglion, amacrine, bipolar and horizontal cells long after they had exited the cell cycle, a pattern that was maintained in juveniles and adults. Our results on DCX expression in the retina are compatible with a role for DCX in cell

  9. Glio-vascular modifications caused by Aquaporin-4 deletion in the mouse retina.

    PubMed

    Nicchia, Grazia Paola; Pisani, Francesco; Simone, Laura; Cibelli, Antonio; Mola, Maria Grazia; Dal Monte, Massimo; Frigeri, Antonio; Bagnoli, Paola; Svelto, Maria

    2016-05-01

    Aquaporin-4 (AQP4) is the Central Nervous System water channel highly expressed at the perivascular glial domain. In the retina, two types of AQP4 expressing glial cells take part in the blood-retinal barrier (BRB), astrocytes and Müller cells. The aim of the present study is to investigate the effect of AQP4 deletion on the retinal vasculature by looking at typical pathological hallmark such as BRB dysfunction and gliotic condition. AQP4 dependent BRB properties were evaluated by measuring the number of extravasations in WT and AQP4 KO retinas by Evans blue injection assay. AQP4 deletion did not affect the retinal vasculature, as assessed by Isolectin B4 staining, but caused BRB impairment to the deep plexus capillaries while the superficial and intermediate capillaries were not compromised. To investigate for gliotic responses caused by AQP4 deletion, Müller cells and astrocytes were analysed by immunofluorescence and western blot, using the Müller cell marker Glutamine Synthetase (GS) and the astrocyte marker GFAP. While GS expression was not altered in AQP4 KO retinas, a strong GFAP upregulation was found at the level of AQP4 KO astrocytes at the superficial plexus and not at Müller cells at the intermediate and deep plexi. These data, together with the upregulation of inflammatory markers (TNF-α, IL-6, IL-1β and ICAM-1) in AQP4 KO retinas indicated AQP4 deletion as responsible for a gliotic phenotype. Interestingly, no GFAP altered expression was found in AQP4 siRNA treated astrocyte primary cultures. All together these results indicate that AQP4 deletion is directly responsible for BRB dysfunction and gliotic condition in the mouse retina. The selective activation of glial cells at the primary plexus suggests that different regulatory elements control the reaction of astrocytes and Müller cells. Finally, GFAP upregulation is strictly linked to gliovascular crosstalk, as it is absent in astrocytes in culture. This study is useful to understand the role

  10. Active synthesis of C24:5, n-3 fatty acid in retina.

    PubMed Central

    Rotstein, N P; Pennacchiotti, G L; Sprecher, H; Aveldaño, M I

    1996-01-01

    The formation of 14C-labelled long-chain and very-long-chain (n-3) pentaenoic and hexaenoic fatty acids was studied in bovine retina by following the metabolism of. [14C]-docosapentaenoate [C22:5, n-3 fatty acid (22:5 n-3)], [14C]-docosahexaenoate (22:6 n-3), and [14C]acetate. With similar amounts of 22:5 n-3 and 22:6 n-3 as substrates, the former was actively transformed into 24:5 n-3, whereas the latter was virtually unmodified. Labelled 24:5, 26:5, 24:6 and 22:6 were formed from [1-14C]22:5 n-3, showing that pentaenoic fatty acids including 24:5 n-3 can be elongated and desaturated within the retina. When retinal microsomes were incubated with [1-14C]22:5 n-3, 24:5 n-3 was the only fatty acid formed. In retinas incubated with [14C]acetate, 24:5 n-3 was the most highly labelled fatty acid among the polyenes synthesized, 24:6 n-3 being a minor product. Such selectivity in the elongation of two fatty acids identical in length, 22:5 n-3 and 22:6 n-3, despite the fact that 22:5 is a minor and 22:6 a major fatty acid constituent of retina, suggests that the active formation of 24:5 n-3 plays a key role in n-3 polyunsaturated fatty acid (PUFA) metabolism. This compound might give rise to even longer pentaenes via elongation, and to the major PUFAs of retina, 22:6 n-3, by 6-desaturation and chain shortening. Of all retinal lipids, a minor component, triacylglycerol (TG), incorporated the largest amounts of [14C]22:5 and 22:6. TG also concentrated most of the [14C]24:5 formed in retina, whether from [14C]22:5 n-3 or from [14C]acetate, suggesting an important role for this lipid in supporting PUFA metabolism and the synthesis of 22:6 n-3. PMID:8670163

  11. Pre-exposure to low-power diode laser irradiation promotes cytoprotection in the rat retina.

    PubMed

    Sun, Yue; Zhang, Shisheng; Liao, Huaping; Wang, Jing; Wang, Ling

    2015-01-01

    The aim of this study was to investigate whether pre-exposure to low-power laser irradiation can provoke an effect on cellular protection in the rat retina. The right eyes of 40 rats were exposed to a 3-mm diode laser beam for 1 min in different light intensities and different experimental sets: group A low power of 60 mW (34.27 J/cm(2) on the retina in consideration of the energy losses along the optical pathway) prior to high power of 80 mW (44.88 J/cm(2) on the retina in consideration of the energy losses along the optical pathway), group B high power, group C low power, group D (the left eyes from the counterpart of group A) and group E (untreated rat eyes) as controls. Morphological retinal change retinas were assessed using light microscopy and/or transmission electron microscopy. Heat shock protein (Hsp) 70 and cleaved caspase 3 protein expression were analyzed by immunohistochemical staining and Western blot. Cellular injury was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Hsp 70 expression in the inner plexiform layer and the outer plexiform layer in group A were 73.09 ± 6.49 and 78.03 ± 3.05%, respectively, which was significantly higher (P < 0.05) than those observed in group B (59.07 ± 1.40 and 32.25 ± 4.26%, respectively). The Hsp70/β-actin ratio was 0.49 ± 0.06 in group C, which was significantly higher (P < 0.05) than that of group B (0.27 ± 0.04). Cleaved caspase 3 expression in group C both was significantly lower than that observed in group B. TUNEL staining showed that positive cells in the outer nuclear layer and inner nuclear layer in group A were significantly lower than those of group B. Pre-exposure to a 60-mW (34.27 J/cm(2) on the retina) power laser irradiation stimulates a hyperexpression of Hsp70 together with a hypoexpression of cleaved caspase 3 in rat retina, which may suggest a cellular protective effect. PMID:25048854

  12. The elevation of intraocular pressure is associated with apoptosis and increased immunoreactivity for nitric oxide synthase in rat retina whereas the effectiveness of retina derived relaxing factor is unaffected.

    PubMed

    Takır, Selçuk; Gürel-Gürevin, Ebru; Toprak, Ayça; Demirci-Tansel, Cihan; Uydeş-Doğan, B Sönmez

    2016-04-01

    Glaucoma is a progressive ocular disease that stands in the upper rank for the cause of blindness in worldwide. In the present study, we aimed to elucidate the possible disturbances occurred in the layers of retina due to an increase in intraocular pressure (IOP) and to verify the effectiveness of retina derived relaxing factor, i.e., RRF in this pathologic condition. The increase in IOP was induced by cauterization of the three of episcleral veins simultaneously in rats. After 8 weeks period, the retinas excised from the vein cauterized eyes were evaluated for the possible histopathological and ultrastructural alterations as well as for the relaxing effects on isolated bovine retinal and rat mesenteric arteries, in comparison with the retinas obtained from contralateral sham-operated eyes. In the retinas of IOP-elevated eyes, profound morphological deteriorations were determined in the ganglion and outer nuclear cell layers which were associated with an increased number of TUNEL positive cells in the ganglion and inner nuclear cell layers. Increased immunohistochemical stainings for three isoforms of nitric oxide synthase (NOS) were defined in almost all layers of the retinas of IOP-elevated eyes, in which eNOS was abundant particularly in the inner plexiform and ganglion cell layers. An irregular basal folding of retinal pigment epithelium (RPE) and an increased inter lamellar space of photoreceptor cell layer furtherly characterized the prominent degeneration of those layers in the retinas of IOP-elevated eyes. On the other hand, the relaxing effects of the retina obtained from IOP-elevated eyes were determined to be unchanged on the retinal and mesenteric arteries precontracted either with prostaglandin F2α (PGF2α, 30 μM) or potassium chloride (K(+), 100 mM), when compared with the relaxations of control retina obtained from contralateral sham-operated eyes. Overall, these findings suggested that the elevation of IOP induces prominent structural changes in

  13. Periscope for noninvasive two-photon imaging of murine retina in vivo

    PubMed Central

    Stremplewski, Patrycjusz; Komar, Katarzyna; Palczewski, Krzysztof; Wojtkowski, Maciej; Palczewska, Grazyna

    2015-01-01

    Two-photon microscopy allows visualization of subcellular structures in the living animal retina. In previously reported experiments it was necessary to apply a contact lens to each subject. Extending this technology to larger animals would require fitting a custom contact lens to each animal and cumbersome placement of the living animal head on microscope stage. Here we demonstrate a new device, periscope, for coupling light energy into mouse eye and capturing emitted fluorescence. Using this periscope we obtained images of the RPE and their subcellular organelles, retinosomes, with larger field of view than previously reported. This periscope provides an interface with a commercial microscope, does not require contact lens and its design could be modified to image retina in larger animals. PMID:26417507

  14. Space-time wiring specificity supports direction selectivity in the retina

    PubMed Central

    Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C.; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F.; Campos, Michael; Denk, Winfried; Seung, H. Sebastian

    2014-01-01

    How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, we reconstructed Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of “citizen neuroscientists.” Based on quantitative analyses of contact area and branch depth in the retina, we found evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, while another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such “space-time wiring specificity” could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma. PMID:24805243

  15. Evaluating the Accuracy of Optic Nerve Detections in Retina Imaging Using Complementary Methods

    SciTech Connect

    Karnowski, Thomas Paul; Aykac, Deniz; Chaum, Edward; Giancardo, Luca; Tobin Jr, Kenneth William

    2009-01-01

    The detection of the optic nerve in retina images is a key element of detecting the anatomical structure of the retina. In this work we report on the fusion of two complementary optic nerve detection methods. The methods are complementary in the sense that they use different fundamental queues for locating the optic nerve. By fusing the methods through applying simple distance-based threshold, a confidence level may be assigned to the quality of the optic nerve detection. In a practical screening system this metric can be used to determine if the images should be immediately reviewed by a physician or if further automatic processing is feasible. We report on the results for two different data sets and show that the use of the threshold improves detection quality.

  16. The area centralis in the chicken retina contains efferent target amacrine cells

    PubMed Central

    Weller, Cynthia; Lindstrom, Sarah H.; De Grip, Willem J.; Wilson, Martin

    2012-01-01

    The retinas of birds receive a substantial efferent, or centrifugal, input from a midbrain nucleus. The function of this input is presently unclear but previous work in the pigeon has shown that efferent input is excluded from the area centralis, suggesting that the functions of the area centralis and the efferent system are incompatible. Using an antibody specific to rods, we have identified the area centralis in another species, the chicken, and mapped the distribution of the unique amacrine cells that are the postsynaptic partners of efferent fibers. Efferent target amacrine cells are found within the chicken area centralis and their density is continuous across the border of the area centralis. In contrast to the pigeon retina then, we conclude that the chicken area centralis receives efferent input. We suggest that the difference between the 2 species is attributable to the presence of a fovea within the area centralis of the pigeon and its absence from that of the chicken. PMID:19296862

  17. Programmable active pixel sensor to investigate neural interactions within the retina

    NASA Astrophysics Data System (ADS)

    Hart, Matthew D.; Prydderch, Mark L.; Morrison, James D.; Murdoch, Derek; Mathieson, Keith

    2009-05-01

    Detection of the visual scene by the eye and the resultant neural interactions of the retina-brain system give us our perception of sight. We have developed an Active Pixel Sensor (APS) to be used as a tool for both furthering understanding of these interactions via experimentation with the retina and to make developments towards a realisable retinal prosthesis. The sensor consists of 469 pixels in a hexagonal array. The pixels are interconnected by a programmable neural network to mimic lateral interactions between retinal cells. Outputs from the sensor are in the form of biphasic current pulse trains suitable to stimulate retinal cells via a biocompatible array. The APS will be described with initial characterisation and test results.

  18. Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina

    PubMed Central

    Wang, Tzu-Ming; Holzhausen, Lars C.; Kramer, Richard H.

    2014-01-01

    The reciprocal synapse between photoreceptors and horizontal cells (HCs) underlies lateral inhibition and establishes the antagonistic center-surround receptive fields of retinal neurons, to enhance visual contrast. Despite decades of study, the signal mediating negative feedback from HCs to cones has remained controversial because the small, invaginated synaptic cleft has precluded measurement. Using zebrafish retinas, we show that light elicits a change in synaptic proton concentration with the correct magnitude, kinetics and spatial dependence to account for lateral inhibition. Light, which hyperpolarizes HCs, causes synaptic alkalinization, whereas activating an exogenously expressed ligand-gated Na+ channel, which depolarizes HCs, causes synaptic acidification. While acidification was prevented by blocking a proton pump, re-alkalinization was prevented by blocking proton-permeant ion channels, suggesting that distinct mechanisms underlie proton efflux and influx. These findings reveal that protons mediate lateral inhibition in the retina, raising the possibility that protons are unrecognized retrograde messengers elsewhere in the nervous system. PMID:24441679

  19. Readout circuit design of the retina-like CMOS image sensor

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

    Readout circuit is designed for a special retina-like CMOS image sensor. To realize the pixels timing drive and readout of the sensor, the Altera's Cyclone II FPGA is used as a control chip. The voltage of the sensor is supported by a voltage chip initialized by SPI with AVR MCU system. The analog image signal outputted by the sensor is converted to digital image data by 12-bits A/D converter ADS807 and the digital data is memorized in the SRAM. Using the Camera-link image grabber, the data stored in SRAM is transformed to image shown on PC. Experimental results show the circuit works well on retina-like CMOS timing drive and image readout and images can be displayed properly on the PC.

  20. Development and pathological changes of neurovascular unit regulated by hypoxia response in the retina.

    PubMed

    Kurihara, T

    2016-01-01

    Retina is a highly vascularized tissue with a high oxygen and metabolic demand receiving light located in the back of the eye. The development and the maintenance of the retinal vasculature are important to regulate the homeostasis in the tissue. α Subunits of hypoxia-inducible factor (HIF) are key molecules in hypoxia response inducing genes required for cell survival such as vascular endothelial growth factor under hypoxia. Neurons, glia, and vascular endothelium cells interdependently form neurovascular unit in the retina tightly regulated by hypoxia response via HIF expression. A corruption of the precise hypoxia response in the developmental or matured retinal tissue may lead congenital vascular anomalies or adult neovascular ocular diseases. To regulate hypoxia response through HIF activity would be an ideal therapeutic target for these vision-threatening eye diseases. PMID:27130417

  1. Three-Dimensional Reconstruction of Blood Vessels of the Human Retina by Fractal Interpolation

    PubMed Central

    Guedri, Hichem; Malek, Jihen; Belmabrouk, Hafedh

    2015-01-01

    In this work, data from two-dimensional (2D) images of the human retina were taken as a case study. First, the characteristic data points had been removed using the Douglas–Peucker (DP) method, and subsequently, more data points were added using random fractal interpolation approach, to reconstruct a three-dimensional (3D) model of the blood vessel. By visualizing the result, we can see that all the small blood vessels in the human retina are more visible and detailed. This algorithm of 3D reconstruction has the advantage of being fast with calculation time less than 40 s and also can reduce the 3D image storage level on a disk with a reduction ratio between 78% and 96.65%. PMID:27222695

  2. Differentiation of cones in cultured rabbit retina: effects of retinal pigment epithelial cell-conditioned medium.

    PubMed

    Mack, Andreas F; Uhlmann, Daniela; Germer, Angela; Szél, Agoston; Enzmann, Volker; Reichenbach, Andreas

    2003-04-24

    This study was aimed at investigating the postnatal differentiation of cone photoreceptors in the rabbit retina in an organotypic explant culture system. Both short wavelength (S) and middle wavelength (M) cone opsins were expressed in culture but M cones appeared only in retinal explants from the dorsal half of the eye. Stimulating the explants with retinal pigment epithelial cell (RPE) conditioned medium resulted in a suppression of opsin expression despite of an increase of the number of presumptive peanut agglutinin-labeled cones. These results suggest that at birth the immature cones are largely undetermined in terms of their final cone identity although some positional information ('dorsal' vs. 'ventral' retina) is present. Furthermore, factors from RPE may inhibit as well as stimulate different steps of cone cell differentiation. PMID:12676342

  3. Sonic hedgehog promotes stem-cell potential of Mueller glia in the mammalian retina

    SciTech Connect

    Wan Jin; Zheng Hua; Xiao Honglei; She Zhenjue; Zhou Guomin

    2007-11-16

    Mueller glia have been demonstrated to display stem-cell properties after retinal damage. Here, we report this potential can be regulated by Sonic hedgehog (Shh) signaling. Shh can stimulate proliferation of Mueller glia through its receptor and target gene expressed on them, furthermore, Shh-treated Mueller glia are induced to dedifferentiate by expressing progenitor-specific markers, and then adopt cell fate of rod photoreceptor. Inhibition of signaling by cyclopamine inhibits proliferation and dedifferentiation. Intraocular injection of Shh promotes Mueller glia activation in the photoreceptor-damaged retina, Shh also enhances neurogenic potential by producing more rhodopsin-positive photoreceptors from Mueller glia-derived cells. Together, these results provide evidences that Mueller glia act as potential stem cells in mammalian retina, Shh may have therapeutic effects on these cells for promoting the regeneration of retinal neurons.

  4. Single-stranded oligonucleotide-mediated in vivo gene repair in the rd1 retina

    PubMed Central

    Andrieu-Soler, Charlotte; Halhal, Mounia; Boatright, Jeffrey H.; Padove, Staci A.; Nickerson, John M.; Stodulkova, Eva; Stewart, Rachael E.; Ciavatta, Vincent T.; Doat, Marc; Jeanny, Jean-Claude; de Bizemont, Therèse; Sennlaub, Florian; Courtois, Yves

    2007-01-01

    Purpose The aim of this study was to test whether oligonucleotide-targeted gene repair can correct the point mutation in genomic DNA of PDE6brd1 (rd1) mouse retinas in vivo. Methods Oligonucleotides (ODNs) of 25 nucleotide length and complementary to genomic sequence subsuming the rd1 point mutation in the gene encoding the β-subunit of rod photoreceptor cGMP-phosphodiesterase (β-PDE), were synthesized with a wild type nucleotide base at the rd1 point mutation position. Control ODNs contained the same nucleotide bases as the wild type ODNs but with varying degrees of sequence mismatch. We previously developed a repeatable and relatively non-invasive technique to enhance ODN delivery to photoreceptor nuclei using transpalpebral iontophoresis prior to intravitreal ODN injection. Three such treatments were performed on C3H/henJ (rd1) mouse pups before postnatal day (PN) 9. Treatment outcomes were evaluated at PN28 or PN33, when retinal degeneration was nearly complete in the untreated rd1 mice. The effect of treatment on photoreceptor survival was evaluated by counting the number of nuclei of photoreceptor cells and by assessing rhodopsin immunohistochemistry on flat-mount retinas and sections. Gene repair in the retina was quantified by allele-specific real time PCR and by detection of β-PDE-immunoreactive photoreceptors. Confirmatory experiments were conducted using independent rd1 colonies in separate laboratories. These experiments had an additional negative control ODN that contained the rd1 mutant nucleotide base at the rd1 point mutation site such that the sole difference between treatment with wild type and control ODN was the single base at the rd1 point mutation site. Results Iontophoresis enhanced the penetration of intravitreally injected ODNs in all retinal layers. Using this delivery technique, significant survival of photoreceptors was observed in retinas from eyes treated with wild type ODNs but not control ODNs as demonstrated by cell counting and

  5. Automated pathologies detection in retina digital images based on complex continuous wavelet transform phase angles.

    PubMed

    Lahmiri, Salim; Gargour, Christian S; Gabrea, Marcel

    2014-10-01

    An automated diagnosis system that uses complex continuous wavelet transform (CWT) to process retina digital images and support vector machines (SVMs) for classification purposes is presented. In particular, each retina image is transformed into two one-dimensional signals by concatenating image rows and columns separately. The mathematical norm of phase angles found in each one-dimensional signal at each level of CWT decomposition are relied on to characterise the texture of normal images against abnormal images affected by exudates, drusen and microaneurysms. The leave-one-out cross-validation method was adopted to conduct experiments and the results from the SVM show that the proposed approach gives better results than those obtained by other methods based on the correct classification rate, sensitivity and specificity. PMID:26609393

  6. Cytopathology of the brain and retina of embryonic surf smelt (Hypomesus pretiosus) exposed to crude oil

    SciTech Connect

    Hawkes, J.W.; Stehr, C.M.

    1982-02-01

    In laboratory experiments, surf smelt (Hypomesus pretiosus) embryos were exposed to 54 or 113 ppb of the seawater-accommodated fraction (SWAF) of Cook Inlet crude oil (CICO) for 3 hr per day, beginning 6 days after fertilization. Embryos 21 and 27 days old (just prior to hatching) exposed to CICO were examined for morphological abnormalities. The only tissues that showed morphological changes in both the 21- and 27-day-old CICO-exposed smelt were the forebrain and the neuronal layer of the retina: both contained numerous necrotic neurons. The retina receptor cells appeared normal in 21-day-old exposed smelt; in contrast, in 27-day-old treated embryos the ellipsoid and myoid regions of the receptor cell inner segments were severely damaged. Further impact from the SWAF of CICO on developing smelt was indicated by a lower hatching success: approximately 10% in the exposed groups as compared to 50% in the controls.

  7. Regeneration of the retina: toward stem cell therapy for degenerative retinal diseases.

    PubMed

    Jeon, Sohee; Oh, Il-Hoan

    2015-04-01

    Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases. PMID:25560700

  8. Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

    PubMed Central

    Buhr, Ethan D.; Yue, Wendy W. S.; Ren, Xiaozhi; Jiang, Zheng; Liao, Hsi-Wen Rock; Mei, Xue; Vemaraju, Shruti; Nguyen, Minh-Thanh; Reed, Randall R.; Lang, Richard A.; Yau, King-Wai; Van Gelder, Russell N.

    2015-01-01

    The molecular circadian clocks in the mammalian retina are locally synchronized by environmental light cycles independent of the suprachiasmatic nuclei (SCN) in the brain. Unexpectedly, this entrainment does not require rods, cones, or melanopsin (OPN4), possibly suggesting the involvement of another retinal photopigment. Here, we show that the ex vivo mouse retinal rhythm is most sensitive to short-wavelength light but that this photoentrainment requires neither the short-wavelength–sensitive cone pigment [S-pigment or cone opsin (OPN1SW)] nor encephalopsin (OPN3). However, retinas lacking neuropsin (OPN5) fail to photoentrain, even though other visual functions appear largely normal. Initial evidence suggests that OPN5 is expressed in select retinal ganglion cells. Remarkably, the mouse corneal circadian rhythm is also photoentrainable ex vivo, and this photoentrainment likewise requires OPN5. Our findings reveal a light-sensing function for mammalian OPN5, until now an orphan opsin. PMID:26392540

  9. Electroretinography: A biopotential to assess the function/dysfunction of the retina

    NASA Astrophysics Data System (ADS)

    Quintana, Quinteros; Benedetto, M. L.; Maldonado, M. M.; de Payer E., A. C. Vera; Contin, M. A.

    2016-04-01

    The Electroretinography (ERG) is a noninvasive technique that allows the assessment of functional integrity of the retina. The ERG recordings are biopotencials acquired in the corneal surface as a response of retinal tissue against controlled light stimuli. In clinical ophthalmology ERG is not commonly used but nowadays, because of the high incidence of degenerative diseases of the retina (RD), its use should be increased. Like other biopotentials as electrocardiography (ECG), electroencephalogram (EEG) and electromyography (EMG), ERG is a low amplitude signal, in this case a few hundred of microvolts (µV), which must be fitted and processed. The ERG signals are affected in morphology in the presence of pathologies that affects the integrity of the different retinal cell groups, for example due to some RD. In advanced cases of RD recordings can be abolished in the time domain; and yet in them it is believed that there is relevant clinical information making the ERG a great potential diagnostic tool.

  10. Gliosis Can Impede Integration Following Photoreceptor Transplantation into the Diseased Retina.

    PubMed

    Hippert, Claire; Graca, Anna B; Pearson, Rachael A

    2016-01-01

    Retinal degenerations leading to the loss of photoreceptor (PR) cells are a major cause of vision impairment and untreatable blindness. There are few clinical treatments and none can reverse the loss of vision. With the rapid advances in stem cell biology and techniques in cell transplantation, PR replacement by transplantation represents a broad treatment strategy applicable to many types of degeneration. The number of donor cells that integrate into the recipient retina determines transplantation success, yet the degenerating retinae presents a number of barriers that can impede effective integration. Here, we briefly review recent advances in the field of PR transplantation. We then describe how different aspects of gliosis may impact on cell integration efficiency. PMID:26427462

  11. Pannexin1 Channel Proteins in the Zebrafish Retina Have Shared and Unique Properties

    PubMed Central

    Kurtenbach, Sarah; Prochnow, Nora; Kurtenbach, Stefan; Klooster, Jan; Zoidl, Christiane; Dermietzel, Rolf; Kamermans, Maarten; Zoidl, Georg

    2013-01-01

    In mammals, a single pannexin1 gene (Panx1) is widely expressed in the CNS including the inner and outer retinae, forming large-pore voltage-gated membrane channels, which are involved in calcium and ATP signaling. Previously, we discovered that zebrafish lack Panx1 expression in the inner retina, with drPanx1a exclusively expressed in horizontal cells of the outer retina. Here, we characterize a second drPanx1 protein, drPanx1b, generated by whole-genome duplications during teleost evolution. Homology searches strongly support the presence of pannexin sequences in cartilaginous fish and provide evidence that pannexins evolved when urochordata and chordata evolution split. Further, we confirm Panx1 ohnologs being solely present in teleosts. A hallmark of differential expression of drPanx1a and drPanx1b in various zebrafish brain areas is the non-overlapping protein localization of drPanx1a in the outer and drPanx1b in the inner fish retina. A functional comparison of the evolutionary distant fish and mouse Panx1s revealed both, preserved and unique properties. Preserved functions are the capability to form channels opening at resting potential, which are sensitive to known gap junction and hemichannel blockers, intracellular calcium, extracellular ATP and pH changes. However, drPanx1b is unique due to its highly complex glycosylation pattern and distinct electrophysiological gating kinetics. The existence of two Panx1 proteins in zebrafish displaying distinct tissue distribution, protein modification and electrophysiological properties, suggests that both proteins fulfill different functions in vivo. PMID:24194896

  12. The RNA binding protein RBPMS is a selective marker of ganglion cells in the mammalian retina

    PubMed Central

    Rodriguez, Allen R.; de Sevilla Müller, Luis Pérez; Brecha, Nicholas C.

    2014-01-01

    There are few neurochemical markers that reliably identify retinal ganglion cells (RGCs), which are a heterogeneous population of cells that integrate and transmit the visual signal from the retina to the central visual nuclei. We have developed and characterized a new set of affinity purified guinea pig and rabbit antibodies against RNA-binding protein with multiple splicing (RBPMS). On Western blots these antibodies recognize a single band at ~24 kDa, corresponding to RBPMS, and they strongly label RGC and displaced RGC (dRGC) somata in mouse, rat, guinea pig, rabbit and monkey retina. RBPMS immunoreactive cells and RGCs identified by other techniques have a similar range of somal diameters and areas. The density of RBPMS cells in mouse and rat retina is comparable to earlier semi-quantitative estimates of RGCs. RBPMS is mainly expressed in medium and large DAPI-, DRAQ5-, NeuroTrace- and NeuN-stained cells in the ganglion cell layer (GCL), and RBPMS is not expressed in syntaxin (HPC-1) immunoreactive cells in the inner nuclear layer (INL) and GCL, consistent with their identity as RGCs, and not displaced amacrine cells. In mouse and rat retina, most RBPMS cells are lost following optic nerve crush or transection at three weeks, and all Brn3a, SMI-32 and melanopsin immunoreactive RGCs also express RBPMS immunoreactivity. RBPMS immunoreactivity is localized to CFP-fluorescent RGCs in the B6.Cg-Tg(Thy1-CFP)23Jrs/J mouse line. These findings show that antibodies against RBPMS are robust reagents that exclusively identify RGCs and dRGCs in multiple mammalian species, and they will be especially useful for quantification of RGCs. PMID:24318667

  13. Reflectance Decreases before Thickness Changes in the Retinal Nerve Fiber Layer in Glaucomatous Retinas

    PubMed Central

    Zhou, Ye; Kong, Wei; Knighton, Robert W.

    2011-01-01

    Purpose. Glaucoma damages the retinal never fiber layer (RNFL). RNFL thickness, measured with optical coherence tomography (OCT), is often used in clinical assessment of the damage. In this study the relation between the RNFL reflectance and thickness at early stages of glaucoma was investigated. Methods. A rat model of glaucoma was used that involved laser photocoagulation of the trabecular meshwork. The reflectance of the RNFL in an isolated retina was measured, followed by immunohistochemical staining of the axonal cytoskeleton. RNFL thickness was measured by confocal fluorescence imaging. RNFL reflectance was calculated for bundle areas located at radii of 0.22, 0.33, and 0.44 mm from the optic nerve head (ONH) center. Linear regression was used to study the relation between reflectance and thickness. For glaucomatous eyes, only those bundles with no apparent structural damage were used. Results. Bundles in 11 control retinas and 10 treated retinas were examined. Bundle thickness of both groups at each radius was similar (P = 0.89). The reflectance of the bundles at radii of 0.33 and 0.44 mm was found to be similar in both control and treated retinas (P > 0.5). However, the reflectance of the bundles at the 0.22-mm radius decreased significantly in the treated group (P = 0.005). Conclusions. Elevation of intraocular pressure causes decrease in RNFL reflectance for bundles near the ONH. Change in RNFL reflectance precedes thinning of the RNFL. The results suggest that a decrease in RNFL reflectance near the ONH is an early sign of glaucomatous damage. PMID:21730345

  14. PGC-1α Determines Light Damage Susceptibility of the Murine Retina

    PubMed Central

    Egger, Anna; Samardzija, Marijana; Sothilingam, Vithiyanjali; Tanimoto, Naoyuki; Lange, Christina; Salatino, Silvia; Fang, Lei; Garcia-Garrido, Marina; Beck, Susanne; Okoniewski, Michal J.; Neutzner, Albert; Seeliger, Mathias W.; Grimm, Christian; Handschin, Christoph

    2012-01-01

    The peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) proteins are key regulators of cellular bioenergetics and are accordingly expressed in tissues with a high energetic demand. For example, PGC-1α and PGC-1β control organ function of brown adipose tissue, heart, brain, liver and skeletal muscle. Surprisingly, despite their prominent role in the control of mitochondrial biogenesis and oxidative metabolism, expression and function of the PGC-1 coactivators in the retina, an organ with one of the highest energy demands per tissue weight, are completely unknown. Moreover, the molecular mechanisms that coordinate energy production with repair processes in the damaged retina remain enigmatic. In the present study, we thus investigated the expression and function of the PGC-1 coactivators in the healthy and the damaged retina. We show that PGC-1α and PGC-1β are found at high levels in different structures of the mouse retina, most prominently in the photoreceptors. Furthermore, PGC-1α knockout mice suffer from a striking deterioration in retinal morphology and function upon detrimental light exposure. Gene expression studies revealed dysregulation of all major pathways involved in retinal damage and apoptosis, repair and renewal in the PGC-1α knockouts. The light-induced increase in apoptosis in vivo in the absence of PGC-1α was substantiated in vitro, where overexpression of PGC-1α evoked strong anti-apoptotic effects. Finally, we found that retinal levels of PGC-1 expression are reduced in different mouse models for retinitis pigmentosa. We demonstrate that PGC-1α is a central coordinator of energy production and, importantly, all of the major processes involved in retinal damage and subsequent repair. Together with the observed dysregulation of PGC-1α and PGC-1β in retinitis pigmentosa mouse models, these findings thus imply that PGC-1α might be an attractive target for therapeutic approaches aimed at retinal degeneration diseases. PMID

  15. In Vivo Visualization of Endoplasmic Reticulum Stress in the Retina Using the ERAI Reporter Mouse

    PubMed Central

    Alavi, Marcel V.; Chiang, Wei-Chieh; Kroeger, Heike; Yasumura, Douglas; Matthes, Michael T.; Iwawaki, Takao; LaVail, Matthew M.; Gould, Douglas B.; Lin, Jonathan H.

    2015-01-01

    Purpose Endoplasmic reticulum (ER) stress activates inositol requiring enzyme 1 (IRE1), a key regulator of the unfolded protein response. The ER stress activated indicator (ERAI) transgenic mouse expresses a yellow fluorescent GFP variant (Venus) when IRE1 is activated by ER stress. We tested whether ERAI mice would allow for real-time longitudinal studies of ER stress in living mouse eyes. Methods We chemically and genetically induced ER stress, and qualitatively and quantitatively studied the Venus signal by fluorescence ophthalmoscopy. We determined retinal cell types that contribute to the signal by immunohistology, and we performed molecular and biochemical assays using whole retinal lysates to assess activity of the IRE1 pathway. Results We found qualitative increase in vivo in fluorescence signal at sites of intravitreal tunicamycin injection in ERAI eyes, and quantitative increase in ERAI mice mated to RhoP23H mice expressing ER stress-inducing misfolded rhodopsin protein. As expected, we found that increased Venus signal arose primarily from photoreceptors in RhoP23H/+;ERAI mice. We found increased Xbp1S and XBP1s transcriptional target mRNA levels in RhoP23H/+;ERAI retinas compared to Rho+/+;ERAI retinas, and that Venus signal increased in ERAI retinas as a function of age. Conclusions Fluorescence ophthalmoscopy of ERAI mice enables in vivo visualization of retinas undergoing ER stress. ER stress activated indicator mice enable identification of individual retinal cells undergoing ER stress by immunohistochemistry. ER stress activated indicator mice show higher Venus signal at older ages, likely arising from amplification of basal retinal ER stress levels by GFP's inherent stability. PMID:26513501

  16. Lipid nanoparticles as drug/gene delivery systems to the retina.

    PubMed

    del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

    2013-03-01

    This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market. PMID:23286300

  17. The effects of direct-current magnetic fields on turtle retinas vitro

    SciTech Connect

    Raybourn, M.S.

    1983-05-13

    Direct-current magnetic fields of 10 to 100 gauss cause a significant short-term reduction of the in vitro electroretinographic b-wave response in turtle retina. This response compression is not accompanied by the usual reduction in retinal sensitivity that occurs with background illumination. Furthermore, this effect is obtained only briefly after the offset of ambient lighting in the diurnal light-dark cycle of nonhibernating animals.

  18. Circuit design for the retina-like image sensor based on space-variant lens array

    NASA Astrophysics Data System (ADS)

    Gao, Hongxun; Hao, Qun; Jin, Xuefeng; Cao, Jie; Liu, Yue; Song, Yong; Fan, Fan

    2013-12-01

    Retina-like image sensor is based on the non-uniformity of the human eyes and the log-polar coordinate theory. It has advantages of high-quality data compression and redundant information elimination. However, retina-like image sensors based on the CMOS craft have drawbacks such as high cost, low sensitivity and signal outputting efficiency and updating inconvenience. Therefore, this paper proposes a retina-like image sensor based on space-variant lens array, focusing on the circuit design to provide circuit support to the whole system. The circuit includes the following parts: (1) A photo-detector array with a lens array to convert optical signals to electrical signals; (2) a strobe circuit for time-gating of the pixels and parallel paths for high-speed transmission of the data; (3) a high-precision digital potentiometer for the I-V conversion, ratio normalization and sensitivity adjustment, a programmable gain amplifier for automatic generation control(AGC), and a A/D converter for the A/D conversion in every path; (4) the digital data is displayed on LCD and stored temporarily in DDR2 SDRAM; (5) a USB port to transfer the data to PC; (6) the whole system is controlled by FPGA. This circuit has advantages as lower cost, larger pixels, updating convenience and higher signal outputting efficiency. Experiments have proved that the grayscale output of every pixel basically matches the target and a non-uniform image of the target is ideally achieved in real time. The circuit can provide adequate technical support to retina-like image sensors based on space-variant lens array.

  19. Effects of Primary Blast Overpressure on Retina and Optic Tract in Rats.

    PubMed

    DeMar, James; Sharrow, Keith; Hill, Miya; Berman, Jonathan; Oliver, Thomas; Long, Joseph

    2016-01-01

    Blast has been the leading cause of injury, particularly traumatic brain injury and visual system injury, in combat operations in Iraq and Afghanistan. We determined the effect of shock tube-generated primary blast on retinal electrophysiology and on retinal and brain optic tract histopathology in a rat model. The amplitude of a- and b-waves on the electroretinogram (ERG) for both right and left eyes were measured prior to a battlefield simulation Friedlander-type blast wave and on 1, 7, and 14 days thereafter. Histopathologic findings of the right and left retina and the right and left optic tracts (2.8 mm postoptic chiasm) were evaluated 14 days after the blast. For two experiments in which the right eye was oriented to the blast, the amplitude of ERG a- and b-waves at 7 days post blast on the right side but not on the left side was diminished compared to that of sham animals (P = 0.005-0.01) Histopathologic injury scores at 14 days post blast for the right retina but not the left retina were higher than for sham animals (P = 0.01), and histopathologic injury scores at 14 days for both optic tracts were markedly higher than for shams (P < 0.0001). Exposure of one eye to a blast wave, comparable to that causing human injury, produced injury to the retina as determined by ERG and histopathology, and to both postchiasmatic optic tracts as determined by histopathology. This model may be useful for analyzing the effect of therapeutic interventions on retinal damage due to primary blast waves. PMID:27199884

  20. Unidirectional Photoreceptor-to-Müller Glia Coupling and Unique K+ Channel Expression in Caiman Retina

    PubMed Central

    Rivera, Yomarie; Benedikt, Jan; Ulbricht, Elke; Karl, Anett; Dávila, José; Savvinov, Alexey; Kucheryavykh, Yuriy; Inyushin, Mikhail; Cubano, Luis A.; Pannicke, Thomas; Veh, Rüdiger W.; Francke, Mike; Verkhratsky, Alexei; Eaton, Misty J.; Reichenbach, Andreas; Skatchkov, Serguei N.

    2014-01-01

    Background Müller cells, the principal glial cells of the vertebrate retina, are fundamental for the maintenance and function of neuronal cells. In most vertebrates, including humans, Müller cells abundantly express Kir4.1 inwardly rectifying potassium channels responsible for hyperpolarized membrane potential and for various vital functions such as potassium buffering and glutamate clearance; inter-species differences in Kir4.1 expression were, however, observed. Localization and function of potassium channels in Müller cells from the retina of crocodiles remain, hitherto, unknown. Methods We studied retinae of the Spectacled caiman (Caiman crocodilus fuscus), endowed with both diurnal and nocturnal vision, by (i) immunohistochemistry, (ii) whole-cell voltage-clamp, and (iii) fluorescent dye tracing to investigate K+ channel distribution and glia-to-neuron communications. Results Immunohistochemistry revealed that caiman Müller cells, similarly to other vertebrates, express vimentin, GFAP, S100β, and glutamine synthetase. In contrast, Kir4.1 channel protein was not found in Müller cells but was localized in photoreceptor cells. Instead, 2P-domain TASK-1 channels were expressed in Müller cells. Electrophysiological properties of enzymatically dissociated Müller cells without photoreceptors and isolated Müller cells with adhering photoreceptors were significantly different. This suggests ion coupling between Müller cells and photoreceptors in the caiman retina. Sulforhodamine-B injected into cones permeated to adhering Müller cells thus revealing a uni-directional dye coupling. Conclusion Our data indicate that caiman Müller glial cells are unique among vertebrates studied so far by predominantly expressing TASK-1 rather than Kir4.1 K+ channels and by bi-directional ion and uni-directional dye coupling to photoreceptor cells. This coupling may play an important role in specific glia-neuron signaling pathways and in a new type of K+ buffering. PMID

  1. Expression of ionotropic glutamate receptors, AMPA, kainite and NMDA, in the pigeon retina.

    PubMed

    Atoji, Yasuro

    2015-07-01

    Glutamate is an excitatory neurotransmitter in the vertebrate retina. A previous study found vesicular glutamate transporter 2 (vGluT2) mRNA in the pigeon retina, suggesting that bipolar and ganglion cells are glutamatergic. The present study examined the localization of ionotropic glutamate receptors to identify receptor cells in the pigeon retina using in situ hybridization histochemistry. Nine subunits of AMPA receptor (GluA1, GluA2, GluA3, and GluA4), kainate receptor (GluK1, GluK2, and GluK4), and NMDA receptor (GluN1 and GluN2A) were found to be expressed in the inner nuclear layer (INL) and ganglion cell layers. GluA1, GluA2, GluA3, and GluA4 were primarily expressed in the inner half of INL, and the signal intensity was strong for GluA2, GluA3, and GluA4. GluK1 was intensely expressed in the outer half of INL, whereas GluK2 and GluK4 were mainly localized in the inner half of INL. GluN1 and GluN2A were moderately expressed in the inner half of INL. Horizontal cells expressed GluA3 and GluA4, and ganglion cells expressed all subunits examined. These results suggest that the glutamatergic neurotransmission in the pigeon retina is similar to that in mammals. PMID:25983186

  2. Morphology and function of three VIP-expressing amacrine cell types in the mouse retina.

    PubMed

    Akrouh, Alejandro; Kerschensteiner, Daniel

    2015-10-01

    Amacrine cells (ACs) are the most diverse class of neurons in the retina. The variety of signals provided by ACs allows the retina to encode a wide range of visual features. Of the 30-50 AC types in mammalian species, few have been studied in detail. Here, we combine genetic and viral strategies to identify and to characterize morphologically three vasoactive intestinal polypeptide-expressing GABAergic AC types (VIP1-, VIP2-, and VIP3-ACs) in mice. Somata of VIP1- and VIP2-ACs reside in the inner nuclear layer and somata of VIP3-ACs in the ganglion cell layer, and they show asymmetric distributions along the dorsoventral axis of the retina. Neurite arbors of VIP-ACs differ in size (VIP1-ACs ≈ VIP3-ACs > VIP2-ACs) and stratify in distinct sublaminae of the inner plexiform layer. To analyze light responses and underlying synaptic inputs, we target VIP-ACs under 2-photon guidance for patch-clamp recordings. VIP1-ACs depolarize strongly to light increments (ON) over a wide range of stimulus sizes but show size-selective responses to light decrements (OFF), depolarizing to small and hyperpolarizing to large stimuli. The switch in polarity of OFF responses is caused by pre- and postsynaptic surround inhibition. VIP2- and VIP3-ACs both show small depolarizations to ON stimuli and large hyperpolarizations to OFF stimuli but differ in their spatial response profiles. Depolarizations are caused by ON excitation outweighing ON inhibition, whereas hyperpolarizations result from pre- and postsynaptic OFF-ON crossover inhibition. VIP1-, VIP2-, and VIP3-ACs thus differ in response polarity and spatial tuning and contribute to the diversity of inhibitory and neuromodulatory signals in the retina. PMID:26311183

  3. Effects of Primary Blast Overpressure on Retina and Optic Tract in Rats

    PubMed Central

    DeMar, James; Sharrow, Keith; Hill, Miya; Berman, Jonathan; Oliver, Thomas; Long, Joseph

    2016-01-01

    Blast has been the leading cause of injury, particularly traumatic brain injury and visual system injury, in combat operations in Iraq and Afghanistan. We determined the effect of shock tube-generated primary blast on retinal electrophysiology and on retinal and brain optic tract histopathology in a rat model. The amplitude of a- and b-waves on the electroretinogram (ERG) for both right and left eyes were measured prior to a battlefield simulation Friedlander-type blast wave and on 1, 7, and 14 days thereafter. Histopathologic findings of the right and left retina and the right and left optic tracts (2.8 mm postoptic chiasm) were evaluated 14 days after the blast. For two experiments in which the right eye was oriented to the blast, the amplitude of ERG a- and b-waves at 7 days post blast on the right side but not on the left side was diminished compared to that of sham animals (P = 0.005–0.01) Histopathologic injury scores at 14 days post blast for the right retina but not the left retina were higher than for sham animals (P = 0.01), and histopathologic injury scores at 14 days for both optic tracts were markedly higher than for shams (P < 0.0001). Exposure of one eye to a blast wave, comparable to that causing human injury, produced injury to the retina as determined by ERG and histopathology, and to both postchiasmatic optic tracts as determined by histopathology. This model may be useful for analyzing the effect of therapeutic interventions on retinal damage due to primary blast waves. PMID:27199884

  4. Distinct nuclear localization patterns of DNA methyltransferases in developing and mature mammalian retina.

    PubMed

    Nasonkin, Igor O; Lazo, Kevin; Hambright, Dustin; Brooks, Matthew; Fariss, Robert; Swaroop, Anand

    2011-07-01

    DNA methyltransferases--DNMT1, DNMT3a, and DNMT3b--produce methylation patterns that dynamically regulate chromatin remodeling and gene expression. The vertebrate retina provides an ideal model to elucidate molecular control of neurogenesis as all neuronal cell types and Müller glia are generated in a conserved order from common pools of progenitor cells. As a prelude to exploring epigenetic regulation of mammalian retinal development, we investigated the expression of Dnmt1, Dnmt3a, and Dnmt3b in the mouse retina from embryonic day (E) 10.5 to 10 months of age. High levels of transcripts for all three Dnmt genes were observed in early stages of retinal differentiation, with significantly reduced expression after birth. Although DNMT1 protein is abundant in retinal progenitors at E10.5, it becomes restricted to postmitotic cells by E15.5. Most cells in the postnatal retina show nuclear immunostaining of DNMT1; however, the photoreceptors exhibit distinctive patterns. In rods, weak expression of DNMT1 is detected in perinuclear region and in the nucleus, whereas a strong nuclear labeling is evident in cones. DNMT3a and DNMT3b show a discrete pattern in developing retina with high expression at E11.5, little or no immunostaining by E15.5, and then postnatal expression overlapping with DNMT1 in early born neurons (ganglion, amacrine and horizontal cells, and cones). Robust nuclear localization of DNMTs in cones compared to rods suggests a potential role of DNA methylation in differential remodeling of chromatin in these two specialized neurons. Our studies indicate that DNA methyltransferases contribute to the establishment and maturation of cell fates during retinal development. PMID:21452232

  5. The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice

    PubMed Central

    Yi, Yun-Min; Cai, Li; Shao, Yi; Xu, Man; Yi, Jing-Lin

    2015-01-01

    AIM To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE+/− mice (AChE knockout mice) of various ages. METHODS Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 µmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE+/− mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer. RESULTS Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE+/− mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE+/− mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05). CONCLUSION In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina. PMID:26558196

  6. The retina dose-area histogram: a metric for quantitatively comparing rival eye plaque treatment options

    PubMed Central

    2013-01-01

    Purpose Episcleral plaques have a history of over a half century in the delivery of radiation therapy to intraocular tumors such as choroidal melanoma. Although the tumor control rate is high, vision-impairing complications subsequent to treatment remain an issue. Notable, late complications are radiation retinopathy and maculopathy. The obvious way to reduce the risk of radiation damage to the retina is to conform the prescribed isodose surface to the tumor base and to reduce the dose delivered to the surrounding healthy retina, especially the macula. Using a fusion of fundus photography, ultrasound and CT images, tumor size, shape and location within the eye can be accurately simulated as part of the radiation planning process. In this work an adaptation of the dose-volume histogram (DVH), the retina dose-area histogram (RDAH) is introduced as a metric to help compare rival plaque designs and conformal treatment planning options with the goal of reducing radiation retinopathy. Material and methods The RDAH is calculated by transforming a digitized fundus-photo collage of the tumor into a rasterized polar map of the retinal surface known as a retinal diagram (RD). The perimeter of the tumor base is digitized on the RD and its area computed. Area and radiation dose are calculated for every pixel in the RD. Results The areal resolution of the RDAH is a function of the pixel resolution of the raster image used to display the RD and the number of polygon edges used to digitize the perimeter of the tumor base. A practical demonstration is presented. Conclusions The RDAH provides a quantitative metric by which episcleral plaque treatment plan options may be evaluated and compared in order to confirm adequate dosimetric coverage of the tumor and margin, and to help minimize dose to the macula and retina. PMID:23634152

  7. Lateral Inhibition in the Vertebrate Retina: The Case of the Missing Neurotransmitter

    PubMed Central

    Kramer, Richard H.; Davenport, Christopher M.

    2015-01-01

    Lateral inhibition at the first synapse in the retina is important for visual perception, enhancing image contrast, color discrimination, and light adaptation. Despite decades of research, the feedback signal from horizontal cells to photoreceptors that generates lateral inhibition remains uncertain. GABA, protons, or an ephaptic mechanism have all been suggested as the primary mediator of feedback. However, the complexity of the reciprocal cone to horizontal cell synapse has left the identity of the feedback signal an unsolved mystery. PMID:26656622

  8. Effect of increased oxygen tension on flicker-induced vasodilatation in the human retina

    PubMed Central

    Palkovits, Stefan; Told, Reinhard; Boltz, Agnes; Schmidl, Doreen; Popa Cherecheanu, Alina; Schmetterer, Leopold; Garhöfer, Gerhard

    2014-01-01

    In the retina, blood flow and neural activity are tightly coupled. Stimulation of the retina with flickering light is accompanied by an increase in blood flow. The current study seeks to investigate whether an increase in oxygen tension modulates flicker (FL)-induced vasodilatation in the human retina. A total of 52 healthy volunteers were included. Via a breathing mask, 100% oxygen (O2) was administered in one, a mixture of 8% carbon dioxide and 92% oxygen (C/O) in a second cohort. Retinal vessel diameters were measured with a Vessel Analyzer and FL responses were assessed before and during the breathing periods. At baseline, FL stimulation increased retinal vessel diameters by +3.7±2.3% in arteries and by +5.1±3.7% in veins. Breathing of C/O led to a decrease in arterial (−9.0±6.9%) and venous (−11.3±5.9%) vessel calibers. Flicker response was increased to 5.7±2.5% in arteries and to 8.6±4.1% in veins. Breathing of pure O2 induced a vasoconstriction of vessel diameters by −14.0±5.3% in arteries and −18.4±7.0% in veins and increased FL responses in arteries (+6.2±2.8%) and veins (+7.2±3.1%). Systemic hyperoxia increases FL-induced retinal vasodilatation in the retina. The mechanism by which oxygen modulates the hyperemic response to FL stimulation remains to be elucidated. PMID:25248833

  9. Expression of netrin-1 receptors in retina of oxygen-induced retinopathy in mice

    PubMed Central

    2014-01-01

    Background Netrin-1 has been reported to promote retinal neovascularization in oxygen-induced retinopathy (OIR). However, netrin-1 receptors, which may mediate netrin-1 action during retinal neovascularization, have not been characterized. In this study, we investigated netrin-1 receptor subtype expression and associated changes in the retinas of mice with OIR. Methods C57BL/6J mice were exposed to 75±2% oxygen for 5 days and then returned to normal air to induce retinal neovascularization. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were used to examine the expression of netrin-1 receptor subtypes in the mouse retinas. Double staining of netrin-1 receptor subtypes and isolectin B4 was used to determine the location of the netrin-1 receptor subtypes in the retinas. Inhibition of retinal neovascularization was achieved by UNC5B shRNA plasmid intravitreal injection. Retinal neovascularization was examined by fluorescein angiography and quantification of preretinal neovascular nuclei in retinal sections. Results RT-PCR results showed that, except for UNC5A, netrin-1 receptor subtypes UNC5B, UNC5C, UNC5D, DCC, neogenin, and A2b were all expressed in the retinas of OIR mice 17 days after birth. Western blots showed that only UNC5B expression was significantly increased on that day, and immunofluorescence results showed that only UNC5B and neogenin were expressed in retinal vessels. Treatment of OIR mice with the UNC5B shRNA plasmid dramatically reduced neovascular tufts and neovascular outgrowth into the inner limiting membrane. Conclusions UNC5B may promote retinal neovascularization in OIR mice. PMID:25149138

  10. Proteomic Analysis of the Retina: Removal of RPE Alters Outer Segment Assembly and Retinal Protein Expression

    PubMed Central

    Wang, XiaoFei; Nookala, Suba; Narayanan, Chidambarathanu; Giorgianni, Francesco; Beranova-Giorgianni, Sarka; McCollum, Gary; Gerling, Ivan; Penn, John S.; Jablonski, Monica M.

    2008-01-01

    The mechanisms that regulate the complex physiologic task of photoreceptor outer segment assembly remain an enigma. One limiting factor in revealing the mechanism(s) by which this process is modulated is that not all of the role players that participate in this process are known. The purpose of this study was to determine some of the retinal proteins that likely play a critical role in regulating photoreceptor outer segment assembly. To do so, we analyzed and compared the proteome map of tadpole Xenopus laevis retinal pigment epithelium (RPE)-supported retinas containing organized outer segments with that of RPE-deprived retinas containing disorganized outer segments. Solubilized proteins were labeled with CyDye fluors followed by multiplexed two-dimensional separation. The intensity of protein spots and comparison of proteome maps was performed using DeCyder software. Identification of differentially regulated proteins was determined using nanoLC-ESI-MS/MS analysis. We found a total of 27 protein spots, 21 of which were unique proteins, which were differentially expressed in retinas with disorganized outer segments. We predict that in the absence of the RPE, oxidative stress initiates an unfolded protein response. Subsequently, downregulation of several candidate Müller glial cell proteins may explain the inability of photoreceptors to properly fold their outer segment membranes. In this study we have used identification and bioinformatics assessment of proteins that are differentially expressed in retinas with disorganized outer segments as a first step in determining probable key molecules involved in regulating photoreceptor outer segment assembly. PMID:18803304

  11. Gyrate atrophy of the retina and choroid. Two methods for prenatal diagnosis.

    PubMed

    O'Donnell, J J; Sipilä, I; Vannas, A; Sandman, R; Vannas-Sulonen, K

    1981-08-01

    We report two methods for prenatal diagnosis of gyrate atrophy of the retina and choroid caused by an inborn error of ornithine aminotransferase activity. A high pressure liquid chromatography assay measures ornithine aminotransferase accurately and directly in cultured amniotic fluid cells. The differential incorporation of 14C-ornithine and 3H-leucine into cell protein measures OAT directly but rapidly and simply. PMID:7298261

  12. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    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 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, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases. PMID:26677077

  13. Anatomical and Neurochemical Characterization of Dopaminergic Interplexiform Processes in Mouse and Rat Retinas

    PubMed Central

    WITKOVSKY, PAUL; GÁBRIEL, ROBERT; KRIŽAJ, DAVID

    2010-01-01

    Dopaminergic (DA) neurons of mouse and rat retinas are of the interplexiform subtype (DA-IPC), i.e., they send processes distally toward the outer retina, exhibiting numerous varicosities along their course. The primary question we addressed was whether distally located DA-IPC varicosities, identified by tyrosine hydroxylase (TH) immunoreactivity, had the characteristic presynaptic proteins associated with calcium-dependent vesicular release of neurotransmitter. We found that TH immunoreactive varicosities in the outer retina possessed vesicular monoamine transporter 2 and vesicular GABA transporter, but they lacked immunostaining for any of nine subtypes of voltage-dependent calcium channel. Immunoreactivity for other channels that may permit calcium influx such as certain ionotropic glutamate receptors and canonical transient receptor potential channels (TRPCs) was similarly absent, although DA-IPC varicosities did show ryanodine receptor immunoreactivity, indicating the presence of intracellular calcium stores. The synaptic vesicle proteins sv2a and sv2b and certain other proteins associated with the presynaptic membrane were absent from DA-IPC varicosities, but the vesicular SNARE protein, vamp2, was present in a fraction of those varicosities. We identified a presumed second class of IPC that is GABAergic but not dopaminergic. Outer retinal varicosities of this putative GABAergic IPC did colocalize synaptic vesicle protein 2a, suggesting they possessed a conventional vesicular release mechanism. PMID:18615559

  14. Melanopsin and the Non-visual Photochemistry in the Inner Retina of Vertebrates.

    PubMed

    Díaz, Nicolás M; Morera, Luis P; Guido, Mario E

    2016-01-01

    Melanopsin (Opn4), a member of the G-protein-coupled receptor family, is a vitamin A-based opsin in the vertebrate retina that has been shown to be involved in the synchronization of circadian rhythms, pupillary light reflexes, melatonin suppression and other light-regulated tasks. In nonmammalian vertebrates there are two Opn4 genes, Opn4m and Opn4x, the mammalian and Xenopus orthologs respectively. Opn4x is only expressed in nonmammalian vertebrates including reptiles, fish and birds, while Opn4m is found in a subset of retinal ganglion cells (RGCs), the intrinsically photosensitive (ip) RGCs of the inner retina of both mammals and nonmammalian vertebrates. All opsins described utilize retinaldehyde as chromophore, photoisomerized from 11-cis- to all-trans-retinal upon light exposure. Visual retinal photoreceptor cones and rods, responsible for day and night vision respectively, recycle retinoids through a process called the visual cycle that involves the retinal pigment epithelium or glial Müller cells. Although Opn4 has been characterized as a bistable photopigment, little is known about the mechanism/s involved in its chromophore regeneration. In this review, we will attempt to shed light on the visual cycle taking place in the inner retina and discuss the state of the art in the nonvisual photochemistry of vertebrates. PMID:26500165

  15. Effect of light on global gene expression in the neuroglobin-deficient mouse retina

    PubMed Central

    ILMJÄRV, STEN; REIMETS, RIIN; HUNDAHL, CHRISTIAN ANSGAR; LUUK, HENDRIK

    2014-01-01

    Several previous studies have raised controversy over the functional role of neuroglobin (Ngb) in the retina. Certain studies indicate a significant impact of Ngb on retinal physiology, whereas others are conflicting. The present is an observational study that tested the effect of Ngb deficiency on gene expression in dark- and light-adapted mouse retinas. Large-scale gene expression profiling was performed using GeneChip® Mouse Exon 1.0 ST arrays and the results were compared to publicly available data sets. The lack of Ngb was found to have a minor effect on the light-induced retinal gene expression response. In addition, there was no increase in the expression of marker genes associated with hypoxia, endoplasmic reticulum-stress and oxidative stress in the Ngb-deficient retina. By contrast, several genes were identified that appeared to be differentially expressed between the genotypes when the effect of light was ignored. The present study indicates that Ngb deficiency does not lead to major alternations in light-dependent gene expression response, but leads to subtle systemic differences of a currently unknown functional significance. PMID:25279145

  16. Cell type-specific bipolar cell input to ganglion cells in the mouse retina.

    PubMed

    Neumann, S; Hüser, L; Ondreka, K; Auler, N; Haverkamp, S

    2016-03-01

    Many distinct ganglion cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion cell types in the mouse retina receive selective input from specific bipolar cell types or if they sample their synaptic input non-selectively from all bipolar cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 bipolar cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion cell types, which co-stratified with type 2 bipolar cells and assessed the total number of bipolar input synapses and the proportion of synapses deriving from type 2 bipolar cells. Only JAM-B ganglion cells received synaptic input preferentially from bipolar cell types other than type 2 bipolar cells whereas the other analyzed ganglion cell types sampled their bipolar input most likely from all bipolar cell terminals within their dendritic arbor. PMID:26751712

  17. Coherent Anti-Stokes Raman Scattering (CARS) Microscopy: A Novel Technique for Imaging the Retina

    PubMed Central

    Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Lei, Tim C.

    2013-01-01

    Purpose. To image the cellular and noncellular structures of the retina in an intact mouse eye without the application of exogenous fluorescent labels using noninvasive, nondestructive techniques. Methods. Freshly enucleated mouse eyes were imaged using two nonlinear optical techniques: coherent anti-Stokes Raman scattering (CARS) and two-photon autofluorescence (TPAF). Cross sectional transverse sections and sequential flat (en face) sagittal sections were collected from a region of sclera approximately midway between the limbus and optic nerve. Imaging proceeded from the surface of the sclera to a depth of ∼60 μm. Results. The fluorescent signal from collagen fibers within the sclera was evident in the TPAF channel; the scleral collagen fibers showed no organization and appeared randomly packed. The sclera contained regions lacking TPAF and CARS fluorescence of ∼3 to 15 μm in diameter that could represent small vessels or scleral fibroblasts. Intense punctate CARS signals from the retinal pigment epithelial layer were of a size and shape of retinyl storage esters. Rod outer segments could be identified by the CARS signal from their lipid-rich plasma membranes. Conclusions. CARS microscopy can be used to image the outer regions of the mammalian retina without the use of a fluorescent dye or exogenously expressed recombinant protein. With technical advancements, CARS/TPAF may represent a new avenue for noninvasively imaging the retina and might complement modalities currently used in clinical practice. PMID:23580484

  18. Atorvastatin-mediated protection of the retina in a model of diabetes with hyperlipidemia.

    PubMed

    Fernandes, Rosa; Bento, Carla F; Matafome, Paulo; Sena, Cristina M; Seiça, Raquel M; Pereira, Paulo

    2014-12-01

    Insulin resistance, a key feature of obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), results in a variety of metabolic and vascular abnormalities. Metabolic disturbances associated with diabetes could contribute to disrupting the structural and (or) functional integrity of the retina. The effects of atorvastatin on retinal cells in hyperlipidemic T2DM rats have not yet been investigated. We used Goto-Kakizaki (GK) rats fed with an atherogenic diet (AD) for 4 months to investigate whether atorvastatin (administered for 1 month) would slow-down or reverse the progression of lesions in the diabetic retina. Fluorogenic substrates were used to measure the proteasome activities in retinal cells. The production of reactive oxygen species was determined by immunofluorescence in frozen retina sections, using dihydroethydium. Nitrotyrosine levels were assessed using immunohistochemistry. Protein levels of ubiquitin conjugates, free ubiquitin, and ubiquitin activating enzyme E1 were determined with Western blotting. Atorvastatin significantly reduced the levels of oxidative stress that were induced by the AD and restored the proteasome activities in the diabetic GK rats. Atorvastatin therapy significantly improved local oxidative stress levels in GK rats fed with AD. Atorvastatin can, at least in part, restore the ubiquitin proteasome system, and may represent a pharmacological approach to prevent some of the complications associated with diabetic retinopathy. PMID:25404034

  19. Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

    NASA Astrophysics Data System (ADS)

    Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

    2016-08-01

    Objective. The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways. Approach. As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina. Main results. We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells. Significance. Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal ‘tickling’ has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients.

  20. Vision Drives Correlated Activity without Patterned Spontaneous Activity in Developing Xenopus Retina

    PubMed Central

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

    2011-01-01

    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 GABAA 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. PMID:21312343

  1. Wavefront sensorless approaches to adaptive optics for in vivo fluorescence imaging of mouse retina

    NASA Astrophysics Data System (ADS)

    Wahl, Daniel J.; Bonora, Stefano; Mata, Oscar S.; Haunerland, Bengt K.; Zawadzki, Robert J.; Sarunic, Marinko V.; Jian, Yifan

    2016-03-01

    Adaptive optics (AO) is necessary to correct aberrations when imaging the mouse eye with high numerical aperture. In order to obtain cellular resolution, we have implemented wavefront sensorless adaptive optics for in vivo fluorescence imaging of mouse retina. Our approach includes a lens-based system and MEMS deformable mirror for aberration correction. The AO system was constructed with a reflectance channel for structural images and fluorescence channel for functional images. The structural imaging was used in real-time for navigation on the retina using landmarks such as blood vessels. We have also implemented a tunable liquid lens to select the retinal layer of interest at which to perform the optimization. At the desired location on the mouse retina, the optimization algorithm used the fluorescence image data to drive a modal hill-climbing algorithm using an intensity or sharpness image quality metric. The optimization requires ~30 seconds to complete a search up to the 20th Zernike mode. In this report, we have demonstrated the AO performance for high-resolution images of the capillaries in a fluorescence angiography. We have also made progress on an approach to AO with pupil segmentation as a possible sensorless technique suitable for small animal retinal imaging. Pupil segmentation AO was implemented on the same ophthalmic system and imaging performance was demonstrated on fluorescent beads with induced aberrations.

  2. Strain-Independent Increases of Crystallin Proteins in the Retina of Type 1 Diabetic Rats

    PubMed Central

    Heise, Erich A.; Marozas, Lauren M.; Grafton, Sean A.; Green, Katelyn M.; Kirwin, Stefanie J.; Fort, Patrice E.

    2013-01-01

    Diabetic retinopathy is the leading cause of vision loss in working-age individuals in the United States and is expected to continue growing with the increased prevalence of diabetes. Streptozotocin-induced hyperglycemia in rats is the most commonly used model for diabetic retinopathy. Previous studies have shown that this model can lead to different inflammatory changes in the retina depending on the strain of rat. Our previous work has shown that crystallin proteins, including members of the alpha- and beta/gamma-crystallin subfamilies, are upregulated in the STZ rat retina. Crystallin proteins have been implicated in a number of cellular processes, such as neuroprotection, non-native protein folding and vascular remodeling. In this current study, we have demonstrated that unlike other strain-dependent changes, such as inflammatory cytokines and growth factor levels, in the STZ rat, the protein upregulation of crystallins is consistent across the Brown Norway, Long-Evans and Sprague-Dawley rat strains in the context of diabetes. Taken together, these data illustrate the potential critical role played by crystallins, and especially alpha-crystallins, in the retina in the context of diabetes. PMID:24349305

  3. DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina.

    PubMed

    Sasagawa, Shota; Nishimura, Yuhei; Kon, Tetsuo; Yamanaka, Yukiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Okabe, Shiko; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

    2016-01-01

    Intestinal helminths cause iron-deficiency anemia in pregnant women, associated with premature delivery, low birth weight, maternal ill health, and maternal death. Although benzimidazole compounds such as mebendazole (MBZ) are highly efficacious against helminths, there are limited data on its use during pregnancy. In this study, we performed in vivo imaging of the retinas of zebrafish larvae exposed to MBZ, and found that exposure to MBZ during 2 and 3 days post-fertilization caused malformation of the retinal layers. To identify the molecular mechanism underlying the developmental toxicity of MBZ, we performed transcriptome analysis of zebrafish eyes. The analysis revealed that the DNA damage response was involved in the developmental toxicity of MBZ. We were also able to demonstrate that inhibition of ATM significantly attenuated the apoptosis induced by MBZ in the zebrafish retina. These results suggest that MBZ causes developmental toxicity in the zebrafish retina at least partly by activating the DNA damage response, including ATM signaling, providing a potential adverse outcome pathway in the developmental toxicity of MBZ in mammals. PMID:27014071

  4. DEVELOMENT AND NEUROGENIC POTENTIAL OF MÜLLER GLIAL CELLS IN THE VERTEBRATE RETINA

    PubMed Central

    Jadhav, Ashutosh P.; Roesch, Karin; Cepko, Constance L.

    2011-01-01

    Considerable research on normal and diseased states within the retina has focused on neurons. Recent research on glia throughout the central nervous system, including within the retina where Müller glia are the main type of glia, has provided a more in depth view of glial functions in health and disease. Glial cells have been recognized as being vital for the maintenance of a healthy tissue environment, where they actively participate in neuronal activity. More recently, Müller glia have been recognized as being very similar to retinal progenitor cells, particularly when compared at the molecular level using comprehensive expression profiling techniques. The molecular similarities, as well as the developmental events that occur at the end of the genesis period of retinal cells, have led us to propose that Müller glia are a form of late stage retinal progenitor cells. These late stage progenitor cells acquire some specialized glial functions, but do not irreversibly leave the progenitor state. Indeed, Müller glia appear to be able to behave as a progenitor in that they have been shown to proliferate and produce neurons in several instances when an acute injury has been applied to the retina. Enhancement of this response is thus an exciting strategy for retinal repair. PMID:19465144

  5. The Visual Input to the Retina during Natural Head-Free Fixation

    PubMed Central

    Victor, Jonathan D.; Rucci, Michele

    2014-01-01

    Head and eye movements incessantly modulate the luminance signals impinging onto the retina during natural intersaccadic fixation. Yet, little is known about how these fixational movements influence the statistics of retinal stimulation. Here, we provide the first detailed characterization of the visual input to the human retina during normal head-free fixation. We used high-resolution recordings of head and eye movements in a natural viewing task to examine how they jointly transform spatial information into temporal modulations. In agreement with previous studies, we report that both the head and the eyes move considerably during fixation. However, we show that fixational head and eye movements mostly compensate for each other, yielding a spatiotemporal redistribution of the input power to the retina similar to that previously observed under head immobilization. The resulting retinal image motion counterbalances the spectral distribution of natural scenes, giving temporal modulations that are equalized in power over a broad range of spatial frequencies. These findings support the proposal that “ocular drift,” the smooth fixational motion of the eye, is under motor control, and indicate that the spatiotemporal reformatting caused by fixational behavior is an important computational element in the encoding of visual information. PMID:25232108

  6. Experimental implantation of epiretinal retina implants (EPI-RET) with an IOL-type receiver unit

    NASA Astrophysics Data System (ADS)

    Gerding, H.; Benner, F. P.; Taneri, S.

    2007-03-01

    The purpose of this paper is to investigate the surgical feasibility of implantation and long-term structural outcome of retina implant devices with an anterior IOL receiver, a connecting microcable and posterior segment epiretinal microcontacts. Implantation of epiretinal retina (EPI-RET) implants was performed as a one-step surgical procedure including phacoemulsification and pars plana vitrectomy in two adult rabbits. Implants were mechanically stabilized in an anterior position by the lens capsule and in the posterior segment by microtacks with a soft contact collar. Follow-up (6 and 9 months) included regular clinical examination, anterior and posterior segment photography and finally pathohistological evaluation. Implantation was uneventful in case 1 and complicated by vitreous space haemorrhage in case 2. At the end of follow-up, the retina was partially detached in animal 1 and subtotally detached in animal 2. Common features of tissue reaction in both cases were the formation of cyclitic membranes extending around and posterior to the anterior IOL receiver. In addition to that severe proliferations developed around microcables, microcontacts and microtacks forming a tissue capsule around posterior segment foreign materials. Retinal areas in contact to implant devices presented a severe structural damage and disorganization. Results of this preliminary trial suggest that the application of epiretinal prostheses with large diameter IOL receivers may be a critical issue and can give rise to an unfavourable outcome. Further systematic investigation ought to be performed involving a larger number of animals, modified implants and perhaps other species.

  7. Diacylglycerol O-Acyltransferase Type-1 Synthesizes Retinyl Esters in the Retina and Retinal Pigment Epithelium

    PubMed Central

    Kaylor, Joanna J.; Radu, Roxana A.; Bischoff, Nicholas; Makshanoff, Jacob; Hu, Jane; Lloyd, Marcia; Eddington, Shannan; Bianconi, Tran; Bok, Dean; Travis, Gabriel H.

    2015-01-01

    Retinyl esters represent an insoluble storage form of vitamin A and are substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment epithelium (RPE). The major retinyl-ester synthase in RPE cells is lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent retinyl-ester synthase activity has been observed in RPE homogenates but the protein responsible has not been identified. Here we show that diacylglycerol O-acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including RPE and Müller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in dgat1 -/- mice has no effect on retinal anatomy or the ultrastructure of photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in dgat1 -/- mice were also normal. However, the normal build-up of all-trans-retinyl esters (all-trans-RE’s) in the RPE during the first hour after a deep photobleach of visual pigments in the retina was not seen in dgat1 -/- mice. Further, total retinyl-ester synthase activity was reduced in both dgat1 -/- retina and RPE. PMID:25974161

  8. Rhodopsin and retinochrome in the retina of a marine gastropod, Conomulex luhuanus.

    PubMed

    Ozaki, K; Terakita, A; Hara, R; Hara, T

    1986-01-01

    Photopigments in the conch retina were examined with special attention given to the photic vesicles characteristic of gastropod photoreceptors. Three different fractions of visual cell fragments were prepared from the retina: the MV-fraction containing the rhabdomal microvilli, and the PVH- and PVL-fractions containing the photic vesicles located in the visual cell body. Rhodopsin was found in the MV-fraction (lambda max = 474 nm), and yielded a photoequilibrium mixture with metarhodopsin (lambda max = 512 nm) on irradiation with blue light. Retinochrome was found in both of the PVH- and PVL-fractions (lambda max = approximately 510 nm), and was bleached into metaretinochrome by exposure to orange light, showing no marked shift of the absorption peak. Unlike the PVH-fraction, the PVL-fraction contains much aporetinochrome in addition to retinochrome, suggesting that the large mass of photic vesicles around the nucleus may serve as storage for retinal in retinochrome and for newly synthesized aporetinochrome. The total amount of retinochrome in the retina was several times higher than that of rhodopsin, distinguishing the gastropod eye from the cephalopod eye. PMID:3750849

  9. MEMS scanner mirror based system for retina scanning and in eye projection

    NASA Astrophysics Data System (ADS)

    Woittennek, Franziska; Knobbe, Jens; Pügner, Tino; Dallmann, Hans-Georg; Schelinski, Uwe; Grüger, Heinrich

    2015-02-01

    Many applications could benefit from miniaturized systems to scan blood vessels behind the retina in the human eye, so called "retina scanning". This reaches from access control to sophisticated security applications and medical devices. High volume systems for consumer applications require low cost and a user friendly operation. For example this includes no need for removal of glasses and self-adjustment, in turn guidance of focus and point of attraction by simultaneous projection for the user. A new system has been designed based on the well-known resonantly driven 2-d scanner mirror of Fraunhofer IPMS. A combined NIR and VIS laser system illuminates the eye through an eye piece designed for an operating distance allowing the use of glasses and granting sufficient field of view. This usability feature was considered to be more important than highest miniaturization. The modulated VIS laser facilitates the projection of an image directly onto the retina. The backscattered light from the continuous NIR laser contains the information of the blood vessels and is detected by a highly sensitive photo diode. A demonstrational setup has been realized including readout and driving electronics. The laser power was adjusted to an eye-secure level. Additional security features were integrated. Test measurements revealed promising results. In a first demonstration application the detection of biometric pattern of the blood vessels was evaluated for issues authentication in.

  10. L-glutamic acid: a neurotransmitter candidate for cone photoreceptors in human and rat retinas.

    PubMed Central

    Brandon, C; Lam, D M

    1983-01-01

    We have combined immunocytochemical localization of L-aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1; glutamic-oxaloacetic transaminase) with autoradiographic localization of high-affinity uptake sites for L-glutamate or L-aspartate to identify the neurotransmitters of mammalian photoreceptors. In both human and rat retinas, high aspartate aminotransferase immunoreactivity is found in cones but not in rods; certain putative bipolar and amacrine cells are also heavily stained. In the human retina, and perhaps also in the rat retina, cones possess a high-affinity uptake mechanism for L-glutamate but not L-aspartate, whereas rods and Müller (glial) cells take up both L-glutamate and L-aspartate. Taken together, our results indicate that (i) L-glutamate is much more likely than L-aspartate to be the transmitter for human cones, and possibly for cones of other mammalian species as well, and (ii) major differences exist between mammalian cones and rods in the transport and metabolism or utilization of L-aspartate and L-glutamate. Images PMID:6136039

  11. DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina

    PubMed Central

    Sasagawa, Shota; Nishimura, Yuhei; Kon, Tetsuo; Yamanaka, Yukiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Okabe, Shiko; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

    2016-01-01

    Intestinal helminths cause iron-deficiency anemia in pregnant women, associated with premature delivery, low birth weight, maternal ill health, and maternal death. Although benzimidazole compounds such as mebendazole (MBZ) are highly efficacious against helminths, there are limited data on its use during pregnancy. In this study, we performed in vivo imaging of the retinas of zebrafish larvae exposed to MBZ, and found that exposure to MBZ during 2 and 3 days post-fertilization caused malformation of the retinal layers. To identify the molecular mechanism underlying the developmental toxicity of MBZ, we performed transcriptome analysis of zebrafish eyes. The analysis revealed that the DNA damage response was involved in the developmental toxicity of MBZ. We were also able to demonstrate that inhibition of ATM significantly attenuated the apoptosis induced by MBZ in the zebrafish retina. These results suggest that MBZ causes developmental toxicity in the zebrafish retina at least partly by activating the DNA damage response, including ATM signaling, providing a potential adverse outcome pathway in the developmental toxicity of MBZ in mammals. PMID:27014071

  12. Olfactory stimulation selectively modulates the OFF pathway in the retina of zebrafish.

    PubMed

    Esposti, Federico; Johnston, Jamie; Rosa, Juliana M; Leung, Kin-Mei; Lagnado, Leon

    2013-07-10

    Cross-modal regulation of visual performance by olfactory stimuli begins in the retina, where dopaminergic interneurons receive projections from the olfactory bulb. However, we do not understand how olfactory stimuli alter the processing of visual signals within the retina. We investigated this question by in vivo imaging activity in transgenic zebrafish expressing SyGCaMP2 in bipolar cell terminals and GCaMP3.5 in ganglion cells. The food-related amino acid methionine reduced the gain and increased sensitivity of responses to luminance and contrast transmitted through OFF bipolar cells but not ON. The effects of olfactory stimulus were blocked by inhibiting dopamine uptake and release. Activation of dopamine receptors increased the gain of synaptic transmission in vivo and potentiated synaptic calcium currents in isolated bipolar cells. These results indicate that olfactory stimuli alter the sensitivity of the retina through the dopaminergic regulation of presynaptic calcium channels that control the gain of synaptic transmission through OFF bipolar cells. PMID:23849198

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

    NASA Astrophysics Data System (ADS)

    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.

  14. The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications.

    PubMed

    Schwitzer, Thomas; Schwan, Raymund; Angioi-Duprez, Karine; Giersch, Anne; Laprevote, Vincent

    2016-01-01

    Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing. PMID:26881099

  15. Polycomb repressive complex PRC2 regulates Xenopus retina development downstream of Wnt/β-catenin signaling

    PubMed Central

    Aldiri, Issam; Moore, Kathryn B.; Hutcheson, David A.; Zhang, Jianmin; Vetter, Monica L.

    2013-01-01

    The histone methyltransferase complex PRC2 controls key steps in developmental transitions and cell fate choices; however, its roles in vertebrate eye development remain unknown. Here, we report that in Xenopus, PRC2 regulates the progression of retinal progenitors from proliferation to differentiation. We show that the PRC2 core components are enriched in retinal progenitors and downregulated in differentiated cells. Knockdown of the PRC2 core component Ezh2 leads to reduced retinal progenitor proliferation, in part due to upregulation of the Cdk inhibitor p15Ink4b. In addition, although PRC2 knockdown does not alter eye patterning, retinal progenitor gene expression or expression of the neural competence factor Sox2, it does cause suppression of proneural bHLH gene expression, indicating that PRC2 is crucial for the initiation of neural differentiation in the retina. Consistent with this, knocking down or blocking PRC2 function constrains the generation of most retinal neural cell types and promotes a Müller glial cell fate decision. We also show that Wnt/β-catenin signaling acting through the receptor Frizzled 5, but independent of Sox2, regulates expression of key PRC2 subunits in the developing retina. This is consistent with a role for this pathway in coordinating proliferation and the transition to neurogenesis in the Xenopus retina. Our data establish PRC2 as a regulator of proliferation and differentiation during eye development. PMID:23739135

  16. Current Progress in Deciphering Importance of VLC-PUFA in the Retina.

    PubMed

    Bennett, Lea D; Anderson, Robert E

    2016-01-01

    Stargardt-like macular dystrophy-3 (STGD3) is a juvenile-onset disease caused by mutations in ELOVL4 (elongation of very long fatty acids-4). This gene product catalyzes the elongation of long chain saturated and polyunsaturated fatty acids (LC-FAs and LC-PUFAs) into very long chain FAs and PUFAs (VLC-FAs and VLC-PUFAs). These mutations cause a frame shift in the ELOVL4 transcript, introducing a premature stop codon that results in the translation of a truncated protein that has lost a C-terminus endoplasmic reticulum (ER) retention/retrieval signal. The truncated protein is not targeted to the ER, the site of very long-chain PUFA (VLC-PUFA; 28-40 carbons) synthesis. Expression of the ELOVL4 gene is limited mainly to the brain, testis, skin, and photoreceptor cells of the retina. While the skin and brain contain very long chain saturated fatty acids (VLC-FAs), the other tissues expressing ELOVL4 contain VLC-PUFAs, with sperm and the retina having the highest levels. This review focuses on the current information available concerning the role of VLC-PUFAs in the retina. PMID:26427405

  17. Ultrafast laser assisted microinjection enables distinct spatial localization pattern in cells and retina

    NASA Astrophysics Data System (ADS)

    Gu, L.; Shivalingaiah, S.; Mohanty, S. K.

    2011-03-01

    Laser microbeam has enabled highly precise non-contact delivery of exogenous materials into targeted cells, which has been a highly challenging task while using traditional methods without compromising cell viability. We report distinct spatial localization of impermeable substances into mammalian cells and goldfish retinal cells in explants subsequent to ultrafast laser microbeam assisted injection, realized by focusing a near infrared tunable Ti: sapphire laser beam. Introduction of impermeable dye into the cell through localized pore formation was confirmed by distinct fluorescence at the site of pore formation on the membrane and its spatiotemporal diffusion pattern through the nucleus. Indirect optoporation by bubble formation, external to cell, led to a similar spatial diffusion pattern but with a larger time constant for injection. Using optimized laser intensity, exposure and spatial irradiation pattern, desired spatial transfection patterns in goldfish retina explants were achieved as confirmed by expression of injected plasmids encoded for light-activable channelrhodopsin-2 (ChR2) ion channel tagged with fluorescent protein. Laser assisted delivery of exogenous material into specific area of three-dimensional neuronal tissue, such as the retina, will help to understand the functioning of neuronal circuitry of normal and degenerated retina.

  18. Membrane docosahexaenoate is supplied to the developing brain and retina by the liver

    SciTech Connect

    Scott, B.L.; Bazan, N.G. )

    1989-04-01

    Docosahexaenoic acid is concentrated in phospholipids of cellular membranes from brain and retina. Although linolenic acid is the major {omega}3 fatty acid of mouse dams' milk, 22:6 is the prevalent {omega}3 fatty acid in serum and tissues. Intraperitoneal injection of (1-{sup 14}C)18:3 into 3-day-old mouse pups resulted in liver and serum lipid labeling that was initially high, followed by a rapid decline. In contrast, labeling of brain and retinal lipids were initially low and increased with time. Labeled 22:6 first appeared in liver 2 hr after injection and later in brain and retina. The authors suggest that 22:6 synthesized from 18:3 by the liver is secreted into the bloodstream in lipoproteins, taken up by brain and retina, and incorporated into cell membranes. They hypothesize that the 22;6 requirements of membranes (e.g., during synaptogenesis, photoreceptor membrane biogenesis, or repair after ischemic injury or neurodegenerative disorders) are met by a signal that is sent by the appropriate tissues to the liver to evoke the secretion of 22:6-containing lipoproteins.

  19. Portable Raman spectroscopy using retina-safe (1550 nm) laser excitation

    NASA Astrophysics Data System (ADS)

    Brouillette, Carl; Smith, Wayne; Donahue, Michael; Huang, Hermes; Shende, Chetan; Sengupta, Atanu; Inscore, Frank; Patient, Michael; Farquharson, Stuart

    2012-06-01

    The use of portable Raman analyzers to identify unknown substances in the field has grown dramatically during the past decade. Measurements often require the laser beam to exit the confines of the sample compartment, which increases the potential of eye or skin damage. This is especially true for most commercial analyzers, which use 785 nm laser excitation. To overcome this safety concern, we have built a portable FT-Raman analyzer using a 1550 nm retina-safe excitation laser. Excitation at 1550 nm falls within the 1400 to 2000 nm retina-safe range, so called because the least amount of damage to the eye occurs in this spectral region. In contrast to wavelengths below 1400 nm, the retina-safe wavelengths are not focused by the eye, but are absorbed by the cornea, aqueous and vitreous humor. Here we compare the performance of this system to measurements of explosives at shorter wavelengths, as well as its ability to measure surface-enhanced Raman spectra of several chemicals, including the food contaminant melamine.

  20. Design of a MEMS-based retina scanning system for biometric authentication

    NASA Astrophysics Data System (ADS)

    Woittennek, Franziska; Knobbe, Jens; Pügner, Tino; Schelinski, Uwe; Grüger, Heinrich

    2014-05-01

    There is an increasing need for reliable authentication for a number of applications such as e commerce. Common authentication methods based on ownership (ID card) or knowledge factors (password, PIN) are often prone to manipulations and may therefore be not safe enough. Various inherence factor based methods like fingerprint, retinal pattern or voice identifications are considered more secure. Retina scanning in particular offers both low false rejection rate (FRR) and low false acceptance rate (FAR) with about one in a million. Images of the retina with its characteristic pattern of blood vessels can be made with either a fundus camera or laser scanning methods. The present work describes the optical design of a new compact retina laser scanner which is based on MEMS (Micro Electric Mechanical System) technology. The use of a dual axis micro scanning mirror for laser beam deflection enables a more compact and robust design compared to classical systems. The scanner exhibits a full field of view of 10° which corresponds to an area of 4 mm2 on the retinal surface surrounding the optical disc. The system works in the near infrared and is designed for use under ambient light conditions, which implies a pupil diameter of 1.5 mm. Furthermore it features a long eye relief of 30 mm so that it can be conveniently used by persons wearing glasses. The optical design requirements and the optical performance are discussed in terms of spot diagrams and ray fan plots.

  1. Melanopsin-mediated post-illumination pupil response in the peripheral retina.

    PubMed

    Joyce, Daniel S; Feigl, Beatrix; Zele, Andrew J

    2016-06-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size by integrating extrinsic rod and cone signals with intrinsic melanopsin-mediated phototransduction. Light adapted pupil diameter is determined by the corneal flux density (CFD), and for central visual field stimulation the melanopsin-mediated post-illumination pupil response (PIPR) follows this same CFD relationship. Rods, cones, and ipRGCs vary in size, density, and distribution across the retina, but how these differences affect the amplitude and timing of the extrinsic and intrinsic pupil light reflex in the central and peripheral retina is unknown. We determined the relationship between stimulus area and photon flux with stimuli constant for CFD, irradiance, or area at central (0°) and peripheral (20°) eccentricities with high and low melanopsin excitation. We show that the pupil constriction amplitude was similar at both eccentricities and the time to minimum diameter increased as melanopsin excitation increased. In contrast, the peripheral PIPR follows a CFD relationship but with lower amplitude compared with that at the fovea. This indicates differences in the spatial and temporal characteristics of extrinsic and intrinsic ipRGC inputs to the pupil control pathway for the central and peripheral retina. The eccentricity-dependent change in PIPR amplitude may be analogous to the hill of vision observed in visual perimetry; such knowledge is an important precursor to the development of pupil perimetry paradigms to measure the PIPR in select regions of the visual field. PMID:27271992

  2. Early changes in system [Formula: see text] and glutathione in the retina of diabetic rats.

    PubMed

    Carpi-Santos, Raul; Ferreira, Marcos Josf; Pereira Netto, Annibal Duarte; Giestal-de-Araujo, Elizabeth; Ventura, Ana Lucia Marques; Cossenza, Marcelo; Calaza, Karin C

    2016-05-01

    Diabetic retinopathy (DR), the main cause of blindness among diabetic patients, affects both neuronal and vascular cells of the retina. Studies show that neuronal cell death begins after 4 weeks of diabetes and could be related with an increase in oxidative stress. System [Formula: see text] is a glutamate/cystine exchanger, formed by a catalytic subunit called xCT and a regulatory subunit 4F2hc, whose activity is crucial to the synthesis of glutathione, which is a key antioxidant molecule for cells. Although some studies have shown that glutamate transport mediated by excitatory amino acid transporters (EAATs) in diabetic rats is downregulated, there are no studies investigating system [Formula: see text] in this context. To evaluate whether system [Formula: see text] is modified by early onset of diabetes, primary retinal cell culture exposed to high glucose and retinas of rats 3 weeks after streptozotocin injection were used. We observed that xCT subunit protein expression both in cultures and in vivo were diminished. Furthermore, system [Formula: see text] activity and GSH levels were also decreased whereas oxidative stress was increased in retinas of diabetic animals. Therefore, this study raises the possibility that alterations in system [Formula: see text] expression and activity could occur during early onset of diabetes. In that way, system [Formula: see text] modifications could be related to increased ROS in diabetic retinopathy. PMID:26706282

  3. Neuroprotective effect of Myo/Nog cells in the stressed retina.

    PubMed

    Bravo-Nuevo, Arturo; Brandli, Alice A; Gerhart, Jacquelyn; Nichols, Jennifer; Pitts, Meghan; Sutera, Christopher K; Assali, Sarah; Scheinfeld, Victoria; Prendergast, George C; Stone, Jonathan; George-Weinstein, Mindy

    2016-05-01

    Myo/Nog cells are essential for eye development in the chick embryo and respond to injury in adult tissues. These cells express mRNA for the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein (BMP) inhibitor Noggin and the cell surface protein recognized by the G8 monoclonal antibody (mAb). In this study, we determined that Myo/Nog cells are present in low numbers in the retina of the mouse eye. G8-positive Myo/Nog cells were distinguished from neuronal, Müller and microglial cells that were identified with antibodies to calretinin, Chx10, glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1, respectively. In the neonatal retina, the number of Myo/Nog cells increased in parallel with cell death induced by transient exposure to hyperoxia. In this model of retinopathy of prematurity, depletion of Myo/Nog cells by intravitreal injection of the G8 mAb and complement increased cell death. These findings demonstrate that Myo/Nog cells are a distinct population of cells, not previously described in the retina, which increases in response to retinal damage and mitigate hypoxia-induced cell death. PMID:26688580

  4. Ocular delivery of compacted DNA-nanoparticles does not elicit toxicity in the mouse retina.

    PubMed

    Ding, Xi-Qin; Quiambao, Alexander B; Fitzgerald, J Browning; Cooper, Mark J; Conley, Shannon M; Naash, Muna I

    2009-01-01

    Subretinal delivery of polyethylene glycol-substituted lysine peptide (CK30PEG)-compacted DNA nanoparticles results in efficient gene expression in retinal cells. This work evaluates the ocular safety of compacted DNA nanoparticles. CK30PEG-compacted nanoparticles containing an EGFP expression plasmid were subretinally injected in adult mice (1 microl at 0.3, 1.0 and 3.0 microg/microl). Retinas were examined for signs of inflammation at 1, 2, 4 and 7 days post-injection. Neither infiltration of polymorphonuclear neutrophils or lymphocytes was detected in retinas. In addition, elevation of macrophage marker F4/80 or myeloid marker myeloperoxidase was not detected in the injected eyes. The chemokine KC mRNA increased 3-4 fold in eyes injected with either nanoparticles or saline at 1 day post-injection, but returned to control levels at 2 days post-injection. No elevation of KC protein was observed in these mice. The monocyte chemotactic protein-1, increased 3-4 fold at 1 day post-injection for both nanoparticle and saline injected eyes, but also returned to control levels at 2 days. No elevations of tumor necrosis factor alpha mRNA or protein were detected. These investigations show no signs of local inflammatory responses associated with subretinal injection of compacted DNA nanoparticles, indicating that the retina may be a suitable target for clinical nanoparticle-based interventions. PMID:19823583

  5. Vessel segmentation in 3D spectral OCT scans of the retina

    NASA Astrophysics Data System (ADS)

    Niemeijer, Meindert; Garvin, Mona K.; van Ginneken, Bram; Sonka, Milan; Abràmoff, Michael D.

    2008-03-01

    The latest generation of spectral optical coherence tomography (OCT) scanners is able to image 3D cross-sectional volumes of the retina at a high resolution and high speed. These scans offer a detailed view of the structure of the retina. Automated segmentation of the vessels in these volumes may lead to more objective diagnosis of retinal vascular disease including hypertensive retinopathy, retinopathy of prematurity. Additionally, vessel segmentation can allow color fundus images to be registered to these 3D volumes, possibly leading to a better understanding of the structure and localization of retinal structures and lesions. In this paper we present a method for automatically segmenting the vessels in a 3D OCT volume. First, the retina is automatically segmented into multiple layers, using simultaneous segmentation of their boundary surfaces in 3D. Next, a 2D projection of the vessels is produced by only using information from certain segmented layers. Finally, a supervised, pixel classification based vessel segmentation approach is applied to the projection image. We compared the influence of two methods for the projection on the performance of the vessel segmentation on 10 optic nerve head centered 3D OCT scans. The method was trained on 5 independent scans. Using ROC analysis, our proposed vessel segmentation system obtains an area under the curve of 0.970 when compared with the segmentation of a human observer.

  6. Constitutive Overexpression of Human Erythropoietin Protects the Mouse Retina against Induced But Not Inherited Retinal Degeneration

    PubMed Central

    Grimm, Christian; Wenzel, Andreas; Stanescu, Dinu; Samardzija, Marijana; Hotop, Svenja; Groszer, Mathias; Naash, Muna; Gassmann, Max; Remé, Charlotte

    2010-01-01

    Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinant human Epo (huEpo) protects the mouse retina against light-induced degeneration by inhibiting photoreceptor cell apoptosis. Because photoreceptor apoptosis is also the common path to cell loss in retinal dystrophies such as retinitis pigmentosa (RP), we tested whether high levels of huEpo would reduce apoptotic cell death in two mouse models of human RP. We combined the two respective mutant mouse lines with a transgenic line (tg6) that constitutively overexpresses huEpo mainly in neural tissues. Transgenic expression of huEpo caused constitutively high levels of Epo in the retina and protected photoreceptors against light-induced degeneration; however, the presence of high levels of huEpo did not affect the course or the extent of retinal degeneration in a light-independent (rd1) and a light-accelerated (VPP) mouse model of RP. Similarly, repetitive intraperitoneal injections of recombinant huEpo did not protect the retina in the rd1 and the VPP mouse. Lack of neuroprotection by Epo in the two models of inherited retinal degeneration was not caused by adaptational downregulation of Epo receptor. Our results suggest that apoptotic mechanisms during acute, light-induced photoreceptor cell death differ from those in genetically based retinal degeneration. Therapeutic intervention with cell death in inherited retinal degeneration may therefore require different drugs and treatments. PMID:15215287

  7. Making the gradient: Thyroid hormone regulates cone opsin expression in the developing mouse retina

    PubMed Central

    Roberts, Melanie R.; Srinivas, Maya; Forrest, Douglas; Morreale de Escobar, Gabriella; Reh, Thomas A.

    2006-01-01

    Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short wavelength (S) opsin. The number and spatial organization of cone types varies dramatically among species, presumably to fine-tune the retina for different visual environments. In the mouse, S- and M-opsin are expressed in an opposing dorsal–ventral gradient. We previously reported that cone opsin patterning requires thyroid hormone β2, a nuclear hormone receptor that regulates transcription in conjunction with its ligand, thyroid hormone (TH). Here we show that exogenous TH inhibits S-opsin expression, but activates M-opsin expression. Binding of endogenous TH to TRβ2 is required to inhibit S-opsin and to activate M-opsin. TH is symmetrically distributed in the retina at birth as S-opsin expression begins, but becomes elevated in the dorsal retina at the time of M-opsin onset (postnatal day 10). Our results show that TH is a critical regulator of both S-opsin and M-opsin, and suggest that a TH gradient may play a role in establishing the gradient of M-opsin. These results also suggest that the ratio and patterning of cone types may be determined by TH availability during retinal development. PMID:16606843

  8. The scotopic electroretinogram of the sugar glider related to histological features of its retina.

    PubMed

    Akula, James D; Esdaille, Tricia M; Caffé, A Romeo; Naarendorp, Franklin

    2011-11-01

    The flash electroretinogram (ERG) was used to characterize the scotopic retinal function in a marsupial. Key parameter values of the a- and b-waves of adult male sugar gliders, Petaurus breviceps breviceps, elicited with ganzfeld flashes were determined under dark- and light-adapted conditions. Using standard histological methods, the thicknesses of the major layers of the retina were assessed to provide insight into the nature of the ERG responses. The ERG and histological results were compared to corresponding data for placental C57Bl/6 mice to establish whether the functional retinal specialization that underlies scotopic visual function in a marsupial parallels that of a placental mouse. The sensitivity of the a-wave assessed with the Lamb and Pugh (Invest Ophthalmol Vis Sci 47:5138-5152, 2006) "model" and that of the b-wave assessed with standard methods were lower in the sugar glider compared to the mouse. The thickness of the sugar glider retina was two-third of that of the mouse. The high-intensity flash ERG of the sugar glider substantially differed in shape from that of the mouse reflecting perhaps structural and functional differences between the two species at the level of the inner retina. PMID:21744008

  9. Diffusion and consumption of oxygen in the superfused retina of the drone (Apis mellifera) in darkness.

    PubMed

    Tsacopoulos, M; Poitry, S; Borsellino, A

    1981-06-01

    Double-barreled O2 microelectrodes were used to study O2 diffusion and consumption in the superfused drone (Apis mellifera) retina in darkness at 22 degrees C. Po2 was measured at different sites in the bath and retinas. It was found that diffusion was essentially in one dimension and that the rate of O2 consumption (Q) was practically constant (on the macroscale) down to Po2 s less than 20 mm Hg, a situation that greatly simplified the analysis. The value obtained for Q was 18 +/- 0.7 (SEM) microliter O2/cm3 tissue . min (n = 10), and Krogh's permeation coefficient (alpha D) was 3.24 +/- 0.18 (SEM) X 10(-5) ml O1/min . atm . cm (n = 10). Calculations indicate that only a small fraction of this Q in darkness is necessary for the energy requirements of the sodium pump. the diffusion coefficient (D) in the retina was measured by abruptly cutting off diffusion from the bath and analyzing the time-course of the fall in Po2 at the surface of the tissue. The mean value of D was 1.03 +/- 0.08 (SEM) X 10(-5) cm2/s (n = 10). From alpha D and D, the solubility coefficient alpha was calculated to be 54 +/- 4.0 (SEM) microliter O2 STP/cm3 . atm (n = 10), approximately 1.8 times that for water. PMID:7264598

  10. The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications

    PubMed Central

    Schwitzer, Thomas; Schwan, Raymund; Angioi-Duprez, Karine; Giersch, Anne; Laprevote, Vincent

    2016-01-01

    Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing. PMID:26881099

  11. Effect of high potassium on dopamine receptor activity in bovine retina

    SciTech Connect

    Ackerman, J.M.

    1989-01-01

    In the present study, the hypothesis that dopamine released by light caused a subsensitivity of the dopamine receptor was investigated. Bovine eyes were obtained from a slaughterhouse, and retinas were dissected in a dark room. Filter binding assays were developed to measure agonist and antagonist binding to the dopamine receptor using ({sup 3}H)dopamine and ({sup 3}H)SCH 23390, respectively, in a retinal membrane fraction. Adenylate cyclase activation was measured by the production of ({sup 32}P)cyclic AMP from {sup 32}ATP. In desensitization experiments, bovine retinas were incubated for fifteen minutes with 56 mM potassium, which also causes a release of dopamine in retinas were washed, and membranes were prepared. The stimulation of adenylate cyclase evoked by dopamine and radiolabeled agonist and antagonist binding were measured. In the receptor binding characterization studies, the dissociation constant and the maximum number of binding sites were obtained for ({sup 3}H)dopamine and ({sup 3}H)SCH 23390 binding.

  12. Imaging pulse wave velocity in mouse retina using swept-source OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Song, Shaozhen; Wei, Wei; Wang, Ruikang K.

    2016-03-01

    Blood vessel dynamics has been a significant subject in cardiology and internal medicine, and pulse wave velocity (PWV) on artery vessels is a classic evaluation of arterial distensibility, and has never been ascertained as a cardiovascular risk marker. The aim of this study is to develop a high speed imaging technique to capture the pulsatile motion on mouse retina arteries with the ability to quantify PWV on any arterial vessels. We demonstrate a new non-invasive method to assess the vessel dynamics on mouse retina. A Swept-source optical coherence tomography (SS-OCT) system is used for imaging micro-scale blood vessel motion. The phase-stabilized SS-OCT provides a typical displacement sensitivity of 20 nm. The frame rate of imaging is ~16 kHz, at A-line rate of ~1.62 MHz, which allows the detection of transient pulse waves with adequate temporal resolution. Imaging volumes with repeated B-scans are obtained on mouse retina capillary bed, and the mouse oxymeter signal is recorded simultaneously. The pulse wave on artery and vein are resolved, and with the synchronized heart beat signal, the temporal delay on different vessel locations is determined. The vessel specific measurement of PWV is achieved for the first time with SS-OCT, for pulse waves propagating more than 100 cm/s. Using the novel methodology of retinal PWV assessment, it is hoped that the clinical OCT scans can provide extended diagnostic information of cardiology functionalities.

  13. Image rotation-elimination based on a retina-like sensor

    NASA Astrophysics Data System (ADS)

    Cao, Fengmei; Lin, Yabin; Bai, Tingzhu; Wang, Fan

    2015-12-01

    The pixels of a retina-like sensor are arranged in concentric rings, and the output image is given in log-polar coordinates. Thus, additional residual errors will not be produced when the output image is rotated. Therefore, retina-like sensors have obvious advantages and many prospects for applications in the fields of image rotation and rapid image rotation-elimination. In this study, a theory concerning the image rotation of a retina-like sensor is proposed, and a solution based on the theory is presented and realized for eliminating image rotation caused by camera rotation. The camera rotation angle is obtained using a microelectromechanical systems digital accelerometer and gyroscope; only the readout sequence of each row from static random-access memory must be changed to achieve image rotation-elimination. Several image rotation-elimination experiments have been performed which show that the proposed solution is simple, accurate, and rapid. This rapid image rotation-elimination method can be used in fields that require higher image rotation-elimination processing speeds.

  14. Nam Con Son Basin

    SciTech Connect

    Tin, N.T.; Ty, N.D.; Hung, L.T.

    1994-07-01

    The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.

  15. Diversity of Retinal Ganglion Cells Identified by Transient GFP Transfection in Organotypic Tissue Culture of Adult Marmoset Monkey Retina

    PubMed Central

    Moritoh, Satoru; Komatsu, Yusuke; Yamamori, Tetsuo; Koizumi, Amane

    2013-01-01

    The mammalian retina has more diversity of neurons than scientists had once believed in order to establish complicated vision processing. In the monkey retina, morphological diversity of retinal ganglion cells (RGCs) besides dominant midget and parasol cells has been suggested. However, characteristic subtypes of RGCs in other species such as bistratified direction-selective ganglion cells (DSGC) have not yet been identified. Increasing interest has been shown in the common marmoset (Callithrix jacchus) monkey as a “super-model” of neuroscientific research. Here, we established organotypic tissue culture of the adult marmoset monkey retina with particle-mediated gene transfer of GFP to survey the morphological diversity of RGCs. We successfully incubated adult marmoset monkey retinas for 2 to 4 days ex vivo for transient expression of GFP. We morphologically examined 121 RGCs out of more than 3240 GFP-transfected cells in 5 retinas. Among them, we identified monostratified or broadly stratified ganglion cells (midget, parasol, sparse, recursive, thorny, and broad thorny ganglion cells), and bistratified ganglion cells (recursive, large, and small bistratified ganglion cells [blue-ON/yellow-OFF-like]). By this survey, we also found a candidate for bistratified DSGC whose dendrites were well cofasciculated with ChAT-positive starburst dendrites, costratified with ON and OFF ChAT bands, and had honeycomb-shaped dendritic arbors morphologically similar to those in rabbits. Our genetic engineering method provides a new approach to future investigation for morphological and functional diversity of RGCs in the monkey retina. PMID:23336011

  16. Changes in metabolic proteins in ex vivo rat retina during glutamate-induced neural progenitor cell induction.

    PubMed

    Tokuda, Kazuhiro; Kuramitsu, Yasuhiro; Baron, Byron; Kitagawa, Takao; Tokuda, Nobuko; Kobayashi, Masaaki; Kimura, Kazuhiro; Sonoda, Koh-Hei; Nakamura, Kazuyuki

    2016-08-01

    Understanding how energy metabolism and related proteins influence neural progenitor cells in adult tissues is critical for developing new strategies in clinical tissue regeneration therapy. We have recently reported that a subtoxic concentration of glutamate-induced neural progenitor cells in the mature ex vivo rat retina. We herein explore changes in the metabolic pathways during the process. We firstly observed an increase in lactate and lactate dehydrogenase concentration in the glutamate-treated retina. We then investigated the levels of glycolytic enzymes and confirmed significant upregulation of pyruvate kinase M type (PKM), especially PKM2, enolase, phosphoglycerate mutase 1 (PGAM1), and inosine-5'-monophosphate dehydrogenase (IMPDH1) in the glutamate-treated retina compared to the untreated retina. An analysis of the subcellular localization of PKM2 revealed nuclear translocation in the treated retina, which has been reported to regulate cell cycle proliferation and glycolytic enzymes. Our findings indicate that the mature rat retina undergoes an increase in aerobic glycolysis. PKM2, both in the cytoplasm and in the nucleus, may thus play an important role during neural progenitor cell induction, as it does in other proliferating cells. PMID:27421851

  17. PhTx3-4, a Spider Toxin Calcium Channel Blocker, Reduces NMDA-Induced Injury of the Retina

    PubMed Central

    Binda, Nancy Scardua; Porto Petruceli Carayon, Charles; Agostini, Rafael Mourão; do Nascimento Pinheiro, Ana Cristina; Nascimento Cordeiro, Marta; Romano Silva, Marco Aurélio; Figueira Silva, Juliana; Rita Pereira, Elizete Maria; da Silva Junior, Claudio Antonio; de Castro Junior, Célio José; Sena Guimarães, Andre Luiz; Gomez, Marcus Vinicius

    2016-01-01

    The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-d-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels. PMID:26978403

  18. PhTx3-4, a Spider Toxin Calcium Channel Blocker, Reduces NMDA-Induced Injury of the Retina.

    PubMed

    Binda, Nancy Scardua; Porto Petruceli Carayon, Charles; Agostini, Rafael Mourão; do Nascimento Pinheiro, Ana Cristina; Nascimento Cordeiro, Marta; Romano Silva, Marco Aurélio; Figueira Silva, Juliana; Rita Pereira, Elizete Maria; da Silva Junior, Claudio Antonio; de Castro Junior, Célio José; Sena Guimarães, Andre Luiz; Gomez, Marcus Vinicius

    2016-01-01

    The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-d-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels. PMID:26978403

  19. Functional diversity of melanopsins and their global expression in the teleost retina.

    PubMed

    Davies, Wayne I L; Zheng, Lei; Hughes, Steven; Tamai, T Katherine; Turton, Michael; Halford, Stephanie; Foster, Russell G; Whitmore, David; Hankins, Mark W

    2011-12-01

    Melanopsin (OPN4) is an opsin photopigment that, in mammals, confers photosensitivity to retinal ganglion cells and regulates circadian entrainment and pupil constriction. In non-mammalian species, two forms of opn4 exist, and are classified into mammalian-like (m) and non-mammalian-like (x) clades. However, far less is understood of the function of this photopigment family. Here we identify in zebrafish five melanopsins (opn4m-1, opn4m-2, opn4m-3, opn4x-1 and opn4x-2), each encoding a full-length opsin G protein. All five genes are expressed in the adult retina in a largely non-overlapping pattern, as revealed by RNA in situ hybridisation and immunocytochemistry, with at least one melanopsin form present in all neuronal cell types, including cone photoreceptors. This raises the possibility that the teleost retina is globally light sensitive. Electrophysiological and spectrophotometric studies demonstrate that all five zebrafish melanopsins encode a functional photopigment with peak spectral sensitivities that range from 470 to 484 nm, with opn4m-1 and opn4m-3 displaying invertebrate-like bistability, where the retinal chromophore interchanges between cis- and trans-isomers in a light-dependent manner and remains within the opsin binding pocket. In contrast, opn4m-2, opn4x-1 and opn4x-2 are monostable and function more like classical vertebrate-like photopigments, where the chromophore is converted from 11-cis to all-trans retinal upon absorption of a photon, hydrolysed and exits from the binding pocket of the opsin. It is thought that all melanopsins exhibit an invertebrate-like bistability biochemistry. Our novel findings, however, reveal the presence of both invertebrate-like and vertebrate-like forms of melanopsin in the teleost retina, and indicate that photopigment bistability is not a universal property of the melanopsin family. The functional diversity of these teleost melanopsins, together with their widespread expression pattern within the retina

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

    PubMed

    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

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

    NASA Technical Reports Server (NTRS)

    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

  2. Rod phototransduction modulated by bicarbonate in the frog retina: roles of carbonic anhydrase and bicarbonate exchange.

    PubMed Central

    Donner, K; Hemilä, S; Kalamkarov, G; Koskelainen, A; Shevchenko, T

    1990-01-01

    1. Effects on rod phototransduction following manipulation of retinal CO2-HCO3- and H+ fluxes were studied in dark-adapted retinas of the frog and the tiger salamander. 2. Rod photoresponses to brief flashes of light were recorded from the isolated sensory retina as electroretinogram mass receptor potentials and from isolated rods by the suction-pipette technique. The experimental treatments were: (1) varying [CO2] + [HCO3-] in the perfusion fluid: (2) applying acetazolamide (AAA), which inhibits the enzyme carbonic anhydrase (CA); and (3) applying 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) which blocks exchange mechanisms transporting HCO3- across cell membranes. 3. The concentration of the internal transmitter of the rods, cyclic GMP, was biochemically determined from the rod outer segment layer of retinas that had been incubated in the same solutions as were used for perfusion in the electrophysiological experiments. 4. The introduction of 6 mM-sodium bicarbonate to replace half the buffer of a nominally CO2-HCO3(-)-free (12 mM-phosphate or HEPES, [Na+] constant) Ringer solution doubled the cyclic GMP concentration in the rod outer segment layer and increased the saturating response amplitude and the relative sensitivity of rods in the intact retina. 5. The introduction of 0.5 mM-AAA into bicarbonate-containing Ringer solution accelerated the growth of saturated responses and sensitivity. Incubation of the retina in AAA-bicarbonate Ringer solution elevated the concentration of cyclic GMP ninefold compared with the phosphate control. 6. No effects of switching to bicarbonate-AAA Ringer solution were observed in the photocurrent of isolated rods drawn into suction pipettes with only the outer segment protruding into the perfusion fluid. The target of AAA is probably the CA-containing Müller cell. 7. The introduction of DIDS into the perfusate (at normal pH 7.5) set off a continuous decay of photoresponses which finally abolished light sensitivity

  3. Characterization of the retina in the alpha7 nicotinic acetylcholine receptor knockout mouse

    NASA Astrophysics Data System (ADS)

    Smith, Marci L.

    Acetylcholine receptors (AChRs) are involved in visual processing and are expressed by inner retinal neurons in all species studied to date (Keyser et al., 2000; Dmitrieva et al., 2007; Liu et al., 2009), but their distribution in the mouse retina remains unknown. Reductions in alpha7 nicotinic AChRs (nAChRs) are thought to contribute to memory and visual deficits observed in Alzheimer's and schizophrenia (Coyle et al., 1983; Nordberg et al., 1999; Leonard et al., 2006). However, the alpha7 nAChR knockout (KO) mouse has a mild phenotype (Paylor et al., 1998; Fernandes et al., 2006; Young et al., 2007; Origlia et al., 2012). The purpose of this study was to determine the expression of AChRs in wildtype (WT) mouse retina and to assess whether up-regulation of other AChRs in the alpha7 nAChR KO retina may explain the minimal deficits described in the KO mouse. Reverse-transcriptase PCR (RT-PCR) showed that mRNA transcripts for alpha2-7, alpha 9, alpha10, beta2-4 nAChR subunits and m1-m5 muscarinic AChR (mAChR) subtypes were present in WT murine retina. Western blot analysis confirmed the presence of alpha3-5, alpha9, and m1-m5 AChR proteins and immunohistochemical analysis demonstrated nAChR and mAChR proteins expressed by subsets of bipolar, amacrine and ganglion cells. This is the first reported expression of alpha9 and alpha10 nAChR transcripts and alpha9 nAChR proteins in the retina of any species. Quantitative RT-PCR (qPCR) showed changes in AChR transcript expression in the alpha7 nAChR KO mouse retina relative to WT. Within whole retina alpha2, alpha9, alpha10, beta4, m1 and m4 AChR transcripts were up-regulated, while alpha5 nAChR transcripts were down-regulated. However, cell populations showed subtle differences; m4 mAChR transcripts were up-regulated in the ganglion cell layer and outer portion of the inner nuclear layer (oINL),while beta4 nAChR transcript up-regulation was limited to the oINL. Surprisingly, alpha2, alpha9, beta4, m2 and m4 transcripts were

  4. Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation.

    PubMed

    Mic, Felix A; Molotkov, Andrei; Molotkova, Natalia; Duester, Gregg

    2004-10-01

    Three retinaldehyde dehydrogenase genes (Raldh1, Raldh2, and Raldh3) expressed in unique spatiotemporal patterns may control synthesis of retinoic acid (RA) needed for retina development. However, previous studies indicate that retina formation still proceeds normally in Raldh1-/- mouse embryos lacking RA synthesis in the dorsal neural retina at the optic cup stage. Here, we demonstrate that Raldh2-/- embryos lacking RA synthesis in the optic vesicle exhibit a failure in retina invagination needed to develop an optic cup. This was also observed in Raldh1-/-:Raldh2-/- double mutants, which develop similarly. Both mutants retain RA activity in the lens placode associated with Raldh3 expression, but this RA activity is insufficient to induce optic cup formation. Maternal RA administration at the optic vesicle stage rescues optic cup formation in Raldh2-/- and Raldh1-/-:Raldh2-/- embryos, demonstrating that Raldh1 is not required during rescue of optic cup development. The optic cup of rescued Raldh1-/-:Raldh2-/- embryos exhibits normal RA activity and this is associated with Raldh3 expression in the retina and lens. Thus, RA signaling initiates in the optic vesicle in response to Raldh2 but can be maintained during optic cup formation by a gene other than Raldh1, most likely Raldh3. Loss of optic vesicle RA signaling does not effect expression of early determinants of retina at the optic vesicle stage (Pax6, Six3, Rx, Mitf). Our findings suggest that RA functions as one of the signals needed for invagination of the retina to generate an optic cup. PMID:15366004

  5. Decreased energy requirement of toad retina during light adaptation as demonstrated by 31P nuclear magnetic resonance.

    PubMed Central

    Apte, D V; Ebrey, T G; Dawson, M J

    1993-01-01

    1. The effect of light and dark adaptation on the levels of phosphorus metabolites (nucleotide di- and triphosphates, phosphocreatine, pyridine nucleotide, inorganic phosphate, phosphodiesters, phosphomonoesters, and uridine diphosphate-glucose) in the toad (Bufo marinus) retina and retinal extracts was studied by 31P nuclear magnetic resonance (NMR) spectroscopy. 2. Spectra were acquired using an NMR probe specifically designed for superfusion and illumination of a single retina. Retinae were maintained at a steady state for up to 10 h in an electrolyte solution containing 10 mM Hepes buffer and bubbled with 98% O2-2% CO2, pH 7.8 at 20 degrees C. 3. The intracellular concentrations of the phosphorus metabolites were measured in total darkness or during prolonged exposure to light. The concentration of nucleoside triphosphates (NTP) in the dark-adapted retina was about 1.5 mM and that of phosphocreatine (PCr) was about 0.7 mM. 4. In saturating levels of light, 6.0 x 10(11) or 1.5 x 10(13) quanta s-1 cm-2 at 520 nm, the levels of PCr and phosphomonoesters rose, the levels of NTP and protons (pH) were maintained, and the levels of pyridine nucleotides and nucleotide diphosphates (NDP) fell. 5. A rise in the level of PCr in the presence of an unchanged level of NTP in the light-adapted retina indicates that the energy consumption of the retina is greater in the dark. 6. These results are in agreement with the results of oxygen consumption, glucose dependence, and electrophysiological studies which also indicate that the metabolic energy requirement of the retina decreases in light. PMID:8229802

  6. Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

    PubMed Central

    Gallina, Donika; Zelinka, Christopher; Fischer, Andy J.

    2014-01-01

    Identification of the signaling pathways that influence the reprogramming of Müller glia into neurogenic retinal progenitors is key to harnessing the potential of these cells to regenerate the retina. Glucocorticoid receptor (GCR) signaling is commonly associated with anti-inflammatory responses and GCR agonists are widely used to treat inflammatory diseases of the eye, even though the cellular targets and mechanisms of action in the retina are not well understood. We find that signaling through GCR has a significant impact upon the ability of Müller glia to become proliferating Müller glia-derived progenitor cells (MGPCs). The primary amino acid sequence and pattern of GCR expression in the retina is highly conserved across vertebrate species, including chickens, mice, guinea pigs, dogs and humans. In all of these species we find GCR expressed by the Müller glia. In the chick retina, we find that GCR is expressed by progenitors in the circumferential marginal zone (CMZ) and is upregulated by Müller glia in acutely damaged retinas. Activation of GCR signaling inhibits the formation of MGPCs and antagonizes FGF2/MAPK signaling in the Müller glia. By contrast, we find that inhibition of GCR signaling stimulates the formation of proliferating MGPCs in damaged retinas, and enhances the neuronal differentiation while diminishing glial differentiation. Given the conserved expression pattern of GCR in different vertebrate retinas, we propose that the functions and mechanisms of GCR signaling are highly conserved and are mediated through the Müller glia. We conclude that GCR signaling directly inhibits the formation of MGPCs, at least in part, by interfering with FGF2/MAPK signaling. PMID:25085975

  7. Alterations in Energy Metabolism, Neuroprotection and Visual Signal Transduction in the Retina of Parkinsonian, MPTP-Treated Monkeys

    PubMed Central

    Bru-Martínez, Roque; Herrero, María Trinidad; Fernández-Villalba, Emiliano; Cuenca, Nicolás; Martín-Nieto, José

    2013-01-01

    Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ±1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTP-induced neuronal degeneration in the retina, in similarity to mechanisms thought to

  8. Memantine blocks mitochondrial OPA1 and cytochrome c release, and subsequent apoptotic cell death in glaucomatous retina

    PubMed Central

    Ju, Won-Kyu; Kim, Keun-Young; Angert, Mila; Duong-Polk, Karen X.; Lindsey, James D.; Ellisman, Mark H.; Weinreb, Robert N.

    2009-01-01

    Purpose To determine whether intraocular pressure (IOP) elevation alters OPA1 expression and triggers OPA1 release, as well as whether the uncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist memantine blocks OPA1 release and subsequent apoptotic cell death in glaucomatous DBA/2J mouse retina. Methods Preglaucomatous DBA/2J mice received memantine (5 mg/kg, i.p. injection, twice a day for 3 months) and IOP in the eyes was measured monthly. RGC loss was counted following Fluoro-Gold labeling. OPA1, Dnm1, Bcl-2 and Bax mRNA were measured by Taqman qPCR. OPA1 protein was assessed by immunohistochemistry and Western blot. Apoptotic cell death was assessed by TUNEL staining. Results Memantine treatment significantly increased RGC survival in glaucomatous DBA/2J mice. Memantine treatment increased the 75 kDa OPA1 isoform but did not alter the 80 and 90 kDa isoforms. The isoforms of OPA1 were significantly increased in the cytosol of the vehicle-treated glaucomatous retinas but were significantly decreased in memantine-treated glaucomatous retinas. OPA1 immunoreactivity was decreased in the photoreceptors of both vehicle- and memantine-treated glaucomatous retinas but was increased in the outer plexiform layer of only the memantine-treated glaucomatous retinas. Memantine blocked apoptotic cell death in the GCL, increased Bcl-2 gene expression, and decreased Bax gene expression. Conclusions OPA1 release from mitochondria in glaucomatous mouse retina is inhibited by blockade of glutamate receptor activation. Because this OPA1 effect was accompanied by increased Bcl-2 expression, decreased Bax expression and apoptosis blockade, glutamate receptor activation in the glaucomatous retina may involve a distinct mitochondria-mediated cell death pathway. PMID:18936150

  9. Regression of retinal capillaries following N-methyl-D-aspartate-induced neurotoxicity in the neonatal rat retina.

    PubMed

    Asano, Daiki; Nakahara, Tsutomu; Mori, Asami; Sakamoto, Kenji; Ishii, Kunio

    2015-02-01

    Degeneration of retinal capillaries occurs following N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity, and the degree of capillary degeneration decreases in an age-dependent manner. To determine the role of vascular endothelial growth factor (VEGF) in the high susceptibility of capillaries to neuronal damage during the early postnatal stage, this study compares the vascular regression patterns between NMDA-treated retinas and retinas treated with N-[2-chloro-4-{(6,7-dimethoxy-4-quinazolinyl)oxy}phenyl]-N'-propylurea (KRN633), a VEGF receptor tyrosine kinase inhibitor, in neonatal rats. Two days after a single intravitreal injection of NMDA (200 nmol/eye) on postnatal day (P) 7, substantial retinal neuron loss and delayed expansion of the retinal vascular bed were observed. The reduction in the capillary density in the central retina reached statistical significance 4 days after NMDA treatment. In retinas of rats injected subcutaneously with KRN633 (10 mg/kg) on P7 and P8, simplified vasculature attributable to capillary regression and prevention of endothelial cell growth were seen on P9, whereas no visible changes in the morphology of the retinal layers were observed. The degree of capillary degeneration in NMDA-treated retinas was less than that in KRN633-treated retinas. No apparent changes in immunoreactivities for VEGF were found 2 days after NMDA treatment. These results indicate that neuronal cell loss in the retina precedes retinal capillary degeneration following NMDA treatment, and VEGF-dependent immature capillaries might be more susceptible to NMDA-induced neuronal damage. PMID:25284371

  10. High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs

    PubMed Central

    Karali, Marianthi; Persico, Maria; Mutarelli, Margherita; Carissimo, Annamaria; Pizzo, Mariateresa; Singh Marwah, Veer; Ambrosio, Concetta; Pinelli, Michele; Carrella, Diego; Ferrari, Stefano; Ponzin, Diego; Nigro, Vincenzo; di Bernardo, Diego; Banfi, Sandro

    2016-01-01

    MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina. PMID:26819412

  11. High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs.

    PubMed

    Karali, Marianthi; Persico, Maria; Mutarelli, Margherita; Carissimo, Annamaria; Pizzo, Mariateresa; Singh Marwah, Veer; Ambrosio, Concetta; Pinelli, Michele; Carrella, Diego; Ferrari, Stefano; Ponzin, Diego; Nigro, Vincenzo; di Bernardo, Diego; Banfi, Sandro

    2016-02-29

    MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina. PMID:26819412

  12. Distribution of Mammalian-Like Melanopsin in Cyclostome Retinas Exhibiting a Different Extent of Visual Functions

    PubMed Central

    Sun, Lanfang; Kawano-Yamashita, Emi; Nagata, Takashi; Tsukamoto, Hisao; Furutani, Yuji; Koyanagi, Mitsumasa; Terakita, Akihisa

    2014-01-01

    Mammals contain 1 melanopsin (Opn4) gene that is expressed in a subset of retinal ganglion cells to serve as a photopigment involved in non-image-forming vision such as photoentrainment of circadian rhythms. In contrast, most nonmammalian vertebrates possess multiple melanopsins that are distributed in various types of retinal cells; however, their functions remain unclear. We previously found that the lamprey has only 1 type of mammalian-like melanopsin gene, which is similar to that observed in mammals. Here we investigated the molecular properties and localization of melanopsin in the lamprey and other cyclostome hagfish retinas, which contribute to visual functions including image-forming vision and mainly to non-image-forming vision, respectively. We isolated 1 type of mammalian-like melanopsin cDNA from the eyes of each species. We showed that the recombinant lamprey melanopsin was a blue light-sensitive pigment and that both the lamprey and hagfish melanopsins caused light-dependent increases in calcium ion concentration in cultured cells in a manner that was similar to that observed for mammalian melanopsins. We observed that melanopsin was distributed in several types of retinal cells, including horizontal cells and ganglion cells, in the lamprey retina, despite the existence of only 1 melanopsin gene in the lamprey. In contrast, melanopsin was almost specifically distributed to retinal ganglion cells in the hagfish retina. Furthermore, we found that the melanopsin-expressing horizontal cells connected to the rhodopsin-containing short photoreceptor cells in the lamprey. Taken together, our findings suggest that in cyclostomes, the global distribution of melanopsin in retinal cells might not be related to the melanopsin gene number but to the extent of retinal contribution to visual function. PMID:25251771

  13. Effects of IP3R2 Receptor Deletion in the Ischemic Mouse Retina.

    PubMed

    Wagner, Lysann; Pannicke, Thomas; Frommherz, Ina; Sauer, Katja; Chen, Ju; Grosche, Antje

    2016-04-01

    Glial cells in the diseased nervous system undergo a process known as reactive gliosis. Gliosis of retinal Müller glial cells is characterized by an upregulation of glial fibrillary acidic protein and frequently by a reduction of inward K(+) current amplitudes. Purinergic signaling is assumed to be involved in gliotic processes. As previously shown, lack of the nucleotide receptor P2Y1 leads to an altered regulation of K(+) currents in Müller cells of the ischemic retina. Here, we asked first whether this effect is mediated by the IP3 receptor subtype 2 (IP3R2) known as the major downstream signaling target of P2Y1 in Müller cells. The second question was whether lack of IP3R2 affects neuronal survival in the control and ischemic retina. Ischemia was induced in wild type and IP3R2-deficient (IP 3 R2 (-/-)) mice by transient elevation of the intraocular pressure. Immunostaining and TUNEL labelling were used to quantify neuronal cell loss. The downregulation of inward K(+) currents in Müller cells from ischemic IP 3 R2 (-/-) retinae was less strong than in wild type animals. The reduction of the number of cells in the ganglion cell layer and of calretinin- and calbindin-positive cells 7 days after ischemia was similar in wild type and IP 3 R2 (-/-) mice. However, IP3R2 deficiency led to an increased number of TUNEL-positive cells in the outer nuclear layer at 1 day and to an enhanced postischemic loss of photoreceptors 7 days after ischemia. This implies that IP3R2 is involved in some but not all aspects of signaling in Müller cells after an ischemic insult. PMID:26446037

  14. Effect of long-term weightlessness on retina and optic nerve in tail-suspension rats

    PubMed Central

    Zhao, Hong-Wei; Zhao, Jun; Hu, Lian-Na; Liang, Jing-Nan; Shi, Yuan-Yuan; Nie, Chuang; Qiu, Chang-Yu; Nan, Xin-Shuai; Li, Yu-Xin; Gao, Fu-Lin; Liu, Yi; Dong, Yu; Luo, Ling

    2016-01-01

    AIM To evaluate the effect of long-term weightlessness on retina and optic nerve in tail-suspension (TS) rats. METHODS A stimulated weightlessness model was established by suspending rats' tail. After 12wk, the ultrastructure and the number of optic nerve axons were observed by transmission electron microscope. The number of survival retinal ganglion cells (RGCs) was calculated by fluorescent gold retrograde labeling. Retina cells apoptosis was detected by TUNEL staining. The function of optic nerve and retina was evaluated by the visual evoked potential (VEP) and oscillatory potentials (Ops). RESULTS The optic nerve axons were swollen and sparsely aligned, and the lamellar separation and myelin disintegration occurred after 12wk in TS rats. The density of optic nerve axons was 32.23±3.92 (vs 37.43±4.13, P=0.0145), the RGCs density was 1645±46 cells/mm2 (vs 1867±54 cells/mm2 P=0.0000), the incidence rate of retinal cells apoptosis was 5.38%±0.53% (vs 4.75%±0.54%, P=0.0238), the amplitude of VEP-P100 was 15.43±2.14 µV (vs 17.67±2.17 µV, P=0.0424), the latency of VEP-P100 was 69.05±5.34ms (vs 62.43±4.87ms P=0.0143) and the sum amplitude of Ops was 81.05±8.34 µV (vs 91.67±10.21 µV, P=0.0280) in TS group and the control group, respectively. CONCLUSION Long-term weightlessness can induce the ultrastructural changes and functional depress of the optic nerve, as well as retinal cell damages in TS rats. PMID:27366682

  15. Identification of Radial Glia Progenitors in the Developing and Adult Retina of Sharks

    PubMed Central

    Sánchez-Farías, Nuria; Candal, Eva

    2016-01-01

    Neural stem cells give rise to transient progenitors termed neuroepithelial cells (NECs) and radial glial cells (RGCs). RGCs represent the major source of neurons, glia and adult stem cells in several regions of the central nervous system (CNS). RGCs are mostly transient in mammals, but they are widely maintained in the adult CNS of fishes, where they continue to be morphologically similar to RGCs in the mammalian brain and fulfill similar roles as progenitors and guide for migrating neurons. The retina of fishes offers an exceptional model to approach the study of adult neurogenesis because of the presence of constitutive proliferation from the ciliary marginal zone (CMZ), containing NECs, and from adult glial cells with radial morphology (the Müller glia). However, the cellular hierarchies and precise contribution of different types of progenitors to adult neurogenesis remain unsolved. We have analyzed the transition from NECs to RGCs and RGC differentiation in the retina of the cartilaginous fish Scyliorhinus canicula, which offers a particularly good spatial and temporal frame to investigate this process. We have characterized progenitor and adult RGCs by immunohistochemical detection of glial markers as glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). We have compared the emergence and localization of glial markers with that of proliferating cell nuclear antigen (PCNA, a proliferation maker) and Doublecortin (DCX, which increases at early stages of neuronal differentiation). During retinal development, GFAP-immunoreactive NECs located in the most peripheral CMZ (CMZp) codistribute with DCX-immunonegative cells. GFAP-immunoreactive RGCs and Müller cells are located in successive more central parts of the retina and codistribute with DCX- and DCX/GS-immunoreactive cells, respectively. The same types of progenitors are found in juveniles, suggesting that the contribution of the CMZ to adult neurogenesis implies a transition through the

  16. Destructive Changes in the Neuronal Structure of the FVB/N Mouse Retina

    PubMed Central

    Yang, Jinnan; Nan, ChangLong; Ripps, Harris; Shen, Wen

    2015-01-01

    We applied a series of selective antibodies for labeling the various cell types in the mammalian retina. These were used to identify the progressive loss of neurons in the FVB/N mouse, a model of early onset retinal degeneration produced by a mutation in the pde6b gene. The immunocytochemical studies, together with electroretinogram (ERG) recordings, enabled us to examine the time course of the degenerative changes that extended from the photoreceptors to the ganglion cells at the proximal end of the retina. Our study indicates that photoreceptors in FVB/N undergo a rapid degeneration within three postnatal weeks, and that there is a concomitant loss of retinal neurons in the inner nuclear layer. Although the loss of rods was detected at an earlier age during which time M- and S-opsin molecules were translocated to the cone nuclei; by 6 months all cones had also degenerated. Neuronal remodeling was also seen in the second-order neurons with horizontal cells sprouting processes proximally and dendritic retraction in rod-driven bipolar cells. Interestingly, the morphology of cone-driven bipolar cells were affected less by the disease process. The cellular structure of inner retinal neurons, i.e., ChAT amacrine cells, ganglion cells, and melanopsin-positive ganglion cells did not exhibit any gross changes of cell densities and appeared to be relatively unaffected by the massive photoreceptor degeneration in the distal retina. However, Muller cell processes began to express GFAP at their endfeet at p14, and it climbed progressively to the cell’s distal ends by 6 months. Our study indicates that FVB/N mouse provides a useful model with which to assess possible intervention strategies to arrest photoreceptor death in related diseases. PMID:26091175

  17. Destructive Changes in the Neuronal Structure of the FVB/N Mouse Retina.

    PubMed

    Yang, Jinnan; Nan, ChangLong; Ripps, Harris; Shen, Wen

    2015-01-01

    We applied a series of selective antibodies for labeling the various cell types in the mammalian retina. These were used to identify the progressive loss of neurons in the FVB/N mouse, a model of early onset retinal degeneration produced by a mutation in the pde6b gene. The immunocytochemical studies, together with electroretinogram (ERG) recordings, enabled us to examine the time course of the degenerative changes that extended from the photoreceptors to the ganglion cells at the proximal end of the retina. Our study indicates that photoreceptors in FVB/N undergo a rapid degeneration within three postnatal weeks, and that there is a concomitant loss of retinal neurons in the inner nuclear layer. Although the loss of rods was detected at an earlier age during which time M- and S-opsin molecules were translocated to the cone nuclei; by 6 months all cones had also degenerated. Neuronal remodeling was also seen in the second-order neurons with horizontal cells sprouting processes proximally and dendritic retraction in rod-driven bipolar cells. Interestingly, the morphology of cone-driven bipolar cells were affected less by the disease process. The cellular structure of inner retinal neurons, i.e., ChAT amacrine cells, ganglion cells, and melanopsin-positive ganglion cells did not exhibit any gross changes of cell densities and appeared to be relatively unaffected by the massive photoreceptor degeneration in the distal retina. However, Muller cell processes began to express GFAP at their endfeet at p14, and it climbed progressively to the cell's distal ends by 6 months. Our study indicates that FVB/N mouse provides a useful model with which to assess possible intervention strategies to arrest photoreceptor death in related diseases. PMID:26091175

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

    PubMed Central

    Cécyre, Bruno; Monette, Marjorie; Beudjekian, Liza; Casanova, Christian; Bouchard, Jean-François

    2014-01-01

    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. PMID:25565975

  19. Carcinine Has 4-Hydroxynonenal Scavenging Property and Neuroprotective Effect in Mouse Retina

    PubMed Central

    Marchette, Lea D.; Wang, Huaiwen; Li, Feng; Babizhayev, Mark A.; Kasus-Jacobi, Anne

    2012-01-01

    Purpose. Oxidative stress induces retinal damage and contributes to vision loss in progressive retinopathies. Carcinine (β-alanyl-histamine) is a natural imidazole-containing peptide derivative with antioxidant activity. It is predicted to scavenge 4-hydroxynonenal (4-HNE), a toxic product of lipid oxidation. The aim of this study was to confirm the 4-HNE scavenging effect and evaluate the neuroprotective effect of carcinine in mouse retina subjected to oxidative stress. Methods. HPLC coupled with mass spectrometry was used to analyze carcinine and 4-HNE-carcinine adduct. Protection of retinal proteins from modification by 4-HNE was tested by incubating carcinine with retinal protein extract and 4-HNE. Modified retinal proteins were quantified by dot-blot analysis. Mice were treated with carcinine (intravitreal injection and gavage) and exposed to bright light to induce oxidative damage in the retina. Photoreceptor degeneration was measured by histology and electroretinography. Retinal levels of retinol dehydrogenase 12 (RDH12) were measured by immunoblot analysis, after exposure to bright light and in retinal explants after exposure to 4-HNE. Results. The ability of carcinine to form an adduct with 4-HNE, as well as to prevent and even reverse the adduction of retinal proteins by the toxic aldehyde was demonstrated in vitro. Carcinine, administered by intravitreal injection or gavage, strongly protected mouse retina against light-induced photoreceptor degeneration and had a protective effect on RHD12, a protein found specifically in photoreceptor cells. Conclusions. This study suggests that carcinine can be administered noninvasively to efficiently protect photoreceptor cells from oxidative damage. Carcinine could be administered daily to prevent vision loss in progressive retinopathies. PMID:22577078

  20. Heterogeneous Expression of the Core Circadian Clock Proteins among Neuronal Cell Types in Mouse Retina

    PubMed Central

    Liu, Xiaoqin; Zhang, Zhijing; Ribelayga, Christophe P.

    2012-01-01

    Circadian rhythms in metabolism, physiology, and behavior originate from cell-autonomous circadian clocks located in many organs and structures throughout the body and that share a common molecular mechanism based on the clock genes and their protein products. In the mammalian neural retina, despite evidence supporting the presence of several circadian clocks regulating many facets of retinal physiology and function, the exact cellular location and genetic signature of the retinal clock cells remain largely unknown. Here we examined the expression of the core circadian clock proteins CLOCK, BMAL1, NPAS2, PERIOD 1(PER1), PERIOD 2 (PER2), and CRYPTOCHROME2 (CRY2) in identified neurons of the mouse retina during daily and circadian cycles. We found concurrent clock protein expression in most retinal neurons, including cone photoreceptors, dopaminergic amacrine cells, and melanopsin-expressing intrinsically photosensitive ganglion cells. Remarkably, diurnal and circadian rhythms of expression of all clock proteins were observed in the cones whereas only CRY2 expression was found to be rhythmic in the dopaminergic amacrine cells. Only a low level of expression of the clock proteins was detected in the rods at any time of the daily or circadian cycle. Our observations provide evidence that cones and not rods are cell-autonomous circadian clocks and reveal an important disparity in the expression of the core clock components among neuronal cell types. We propose that the overall temporal architecture of the mammalian retina does not result from the synchronous activity of pervasive identical clocks but rather reflects the cellular and regional heterogeneity in clock function within retinal tissue. PMID:23189207

  1. Relationship of ocular pigmentation to the boundaries of dorsal and ventral retina in a nonmammalian vertebrate.

    PubMed

    Springer, A D; Mednick, A S

    1986-03-01

    The goldfish eye and retina are partitioned traditionally into dorsal and ventral sectors by a horizontal meridian that passes through the optic disc and is perpendicular to a vertical meridian that extends from the remnant of the choroid fissure through the optic disc. Axons of retinal ganglion cells (RGCs) situated above the horizontal meridian are thought to reach the optic tectum via the ventrolateral optic tract and axons of RGCs situated below the horizontal meridian are thought to reach the optic tectum via the dorsomedial optic tract. When cobaltous-lysine was applied to small temporal retinal slits that were centered on the traditional horizontal meridian, filled fibers were found in the dorsomedial, but not in the ventrolateral, optic tract (Springer and Mednick, '83). Since cobalt-filled axons should have been found in both optic tracts, the traditional horizontal meridian does not indicate the actual boundary between dorsal and ventral retina. We report here that the goldfish iris contains nasal and temporal pigmentation lines (darts) that are each located approximately 21 degrees above the traditional horizontal retinal meridian. Cobalt applied to retinal slits located just above the darts filled RGC axons in the ventrolateral optic tract and cobalt applied to retinal slits just below the darts filled RGC axons in the dorsomedial optic tract. Converging evidence for the reliability of the darts as indicators of the boundary between dorsal and ventral retina was obtained by applying cobalt to severed RGC axons along the dorsomedial edge of the tectum. Cobalt-filled RGCs were found below the nasal dart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2420839

  2. Phase-sensitive imaging of the outer retina using optical coherence tomography and adaptive optics

    PubMed Central

    Jonnal, Ravi S.; Kocaoglu, Omer P.; Wang, Qiang; Lee, Sangyeol; Miller, Donald T.

    2011-01-01

    The cone photoreceptor’s outer segment (OS) experiences changes in optical path length, both in response to visible stimuli and as a matter of its daily course of renewal and shedding. These changes are of interest, to quantify function in healthy cells and assess dysfunction in diseased ones. While optical coherence tomography (OCT), combined with adaptive optics (AO), has permitted unprecedented three-dimensional resolution in the living retina, it has not generally been able to measure these OS dynamics, whose scale is smaller than OCT’s axial resolution of a few microns. A possible solution is to take advantage of the phase information encoded in the OCT signal. Phase-sensitive implementations of spectral-domain optical coherence tomography (SD-OCT) have been demonstrated, capable of resolving sample axial displacements much smaller than the imaging wavelength, but these have been limited to ex vivo samples. In this paper we present a novel technique for retrieving phase information from OCT volumes of the outer retina. The key component of our technique is quantification of phase differences within the retina. We provide a quantitative analysis of such phase information and show that–when combined with appropriate methods for filtering and unwrapping–it can improve the sensitivity to OS length change by more than an order of magnitude, down to 45 nm, slightly thicker than a single OS disc. We further show that phase sensitivity drops off with retinal eccentricity, and that the best location for phase imaging is close to the fovea. We apply the technique to the measurement of sub-resolution changes in the OS over matters of hours. Using custom software for registration and tracking, these microscopic changes are monitored in hundreds of cones over time. In two subjects, the OS was found to have average elongation rates of 150 nm/hr, values which agree with our previous findings. PMID:22254172

  3. Nitric oxide production and the expression of two nitric oxide synthases in the avian retina.

    PubMed

    Tekmen-Clark, Merve; Gleason, Evanna

    2013-05-01

    Nitric oxide (NO) is known to exert multiple effects on the function of many retinal neurons and their synapses. Therefore, it is equally important to understand the potential sources of NO within the retina. To explore this, we employ a combination of 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM) based NO detection and immunohistochemistry for the NO synthetic enzymes, neuronal and endothelial nitric oxide synthase (nNOS and eNOS). We find DAF signals in photoreceptors, horizontal cells, amacrine cells, efferent synapses, Müller cells, and cells in the ganglion cell layer (GCL). nNOS immunoreactivity was consistent with the DAF signal with the exception that horizontal cells and Müller cells were not clearly labeled. eNOS-like immunoreactivity (eNOS-LI) was more widespread with photoreceptors, horizontal cells, occasional bipolar cells, amacrine cells, Müller cells, and cells in the GCL all showing labeling. Double labeling with antibodies raised against calretinin, syntaxin, and glutamine synthetase confirmed that horizontal cells, amacrine cells, and Müller cells (respectively) were expressing eNOS-LI. Although little or no nNOS labeling is observed in horizontal cells or Müller cells, the expression of eNOS-LI is consistent with the ability of these cells to produce NO. Together these results suggest that the capability to produce NO is widespread in the chicken retina. We propose that multiple forms of regulation for nNOS and eNOS play a role in the patterning of NO production in the chicken retina. PMID:23721886

  4. Redox mechanisms in pathological angiogenesis in the retina: roles for NADPH oxidase.

    PubMed

    Chan, Elsa C; Liu, Guei-Sheung; Dusting, Gregory J

    2015-01-01

    Pathological angiogenesis in the retina is a leading cause of serious vision loss in potentially blinding eye diseases, including proliferative diabetic retinopathy, retinopathy of prematurity and the wet form of age-related macular degeneration. Hypoxia is thought to be the driver of pathological angiogenesis, and transcription factors such as hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) are key mediators in these processes. Current treatments employ either laser photocoagulation or intravitreal injection of therapeutic antibodies for VEGF, in order to arrest the growth of leaky blood vessels in the avascular vitreous cavity and to restore visual acuity. However, all such therapeutic approaches are limited by low or variable efficacy, and the inconvenience, risk and financial burden of such treatments, which need to be given frequently. The lack of noninvasive and efficacious therapy has therefore driven the search for alternative strategies. We have been interested in the roles of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, which when produced intracellularly at low concentration can act as second messengers to regulate physiological and pathological angiogenesis. Accumulating evidence suggests NADPH oxidase-dependent ROS are involved in regulation of the angiogenic signalling pathways of HIF and VEGF. Suppressing pathological neovascularisation in the retina by manipulating such redox mechanisms appears to be an attractive and clinically translatable therapeutic strategy to treat proliferative neovascular eye diseases. Here we provide a brief overview of the roles of NADPH oxidase in the sensing and regulation processes involving HIF and VEGF that contribute to the development of pathological angiogenesis in the retina. PMID:26510439

  5. Genetic Dissection of Rod and Cone Pathways in the Dark-Adapted Mouse Retina

    PubMed Central

    Abd-El-Barr, Muhammad M.; Pennesi, Mark E.; Saszik, Shannon M.; Barrow, Andrew J.; Lem, Janis; Bramblett, Debra E.; Paul, David L.; Frishman, Laura J.; Wu, Samuel M.

    2009-01-01

    A monumental task of the mammalian retina is to encode an enormous range (>109-fold) of light intensities experienced by the animal in natural environments. Retinal neurons carry out this task by dividing labor into many parallel rod and cone synaptic pathways. Here we study the operational plan of various rod- and cone-mediated pathways by analyzing electroretinograms (ERGs), primarily b-wave responses, in dark-adapted wildtype, connexin36 knockout, depolarizing rod–bipolar cell (DBCR) knockout, and rod transducin alpha-subunit knockout mice [WT, Cx36(−/−), Bhlhb4(−/−), and Trα(−/−)]. To provide additional insight into the cellular origins of various components of the ERG, we compared dark-adapted ERG responses with response dynamic ranges of individual retinal cells recorded with patch electrodes from dark-adapted mouse retinas published from other studies. Our results suggest that the connexin36-mediated rod–cone coupling is weak when light stimulation is weak and becomes stronger as light stimulation increases in strength and that rod signals may be transmitted to some DBCCs via direct chemical synapses. Moreover, our analysis indicates that DBCR responses contribute about 80% of the overall DBC response to scotopic light and that rod and cone signals contribute almost equally to the overall DBC responses when stimuli are strong enough to saturate the rod bipolar cell response. Furthermore, our study demonstrates that analysis of ERG b-wave of dark-adapted, pathway-specific mutants can be used as an in vivo tool for dissecting rod and cone synaptic pathways and for studying the functions of pathway-specific gene products in the retina. PMID:19587322

  6. Spectral distribution of local field potential responses to electrical stimulation of the retina

    NASA Astrophysics Data System (ADS)

    Wong, Yan T.; Halupka, Kerry; Kameneva, Tatiana; Cloherty, Shaun L.; Grayden, David B.; Burkitt, Anthony N.; Meffin, Hamish; Shivdasani, Mohit N.

    2016-06-01

    Objective. Different frequency bands of the local field potential (LFP) have been shown to reflect neuronal activity occurring at varying cortical scales. As such, recordings of the LFP may offer a novel way to test the efficacy of neural prostheses and allow improvement of stimulation strategies via neural feedback. Here we use LFP measurements from visual cortex to characterize neural responses to electrical stimulation of the retina. We aim to show that the LFP is a viable signal that contains sufficient information to optimize the performance of sensory neural prostheses. Approach. Clinically relevant electrode arrays were implanted in the suprachoroidal space of one eye in four felines. LFPs were simultaneously recorded in response to stimulation of individual electrodes using penetrating microelectrode arrays from the visual cortex. The frequency response of each electrode was extracted using multi-taper spectral analysis and the uniqueness of the responses was determined via a linear decoder. Main results. We found that cortical LFPs are reliably modulated by electrical stimulation of the retina and that the responses are spatially localized. We further characterized the spectral distribution of responses, with maximum information being contained in the low and high gamma bands. Finally, we found that LFP responses are unique to a large range of stimulus parameters (∼40) with a maximum conveyable information rate of 6.1 bits. Significance. These results show that the LFP can be used to validate responses to electrical stimulation of the retina and we provide the first steps towards using these responses to provide more efficacious stimulation strategies.

  7. Electrical responses and photopigments of twin cones in the retina of the walleye.

    PubMed Central

    Burkhardt, D A; Hassin, G; Levine, J S; MacNichol, E F

    1980-01-01

    1. The properties of twin and single cones in the retina of the walleye (Stizostedion vitreum vitreum) were studied by intracellular recording, dye injection and microspectrophotometry. 2. Twin cones generate hyperpolarizing responses to central illumination, can receive depolarizing influences (feed-back) from the receptive field surround, and show no detectable dye coupling when injected with Procion yellow. In seventeen of eighteen dye-injected cones, fluorescence was intense in the inner segment and undetectable or weak in the cone pedicle. 3. Both members of the twin cone contain the same photopigment in their outer segments. It absorbs maximally at about 605 nm. 4. A 533 nm green-sensitive photopigment was found in single cones. No blue-sensitive cones have been found. 5. With the exception of a modest discrepancy in the violet, the absorptance spectrum of the 605 nm photopigment of twin cones agrees closely with the action spectrum measured by intracellular recording. 6. The spectral properties established by the twin cone's photopigment are not detectably altered by the hyperpolarizing influences arising from nearby cones or by the depolarizing influences arising from the receptive field surround. 7. The twin cones of the walleye retina are thus "identical twins', both photochemically and physiologically, and seem designed to function as long-wave, spectrally univariant receptor units for colour vision. 8. The available evidence suggests that identical twin cones differ functionally from double cones and non-identical twin cones. 9. Although they outnumber single cones by about three to one in adults, identifiable twin cones were rarely observed in the cone population of retinas examined 3-5 days after birth. If walleye twin cones develop by fusion of single cones this process apparently occurs only for cones containing the 605 nm photopigment. Images Plate 1 PMID:7252864

  8. Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD transgenic mice.

    PubMed

    Pogue, A I; Dua, P; Hill, J M; Lukiw, W J

    2015-11-01

    At least 57 murine transgenic models for Alzheimer's disease (Tg-AD) have been developed to overexpress the 42 amino acid amyloid-beta (Aβ42) peptide in the central nervous system (CNS). These 'humanized murine Tg-AD models' have greatly expanded our understanding of the contribution of Aβ42 peptide-mediated pro-inflammatory neuropathology to the AD process. A number of independent laboratories using different amyloid-overexpressing Tg-AD models have shown that supplementation of murine Tg-AD diets and/or drinking water with aluminum significantly enhances Aβ42 peptide-mediated inflammatory pathology and AD-type cognitive change compared to animals receiving control diets. In humans AD-type pathology appears to originate in the limbic system and progressively spreads into primary processing and sensory regions such as the retina. In these studies, for the first time, we assess the propagation of Aβ42 and inflammatory signals into the retina of 5xFAD Tg-AD amyloid-overexpressing mice whose diets were supplemented with aluminum. The two most interesting findings were (1) that similar to other Tg-AD models, there was a significantly accelerated development of Aβ42 and inflammatory pathology in 5xFAD Tg-AD mice fed aluminum; and (2) in aluminum-supplemented animals, markers for inflammatory pathology appeared in both the brain and the retina as evidenced by an evolving presence of Aβ42 peptides, and accompanied by inflammatory markers - cyclooxygenase-2 (COX-2) and C-reactive protein (CRP). The results indicate that in the 5xFAD Tg-AD model aluminum not only enhances an Aβ42-mediated inflammatory degeneration of the brain but also appears to induce AD-type pathology in an anatomically-linked primary sensory area that involves vision. PMID:26213226

  9. Developmental changes in the expression level of connexin36 in the rat retina.

    PubMed

    Kovács-Öller, Tamás; Raics, Katalin; Orbán, József; Nyitrai, Miklós; Völgyi, Béla

    2014-11-01

    Connexin36 (Cx36) is the major gap junction forming protein in the brain and the retina; thus, alterations in its expression indicate changes in the corresponding circuitry. Many structural changes occur in the early postnatal retina before functional neuronal circuits are finalized, including those that incorporate gap junctions. To reveal the time-lapse formation of inner retinal gap junctions, we examine the developing postnatal rat retina from birth (P0) to young adult age (P20) and follow the expression of Cx36 in the mRNA and protein levels. We found a continuous elevation in the expression of both the Cx36 transcript and protein between P0 and P20 and a somewhat delayed Cx36 plaque formation throughout the inner plexiform layer (IPL) starting at P10. By using tristratificated calretinin positive (CaR(+)) fibers in the IPL as a guide, we detected a clear preference of Cx36 plaques for the ON sublamina from the earliest time of detection. This distributional preference became more pronounced at P15 and P20 due to the emergence and widespread expression of large (>0.1 μm(2)) Cx36 plaques in the ON sublamina. Finally, we showed that parvalbumin-positive (PV(+)) AII amacrine cell dendrites colocalize with Cx36 plaques as early as P10 in strata 3 and 4, whereas colocalizations in stratum 5 became characteristic only around P20. We conclude that Cx36 expression in the rat IPL displays a characteristic succession of changes during retinogenesis reflecting the formation of the underlying electrical synaptic circuitry. In particular, AII cell gap junctions, first formed with ON cone bipolar cells and later with other AII amacrine cells, accounted for the observed Cx36 expressional changes. PMID:25110193

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

    PubMed

    Bronzetti, Elena; Artico, M; Kovacs, I; Felici, L M; Magliulo, G; Vignone, D; D'Ambrosio, A; Forte, F; Di Liddo, R; Feher, J

    2007-01-01

    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. PMID:18162454

  11. Pharmacological differences between the D-2 autoreceptor and the D-1 dopamine receptor in rabbit retina

    SciTech Connect

    Dubocovich, M.L.; Weiner, N.

    1985-06-01

    The effect of dopamine receptor agonists and antagonists was studied on the calcium-dependent release of (/sup 3/H)dopamine elicited by field stimulation at 3 Hz for a duration of 1 min (20 mA, 2 msec) from the rabbit retina in vitro and on adenylate cyclase activity in homogenates of rabbit retina. The relative order of potency of dopamine receptor agonists to inhibit the stimulation-evoked (/sup 3/H)dopamine release was pergolide greater than bromocriptine greater than apomorphine greater than LY 141865 greater than N,N-di-n-propyldopamine greater than or equal to dopamine. The relative order of potencies of dopamine receptor antagonists to increase (/sup 3/H)dopamine release was: S-sulpiride greater than or equal to domperidone greater than or equal to spiroperidol greater than metoclopramide greater than fluphenazine greater than or equal to R-sulpiride. alpha-Flupenthixol (0.01-1 microM) and (+)-butaclamol (0.01-1 microM) did not increase (/sup 3/H)dopamine overflow when added alone, but they antagonized the concentration-dependent inhibitory effect of apomorphine (0.1-10 microM). These results suggest that the dopamine inhibitory autoreceptor involved in the modulation of dopamine release from the rabbit retina possesses the pharmacological characteristics of a D-2 dopamine receptor. Maximal stimulation by 30 microM dopamine resulted in a 3-fold increase in adenylate cyclase activity with half-maximal stimulation occurring at a concentration of 2.46 microM. Apomorphine and pergolide elicited a partial stimulation of adenylate cyclase activity. However, at low concentrations both compounds were more potent than dopamine.

  12. The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina

    PubMed Central

    Xiong, Wei-Hong; Pang, Ji-Jie; Pennesi, Mark E.; Duvoisin, Robert M.; Wu, Samuel M.; Morgans, Catherine W.

    2015-01-01

    Purpose Protein kinase C α (PKCα) is abundantly expressed in rod bipolar cells (RBCs) in the retina, yet the physiological function of PKCα in these cells is not well understood. To elucidate the role of PKCα in visual processing in the eye, we examined the effect of genetic deletion of PKCα on the ERG and on RBC light responses in the mouse. Methods Immunofluorescent labeling was performed on wild-type (WT), TRPM1 knockout, and PKCα knockout (PKC-KO) retina. Scotopic and photopic ERGs were recorded from WT and PKC-KO mice. Light responses of RBCs were measured using whole-cell recordings in retinal slices from WT and PKC-KO mice. Results Protein kinase C alpha expression in RBCs is correlated with the activity state of the cell. Rod bipolar cells dendrites are a major site of PKCα phosphorylation. Electroretinogram recordings indicated that loss of PKCα affects the scotopic b-wave, including a larger peak amplitude, longer implicit time, and broader width of the b-wave. There were no differences in the ERG a- or c-wave between PKCα KO and WT mice, indicating no measurable effect of PKCα in photoreceptors or the RPE. The photopic ERG was unaffected consistent with the lack of detectable PKCα in cone bipolar cells. Whole-cell recordings from RBCs in PKC-KO retinal slices revealed that, compared with WT, RBC light responses in the PKC-KO retina are delayed and of longer duration. Conclusions Protein kinase C alpha plays an important modulatory role in RBCs, regulating both the peak amplitude and temporal properties of the RBC light response in the rod visual pathway. PMID:26230760

  13. The supply of metabolic substrate from glia to photoreceptors in the retina of the honeybee drone.

    PubMed

    Tsacopoulos, M; Coles, J A; Van de Werve, G

    1987-01-01

    1. The drone retina is composed essentially of only two types of cells: a population of identical photoreceptor cells occupying 38% of the volume is embedded in a syncytium of glia (called outer pigment cells). Nearly all the mitochondria are in the photoreceptors. 2. A retinal slice consumes 18 microliter O2 (ml tissue)-1 min-1 in the dark for up to 6 h, even without exogenous substrate; in 6 h this would require the equivalent of 127 mM glucose in the photoreceptors or 8.7 mg glycogen (ml tissue)-1. 3. Freshly dissected retinas contain about 45 mg glycogen (ml tissue)-1, but this appears, from electron micrographs and from the PAS reaction, to be exclusively in the glia. After superfusion with substrate-free Ringer solution for 30 min, slices of retina contained less than 20 microM glucose. It therefore appears that to sustain respiration, carbohydrate substrate must be transferred from the glia to the photoreceptors. 4. Even after 6 h superfusion with substrate-free Ringer solution O2 consumption (QO2) was not increased by exogenous glucose, pyruvate, trehalose or lactate, nor decreased by 2-deoxy-D-glucose. QO2 was increased 2-3 fold by either light stimulation or (for at least 20 min) by 50 microM dinitrophenol. 5. QO2 was only slightly reduced when Na-dependent glucose transport was inhibited either by reduction of extracellular [Na+], or the presence of phlorizin. 6. It is suggested that drone retinal function does not require the uptake of glucose by the photoreceptors, but that the glia do take up glucose. PMID:3503929

  14. Evaluation of the percentage of ganglion cells in the ganglion cell layer of the rodent retina

    PubMed Central

    Schlamp, Cassandra L.; Montgomery, Angela D.; Mac Nair, Caitlin E.; Schuart, Claudia; Willmer, Daniel J.

    2013-01-01

    Purpose Retinal ganglion cells comprise a percentage of the neurons actually residing in the ganglion cell layer (GCL) of the rodent retina. This estimate is useful to extrapolate ganglion cell loss in models of optic nerve disease, but the values reported in the literature are highly variable depending on the methods used to obtain them. Methods We tested three retrograde labeling methods and two immunostaining methods to calculate ganglion cell number in the mouse retina (C57BL/6). Additionally, a double-stain retrograde staining method was used to label rats (Long-Evans). The number of total neurons was estimated using a nuclear stain and selecting for nuclei that met specific criteria. Cholinergic amacrine cells were identified using transgenic mice expressing Tomato fluorescent protein. Total neurons and total ganglion cell numbers were measured in microscopic fields of 104 µm2 to determine the percentage of neurons comprising ganglion cells in each field. Results Historical estimates of the percentage of ganglion cells in the mouse GCL range from 36.1% to 67.5% depending on the method used. Experimentally, retrograde labeling methods yielded a combined estimate of 50.3% in mice. A retrograde method also yielded a value of 50.21% for rat retinas. Immunolabeling estimates were higher at 64.8%. Immunolabeling may introduce overestimates, however, with non-specific labeling effects, or ectopic expression of antigens in neurons other than ganglion cells. Conclusions Since immunolabeling methods may overestimate ganglion cell numbers, we conclude that 50%, which is consistently derived from retrograde labeling methods, is a reliable estimate of the ganglion cells in the neuronal population of the GCL. PMID:23825918

  15. Influence of transient intraocular pressure elevation during laser in situ keratomileusis on rabbit retina thickness

    PubMed Central

    Zhao, Hai-Xia; Liu, Hui; Niu, Chun-Mei; Guan, Wen-Ying

    2015-01-01

    AIM To utilize tissue micro measurement to study the effect of transient high intraocular pressure (IOP) induced by different durations of suction during laser in situ keratomileusis (LASIK) on rabbit retina thickness. METHODS Sixty healthy New Zealand white rabbits were randomly divided into a control group, and 3 negative-pressure suction groups (20s group, 45s group, and 3min group) and each group was comprised of 15 rabbits (30 eyes); the latter 3 groups were the transient high IOP models. The retinal tissue around the papilledema was separated. Hematoxylin and eosin (HE) staining was carried out to generate slices for light microscopy. The changes in the retina thickness values of each layer were measured for all animals in each group at different postoperative recovery periods and compared with the values recorded for the animals in the control group. The thickness of the retinal tissue showed a normal distribution. The ANOVA was performed by using SPSS13.0 statistic software. RESULTS In the comparison between the 20s and 45s negative-pressure suction groups and the control group, no significant differences were observed, except at 14d. Significant difference was observed between the 3min negative-pressure suction group and the control group, and the retina thickness value of each layer reached a peak at 14d after repair. CONCLUSION Conventional negative suction during LASIK may not lead to significant changes in retinal tissue thickness; however, if the suction duration is increased to 3min, it will cause significant changes in retinal tissue thickness. PMID:26682153

  16. Activation of ganglion cells in wild-type and rd1 mouse retinas with monophasic and biphasic current pulses

    NASA Astrophysics Data System (ADS)

    Jensen, Ralph J.; Rizzo, Joseph F. III

    2009-06-01

    We and other research groups are designing an electronic retinal prosthesis to provide vision for patients who are blind due to photoreceptor degeneration. In this study, we examined the effect of stimulus waveform on the amount of current needed to activate retinal ganglion cells (RGCs) when the retinal neural network is stimulated. Isolated retinas of wild-type and rd1 mice were stimulated with cathodal and anodal monophasic current pulses of 1 ms duration and symmetric biphasic current pulses (1 ms per phase) delivered through an electrode that was located subretinally. For both wild-type and rd1 mouse retinas, cathodal current pulses were least effective in activating most RGCs. The median threshold current for a cathodal current pulse was 2.0-4.4 fold higher than the median threshold current for either an anodal or a biphasic current pulse. In wild-type mouse retinas, the median threshold current for activating RGCs with anodal current pulses was 23% lower than that with biphasic current pulses. In rd1 mouse retinas, the median threshold currents for anodal and biphasic current pulses were about the same. However, the variance in thresholds of rd1 RGCs for biphasic pulse stimulation was much smaller than for anodal pulse stimulation. Thus, a symmetric biphasic current pulse may be the best stimulus for activating the greatest number of RGCs in retinas devoid of photoreceptors.

  17. Exclusive multipotency and preferential asymmetric divisions in post-embryonic neural stem cells of the fish retina

    PubMed Central

    Centanin, Lázaro; Ander, Janina-J.; Hoeckendorf, Burkhard; Lust, Katharina; Kellner, Tanja; Kraemer, Isabel; Urbany, Cedric; Hasel, Eva; Harris, William A.; Simons, Benjamin D.; Wittbrodt, Joachim

    2014-01-01

    The potency of post-embryonic stem cells can only be addressed in the living organism, by labeling single cells after embryonic development and following their descendants. Recently, transplantation experiments involving permanently labeled cells revealed multipotent neural stem cells (NSCs) of embryonic origin in the medaka retina. To analyze whether NSC potency is affected by developmental progression, as reported for the mammalian brain, we developed an inducible toolkit for clonal labeling and non-invasive fate tracking. We used this toolkit to address post-embryonic stem cells in different tissues and to functionally differentiate transient progenitor cells from permanent, bona fide stem cells in the retina. Using temporally controlled clonal induction, we showed that post-embryonic retinal NSCs are exclusively multipotent and give rise to the complete spectrum of cell types in the neural retina. Intriguingly, and in contrast to any other vertebrate stem cell system described so far, long-term analysis of clones indicates a preferential mode of asymmetric cell division. Moreover, following the behavior of clones before and after external stimuli, such as injuries, shows that NSCs in the retina maintained the preference for asymmetric cell division during regenerative responses. We present a comprehensive analysis of individual post-embryonic NSCs in their physiological environment and establish the teleost retina as an ideal model for studying adult stem cell biology at single cell resolution. PMID:25142461

  18. Coupling ex vivo electroporation of mouse retinas and luciferase reporter assays to assess rod-specific promoter activity.

    PubMed

    Boulling, Arnaud; Escher, Pascal

    2016-07-01

    Ex vivo electroporation of mouse retinas is an established tool to modulate gene expression and to study cell type-specific gene expression. Here we coupled ex vivo electroporation to luciferase reporter assays to facilitate the study of rod-photoreceptor-specific gene promoters. The activity of the rod-specific proximal bovine rhodopsin promoter was significantly increased in C57BL/6J wild-type retinas at postnatal days 1 and 7 by 3.4-fold and 8.7-fold respectively. In C57BL/6J Nr2e3(rd7/rd7) retinas, where the rod photoreceptor-specific nuclear receptor Nr2e3 is not expressed, a significant increase by 2.5-fold was only observed at postnatal day 7. Cone-specific S-opsin promoter activity was not modulated in C57BL/6J wild-type and Nr2e3(rd7/rd7) retinas. Taken together, we describe an easily implementable protocol to assess rod-specific promoter activity in a physiological context resembling that of the developing postnatal mouse retina. PMID:27268947

  19. Correlation of spatial intensity distribution of light reaching the retina and restoration of vision by optogenetic stimulation

    NASA Astrophysics Data System (ADS)

    Shivalingaiah, Shivaranjani; Gu, Ling; Mohanty, Samarendra K.

    2011-03-01

    Stimulation of retinal neuronal cells using optogenetics via use of chanelrhodopsin-2 (ChR2) and blue light has opened up a new direction for restoration of vision with respect to treatment of Retinitis pigmentosa (RP). In addition to delivery of ChR2 to specific retinal layer using genetic engineering, threshold level of blue light needs to be delivered onto the retina for generating action potential and successful behavioral outcome. We report measurement of intensity distribution of light reaching the retina of Retinitis pigmentosa (RP) mouse models and compared those results with theoretical simulations of light propagation in eye. The parameters for the stimulating source positioning in front of eye was determined for optimal light delivery to the retina. In contrast to earlier viral method based delivery of ChR2 onto retinal ganglion cells, in-vivo electroporation method was employed for retina-transfection of RP mice. The behavioral improvement in mice with Thy1-ChR2-YFP transfected retina, expressing ChR2 in retinal ganglion cells, was found to correlate with stimulation intensity.

  20. OCT angiography by absolute intensity difference applied to normal and diseased human retinas

    PubMed Central

    Ruminski, Daniel; Sikorski, Bartosz L.; Bukowska, Danuta; Szkulmowski, Maciej; Krawiec, Krzysztof; Malukiewicz, Grazyna; Bieganowski, Lech; Wojtkowski, Maciej

    2015-01-01

    We compare four optical coherence tomography techniques for noninvasive visualization of microcapillary network in the human retina and murine cortex. We perform phantom studies to investigate contrast-to-noise ratio for angiographic images obtained with each of the algorithm. We show that the computationally simplest absolute intensity difference angiographic OCT algorithm that bases only on two cross-sectional intensity images may be successfully used in clinical study of healthy eyes and eyes with diabetic maculopathy and branch retinal vein occlusion. PMID:26309740

  1. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina.

    PubMed

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  2. Effects of the long-term use of perfluoroperhydrophenanthrene on the retina.

    PubMed

    Batman, C; Cekic, O

    1998-02-01

    Perfluorocarbon liquids have gained wide acceptance as intraoperative tools that can simplify vitreoretinal surgical maneuvers. These low-viscosity liquids facilitate injection into the eye and removal from the eye during surgery. Tolerance to perfluoroperhydrophenanthrene and the development of proliferative vitreoretinopathy with its extended use are not clear. The authors present the clinical and histologic findings of a patient, previously lost to follow-up, who was examined after several weeks of intraocular tamponade with perfluoroperhydrophenanthrene. Damage to the retina was seen in response to the long-term postoperative use of perfluoroperhydrophenanthrene. PMID:9507258

  3. Imaging translucent cell bodies in the living mouse retina without contrast agents.

    PubMed

    Guevara-Torres, A; Williams, D R; Schallek, J B

    2015-06-01

    The transparency of most retinal cell classes typically precludes imaging them in the living eye; unless invasive methods are used that deploy extrinsic contrast agents. Using an adaptive optics scanning light ophthalmoscope (AOSLO) and capitalizing on the large numerical aperture of the mouse eye, we enhanced the contrast from otherwise transparent cells by subtracting the left from the right half of the light distribution in the detector plane. With this approach, it is possible to image the distal processes of photoreceptors, their more proximal cell bodies and the mosaic of horizontal cells in the living mouse retina. PMID:26114032

  4. Distribution of light in the human retina under natural viewing conditions

    NASA Astrophysics Data System (ADS)

    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. Gibbs distribution analysis of temporal correlations structure in retina ganglion cells

    PubMed Central

    Vasquez, J. C.; Marre, O.; Palacios, A.G.; Berry, M.J.; Cessac, B.

    2012-01-01

    We present a method to estimate Gibbs distributions with spatio-temporal constraints on spike trains statistics. We apply this method to spike trains recorded from ganglion cells of the salamander retina, in response to natural movies. Our analysis, restricted to a few neurons, performs more accurately than pairwise synchronization models (Ising) or the 1-time step Markov models (Marre et al. (2009)) to describe the statistics of spatio-temporal spike patterns and emphasizes the role of higher order spatio-temporal interactions. PMID:22115900

  6. BACE1 in the retina: a sensitive biomarker for monitoring early pathological changes in Alzheimer's disease

    PubMed Central

    Li, Lan; Luo, Jia; Chen, Dan; Tong, Jian-bin; Zeng, Le-ping; Cao, Yan-qun; Xiang, Jian; Luo, Xue-gang; Shi, Jing-ming; Wang, Hui; Huang, Ju-fang

    2016-01-01

    Because of a lack of sensitive biomarkers, the diagnosis of Alzheimer's disease (AD) cannot be made prior to symptom manifestation. Therefore, it is crucial to identify novel biomarkers for the presymptomatic diagnosis of AD. While brain lesions are a major feature of AD, retinal pathological changes also occur in patients. In this study, we investigated the temporal changes in β-site APP-cleaving enzyme 1 (BACE1) expression in the retina and brain to determine whether it could serve as a suitable biomarker for early monitoring of AD. APP/PS-1 transgenic mice, 3, 6 and 8 months of age, were used as an experimental group, and age-matched C57/BL6 wild-type mice served as the control group. In the Morris water maze test, there were no significant differences in escape latency or in the number of crossings in the target area among mice of different ages. Compared with wild-type mice, no changes in learning or memory abilities were detected in transgenic mice at 3 months of age. However, compared with wild-type mice, the escape latency was significantly increased in transgenic mice at 6 months, starting on day 3, and at 8 months, starting on day 2, during Morris water maze training. In addition, the number of crossings of the target area was significantly decreased in transgenic mice. The learning and memory abilities of transgenic mice were further worsened at 8 months of age. Immunohistochemical staining revealed no BACE1 plaques in wild-type mice at 3, 6 or 8 months or in transgenic mice at 3 months, but they were clearly found in the entorhinal cortex, hippocampus and prefrontal cortex of transgenic mice at 6 and 8 months. BACE1 expression was not detected in the retina of wild-type mice at 3 months, but weak BACE1 expression was detected in the ganglion cell layer, inner plexiform layer and outer plexiform layer at 6 and 8 months. In transgenic mice, BACE1 expression in the ganglion cell layer was increased at 3 months, and BACE1 expression in the ganglion cell

  7. Glycinergic input of widefield, displaced amacrine cells of the mouse retina.

    PubMed

    Majumdar, Sriparna; Weiss, Jan; Wässle, Heinz

    2009-08-01

    Glycine receptors (GlyRs) of displaced amacrine cells of the mouse retina were analysed using whole cell recordings and immunocytochemical staining with subunit-specific antibodies. During the recordings the cells were filled with a fluorescent tracer and 11 different morphological types could be identified. The studies were performed in wild-type mice and in mutant mice deficient in the GlyRalpha1 (Glra1(spd-ot), 'oscillator' mouse), the GlyRalpha2 (Glra2(-/-)) and the GlyRalpha3 subunit (Glra3(-/-)). Based on their responses to the application of exogenous glycine in the retinas of wild-type and mutant mice, the cells were grouped into three major classes: group I cells (comprising the morphological types MA-S5, MA-S1, MA-S1/S5, A17, PA-S1, PA-S5 and WA-S1), group II cells (comprising the morphological types PA-S4, WA-S3 and WA-multi) and ON-starburst cells. For further analysis, spontaneous inhibitory postsynaptic currents (sIPSCs) were measured both in wild-type and mutant mouse retinas. Glycinergic sIPSCs and glycine induced currents of group I cells remained unaltered across wild-type and the three mutant mice (mean decay time constant of sIPSCs, tau approximately 25 ms). Group II cells showed glycinergic sIPSCs and glycine induced currents in wild-type, Glra1(spd-ot) and Glra3(-/-) mice (tau approximately 25 ms); however, glycinergic currents were absent in group II cells of Glra2(-/-) mice. Glycine induced currents and sIPSCs recorded from ON-starburst amacrine cells did not differ significantly between wild-type and the mutant mouse retinas (tau approximately 50-70 ms). We propose that GlyRs of group II cells are dominated by the alpha2 subunit; GlyRs of ON-starburst amacrine cells appear to be dominated by the alpha4 subunit. PMID:19528249

  8. Real time tracking with a silicon telescope prototype using the "artificial retina" algorithm

    NASA Astrophysics Data System (ADS)

    Abba, A.; Bedeschi, F.; Caponio, F.; Cenci, R.; Citterio, M.; Coelli, S.; Fu, J.; Geraci, A.; Grizzuti, M.; Lusardi, N.; Marino, P.; Monti, M.; Morello, M. J.; Neri, N.; Ninci, D.; Petruzzo, M.; Piucci, A.; Punzi, G.; Ristori, L.; Spinella, F.; Stracka, S.; Tonelli, D.; Walsh, J.

    2016-07-01

    We present the first prototype of a silicon tracker using the artificial retina algorithm for fast track finding. The algorithm is inspired by the neurobiological mechanism of recognition of edges in mammals visual cortex. It is based on extensive parallelization and is implemented on commercial FPGAs allowing us to reconstruct real time tracks with offline-like quality and < 1 μs latencies. The practical device consists of a telescope with 8 single-sided silicon strip sensors and custom DAQ boards equipped with Xilinx Kintex 7 FPGAs that perform the readout of the sensors and the track reconstruction in real time.

  9. Docosahexaenoic acid (22:6, n-3) is metabolized to lipoxygenase reaction products in the retina.

    PubMed

    Bazan, N G; Birkle, D L; Reddy, T S

    1984-12-14

    Docosahexaenoic acid (22:6, n-3), a major component of retinal phospholipids, is a substrate for active lipoxygenation in intact canine retinas incubated in vitro with [U-14C]docosahexaenoic acid. The major lipoxygenase reaction product was identified by high performance liquid chromatography and gas chromatography-mass spectrometry as 11-hydroxy-4,7,9-(trans)13,16,19 docosahexaenoic acid. Other mono- and di-hydroxy derivatives also were detected. The synthesis of these compounds was inhibited by the antioxidant and lipoxygenase inhibitor, nordihydroguaiaretic acid, but was not inhibited by indomethacin or esculetin. PMID:6240268

  10. Extracellular Matrix Components Regulate Cellular Polarity and Tissue Structure in the Developing and Mature Retina

    PubMed Central

    Varshney, Shweta; Hunter, Dale D.; Brunken, William J.

    2015-01-01

    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. PMID:26730321

  11. Cell-specific DNA methylation patterns of retina-specific genes.

    PubMed

    Merbs, Shannath L; Khan, Miriam A; Hackler, Laszlo; Oliver, Verity F; Wan, Jun; Qian, Jiang; Zack, Donald J

    2012-01-01

    Many studies have demonstrated that epigenetic mechanisms are important in the regulation of gene expression during embryogenesis, gametogenesis, and other forms of tissue-specific gene regulation. We sought to explore the possible role of epigenetics, specifically DNA methylation, in the establishment and maintenance of cell type-restricted gene expression in the retina. To assess the relationship between DNA methylation status and expression level of retinal genes, bisulfite sequence analysis of the 1000 bp region around the transcription start sites (TSS) of representative rod and cone photoreceptor-specific genes and gene expression analysis were performed in the WERI and Y79 human retinoblastoma cell lines. Next, the homologous genes in mouse were bisulfite sequenced in the retina and in non-expressing tissues. Finally, bisulfite sequencing was performed on isolated photoreceptor and non-photoreceptor retinal cells isolated by laser capture microdissection. Differential methylation of rhodopsin (RHO), retinal binding protein 3 (RBP3, IRBP) cone opsin, short-wave-sensitive (OPN1SW), cone opsin, middle-wave-sensitive (OPN1MW), and cone opsin, long-wave-sensitive (OPN1LW) was found in the retinoblastoma cell lines that inversely correlated with gene expression levels. Similarly, we found tissue-specific hypomethylation of the promoter region of Rho and Rbp3 in mouse retina as compared to non-expressing tissues, and also observed hypomethylation of retinal-expressed microRNAs. The Rho and Rbp3 promoter regions were unmethylated in expressing photoreceptor cells and methylated in non-expressing, non-photoreceptor cells from the inner nuclear layer. A third regional hypomethylation pattern of photoreceptor-specific genes was seen in a subpopulation of non-expressing photoreceptors (Rho in cones from the Nrl -/- mouse and Opn1sw in rods). These results demonstrate that a number of photoreceptor-specific genes have cell-specific differential DNA methylation that

  12. Oxygen consumption and distribution in the Long-Evans rat retina

    PubMed Central

    Lau, Jennifer C.M.; Linsenmeier, Robert A.

    2012-01-01

    The purpose of this study was to investigate the oxygen distribution and consumption in the pigmented Long-Evans rat retina in vivo during dark and light adaptation, and to compare these results to previous work on cat and albino rat. Double-barreled microelectrodes recorded both intraretinal PO2 depth profiles and the electroretinogram (ERG), which was used to identify the boundaries of the retina. Light adaptation decreased photoreceptor oxygen consumption per unit volume (Qav) from 3.0±0.4 ml•100 g−1•min−1 (mean ± SEM) in darkness to 1.8±0.2 ml•100 g−1•min−1 and increased minimum outer retinal PO2 at the inner segments (Pmin) from 17.4±3.0 to 29.9±5.3 mmHg. The effects of light on outer retinal PO2 and Qav were similar to those previously observed in cat, monkey, and albino rats; however, dark-adapted Pmin was higher in rat than cat. The parameters derived from fitting the oxygen diffusion model to the rat data were compared to those from cat. Oxygen consumption of the inner segments (Q2) and choroidal PO2 (PC) in rat and cat were similar. Pmin was higher in rat than in cat for two reasons: first, rat photoreceptors have a shorter oxygen consuming region; and second, the retinal circulation supplied a greater fraction of consumed oxygen to rat photoreceptors. The average PO2 across the inner retina (PIR) was not different in dark adaptation (25.4±4.8 mm Hg) and light adaptation (28.8±5.4 mmHg) when measured from PO2 profiles. However, with the microelectrode stationary at 9–18% retinal depth, a small consistent decrease in PO2 occurred during illumination. Flickering light at 6 Hz decreased inner retinal PO2 significantly more than an equivalent steady illumination, suggesting that changes in blood flow did not completely compensate for increased metabolism. This study comprehensively characterized rat retinal oxygenation in both light and dark, and determined the similarities and differences between rat and cat retinas. PMID:22828049

  13. Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina.

    PubMed

    Guo, Xian Jun; Tian, Xue Song; Ruan, Zhi; Chen, Yu Ting; Wu, Lei; Gong, Qi; Wang, Wei; Zhang, Hai Yan

    2014-08-01

    Although permanent bilateral common carotid artery occlusion (2VO) has been demonstrated to induce retinal injury, there is still a lack of systematic research on the complex processing of retinal degeneration. In the present study, time-dependent (at three, 14, 60 days after 2VO surgery) changes of neurotrophic and inflammatory systems, as well as cAMP-responsive element binding protein (CREB) signaling, which has been previously reported to effectively regulate these two systems, were evaluated. First, a morphological study confirmed that 2VO surgery progressively induced severe inner retinal degeneration and down-regulation of synaptic proteins, PSD95 and synaptophysin. The mRNA or protein levels of neurotrophic factors (NGF, BDNF, NT-3 and GDNF) and their receptors (TrkA, TrkB and TrkC) showed marked and persistent down-regulation in the rat retina since three days after 2VO surgery, whereas the gene transcription levels of CNTF were increased and p75(NTR) mRNA levels remained unchanged. In contrast to inner retinal degeneration, retinal Müller cells displayed rapid and prolonged activation since three days after 2VO lesion, whereas the microglia cell number, and TNF-α and IL-1β levels showed a robust increase with a maximal effect at three days and returned to levels that were slightly over baseline at 14 and 60 days after 2VO lesion. Interestingly, the gene expression levels of iNOS significantly decreased in the rat retina at both three and 14 days after 2VO surgery. Finally, as we hypothesized, remarkable reduction of CREB and extracellular signal-regulated kinase (ERK) phosphorylation levels were observed in the rat retina at three days after 2VO surgery. Thus, for the first time, our study demonstrated that chronic ischemia induced long-term aberrant CREB signaling and time-dependent progressive dysregulation of neurotrophic and inflammatory systems in the retina, which may provide important clues for a better understanding of the pathogenesis of

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

    PubMed Central

    Dvoriantchikova, Galina; Perea-Martinez, Isabel; Pappas, Steve; Barry, Ariel Faye; Danek, Dagmara; Dvoriantchikova, Xenia; Pelaez, Daniel; Ivanov, Dmitry

    2015-01-01

    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) and pro

  15. Zac1 functions through TGFβII to negatively regulate cell number in the developing retina

    PubMed Central

    Ma, Lin; Cantrup, Robert; Varrault, Annie; Colak, Dilek; Klenin, Natalia; Götz, Magdalena; McFarlane, Sarah; Journot, Laurent; Schuurmans, Carol

    2007-01-01

    Background Organs are programmed to acquire a particular size during development, but the regulatory mechanisms that dictate when dividing progenitor cells should permanently exit the cell cycle and stop producing additional daughter cells are poorly understood. In differentiated tissues, tumor suppressor genes maintain a constant cell number and intact tissue architecture by controlling proliferation, apoptosis and cell dispersal. Here we report a similar role for two tumor suppressor genes, the Zac1 zinc finger transcription factor and that encoding the cytokine TGFβII, in the developing retina. Results Using loss and gain-of-function approaches, we show that Zac1 is an essential negative regulator of retinal size. Zac1 mutants develop hypercellular retinae due to increased progenitor cell proliferation and reduced apoptosis at late developmental stages. Consequently, supernumerary rod photoreceptors and amacrine cells are generated, the latter of which form an ectopic cellular layer, while other retinal cells are present in their normal number and location. Strikingly, Zac1 functions as a direct negative regulator of a rod fate, while acting cell non-autonomously to modulate amacrine cell number. We implicate TGFβII, another tumor suppressor and cytokine, as a Zac1-dependent amacrine cell negative feedback signal. TGFβII and phospho-Smad2/3, its downstream effector, are expressed at reduced levels in Zac1 mutant retinae, and exogenous TGFβII relieves the mutant amacrine cell phenotype. Moreover, treatment of wild-type retinae with a soluble TGFβ inhibitor and TGFβ receptor II (TGFβRII) conditional mutants generate excess amacrine cells, phenocopying the Zac1 mutant phenotype. Conclusion We show here that Zac1 has an essential role in cell number control during retinal development, akin to its role in tumor surveillance in mature tissues. Furthermore, we demonstrate that Zac1 employs a novel cell non-autonomous strategy to regulate amacrine cell number

  16. An analog retina model for detecting dim moving objects against a bright moving background

    NASA Technical Reports Server (NTRS)

    Searfus, R. M.; Colvin, M. E.; Eeckman, F. H.; Teeters, J. L.; Axelrod, T. S.

    1991-01-01

    We are interested in applications that require the ability to track a dim target against a bright, moving background. Since the target signal will be less than or comparable to the variations in the background signal intensity, sophisticated techniques must be employed to detect the target. We present an analog retina model that adapts to the motion of the background in order to enhance targets that have a velocity difference with respect to the background. Computer simulation results and our preliminary concept of an analog 'Z' focal plane implementation are also presented.

  17. Imaging translucent cell bodies in the living mouse retina without contrast agents

    PubMed Central

    Guevara-Torres, A.; Williams, D. R.; Schallek, J. B.

    2015-01-01

    The transparency of most retinal cell classes typically precludes imaging them in the living eye; unless invasive methods are used that deploy extrinsic contrast agents. Using an adaptive optics scanning light ophthalmoscope (AOSLO) and capitalizing on the large numerical aperture of the mouse eye, we enhanced the contrast from otherwise transparent cells by subtracting the left from the right half of the light distribution in the detector plane. With this approach, it is possible to image the distal processes of photoreceptors, their more proximal cell bodies and the mosaic of horizontal cells in the living mouse retina. PMID:26114032

  18. Pathology of iridectomy specimens in gyrate atrophy of the retina and choroid.

    PubMed

    Vannas-Sulonen, K; Vannas, A; O'Donnell, J J; Sipilä, I; Wood, I

    1983-02-01

    Gyrate atrophy of the retina and choroid is an autosomal recessive disease characterized by progressive retinal degeneration and ornithine aminotransferase deficiency. We report here the new histological findings and ultrastructural changes in 3 iridectomy specimens from 2 Finnish patients with gyrate atrophy. The iridectomy specimens were removed during routine cataract extraction and studied with a transmission electron microscope. The dilator muscle showed atrophy, abnormal mitochondria, and tubular aggregate type structures similar to those found in skeletal muscle. Degenerative changes such as extracted cellular matrix, dropout of cellular organelles, and dilated intercellular spaces were observed in the pigmented posterior epithelium and the anterior iris epithelium. PMID:6858648

  19. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina

    PubMed Central

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  20. High-speed imaging of human retina in vivo with swept-source optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lim, H.; Mujat, M.; Kerbage, C.; Lee, E. C.; Chen, Y.; Chen, Teresa C.; de Boer, J. F.

    2006-12-01

    We present the first demonstration of human retinal imaging in vivo using optical frequency domain imaging (OFDI) in the 800-nm range. With 460-μW incident power on the eye, the sensitivity is 91 dB at maximum and >85 dB over 2-mm depth range. The axial resolution is 13 μm in air. We acquired images of retina at 43,200 depth profiles per second and a continuous acquisition speed of 84 frames/s (512 A-lines per frame) could be maintained over more than 2 seconds.

  1. Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina.

    PubMed

    Galindo-Romero, Caridad; Harun-Or-Rashid, Mohammad; Jiménez-López, Manuel; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Hallböök, Finn

    2016-01-01

    We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5-10 μg NMDA caused 30-50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina. PMID:27611432

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

    SciTech Connect

    Karnowski, Thomas Paul; Giancardo, Luca; Li, Yaquin; Tobin Jr, Kenneth William; Chaum, Edward

    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.

  3. Changes in the redox state in the retina and brain during the onset of diabetes in rats.

    PubMed

    Salceda, R; Vilchis, C; Coffe, V; Hernández-Muñoz, R

    1998-06-01

    Diabetic retinopathy is thought to result from chronic changes in the metabolic pathways of the retina. Hyperglycemia leads to increased intracellular glucose concentrations, alterations in glucose degradation and an increase in lactate/pyruvate ratio. We measured lactate content in retina and other ocular and non-ocular tissues from normal and diabetic rats in the early stages of streptozotocin-induced diabetes. The intracellular redox state was calculated from the cytoplasmic [lactate]/[pyruvate] ratio. Elevated lactate concentration were found in retina and cerebral cortex from diabetic rats. These concentrations led to a significant and progressive decrease in the NAD+/NADH ratio, suggesting that altered glucose metabolism is an initial step of retinopathy. It is thus possible that tissues such as cerebral cortex have mechanisms that prevent the damaging effect of lactate produced by hyperglycemia and/or alterations of the intracellular redox state. PMID:9580389

  4. Simulation of the temperature increase in human cadaver retina during direct illumination by 150-kHz femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Hosszufalusi, Nora; Mikula, Eric R.; Juhasz, Tibor

    2011-10-01

    We have developed a two-dimensional computer model to predict the temperature increase of the retina during femtosecond corneal laser flap cutting. Simulating a typical clinical setting for 150-kHz iFS advanced femtosecond laser (0.8- to 1-μJ laser pulse energy and 15-s procedure time at a laser wavelength of 1053 nm), the temperature increase is 0.2°C. Calculated temperature profiles show good agreement with data obtained from ex vivo experiments using human cadaver retina. Simulation results obtained for different commercial femtosecond lasers indicate that during the laser in situ keratomileusis procedure the temperature increase of the retina is insufficient to induce damage.

  5. Defective ceramide synthases in mice cause reduced amplitudes in electroretinograms and altered sphingolipid composition in retina and cornea.

    PubMed

    Brüggen, Bianca; Kremser, Christiane; Bickert, Andreas; Ebel, Philipp; Vom Dorp, Katharina; Schultz, Konrad; Dörmann, Peter; Willecke, Klaus; Dedek, Karin

    2016-07-01

    Complex sphingolipids are strongly expressed in neuronal tissue and contain ceramides in their backbone. Ceramides are synthesized by six ceramide synthases (CerS1-6). Although it is known that each tissue has a unique profile of ceramide synthase expression and ceramide synthases are implicated in several neurodegenerative disorders, the expression of ceramide synthase isoforms has not been investigated in the retina. Here we demonstrate CerS1, CerS2 and CerS4 expression in mouse retina and cornea, with CerS4 ubiquitously expressed in all retinal neurons and Müller cells. To test whether ceramide synthase deficiency affects retinal function, we compared electroretinograms and retina morphology between wild-type and CerS1-, CerS2- and CerS4-deficient mice. Electroretinograms were strongly reduced in amplitude in ceramide synthase-deficient mice, suggesting that signalling in the outer retina is affected. However, the number of photoreceptors and cone outer segment length were unaltered and no changes in retinal layer thickness or synaptic structures were found. Mass spectrometric analyses of ceramides, hexosyl-ceramides and sphingomyelins showed that C20 to C24 acyl-containing species were decreased whereas C16-containing species were increased in the retina of ceramide synthase-deficient mice. Similar but smaller changes were also found in the cornea. Thus, we hypothesize that the replacement of very long-chain fatty acyl residues by shorter C16 residues may affect the electrical properties of retina and cornea, and alter receptor-mediated signal transduction, vesicle-mediated synaptic transmission or corneal light transmission. Future studies need to identify the molecular targets of ceramides or derived sphingolipids in light signal transduction and transmission in the eye. PMID:27086873

  6. Sox2-Deficient Müller Glia Disrupt the Structural and Functional Maturation of the Mammalian Retina

    PubMed Central

    Bachleda, Amelia R.; Pevny, Larysa H.; Weiss, Ellen R.

    2016-01-01

    Purpose Müller glia (MG), the principal glial cells of the vertebrate retina, display quiescent progenitor cell characteristics. They express key progenitor markers, including the high mobility group box transcription factor SOX2 and maintain a progenitor-like morphology. In the embryonic and mature central nervous system, SOX2 maintains neural stem cell identity. However, its function in committed Müller glia has yet to be determined. Methods We use inducible, MG-specific genetic ablation of Sox2 in vivo at the peak of MG genesis to analyze its function in the maturation of murine MG and effects on other cells in the retina. Histologic and functional analysis of the Sox2-deficient retinas is conducted at key points in postnatal development. Results Ablation of Sox2 in the postnatal retina results in disorganization of MG processes in the inner plexiform layer and mislocalized cell bodies in the nuclear layers. This disorganization is concurrent with a thinning of the neural retina and disruption of neuronal processes in the inner and outer plexiform layers. Functional analysis by electroretinography reveals a decrease in the b-wave amplitude. Disruption of MG maturation due to Sox2 ablation therefore negatively affected the function of the retina. Conclusions These results demonstrate a novel role for SOX2 in glial process outgrowth and adhesion, and provide new insights into the essential role Müller glia play in the development of retinal cytoarchitecture. Prior to this work, SOX2 was known to have a primary role in determining cell fate. Our experiments bypass cell fate conversion to establish a new role for SOX2 in a committed cell lineage. PMID:27031842

  7. Retinoic acid metabolic change in retina and choroid of the guinea pig with lens-induced myopia

    PubMed Central

    Mao, Jun-Feng; Liu, Shuang-Zhen; Dou, Xiu-Qiong

    2012-01-01

    AIM To investigate the role of retinoic acid (RA) and retinaldehyde dehydrogenase-2 (RALDH2) of retina and choroid in the guinea pig lens-induced myopic eyes. METHODS Totally 45 guinea pigs, at age of three weeks, were randomly assigned into three groups: the normal control, the lens-induced group and the recovering group. Out of focus was induced by the -6.00D concave lens on the left eye, and lasted for 15 days. All animals underwent biometric measurement (corneal radius of curvature, refraction and axial length). Subsequently, RA content in the retina and RPE/choriod complex was detected by reversed-phase high-performance liquid chromatography. RALDH2 protein in the retina and RPE/choriod complex was evaluated by the immunohistochemical staining and Western blotting. RESULTS After wearing -6.00D lens for 15 days, axial length of the lens-induced eye extends and myopia was formed, with RA contents increasing in both the neural retina and RPE/choroid complex. Comparing with the lens-induced group, myopic degree significantly relieved, and its RA contents in both the neural retina and RPE/choroid complex decreased in the recovering group. In the normal control, RALDH2 protein was expressed positively in the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL) and lateral border of outer nuclear layer (ONL). Retinal RALDH2 protein increased in the lens-induced group, and was also positive in the outer plexiform layer (OPL). In the recovering group, retinal RALDH2 protein attenuated the expression in the OPL turns to negative. RALDH2 protein was not expressed in the choroid of any group. CONCLUSION RA of retina and chorid participates in the regulation of the lens-induced myopia in guinea pigs, which may be related with retinal RALDH2 protein. PMID:23275899

  8. Distribution of Purkinje cell-specific Zebrin-II/aldolase C immunoreactivity in the mouse, rat, rabbit, and human retina.

    PubMed

    Caffé, A R; Von Schantz, M; Szél, A; Voogd, J; Van Veen, T

    1994-10-01

    The developmental, genetic, and biochemical similarities that have been observed between the cerebellum and retina form the basis for ongoing investigations into retinal expression of cerebellar-specific proteins. We have examined the mouse, rat, rabbit, and human retina for expression of a protein that is present in parasagittal Purkinje cell strips and that is recognized by the antibody Zebrin-II. This protein has recently been identified as a member of the aldolase C isoenzymes. Western blotting and immunocytochemistry have been used. The monoclonal antibody Zebrin-II recognized a prominent 36 kDa protein band on immunoblots of both the cerebellum and the retina of the examined species. Immunocytochemistry showed that, in the three nonhuman species, cells were stained in the ganglion cell layer (GCL). In addition, in the mouse and rabbit, cells in the inner nuclear layer (INL) were also labeled. Except for the visual streak, there were more immunopositive cells in the rabbit GCL and INL than in corresponding areas of the mouse retina. In the human, in contrast to the other species, the photoreceptor cell layer was strongly aldolase C immunoreactive. In all species except for the rat, the photoreceptor inner segments also displayed a weak labeling. The results show that this aldolase C isoenzyme is another protein that is selectively expressed by the cerebellum and retina. Furthermore, the retinal expression is species specific, and this pattern seems to show a good correlation with the oxygenation level of the individual compartments. The indication that this aldolase C isoenzyme has specific developmental functions in the retina provides additional clues for our understanding of cerebellar organization. PMID:7814693

  9. Association of Shank 1A Scaffolding Protein with Cone Photoreceptor Terminals in the Mammalian Retina

    PubMed Central

    Stella, Salvatore L.; Vila, Alejandro; Hung, Albert Y.; Rome, Michael E.; Huynh, Uyenchi; Sheng, Morgan; Kreienkamp, Hans-Juergen; Brecha, Nicholas C.

    2012-01-01

    Photoreceptor terminals contain post-synaptic density (PSD) proteins e.g., PSD-95/PSD-93, but their role at photoreceptor synapses is not known. PSDs are generally restricted to post-synaptic boutons in central neurons and form scaffolding with multiple proteins that have structural and functional roles in neuronal signaling. The Shank family of proteins (Shank 1–3) functions as putative anchoring proteins for PSDs and is involved in the organization of cytoskeletal/signaling complexes in neurons. Specifically, Shank 1 is restricted to neurons and interacts with both receptors and signaling molecules at central neurons to regulate plasticity. However, it is not known whether Shank 1 is expressed at photoreceptor terminals. In this study we have investigated Shank 1A localization in the outer retina at photoreceptor terminals. We find that Shank 1A is expressed presynaptically in cone pedicles, but not rod spherules, and it is absent from mice in which the Shank 1 gene is deleted. Shank 1A co-localizes with PSD-95, peanut agglutinin, a marker of cone terminals, and glycogen phosphorylase, a cone specific marker. These findings provide convincing evidence for Shank 1A expression in both the inner and outer plexiform layers, and indicate a potential role for PSD-95/Shank 1 complexes at cone synapses in the outer retina. PMID:22984429

  10. Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina.

    PubMed

    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. PMID:25008417

  11. Glaucoma-inducing Procedure in an In Vivo Rat Model and Whole-mount Retina Preparation.

    PubMed

    Gossman, Cynthia A; Linn, David M; Linn, Cindy

    2016-01-01

    Glaucoma is a disease of the central nervous system affecting retinal ganglion cells (RGCs). RGC axons making up the optic nerve carry visual input to the brain for visual perception. Damage to RGCs and their axons leads to vision loss and/or blindness. Although the specific cause of glaucoma is unknown, the primary risk factor for the disease is an elevated intraocular pressure. Glaucoma-inducing procedures in animal models are a valuable tool to researchers studying the mechanism of RGC death. Such information can lead to the development of effective neuroprotective treatments that could aid in the prevention of vision loss. The protocol in this paper describes a method of inducing glaucoma - like conditions in an in vivo rat model where 50 µl of 2 M hypertonic saline is injected into the episcleral venous plexus. Blanching of the vessels indicates successful injection. This procedure causes loss of RGCs to simulate glaucoma. One month following injection, animals are sacrificed and eyes are removed. Next, the cornea, lens, and vitreous are removed to make an eyecup. The retina is then peeled from the back of the eye and pinned onto sylgard dishes using cactus needles. At this point, neurons in the retina can be stained for analysis. Results from this lab show that approximately 25% of RGCs are lost within one month of the procedure when compared to internal controls. This procedure allows for quantitative analysis of retinal ganglion cell death in an in vivo rat glaucoma model. PMID:27023167

  12. Detection of neuroinflammation through the retina by means of Raman spectroscopy and multivariate analysis

    NASA Astrophysics Data System (ADS)

    Marro, Monica; Taubes, Alice; Villoslada, Pablo; Petrov, Dmitri

    2012-06-01

    Retinal nervous tissue sustains a substantial damage during the autoimmune inflammatory processes characteristic for Multiple Sclerosis (MS). The damage can be characteriz