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Sample records for cone photoreceptor survival

  1. Acute Zonal Cone Photoreceptor Outer Segment Loss.

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    Aleman, Tomas S; Sandhu, Harpal S; Serrano, Leona W; Traband, Anastasia; Lau, Marisa K; Adamus, Grazyna; Avery, Robert A

    2017-05-01

    The diagnostic path presented narrows down the cause of acute vision loss to the cone photoreceptor outer segment and will refocus the search for the cause of similar currently idiopathic conditions. To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. Results of a complete ophthalmic examination, full-field flash electroretinography (ERG) and multifocal ERG, light-adapted achromatic and 2-color dark-adapted perimetry, and microperimetry. Imaging was performed with spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) and short-wavelength (SW) fundus autofluorescence (FAF), and NIR reflectance (REF). The patient was evaluated within a week of the onset of a scotoma in the nasal field of his left eye. Visual acuity was 20/20 OU, and color vision was normal in both eyes. Results of the fundus examination and of SW-FAF and NIR-FAF imaging were normal in both eyes, whereas NIR-REF imaging showed a region of hyporeflectance temporal to the fovea that corresponded with a dense relative scotoma noted on light-adapted static perimetry in the left eye. Loss in the photoreceptor outer segment detected by SD-OCT co-localized with an area of dense cone dysfunction detected on light-adapted perimetry and multifocal ERG but with near-normal rod-mediated vision according to results of 2-color dark-adapted perimetry. Full-field flash ERG findings were normal in both eyes. The outer nuclear layer and inner retinal thicknesses were normal. Localized, isolated cone dysfunction may represent the earliest photoreceptor abnormality or a distinct entity within the acute zonal occult outer retinopathy complex. Acute zonal occult outer retinopathy should be considered in patients with acute vision loss and abnormalities on NIR-REF imaging, especially if

  2. Integrity of the cone photoreceptor mosaic in oligocone trichromacy

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    Michaelides, Michel; Rha, Jungtae; Dees, Elise W

    2011-01-01

    Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these...... that these patients have a reduced number of normal functioning cones (oligocone). This paper has sought to evaluate the integrity of the cone photoreceptor mosaic in four patients previously described as having OT....

  3. Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa.

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    Miao Chen

    Full Text Available Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal degeneration. Whether cone bipolar cells establish regular retinal mosaics and mature morphologies, and resist degeneration are not completely understood. To explore these issues, we backcrossed a transgenic mouse expressing enhanced green fluorescent protein (EGFP in one subset of cone bipolar cells (type 7 into rd1 mice, a classic mouse model of retinal degeneration, to examine the development and survival of cone bipolar cells in a background of retinal degeneration. Our data revealed that both the development and degeneration of cone bipolar cells are independent of the normal activity of cone photoreceptors. We found that type 7 cone bipolar cells achieved a uniform tiling of the retinal surface and developed normal dendritic and axonal arbors without the influence of cone photoreceptor innervation. On the other hand, degeneration of type 7 cone bipolar cells, contrary to our belief of central-to-peripheral progression, was spatially uniform across the retina independent of the spatiotemporal pattern of cone degeneration. The results have important implications for the design of more effective therapies to restore vision in retinal degeneration.

  4. Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

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    Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Redmond, T. Michael; Baehr, Wolfgang; Ding, Xi-Qin

    2014-01-01

    Photoreceptors degenerate in a wide array of hereditary retinal diseases and age-related macular degeneration. There is currently no treatment available for retinal degenerations. While outnumbered roughly 20:1 by rods in the human retina, it is the cones that mediate color vision and visual acuity, and their survival is critical for vision. In this communication, we investigate whether thyroid hormone (TH) signaling affects cone viability in retinal degeneration mouse models. TH signaling is...

  5. Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina.

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    Irie, Shoichi; Sanuki, Rikako; Muranishi, Yuki; Kato, Kimiko; Chaya, Taro; Furukawa, Takahisa

    2015-08-01

    The Rax homeobox gene plays essential roles in multiple processes of vertebrate retina development. Many vertebrate species possess Rax and Rax2 genes, and different functions have been suggested. In contrast, mice contain a single Rax gene, and its functional roles in late retinal development are still unclear. To clarify mouse Rax function in postnatal photoreceptor development and maintenance, we generated conditional knockout mice in which Rax in maturing or mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO mice). When Rax was inactivated in postnatal Rax iCKO mice, developing photoreceptor cells showed a significant decrease in the level of the expression of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a specific decrease in cone cell numbers. In luciferase assays, we found that Rax and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that an optimum Rax expression level to transactivate photoreceptor gene expression exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and their coimmunoprecipitation was observed in cultured cells. Taken together, these results suggest that Rax plays essential roles in the maturation of both cones and rods and in the survival of cones by regulating photoreceptor gene expression with Crx in the postnatal mouse retina. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity

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    Akiko Ueno

    2018-03-01

    Full Text Available Summary: In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. : Ueno et al. finds that Lrit1 plays an important role in regulating the synaptic connection between cone photoreceptors and cone ON-bipolar cells. The Frmpd2-Lrit1-mGluR6 axis is crucial for selective synapse formation in cone photoreceptors and for development of normal visual function. Keywords: retina, circuit, synapse formation, cone photoreceptor cell, ON-bipolar cell, visual acuity

  7. Loss and gain of cone types in vertebrate ciliary photoreceptor evolution.

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    Musser, Jacob M; Arendt, Detlev

    2017-11-01

    Ciliary photoreceptors are a diverse cell type family that comprises the rods and cones of the retina and other related cell types such as pineal photoreceptors. Ciliary photoreceptor evolution has been dynamic during vertebrate evolution with numerous gains and losses of opsin and phototransduction genes, and changes in their expression. For example, early mammals lost all but two cone opsins, indicating loss of cone receptor types in response to nocturnal lifestyle. Our review focuses on the comparison of specifying transcription factors and cell type-specific transcriptome data in vertebrate retinae to build and test hypotheses on ciliary photoreceptor evolution. Regarding cones, recent data reveal that a combination of factors specific for long-wavelength sensitive opsin (Lws)- cones in non-mammalian vertebrates (Thrb and Rxrg) is found across all differentiating cone photoreceptors in mice. This suggests that mammalian ancestors lost all but one ancestral cone type, the Lws-cone. We test this hypothesis by a correlation analysis of cone transcriptomes in mouse and chick, and find that, indeed, transcriptomes of all mouse cones are most highly correlated to avian Lws-cones. These findings underscore the importance of specifying transcription factors in tracking cell type evolution, and shed new light on the mechanisms of cell type loss and gain in retina evolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Retinal cone photoreceptors of the deer mouse Peromyscus maniculatus: development, topography, opsin expression and spectral tuning.

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    Patrick Arbogast

    Full Text Available A quantitative analysis of photoreceptor properties was performed in the retina of the nocturnal deer mouse, Peromyscus maniculatus, using pigmented (wildtype and albino animals. The aim was to establish whether the deer mouse is a more suitable model species than the house mouse for photoreceptor studies, and whether oculocutaneous albinism affects its photoreceptor properties. In retinal flatmounts, cone photoreceptors were identified by opsin immunostaining, and their numbers, spectral types, and distributions across the retina were determined. Rod photoreceptors were counted using differential interference contrast microscopy. Pigmented P. maniculatus have a rod-dominated retina with rod densities of about 450.000/mm(2 and cone densities of 3000-6500/mm(2. Two cone opsins, shortwave sensitive (S and middle-to-longwave sensitive (M, are present and expressed in distinct cone types. Partial sequencing of the S opsin gene strongly supports UV sensitivity of the S cone visual pigment. The S cones constitute a 5-15% minority of the cones. Different from house mouse, S and M cone distributions do not have dorsoventral gradients, and coexpression of both opsins in single cones is exceptional (<2% of the cones. In albino P. maniculatus, rod densities are reduced by approximately 40% (270.000/mm(2. Overall, cone density and the density of cones exclusively expressing S opsin are not significantly different from pigmented P. maniculatus. However, in albino retinas S opsin is coexpressed with M opsin in 60-90% of the cones and therefore the population of cones expressing only M opsin is significantly reduced to 5-25%. In conclusion, deer mouse cone properties largely conform to the general mammalian pattern, hence the deer mouse may be better suited than the house mouse for the study of certain basic cone properties, including the effects of albinism on cone opsin expression.

  9. Analysis of macular cone photoreceptors in a case of occult macular dystrophy

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    Tojo N

    2013-05-01

    Full Text Available Naoki Tojo Tomoko Nakamura Hironori Ozaki Miyako Oka Toshihiko Oiwake Atsushi HayashiDepartment of Ophthalmology, University of Toyama, Toyama, JapanPurpose: To investigate changes in cone photoreceptors with adaptive optics (AO fundus imaging and spectral domain optical coherence tomography (SD-OCT in a case of occult macular dystrophy (OMD.Patient and methods: Both eyes of a 42-year-old woman diagnosed with OMD were examined. We used an AO fundus camera to obtain images of cone photoreceptors in the macula of the OMD subject and five healthy control subjects. Correlations between the AO images and the SD-OCT images were examined. Cone photoreceptors in eight areas in the macula of OMD and healthy control subjects were analyzed and compared.Results: SD-OCT showed a loss of the cone outer-segment tips line outside of the fovea in both eyes of the subject with OMD. The left eye with decreased visual acuity showed a discontinuous photoreceptor inner-segment and outer-segment line and cone outer-segment tips line at the fovea in SD-OCT and loss of cone mosaics as a dark spot in the AO image. In panoramic AO images and cone-density maps, less cone density was observed in a ring-like region outside the fovea than in the peripheral retina. In most of the areas examined, the cone densities were lower in the OMD eyes than in the healthy control eyes.Conclusions: Cone densities in the macula of the OMD patient were greatly decreased. AO images were found to be useful to evaluate morphologic changes in cone photoreceptors in patients with OMD.Keywords: occult macular dystrophy, adaptive optics, cone photoreceptor, cone analysis, optical coherence tomography

  10. Adaptive optics fundus images of cone photoreceptors in the macula of patients with retinitis pigmentosa

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    Tojo N

    2013-01-01

    Full Text Available Naoki Tojo, Tomoko Nakamura, Chiharu Fuchizawa, Toshihiko Oiwake, Atsushi HayashiDepartment of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanBackground: The purpose of this study was to examine cone photoreceptors in the macula of patients with retinitis pigmentosa using an adaptive optics fundus camera and to investigate any correlations between cone photoreceptor density and findings on optical coherence tomography and fundus autofluorescence.Methods: We examined two patients with typical retinitis pigmentosa who underwent ophthalmological examination, including measurement of visual acuity, and gathering of electroretinographic, optical coherence tomographic, fundus autofluorescent, and adaptive optics fundus images. The cone photoreceptors in the adaptive optics images of the two patients with retinitis pigmentosa and five healthy subjects were analyzed.Results: An abnormal parafoveal ring of high-density fundus autofluorescence was observed in the macula in both patients. The border of the ring corresponded to the border of the external limiting membrane and the inner segment and outer segment line in the optical coherence tomographic images. Cone photoreceptors at the abnormal parafoveal ring were blurred and decreased in the adaptive optics images. The blurred area corresponded to the abnormal parafoveal ring in the fundus autofluorescence images. Cone densities were low at the blurred areas and at the nasal and temporal retina along a line from the fovea compared with those of healthy controls. The results for cone spacing and Voronoi domains in the macula corresponded with those for the cone densities.Conclusion: Cone densities were heavily decreased in the macula, especially at the parafoveal ring on high-density fundus autofluorescence in both patients with retinitis pigmentosa. Adaptive optics images enabled us to observe in vivo changes in the cone photoreceptors of

  11. Adaptive optics fundus images of cone photoreceptors in the macula of patients with retinitis pigmentosa.

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    Tojo, Naoki; Nakamura, Tomoko; Fuchizawa, Chiharu; Oiwake, Toshihiko; Hayashi, Atsushi

    2013-01-01

    The purpose of this study was to examine cone photoreceptors in the macula of patients with retinitis pigmentosa using an adaptive optics fundus camera and to investigate any correlations between cone photoreceptor density and findings on optical coherence tomography and fundus autofluorescence. We examined two patients with typical retinitis pigmentosa who underwent ophthalmological examination, including measurement of visual acuity, and gathering of electroretinographic, optical coherence tomographic, fundus autofluorescent, and adaptive optics fundus images. The cone photoreceptors in the adaptive optics images of the two patients with retinitis pigmentosa and five healthy subjects were analyzed. An abnormal parafoveal ring of high-density fundus autofluorescence was observed in the macula in both patients. The border of the ring corresponded to the border of the external limiting membrane and the inner segment and outer segment line in the optical coherence tomographic images. Cone photoreceptors at the abnormal parafoveal ring were blurred and decreased in the adaptive optics images. The blurred area corresponded to the abnormal parafoveal ring in the fundus autofluorescence images. Cone densities were low at the blurred areas and at the nasal and temporal retina along a line from the fovea compared with those of healthy controls. The results for cone spacing and Voronoi domains in the macula corresponded with those for the cone densities. Cone densities were heavily decreased in the macula, especially at the parafoveal ring on high-density fundus autofluorescence in both patients with retinitis pigmentosa. Adaptive optics images enabled us to observe in vivo changes in the cone photoreceptors of patients with retinitis pigmentosa, which corresponded to changes in the optical coherence tomographic and fundus autofluorescence images.

  12. Avian cone photoreceptors tile the retina as five independent, self-organizing mosaics.

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    Yoseph A Kram

    2010-02-01

    Full Text Available The avian retina possesses one of the most sophisticated cone photoreceptor systems among vertebrates. Birds have five types of cones including four single cones, which support tetrachromatic color vision and a double cone, which is thought to mediate achromatic motion perception. Despite this richness, very little is known about the spatial organization of avian cones and its adaptive significance. Here we show that the five cone types of the chicken independently tile the retina as highly ordered mosaics with a characteristic spacing between cones of the same type. Measures of topological order indicate that double cones are more highly ordered than single cones, possibly reflecting their posited role in motion detection. Although cones show spacing interactions that are cell type-specific, all cone types use the same density-dependent yardstick to measure intercone distance. We propose a simple developmental model that can account for these observations. We also show that a single parameter, the global regularity index, defines the regularity of all five cone mosaics. Lastly, we demonstrate similar cone distributions in three additional avian species, suggesting that these patterning principles are universal among birds. Since regular photoreceptor spacing is critical for uniform sampling of visual space, the cone mosaics of the avian retina represent an elegant example of the emergence of adaptive global patterning secondary to simple local interactions between individual photoreceptors. Our results indicate that the evolutionary pressures that gave rise to the avian retina's various adaptations for enhanced color discrimination also acted to fine-tune its spatial sampling of color and luminance.

  13. Roles of glucose in photoreceptor survival.

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    Chertov, Andrei O; Holzhausen, Lars; Kuok, Iok Teng; Couron, Drew; Parker, Ed; Linton, Jonathan D; Sadilek, Martin; Sweet, Ian R; Hurley, James B

    2011-10-07

    Vertebrate photoreceptor neurons have a high demand for metabolic energy, and their viability is very sensitive to genetic and environmental perturbations. We investigated the relationship between energy metabolism and cell death by evaluating the metabolic effects of glucose deprivation on mouse photoreceptors. Oxygen consumption, lactate production, ATP, NADH/NAD(+), TCA cycle intermediates, morphological changes, autophagy, and viability were evaluated. We compared retinas incubated with glucose to retinas deprived of glucose or retinas treated with a mixture of mitochondrion-specific fuels. Rapid and slow phases of cell death were identified. The rapid phase is linked to reduced mitochondrial activity, and the slower phase reflects a need for substrates for cell maintenance and repair.

  14. Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity.

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    Ueno, Akiko; Omori, Yoshihiro; Sugita, Yuko; Watanabe, Satoshi; Chaya, Taro; Kozuka, Takashi; Kon, Tetsuo; Yoshida, Satoyo; Matsushita, Kenji; Kuwahara, Ryusuke; Kajimura, Naoko; Okada, Yasushi; Furukawa, Takahisa

    2018-03-27

    In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

    DEFF Research Database (Denmark)

    Patterson, Emily J.; Wilk, Melissa; Langlo, Christopher S.

    2016-01-01

    encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants......PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations...... to clarify the link between color vision deficiency and cone dysfunction.  METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone...

  16. Synaptojanin 1 is required for endolysosomal trafficking of synaptic proteins in cone photoreceptor inner segments.

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    Ashley A George

    Full Text Available Highly polarized cells such as photoreceptors require precise and efficient strategies for establishing and maintaining the proper subcellular distribution of proteins. The signals and molecular machinery that regulate trafficking and sorting of synaptic proteins within cone inner segments is mostly unknown. In this study, we show that the polyphosphoinositide phosphatase Synaptojanin 1 (SynJ1 is critical for this process. We used transgenic markers for trafficking pathways, electron microscopy, and immunocytochemistry to characterize trafficking defects in cones of the zebrafish mutant, nrc(a14 , which is deficient in phosphoinositide phosphatase, SynJ1. The outer segments and connecting cilia of nrc(a14 cone photoreceptors are normal, but RibeyeB and VAMP2/synaptobrevin, which normally localize to the synapse, accumulate in the nrc(a14 inner segment. The structure of the Endoplasmic Reticulum in nrc(a14 mutant cones is normal. Golgi develop normally, but later become disordered. Large vesicular structures accumulate within nrc(a14 cone photoreceptor inner segments, particularly after prolonged incubation in darkness. Cone inner segments of nrc (a14 mutants also have enlarged acidic vesicles, abnormal late endosomes, and a disruption in autophagy. This last pathway also appears exacerbated by darkness. Taken altogether, these findings show that SynJ1 is required in cones for normal endolysosomal trafficking of synaptic proteins.

  17. Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision.

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    Seeliger, Mathias W; Brombas, Arne; Weiler, Reto; Humphries, Peter; Knop, Gabriel; Tanimoto, Naoyuki; Müller, Frank

    2011-11-08

    Retinal photoreceptors permit visual perception over a wide range of lighting conditions. Rods work best in dim, and cones in bright environments, with considerable functional overlap at intermediate (mesopic) light levels. At many sites in the outer and inner retina where rod and cone signals interact, gap junctions, particularly those containing Connexin36, have been identified. However, little is known about the dynamic processes associated with the convergence of rod and cone system signals into ON- and OFF-pathways. Here we show that proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1. When these channels are absent, sustained rod responses following bright light exposure saturate the retinal network, resulting in a loss of downstream cone signalling. By specific genetic and pharmacological ablation of key signal processing components, regular cone signalling can be restored, thereby identifying the sites involved in functional rod-cone interactions.

  18. Integrity of the cone photoreceptor mosaic in oligocone trichromacy

    DEFF Research Database (Denmark)

    Michaelides, Michel; Rha, Jungtae; Dees, Elise W

    2011-01-01

    Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these......Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed...

  19. Functional Optical Coherence Tomography Enables In Vivo Physiological Assessment of Retinal Rod and Cone Photoreceptors

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    Zhang, Qiuxiang; Lu, Rongwen; Wang, Benquan; Messinger, Jeffrey D.; Curcio, Christine A.; Yao, Xincheng

    2015-04-01

    Transient intrinsic optical signal (IOS) changes have been observed in retinal photoreceptors, suggesting a unique biomarker for eye disease detection. However, clinical deployment of IOS imaging is challenging due to unclear IOS sources and limited signal-to-noise ratios (SNRs). Here, by developing high spatiotemporal resolution optical coherence tomography (OCT) and applying an adaptive algorithm for IOS processing, we were able to record robust IOSs from single-pass measurements. Transient IOSs, which might reflect an early stage of light phototransduction, are consistently observed in the photoreceptor outer segment almost immediately (retinal stimulation. Comparative studies of dark- and light-adapted retinas have demonstrated the feasibility of functional OCT mapping of rod and cone photoreceptors, promising a new method for early disease detection and improved treatment of diseases such as age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage.

  20. ℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa

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    Clérin Emmanuelle

    2011-12-01

    Full Text Available Abstract Background Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. Methods An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. Results The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. Conclusion The automated

  1. ℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa.

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    Clérin, Emmanuelle; Wicker, Nicolas; Mohand-Saïd, Saddek; Poch, Olivier; Sahel, José-Alain; Léveillard, Thierry

    2011-12-20

    Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs) as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. The automated platform ℮-conome used here for retinal disease is a tool that

  2. Optical imaging of human cone photoreceptors directly following the capture of light.

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    Phillip Bedggood

    Full Text Available Capture of light in the photoreceptor outer segment initiates a cascade of chemical events that inhibit neurotransmitter release, ultimately resulting in vision. The massed response of the photoreceptor population can be measured non-invasively by electrical recordings, but responses from individual cells cannot be measured without dissecting the retina. Here we used optical imaging to observe individual human cones in the living eye as they underwent bleaching of photopigment and associated phototransduction. The retina was simultaneously stimulated and observed with high intensity visible light at 1 kHz, using adaptive optics. There was marked variability between individual cones in both photosensitivity and pigment optical density, challenging the conventional assumption that photoreceptors act as identical subunits (coefficient of variation in rate of photoisomerization = 23%. There was also a pronounced inverse correlation between these two parameters (p<10(-7; the temporal evolution of image statistics revealed this to be a dynamic relationship, with cone waveguiding efficiency beginning a dramatic increase within 3 ms of light onset. Beginning as early as 2 ms after light onset and including half of cells by ∼7 ms, cone intensity showed reversals characteristic of interference phenomena, with greater delays in reversal corresponding to cones with more photopigment (p<10(-3. The timing of these changes is argued to best correspond with either the cessation of dark current, or to related events such as changes in intracellular cGMP. Cone intensity also showed fluctuations of high frequency (332±25 Hz and low amplitude (3.0±0.85%. Other groups have shown similar fluctuations that were directly evoked by light; if this corresponds to the same phenomenon, we propose that the amplitude of fluctuation may be increased by the use of a bright flash followed by a brief pause, to allow recovery of cone circulating current.

  3. Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration

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    Kamil Kruczek

    2017-06-01

    Full Text Available The loss of cone photoreceptors that mediate daylight vision represents a leading cause of blindness, for which cell replacement by transplantation offers a promising treatment strategy. Here, we characterize cone differentiation in retinas derived from mouse embryonic stem cells (mESCs. Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransduction-related proteins. We establish that stage-specific inhibition of the Notch pathway increases cone cell differentiation, while retinoic acid signaling regulates cone maturation, comparable with their actions in vivo. MESC-derived cones can be isolated in large numbers and transplanted into adult mouse eyes, showing capacity to survive and mature in the subretinal space of Aipl1−/− mice, a model of end-stage retinal degeneration. Together, this work identifies a robust, renewable cell source for cone replacement by purified cell suspension transplantation.

  4. Tokay gecko photoreceptors achieve rod-like physiology with cone-like proteins.

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    Zhang, Xue; Wensel, Theodore G; Yuan, Ching

    2006-01-01

    The retinal photoreceptors of the nocturnal Tokay gecko (Gekko gekko) consist exclusively of rods by the criteria of morphology and key features of their light responses. Unlike cones, they display robust photoresponses and have relatively slow recovery times. Nonetheless, the major and minor visual pigments identified in gecko rods are of the cone type by sequence and spectroscopic behavior. In the ongoing search for the molecular bases for the physiological differences between cones and rods, we have characterized the molecular biology and biochemistry of the gecko rod phototransduction cascade. We have cloned cDNAs encoding all or part of major protein components of the phototransduction cascade by RT-PCR with degenerate oligonucleotides designed to amplify cone- or rod-like sequences. For all proteins examined we obtained only cone-like and never rod-like sequences. The proteins identified include transducin alpha (Galphat), phosphodiesterase (PDE6) catalytic and inhibitory subunits, cyclic nucleotide-gated channel (CNGalpha) and arrestin. We also cloned cDNA encoding gecko RGS9-1 (Regulator of G Protein Signaling 9, splice variant 1), which is expressed in both rods and cones of all species studied but is typically found at 10-fold higher concentrations in cones, and found that gecko rods contain slightly lower RGS9-1 levels than mammalian rods. Furthermore, we found that the levels of GTPase accelerating protein (GAP) activity and cyclic GMP (cGMP) phosphodiesterase activity were similar in gecko and mammalian rods. These results place substantial constraints on the critical changes needed to convert a cone into a rod in the course of evolution: The many features of phototransduction molecules conserved between those expressed in gecko rods and those expressed in cones cannot explain the physiological differences, whereas the higher levels of RGS9-1 and GAP activity in cones are likely among the essential requirements for the rapid photoresponses of cones.

  5. Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys.

    Science.gov (United States)

    Hass, Charles A; Angueyra, Juan M; Lindbloom-Brown, Zachary; Rieke, Fred; Horwitz, Gregory D

    2015-01-01

    Chromatic sensitivity cannot exceed limits set by noise in the cone photoreceptors. To determine how close neurophysiological and psychophysical chromatic sensitivity come to these limits, we developed a parameter-free model of stimulus encoding in the cone outer segments, and we compared the sensitivity of the model to the psychophysical sensitivity of monkeys performing a detection task and to the sensitivity of individual V1 neurons. Modeled cones had a temporal impulse response and a noise power spectrum that were derived from in vitro recordings of macaque cones, and V1 recordings were made during performance of the detection task. The sensitivity of the simulated cone mosaic, the V1 neurons, and the monkeys were tightly yoked for low-spatiotemporal-frequency isoluminant modulations, indicating high-fidelity signal transmission for this class of stimuli. Under the conditions of our experiments and the assumptions for our model, the signal-to-noise ratio for these stimuli dropped by a factor of ∼3 between the cones and perception. Populations of weakly correlated V1 neurons narrowly exceeded the monkeys' chromatic sensitivity but fell well short of the cones' chromatic sensitivity, suggesting that most of the behavior-limiting noise lies between the cone outer segments and the output of V1. The sensitivity gap between the cones and behavior for achromatic stimuli was larger than for chromatic stimuli, indicating greater postreceptoral noise. The cone mosaic model provides a means to compare visual sensitivity across disparate stimuli and to identify sources of noise that limit visual sensitivity.

  6. Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion.

    Science.gov (United States)

    Hadj-Saïd, Wahiba; Froger, Nicolas; Ivkovic, Ivana; Jiménez-López, Manuel; Dubus, Élisabeth; Dégardin-Chicaud, Julie; Simonutti, Manuel; Quénol, César; Neveux, Nathalie; Villegas-Pérez, María Paz; Agudo-Barriuso, Marta; Vidal-Sanz, Manuel; Sahel, Jose-Alain; Picaud, Serge; García-Ayuso, Diego

    2016-09-01

    Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S- and L- cones) in an animal model of induced taurine depletion. We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their retinal distribution studied using isodensity maps. The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed. This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin+cones, L-opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.

  7. Quantitative analysis of cone photoreceptor distribution and its relationship with axial length, age, and early age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Ryo Obata

    Full Text Available PURPOSE: It has not been clarified whether early age-related macular degeneration (AMD is associated with cone photoreceptor distribution. We used adaptive optics fundus camera to examine cone photoreceptors in the macular area of aged patients and quantitatively analyzed its relationship between the presence of early AMD and cone distribution. METHODS: Sixty cases aged 50 or older were studied. The eyes were examined with funduscopy and spectral-domain optical coherence tomography to exclude the eyes with any abnormalities at two sites of measurement, 2° superior and 5° temporal to the fovea. High-resolution retinal images with cone photoreceptor mosaic were obtained with adaptive optics fundus camera (rtx1, Imagine Eyes, France. After adjusting for axial length, cone packing density was calculated and the relationship with age, axial length, or severity of early AMD based on the age-related eye disease study (AREDS classification was analyzed. RESULTS: Patient's age ranged from 50 to 77, and axial length from 21.7 to 27.5 mm. Mean density in metric units and that in angular units were 24,900 cells/mm2, 2,170 cells/deg2 at 2° superior, and 18,500 cells/mm2, 1,570 cels/deg2 at 5° temporal, respectively. Axial length was significantly correlated with the density calculated in metric units, but not with that in angular units. Age was significantly correlated with the density both in metric and angular units at 2° superior. There was no significant difference in the density in metric and angular units between the eyes with AREDS category one and those with categories two or three. CONCLUSION: Axial length and age were significantly correlated with parafoveal cone photoreceptor distribution. The results do not support that early AMD might influence cone photoreceptor density in the area without drusen or pigment abnormalities.

  8. Multiple rod–cone and cone–rod photoreceptor transmutations in snakes: Evidence from visual opsin gene expression

    Science.gov (United States)

    Simoe, Bruno F; Sampaio, Filipa L.; Loew, Ellis R.; Sanders, Kate L.; Fisher, Robert N.; Hart, Nathan S.; Hunt, David M.; Partridge, Julian C.; Gower, David J.

    2016-01-01

    In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor ‘transmutation’. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels.

  9. Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa

    Science.gov (United States)

    Murakami, Y; Ikeda, Y; Nakatake, S; Tachibana, T; Fujiwara, K; Yoshida, N; Notomi, S; Nakao, S; Hisatomi, T; Miller, J W; Vavvas, DG; Sonoda, KH; Ishibashi, T

    2015-01-01

    Retinitis pigmentosa (RP) refers to a group of inherited retinal degenerations resulting form rod and cone photoreceptor cell death. The rod cell death due to deleterious genetic mutations has been shown to occur mainly through apoptosis, whereas the mechanisms and features of the secondary cone cell death have not been fully elucidated. Our previous study showed that the cone cell death in rd10 mice, an animal model of RP, involves necrotic features and is partly mediated by the receptor interacting protein kinase. However, the relevancy of necrotic cone cell death in human RP patients remains unknown. In the present study, we showed that dying cone cells in rd10 mice exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, live imaging of cone cells by adaptive optics scanning laser ophthalmoscopy revealed significantly increased percentages of enlarged cone cells in the RP patients compared with the control subjects. The vitreous of the RP patients contained significantly higher levels of high-mobility group box-1, which is released extracellularly associated with necrotic cell death. These findings suggest that necrotic enlargement of cone cells is involved in the process of cone degeneration, and that necrosis may be a novel target to prevent or delay the loss of cone-mediated central vision in RP. PMID:27551484

  10. Circulating Reactive Oxidant Causes Apoptosis of Retinal Pigment Epithelium and Cone Photoreceptors in the Mouse Central Retina

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2011-01-01

    Full Text Available Reactive oxidants damage the retinal pigment epithelium (RPE, which is required for viability of overlying photoreceptors. Smoking which leads to chronic accumulation of reactive oxidants in the circulation is linked to age-related macular degeneration (AMD where RPE death is seen along with photoreceptor loss in the central macular region of the retina. It is unclear why this damage is concentrated in the central retina. We asked whether circulating oxidant might specifically target the central retina. Mice were administered the classic reactive oxidant iodate through tail vein injection, and visual acuity was followed by optokinetic response. Histology and apoptosis was examined by H&E and immunostaining. Iodate indeed selectively damaged the central retina, and this damage was highlighted by early apoptosis of RPE in the central retina followed by apoptosis of photoreceptors adjacent to the region of RPE loss–-cones were lost preferentially. The pattern and extent of this damage was independent of exposure to light. We then conclude that circulating oxidant is sufficient to selectively damage the central retina highlighted by sequential apoptosis of RPE and photoreceptors, with cones being the most sensitivity to this RPE loss.

  11. Deletion of the Thyroid Hormone-Activating Type 2 Deiodinase Rescues Cone Photoreceptor Degeneration but Not Deafness in Mice Lacking Type 3 Deiodinase.

    Science.gov (United States)

    Ng, Lily; Liu, Hong; St Germain, Donald L; Hernandez, Arturo; Forrest, Douglas

    2017-06-01

    Type 2 deiodinase amplifies and type 3 deiodinase depletes levels of the active form of thyroid hormone, triiodothyronine. Given the opposing activities of these enzymes, we tested the hypothesis that they counteract each other's developmental functions by investigating whether deletion of type 2 deiodinase (encoded by Dio2) modifies sensory phenotypes in type 3 deiodinase-deficient (Dio3-/-) mice. Dio3-/- mice display degeneration of retinal cones, the photoreceptors that mediate daylight and color vision. In Dio2-/- mice, cone function was largely normal but deletion of Dio2 in Dio3-/- mice markedly recovered cone numbers and electroretinogram responses, suggesting counterbalancing roles for both enzymes in cone survival. Both Dio3-/- and Dio2-/- strains exhibit deafness with cochlear abnormalities. In Dio3-/-;Dio2-/- mice, deafness was exacerbated rather than alleviated, suggesting unevenly balanced actions by these enzymes during auditory development. Dio3-/- mice also exhibit an atrophic thyroid gland, low thyroxine, and high triiodothyronine levels, but this phenotype was ameliorated in Dio3-/-;Dio2-/- mice, indicating counterbalancing roles for the enzymes in determining the thyroid hormone status. The results suggest that the composite action of these two enzymes is a critical determinant in visual and auditory development and in setting the systemic thyroid hormone status.

  12. Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system.

    LENUS (Irish Health Repository)

    Bhatt, Lavinia

    2010-01-01

    PURPOSE: The production of reactive oxygen species (ROS) can lead to oxidative stress, which is a strong contributory factor to many ocular diseases. In this study, the removal of trophic factors is used as a model system to investigate the effects of stress in the retina. The aims were to determine if both rod and cone photoreceptor cells produce ROS when they are deprived of trophic factor support and to demonstrate if the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes are responsible for this ROS production. METHODS: Retinas were explanted from mice aged between postnatal days 8-10 and cultured overnight. The following morning, confocal microscopy combined with various fluorescent probes was used to detect the production of ROS. Each time peanut agglutinin (PNA), a cone photoreceptor marker, was used to facilitate orientation of the retina. Dihydroethidium and dihydrorhodamine 123 (DHR123) were used to determine which cells produce ROS. Subsequently, western blots of retinal serial sections were used to detect the presence of Noxs in the different retinal layers. The Nox inhibitor apocynin was then tested to determine if it altered the production of ROS within these cells. RESULTS: Live retinal explants, viewed at high magnifications using confocal microscopy, displayed an increase in the fluorescent products of dihydroethidium and DHR123 upon serum removal when compared to controls. DHR123 fluorescence, once oxidized, localized to mitochondria and was found in the same focal plane as the PNA staining. This showed that cones and rods produced ROS when stressed. Retinal serial sectioning established that the photoreceptor layer expressed Nox4, dual oxidase (Duox) 1, and Duox2 at varying levels. Finally, the Nox inhibitor apocynin decreased the burst stimulated by the stress of serum removal. CONCLUSIONS: Confocal microscopy and PNA staining allowed differentiation of cell types within the outermost layers of the retina, demonstrating

  13. Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

    Directory of Open Access Journals (Sweden)

    Ralph W Pridmore

    Full Text Available This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0 in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones. Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

  14. Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

    Science.gov (United States)

    Pridmore, Ralph W

    2013-01-01

    This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors) but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral) functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure) hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique) over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0) in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones.) Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

  15. Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.

    Science.gov (United States)

    Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa

    2010-12-28

    Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

  16. Distribution of retinal cone photoreceptor oil droplets, and identification of associated carotenoids in crow (Corvus macrorhynchos).

    Science.gov (United States)

    Rahman, Mohammad Lutfur; Yoshida, Kazuyuki; Maeda, Isamu; Tanaka, Hideuki; Sugita, Shoei

    2010-06-01

    The topography of cone oil droplets and their carotenoids were investigated in the retina of jungle crow (Corvus macrorhynchos). Fresh retina was sampled for the study of retinal cone oil droplets, and extracted retinal carotenoids were saponified using methods adapted from a recent study, then identified with reverse-phase high-performance liquid chromatography (HPLC). To assess the effects of saponification conditions on carotenoid recovery from crow retina, we varied base concentration and total time of saponification across a wide range of conditions, and again used HPLC to compare carotenoid concentrations. Based on colors, at least four types of oil droplets were recognized, i.e., red, orange, green, and translucent, across the retina. With an average of 91,202 /mm(2), density gradually declines in an eccentric manner from optic disc. In retina, the density and size of droplets are inversely related. In the peripheral zone, oil droplets were significantly larger than those of the central area. The proportion of orange oil droplets (33%) was higher in the central area, whereas green was predominant in other areas. Three types of carotenoid (astaxanthin, galloxanthin and lutein), together with one unknown carotenoid, were recovered from the crow retina; astaxanthin was the dominant carotenoid among them. The recovery of carotenoids was affected by saponification conditions. Astaxanthin was well recovered in weak alkali (0.06 M KOH), in contrast, xanthophyllic carotenoids were best recovered in strong alkali (0.6 M KOH) after 12 h of saponification at freeze temperature.

  17. Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors.

    Science.gov (United States)

    Wang, Y; Smallwood, P M; Cowan, M; Blesh, D; Lawler, A; Nathans, J

    1999-04-27

    This study examines the mechanism of mutually exclusive expression of the human X-linked red and green visual pigment genes in their respective cone photoreceptors by asking whether this expression pattern can be produced in a mammal that normally carries only a single X-linked visual pigment gene. To address this question, we generated transgenic mice that carry a single copy of a minimal human X chromosome visual pigment gene array in which the red and green pigment gene transcription units were replaced, respectively, by alkaline phosphatase and beta-galactosidase reporters. As determined by histochemical staining, the reporters are expressed exclusively in cone photoreceptor cells. In 20 transgenic mice carrying any one of three independent transgene insertion events, an average of 63% of expressing cones have alkaline phosphatase activity, 10% have beta-galactosidase activity, and 27% have activity for both reporters. Thus, mutually exclusive expression of red and green pigment transgenes can be achieved in a large fraction of cones in a dichromat mammal, suggesting a facile evolutionary path for the development of trichromacy after visual pigment gene duplication. These observations are consistent with a model of visual pigment expression in which stochastic pairing occurs between a locus control region and either the red or the green pigment gene promotor.

  18. Individual variation in cone photoreceptor density in house sparrows: implications for between-individual differences in visual resolution and chromatic contrast.

    Science.gov (United States)

    Ensminger, Amanda L; Fernández-Juricic, Esteban

    2014-01-01

    Between-individual variation has been documented in a wide variety of taxa, especially for behavioral characteristics; however, intra-population variation in sensory systems has not received similar attention in wild animals. We measured a key trait of the visual system, the density of retinal cone photoreceptors, in a wild population of house sparrows (Passer domesticus). We tested whether individuals differed from each other in cone densities given within-individual variation across the retina and across eyes. We further tested whether the existing variation could lead to individual differences in two aspects of perception: visual resolution and chromatic contrast. We found consistent between-individual variation in the densities of all five types of avian cones, involved in chromatic and achromatic vision. Using perceptual modeling, we found that this degree of variation translated into significant between-individual differences in visual resolution and the chromatic contrast of a plumage signal that has been associated with mate choice and agonistic interactions. However, there was no evidence for a relationship between individual visual resolution and chromatic contrast. The implication is that some birds may have the sensory potential to perform "better" in certain visual tasks, but not necessarily in both resolution and contrast simultaneously. Overall, our findings (a) highlight the need to consider multiple individuals when characterizing sensory traits of a species, and (b) provide some mechanistic basis for between-individual variation in different behaviors (i.e., animal personalities) and for testing the predictions of several widely accepted hypotheses (e.g., honest signaling).

  19. Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

    KAUST Repository

    Busserolles, Fanny de; Cortesi, Fabio; Helvik, Jon Vidar; Davies, Wayne I. L.; Templin, Rachel M.; Sullivan, Robert K. P.; Michell, Craig T.; Mountford, Jessica K.; Collin, Shaun P.; Irigoien, Xabier; Kaartvedt, Stein; Marshall, Justin

    2017-01-01

    retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone

  20. [Morphological, optical, and structural characteristics of glass sponge spicules and the photoreceptor hypothesis of their survival].

    Science.gov (United States)

    Voznesenskiĭ, S S; Kul'chin, Iu N; Galkina, A N; Sergeev, A A

    2010-01-01

    The morphology, structure, and optical characteristics of spicules of some sea glass sponges have been studied. The results obtained are interpreted from the point of view of their possible role in the survival of the organism of sponges.

  1. Dynamical adaptation in photoreceptors.

    Directory of Open Access Journals (Sweden)

    Damon A Clark

    Full Text Available Adaptation is at the heart of sensation and nowhere is it more salient than in early visual processing. Light adaptation in photoreceptors is doubly dynamical: it depends upon the temporal structure of the input and it affects the temporal structure of the response. We introduce a non-linear dynamical adaptation model of photoreceptors. It is simple enough that it can be solved exactly and simulated with ease; analytical and numerical approaches combined provide both intuition on the behavior of dynamical adaptation and quantitative results to be compared with data. Yet the model is rich enough to capture intricate phenomenology. First, we show that it reproduces the known phenomenology of light response and short-term adaptation. Second, we present new recordings and demonstrate that the model reproduces cone response with great precision. Third, we derive a number of predictions on the response of photoreceptors to sophisticated stimuli such as periodic inputs, various forms of flickering inputs, and natural inputs. In particular, we demonstrate that photoreceptors undergo rapid adaptation of response gain and time scale, over ∼ 300[Formula: see text] ms-i. e., over the time scale of the response itself-and we confirm this prediction with data. For natural inputs, this fast adaptation can modulate the response gain more than tenfold and is hence physiologically relevant.

  2. Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish

    Science.gov (United States)

    Hagerman, Gordon F.; Noel, Nicole C. L.; Cao, Sylvia Y.; DuVal, Michèle G.; Oel, A. Phillip; Allison, W. Ted

    2016-01-01

    Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (Pvision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration. PMID:27893779

  3. Genetic Dissection of Dual Roles for the Transcription Factor six7 in Photoreceptor Development and Patterning in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Mailin Sotolongo-Lopez

    2016-04-01

    Full Text Available The visual system of a particular species is highly adapted to convey detailed ecological and behavioral information essential for survival. The consequences of structural mutations of opsins upon spectral sensitivity and environmental adaptation have been studied in great detail, but lacking is knowledge of the potential influence of alterations in gene regulatory networks upon the diversity of cone subtypes and the variation in the ratio of rods and cones observed in numerous diurnal and nocturnal species. Exploiting photoreceptor patterning in cone-dominated zebrafish, we uncovered two independent mechanisms by which the sine oculis homeobox homolog 7 (six7 regulates photoreceptor development. In a genetic screen, we isolated the lots-of-rods-junior (ljrp23ahub mutation that resulted in an increased number and uniform distribution of rods in otherwise normal appearing larvae. Sequence analysis, genome editing using TALENs and knockdown strategies confirm ljrp23ahub as a hypomorphic allele of six7, a teleost orthologue of six3, with known roles in forebrain patterning and expression of opsins. Based on the lack of predicted protein-coding changes and a deletion of a conserved element upstream of the transcription start site, a cis-regulatory mutation is proposed as the basis of the reduced expression of six7 in ljrp23ahub. Comparison of the phenotypes of the hypomorphic and knock-out alleles provides evidence of two independent roles in photoreceptor development. EdU and PH3 labeling show that the increase in rod number is associated with extended mitosis of photoreceptor progenitors, and TUNEL suggests that the lack of green-sensitive cones is the result of cell death of the cone precursor. These data add six7 to the small but growing list of essential genes for specification and patterning of photoreceptors in non-mammalian vertebrates, and highlight alterations in transcriptional regulation as a potential source of photoreceptor variation

  4. The biochemistry of photoreceptor cells

    International Nuclear Information System (INIS)

    Voaden, M.J.; Marshall, J.; Oraedu, A.C.I.

    1981-01-01

    Photoreceptor cells have high rates of metabolism, and enzyme distributions suggest considerable substrate movement. The authors have used tracer techniques to study the effects of light on photoreceptor metabolism. In vitro, glutamine is metabolized alongside glucose by rat photoreceptors, and is, potentially, a major precursor of the neuroactive amino acids glutamate, aspartate and γ-aminobutyrate (GABA). The utilization of both substrates is decreased by light, as is the turnover of glutamate and aspartate. Tritiated glutamic and aspartic acids are taken up by photoreceptor cells. In the primates all rods but only some cones are labelled, whereas in the guinea pig the picture is reversed. The observations support the premise that glutamate and/or aspartate are photoreceptor neurotransmitters but show that cell and species differences may exist. The authors have been unable to find evidence for the involvement of free radical mechanisms in high light-induced photoreceptor damage but the initial results suggest a reduced metabolism of glutamine and GABA in damaged cells. (Auth.)

  5. The Survival of Morse Cone-Connection Implants with Platform Switch.

    Science.gov (United States)

    Cassetta, Michele; Di Mambro, Alfonso; Giansanti, Matteo; Brandetti, Giulia

    2016-01-01

    The aim of this prospective clinical study was to evaluate the survival up to 5 years of Morse cone-connection implants with platform switch considering the influence of biologically relevant, anatomical, and stress-related variables. STROBE guidelines were followed. Seven hundred forty-eight implants were inserted in 350 patients. Follow-up visits were scheduled at the time of stagetwo surgery (2 months later) and at 6, 12, 24, 36, and 60 months. All implants were initially loaded with a cemented provisional acrylic restoration. The definitive metal-ceramic restorations were cemented at the 6-month follow-up. Implant cumulative survival rates (CSRs) were calculated using life table actuarial method. Survival data were also analyzed by the log-rank test and Cox regression. The statistical analysis was conducted at the patient level. P ≤ .05 was considered as an indicator of statistical significance. During the follow-up (mean: 40 months; SD: 20.27), 28 patients were considered failed (8%). The CSR and its standard error (SE) was 92% ± 2.17%. Patients with implant-supported single crowns had a CSR of 90%, whereas those with implant-supported fixed dental prostheses had a CSR of 93%. The implant diameter (P = .0399) and implant length (P = .0441) were statistically significant. The probability of failure was almost 75% lower for patients with wide rather than standard implants, 91% lower for patients with long implants, and 69% lower for patients with standard implants compared with short implants. The use of Morse cone-connection implants with platform switch is a safe and reliable treatment method. Stress-related variables influence the risk of failure confirming the importance of biomechanical factors in the longevity of osseointegrated implants; thus, the clinician may obtain better results if attention is paid to these factors.

  6. The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision.

    Science.gov (United States)

    Vinberg, Frans; Wang, Tian; De Maria, Alicia; Zhao, Haiqing; Bassnett, Steven; Chen, Jeannie; Kefalov, Vladimir J

    2017-06-26

    Calcium (Ca 2+ ) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca 2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca 2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na + /Ca 2+ , K + exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2: NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca 2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival.

  7. Volumetric imaging of rod and cone photoreceptor structure with a combined adaptive optics-optical coherence tomography-scanning laser ophthalmoscope

    Science.gov (United States)

    Wells-Gray, Elaine M.; Choi, Stacey S.; Zawadzki, Robert J.; Finn, Susanna C.; Greiner, Cherry; Werner, John S.; Doble, Nathan

    2018-03-01

    We have designed and implemented a dual-mode adaptive optics (AO) imaging system that combines spectral domain optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) for in vivo imaging of the human retina. The system simultaneously acquires SLO frames and OCT B-scans at 60 Hz with an OCT volume acquisition time of 4.2 s. Transverse eye motion measured from the SLO is used to register the OCT B-scans to generate three-dimensional (3-D) volumes. Key optical design considerations include: minimizing system aberrations through the use of off-axis relay telescopes, conjugate pupil plane requirements, and the use of dichroic beam splitters to separate and recombine the OCT and SLO beams around the nonshared horizontal scanning mirrors. To demonstrate system performance, AO-OCT-SLO images and measurements are taken from three normal human subjects ranging in retinal eccentricity from the fovea out to 15-deg temporal and 20-deg superior. Also presented are en face OCT projections generated from the registered 3-D volumes. The ability to acquire high-resolution 3-D images of the human retina in the midperiphery and beyond has clinical importance in diseases, such as retinitis pigmentosa and cone-rod dystrophy.

  8. Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure

    Directory of Open Access Journals (Sweden)

    Cameron David A

    2011-08-01

    Full Text Available Abstract Background Retinoic acid (RA is important for vertebrate eye morphogenesis and is a regulator of photoreceptor development in the retina. In the zebrafish, RA treatment of postmitotic photoreceptor precursors has been shown to promote the differentiation of rods and red-sensitive cones while inhibiting the differentiation of blue- and UV-sensitive cones. The roles played by RA and its receptors in modifying photoreceptor fate remain to be determined. Results Treatment of zebrafish embryos with RA, beginning at the time of retinal progenitor cell proliferation and prior to photoreceptor terminal mitosis, resulted in a significant alteration of rod and cone mosaic patterns, suggesting an increase in the production of rods at the expense of red cones. Quantitative pattern analyses documented increased density of rod photoreceptors and reduced local spacing between rod cells, suggesting rods were appearing in locations normally occupied by cone photoreceptors. Cone densities were correspondingly reduced and cone photoreceptor mosaics displayed expanded and less regular spacing. These results were consistent with replacement of approximately 25% of positions normally occupied by red-sensitive cones, with additional rods. Analysis of embryos from a RA-signaling reporter line determined that multiple retinal cell types, including mitotic cells and differentiating rods and cones, are capable of directly responding to RA. The RA receptors RXRγ and RARαb are expressed in patterns consistent with mediating the effects of RA on photoreceptors. Selective knockdown of RARαb expression resulted in a reduction in endogenous RA signaling in the retina. Knockdown of RARαb also caused a reduced production of rods that was not restored by simultaneous treatments with RA. Conclusions These data suggest that developing retinal cells have a dynamic sensitivity to RA during retinal neurogenesis. In zebrafish RA may influence the rod vs. cone cell fate

  9. Genetics Home Reference: cone-rod dystrophy

    Science.gov (United States)

    ... common cause of autosomal recessive cone-rod dystrophy , accounting for 30 to 60 percent of cases. At ... dystrophy play essential roles in the structure and function of specialized light receptor cells (photoreceptors) in the ...

  10. Programming Retinal Stem Cells into Cone Photoreceptors

    Science.gov (United States)

    2015-12-01

    0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response , including the time for reviewing...development. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT...PERIOD: Nothing to report. This is the final report for this award. However, using funds from philanthropic sources we have recently secured (11/2015

  11. Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

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    Hong Hao

    Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

  12. Multimodal Imaging of Photoreceptor Structure in Choroideremia.

    Science.gov (United States)

    Sun, Lynn W; Johnson, Ryan D; Williams, Vesper; Summerfelt, Phyllis; Dubra, Alfredo; Weinberg, David V; Stepien, Kimberly E; Fishman, Gerald A; Carroll, Joseph

    2016-01-01

    Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions. Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques. Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina. Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors.

  13. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, M.

    2015-01-01

    KEY POINTS: In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the

  14. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, Maarten

    2015-01-01

    In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the glutamate

  15. Identification of endogenous fluorophores in the photoreceptors using autofluorescence spectroscopy

    Science.gov (United States)

    Zhao, Lingling; Qu, Junle; Niu, Hanben

    2007-11-01

    In this paper, we present our investigation on the identification of endogenous fluorophores in photoreceptors using autofluorescence spectroscopy, which is performed with an inverted laser scanning confocal microscope equipped with an Argon ion laser and a GreNe laser. In our experiments, individual cones and rods are clearly resolved even in freshly prepared retina samples, without slicing or labeling. The experiment results show that autofluorescence spectrum of the photoreceptors has three peaks approximately at 525nm, 585nm and 665nm. Furthermore, the brightest autofluorescence originates from the photoreceptor outer segments. We can, therefore, come to a conclusion that the peaks at 525nm, 585nm are corresponding to FAD and A2-PE, respectively, which are distributed in the photoreceptor outer segments.

  16. Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina.

    Science.gov (United States)

    Mollick, Tanzina; Mohlin, Camilla; Johansson, Kjell

    2016-09-01

    Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Müller cell gliosis only seemed to be alleviated in terms of reduced Müller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Müller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Bipolar Cell-Photoreceptor Connectivity in the Zebrafish (Danio rerio) Retina

    Science.gov (United States)

    Li, Yong N.; Tsujimura, Taro; Kawamura, Shoji; Dowling, John E.

    2013-01-01

    Bipolar cells convey luminance, spatial and color information from photoreceptors to amacrine and ganglion cells. We studied the photoreceptor connectivity of 321 bipolar cells in the adult zebrafish retina. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was inserted into whole-mounted transgenic zebrafish retinas to label bipolar cells. The photoreceptors that connect to these DiI-labeled cells were identified by transgenic fluorescence or their positions relative to the fluorescent cones, as cones are arranged in a highly-ordered mosaic: rows of alternating blue- (B) and ultraviolet-sensitive (UV) single cones alternate with rows of red- (R) and green-sensitive (G) double cones. Rod terminals intersperse among cone terminals. As many as 18 connectivity subtypes were observed, 9 of which – G, GBUV, RG, RGB, RGBUV, RGRod, RGBRod, RGBUVRod and RRod bipolar cells – accounted for 96% of the population. Based on their axon terminal stratification, these bipolar cells could be further sub-divided into ON, OFF, and ON-OFF cells. The dendritic spread size, soma depth and size, and photoreceptor connections of the 308 bipolar cells within the 9 common connectivity subtypes were determined, and their dendritic tree morphologies and axonal stratification patterns compared. We found that bipolar cells with the same axonal stratification patterns could have heterogeneous photoreceptor connectivity whereas bipolar cells with the same dendritic tree morphology usually had the same photoreceptor connectivity, although their axons might stratify on different levels. PMID:22907678

  18. Rip3 knockdown rescues photoreceptor cell death in blind pde6c zebrafish.

    Science.gov (United States)

    Viringipurampeer, I A; Shan, X; Gregory-Evans, K; Zhang, J P; Mohammadi, Z; Gregory-Evans, C Y

    2014-05-01

    Achromatopsia is a progressive autosomal recessive retinal disease characterized by early loss of cone photoreceptors and later rod photoreceptor loss. In most cases, mutations have been identified in CNGA3, CNGB3, GNAT2, PDE6C or PDE6H genes. Owing to this genetic heterogeneity, mutation-independent therapeutic schemes aimed at preventing cone cell death are very attractive treatment strategies. In pde6c(w59) mutant zebrafish, cone photoreceptors expressed high levels of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3) kinases, key regulators of necroptotic cell death. In contrast, rod photoreceptor cells were alternatively immunopositive for caspase-3 indicating activation of caspase-dependent apoptosis in these cells. Morpholino gene knockdown of rip3 in pde6c(w59) embryos rescued the dying cone photoreceptors by inhibiting the formation of reactive oxygen species and by inhibiting second-order neuron remodelling in the inner retina. In rip3 morphant larvae, visual function was restored in the cones by upregulation of the rod phosphodiesterase genes (pde6a and pde6b), compensating for the lack of cone pde6c suggesting that cones are able to adapt to their local environment. Furthermore, we demonstrated through pharmacological inhibition of RIP1 and RIP3 activity that cone cell death was also delayed. Collectively, these results demonstrate that the underlying mechanism of cone cell death in the pde6c(w59) mutant retina is through necroptosis, whereas rod photoreceptor bystander death occurs through a caspase-dependent mechanism. This suggests that targeting the RIP kinase signalling pathway could be an effective therapeutic intervention in retinal degeneration patients. As bystander cell death is an important feature of many retinal diseases, combinatorial approaches targeting different cell death pathways may evolve as an important general principle in treatment.

  19. Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

    Directory of Open Access Journals (Sweden)

    Cheryl A Arcinue

    Full Text Available To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula compared with age-matched HIV-negative controls.Cohort of patients with known HIV under CART (combination Antiretroviral Therapy treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT to assess retinal layers and retinal thickness.Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior, the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2. A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea. We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer was also significantly thickened in all the different locations scanned compared with HIV-negative controls.Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

  20. Pineal photoreceptor cells are required for maintaining the circadian rhythms of behavioral visual sensitivity in zebrafish.

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    Xinle Li

    Full Text Available In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity.

  1. Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis

    Directory of Open Access Journals (Sweden)

    Joanna H. Tu

    2017-09-01

    Conclusions and importance: Fundus-referenced visual testing proved useful to identify functional cones despite apparent photoreceptor loss identified using AOSLO and SD-OCT. While AOSLO and SD-OCT appear to be sensitive for the detection of abnormal or absent photoreceptors, changes in photoreceptors that are identified with these imaging tools do not correlate completely with visual function in every patient. Fundus-referenced vision testing is a useful tool to indicate the presence of cones that may be amenable to recovery or response to experimental therapies despite not being visible on confocal AOSLO or SD-OCT images.

  2. Excessive Myosin Activity in Mbs Mutants Causes Photoreceptor Movement Out of the Drosophila Eye Disc Epithelium

    OpenAIRE

    Lee, Arnold; Treisman, Jessica E.

    2004-01-01

    Neuronal cells must extend a motile growth cone while maintaining the cell body in its original position. In migrating cells, myosin contraction provides the driving force that pulls the rear of the cell toward the leading edge. We have characterized the function of myosin light chain phosphatase, which down-regulates myosin activity, in Drosophila photoreceptor neurons. Mutations in the gene encoding the myosin binding subunit of this enzyme cause photoreceptors to drop out of the eye disc e...

  3. CRALBP supports the mammalian retinal visual cycle and cone vision

    OpenAIRE

    Xue, Yunlu; Shen, Susan Q.; Jui, Jonathan; Rupp, Alan C.; Byrne, Leah C.; Hattar, Samer; Flannery, John G.; Corbo, Joseph C.; Kefalov, Vladimir J.

    2015-01-01

    Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor-mediated vision loss in patients. It is not known how CRALBP supports cone function or how altered CRALBP leads to cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven visual behavior and light responses. Additionally, M-cone dark ad...

  4. Light adaptation and the evolution of vertebrate photoreceptors.

    Science.gov (United States)

    Morshedian, Ala; Fain, Gordon L

    2017-07-15

    Lamprey are cyclostomes, a group of vertebrates that diverged from lines leading to jawed vertebrates (including mammals) in the late Cambrian, 500 million years ago. It may therefore be possible to infer properties of photoreceptors in early vertebrate progenitors by comparing lamprey to other vertebrates. We show that lamprey rods and cones respond to light much like rods and cones in amphibians and mammals. They operate over a similar range of light intensities and adapt to backgrounds and bleaches nearly identically. These correspondences are pervasive and detailed; they argue for the presence of rods and cones very early in the evolution of vertebrates with properties much like those of rods and cones in existing vertebrate species. The earliest vertebrates were agnathans - fish-like organisms without jaws, which first appeared near the end of the Cambrian radiation. One group of agnathans became cyclostomes, which include lamprey and hagfish. Other agnathans gave rise to jawed vertebrates or gnathostomes, the group including all other existing vertebrate species. Because cyclostomes diverged from other vertebrates 500 million years ago, it may be possible to infer some of the properties of the retina of early vertebrate progenitors by comparing lamprey to other vertebrates. We have previously shown that rods and cones in lamprey respond to light much like photoreceptors in other vertebrates and have a similar sensitivity. We now show that these affinities are even closer. Both rods and cones adapt to background light and to bleaches in a manner almost identical to other vertebrate photoreceptors. The operating range in darkness is nearly the same in lamprey and in amphibian or mammalian rods and cones; moreover background light shifts response-intensity curves downward and to the right over a similar range of ambient intensities. Rods show increment saturation at about the same intensity as mammalian rods, and cones never saturate. Bleaches decrease

  5. Characterization of multiple light damage paradigms reveals regional differences in photoreceptor loss.

    Science.gov (United States)

    Thomas, Jennifer L; Nelson, Craig M; Luo, Xixia; Hyde, David R; Thummel, Ryan

    2012-04-01

    Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely-used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether they differ in regard to the extent of photoreceptor damage or the subsequent regeneration response. Here we report a thorough analysis of the photoreceptor damage and subsequent proliferation response elicited by each individual treatment, as well as by the concomitant use of both treatments. We show a differential loss of rod and cone photoreceptors with each treatment. Additionally, we show that the extent of proliferation observed in the retina directly correlates with the severity of photoreceptor loss. We also demonstrate that both the ventral and posterior regions of the retina are partially protected from light damage. Finally, we show that combining a short ultraviolet exposure followed by a constant bright light treatment largely eliminates the neuroprotected regions, resulting in widespread loss of rod and cone photoreceptors and a robust regenerative response throughout the retina. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Directory of Open Access Journals (Sweden)

    Nawal Zabouri

    Full Text Available Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V1.4(α(1F knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V1.4(α(1F knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  7. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Science.gov (United States)

    Zabouri, Nawal; Haverkamp, Silke

    2013-01-01

    Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V)1.4(α(1F)) knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V)1.4(α(1F)) knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V)1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V)1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V)1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  8. Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells.

    Science.gov (United States)

    Lenzner, Steffen; Prietz, Sandra; Feil, Silke; Nuber, Ulrike A; Ropers, H-Hilger; Berger, Wolfgang

    2002-09-01

    Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP). The gene product is a cystine-knot-containing extracellular signaling molecule of unknown function. In the current study, gene expression was determined in a mouse model of ND, to unravel disease-associated mechanisms at the molecular level. Gene transcription in the eyes of 2-year-old Ndp knockout mice was compared with that in the eyes of age-matched wild-type control animals, by means of cDNA subtraction and microarrays. Clones (n = 3072) from the cDNA subtraction libraries were spotted onto glass slides and hybridized with fluorescently labeled RNA-derived targets. More than 230 differentially expressed clones were sequenced, and their expression patterns were verified by virtual Northern blot analysis. Numerous gene transcripts that are absent or downregulated in the eye of Ndp knockout mice are photoreceptor cell specific. In younger Ndp knockout mice (up to 1 year old), however, all these transcripts were found to be expressed at normal levels. The identification of numerous photoreceptor cell-specific transcripts with a reduced expression in 2-year-old, but not in young, Ndp knockout mice indicates that normal gene expression in these light-sensitive cells of mutant mice is established and maintained over a long period and that rods and cones are affected relatively late in the mouse model of ND. Obviously, the absence of the Ndp gene product is not compatible with long-term survival of photoreceptor cells in the mouse.

  9. A new functional role for mechanistic/mammalian target of rapamycin complex 1 (mTORC1 in the circadian regulation of L-type voltage-gated calcium channels in avian cone photoreceptors.

    Directory of Open Access Journals (Sweden)

    Cathy Chia-Yu Huang

    Full Text Available In the retina, the L-type voltage-gated calcium channels (L-VGCCs are responsible for neurotransmitter release from photoreceptors and are under circadian regulation. Both the current densities and protein expression of L-VGCCs are significantly higher at night than during the day. However, the underlying mechanisms of circadian regulation of L-VGCCs in the retina are not completely understood. In this study, we demonstrated that the mechanistic/mammalian target of rapamycin complex (mTORC signaling pathway participated in the circadian phase-dependent modulation of L-VGCCs. The activities of the mTOR cascade, from mTORC1 to its downstream targets, displayed circadian oscillations throughout the course of a day. Disruption of mTORC1 signaling dampened the L-VGCC current densities, as well as the protein expression of L-VGCCs at night. The decrease of L-VGCCs at night by mTORC1 inhibition was in part due to a reduction of L-VGCCα1 subunit translocation from the cytosol to the plasma membrane. Finally, we showed that mTORC1 was downstream of the phosphatidylionositol 3 kinase-protein kinase B (PI3K-AKT signaling pathway. Taken together, mTORC1 signaling played a role in the circadian regulation of L-VGCCs, in part through regulation of ion channel trafficking and translocation, which brings to light a new functional role for mTORC1: the modulation of ion channel activities.

  10. Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome.

    Science.gov (United States)

    Sun, Lynn W; Johnson, Ryan D; Langlo, Christopher S; Cooper, Robert F; Razeen, Moataz M; Russillo, Madia C; Dubra, Alfredo; Connor, Thomas B; Han, Dennis P; Pennesi, Mark E; Kay, Christine N; Weinberg, David V; Stepien, Kimberly E; Carroll, Joseph

    2016-05-01

    The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO. Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse. Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

  11. Characterization of photoreceptor cell types in the little brown bat Myotis lucifugus (Vespertilionidae).

    Science.gov (United States)

    Feller, K D; Lagerholm, S; Clubwala, R; Silver, M T; Haughey, D; Ryan, J M; Loew, E R; Deutschlander, M E; Kenyon, K L

    2009-12-01

    We report the expression of three visual opsins in the retina of the little brown bat (Myotis lucifugus, Vespertilionidae). Gene sequences for a rod-specific opsin and two cone-specific opsins were cloned from cDNA derived from bat eyes. Comparative sequence analyses indicate that the two cone opsins correspond to an ultraviolet short-wavelength opsin (SWS1) and a long-wavelength opsin (LWS). Immunocytochemistry using antisera to visual opsins revealed that the little brown bat retina contains two types of cone photoreceptors within a rod-dominated background. However, unlike other mammalian photoreceptors, M. lucifugus cones and rods are morphologically indistinguishable by light microscopy. Both photoreceptor types have a thin, elongated outer segment. Using microspectrophotometry we classified the absorption spectrum for the ubiquitous rods. Similar to other mammals, bat rhodopsin has an absorption peak near 500 nm. Although we were unable to confirm a spectral range, cellular and molecular analyses indicate that M. lucifugus expresses two types of cone visual pigments located within the photoreceptor layer. This study provides important insights into the visual capacity of a nocturnal microchiropteran species.

  12. Bifurcation analysis of a photoreceptor interaction model for Retinitis Pigmentosa

    Science.gov (United States)

    Camacho, Erika T.; Radulescu, Anca; Wirkus, Stephen

    2016-09-01

    Retinitis Pigmentosa (RP) is the term used to describe a diverse set of degenerative eye diseases affecting the photoreceptors (rods and cones) in the retina. This work builds on an existing mathematical model of RP that focused on the interaction of the rods and cones. We non-dimensionalize the model and examine the stability of the equilibria. We then numerically investigate other stable modes that are present in the system for various parameter values and relate these modes to the original problem. Our results show that stable modes exist for a wider range of parameter values than the stability of the equilibrium solutions alone, suggesting that additional approaches to preventing cone death may exist.

  13. Rod photoreceptors express GPR55 in the adult vervet monkey retina

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

    2013-01-01

    . 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...

  14. Cold knife cone biopsy

    Science.gov (United States)

    ... biopsy; Pap smear - cone biopsy; HPV - cone biopsy; Human papilloma virus - cone biopsy; Cervix - cone biopsy; Colposcopy - cone biopsy Images Female reproductive anatomy Cold cone biopsy Cold cone removal References Baggish ...

  15. Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

    Science.gov (United States)

    Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

    2016-03-30

    Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization

  16. Cone rod dystrophies

    Science.gov (United States)

    Hamel, Christian P

    2007-01-01

    Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

  17. Cone rod dystrophies

    Directory of Open Access Journals (Sweden)

    Hamel Christian P

    2007-02-01

    Full Text Available Abstract Cone rod dystrophies (CRDs (prevalence 1/40,000 are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP, also called the rod cone dystrophies (RCDs resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7. Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far. The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs, CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs, and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs. It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is

  18. Optical properties of photoreceptor and retinal pigment epithelium cells investigated with adaptive optics optical coherence tomography

    Science.gov (United States)

    Liu, Zhuolin

    Human vision starts when photoreceptors collect and respond to light. Photoreceptors do not function in isolation though, but share close interdependence with neighboring photoreceptors and underlying retinal pigment epithelium (RPE) cells. These cellular interactions are essential for normal function of the photoreceptor-RPE complex, but methods to assess these in the living human eye are limited. One approach that has gained increased promise is high-resolution retinal imaging that has undergone tremendous technological advances over the last two decades to probe the living retina at the cellular level. Pivotal in these advances has been adaptive optics (AO) and optical coherence tomography (OCT) that together allow unprecedented spatial resolution of retinal structures in all three dimensions. Using these high-resolution systems, cone photoreceptor are now routinely imaged in healthy and diseased retina enabling fundamental structural properties of cones to be studied such as cell spacing, packing arrangement, and alignment. Other important cell properties, however, have remained elusive to investigation as even better imaging performance is required and thus has resulted in an incomplete understanding of how cells in the photoreceptor-RPE complex interact with light. To address this technical bottleneck, we expanded the imaging capability of AO-OCT to detect and quantify more accurately and completely the optical properties of cone photoreceptor and RPE cells at the cellular level in the living human retina. The first objective of this thesis was development of a new AO-OCT method that is more precise and sensitive, thus enabling a more detailed view of the 3D optical signature of the photoreceptor-RPE complex than was previously possible (Chapter 2). Using this new system, the second objective was quantifying the waveguide properties of individual cone photoreceptor inner and outer segments across the macula (Chapter 3). The third objective extended the AO

  19. Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes.

    Science.gov (United States)

    Fu, Jinling; Nagashima, Mikiko; Guo, Chuanyu; Raymond, Pamela A; Wei, Xiangyun

    2018-01-01

    Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion. We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a "photoreceptor maintenance index" and statistical analysis of cell counts. Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors. These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.

  20. Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein.

    Science.gov (United States)

    Garrity, P A; Rao, Y; Salecker, I; McGlade, J; Pawson, T; Zipursky, S L

    1996-05-31

    Mutations in the Drosophila gene dreadlocks (dock) disrupt photoreceptor cell (R cell) axon guidance and targeting. Genetic mosaic analysis and cell-type-specific expression of dock transgenes demonstrate dock is required in R cells for proper innervation. Dock protein contains one SH2 and three SH3 domains, implicating it in tyrosine kinase signaling, and is highly related to the human proto-oncogene Nck. Dock expression is detected in R cell growth cones in the target region. We propose Dock transmits signals in the growth cone in response to guidance and targeting cues. These findings provide an important step for dissection of signaling pathways regulating growth cone motility.

  1. Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness.

    Science.gov (United States)

    Carroll, Joseph; Neitz, Maureen; Hofer, Heidi; Neitz, Jay; Williams, David R

    2004-06-01

    There is enormous variation in the X-linked L/M (long/middle wavelength sensitive) gene array underlying "normal" color vision in humans. This variability has been shown to underlie individual variation in color matching behavior. Recently, red-green color blindness has also been shown to be associated with distinctly different genotypes. This has opened the possibility that there may be important phenotypic differences within classically defined groups of color blind individuals. Here, adaptive optics retinal imaging has revealed a mechanism for producing dichromatic color vision in which the expression of a mutant cone photopigment gene leads to the loss of the entire corresponding class of cone photoreceptor cells. Previously, the theory that common forms of inherited color blindness could be caused by the loss of photoreceptor cells had been discounted. We confirm that remarkably, this loss of one-third of the cones does not impair any aspect of vision other than color.

  2. Mef2d is essential for the maturation and integrity of retinal photoreceptor and bipolar cells.

    Science.gov (United States)

    Omori, Yoshihiro; Kitamura, Tamiki; Yoshida, Satoyo; Kuwahara, Ryusuke; Chaya, Taro; Irie, Shoichi; Furukawa, Takahisa

    2015-05-01

    Mef2 transcription factors play a crucial role in cardiac and skeletal muscle differentiation. We found that Mef2d is highly expressed in the mouse retina and its loss causes photoreceptor degeneration similar to that observed in human retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired in Mef2d-/- mice. Immunohistochemistry showed that photoreceptor and bipolar cell synapse protein levels severely decreased in the Mef2d-/- retina. Expression profiling by microarray analysis showed that Mef2d is required for the expression of various genes in photoreceptor and bipolar cells, including cone arrestin, Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We also observed that Mef2d synergistically activates the cone arrestin (Arr3) promoter with Crx, suggesting that functional cooperation between Mef2d and Crx is important for photoreceptor cell gene regulation. Taken together, our results show that Mef2d is essential for photoreceptor and bipolar cell gene expression, either independently or cooperatively with Crx. © 2015 Institution for Protein Research. Genes to Cells published by Wiley Publishing Asia Pty Ltd and the Molecular Biology Society of Japan.

  3. Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope

    Science.gov (United States)

    Dubra, Alfredo; Sulai, Yusufu; Norris, Jennifer L.; Cooper, Robert F.; Dubis, Adam M.; Williams, David R.; Carroll, Joseph

    2011-01-01

    The rod photoreceptors are implicated in a number of devastating retinal diseases. However, routine imaging of these cells has remained elusive, even with the advent of adaptive optics imaging. Here, we present the first in vivo images of the contiguous rod photoreceptor mosaic in nine healthy human subjects. The images were collected with three different confocal adaptive optics scanning ophthalmoscopes at two different institutions, using 680 and 775 nm superluminescent diodes for illumination. Estimates of photoreceptor density and rod:cone ratios in the 5°–15° retinal eccentricity range are consistent with histological findings, confirming our ability to resolve the rod mosaic by averaging multiple registered images, without the need for additional image processing. In one subject, we were able to identify the emergence of the first rods at approximately 190 μm from the foveal center, in agreement with previous histological studies. The rod and cone photoreceptor mosaics appear in focus at different retinal depths, with the rod mosaic best focus (i.e., brightest and sharpest) being at least 10 μm shallower than the cones at retinal eccentricities larger than 8°. This study represents an important step in bringing high-resolution imaging to bear on the study of rod disorders. PMID:21750765

  4. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Kim, Sinae [Division of Biometrics, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Biostatistics, School of Public Health, Rutgers University, New Brunswick, New Jersey (United States); Haider, Syed A. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Xu, Xiaoting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Wu, Alson [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Surakanti, Sujani; Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Langenfeld, John [Division of Surgery, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Yue, Ning J.; Haffty, Bruce G.; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States)

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  5. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

    2015-01-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes

  6. Responses of photoreceptors in Hermissenda.

    Science.gov (United States)

    Akon, D L; Fuortes, M G

    1972-12-01

    The five photoreceptors in the eye of the mollusc Hermissenda crassicornis respond to light with depolarization and firing of impulses. The impulses of any one cell inhibit other cells, but the degree of inhibition differs in different pairs. Evidence is presented to show that the interactions occur at terminal branches of the photoreceptor axons, inside the cerebropleural ganglion. Properties of the generator potential are examined and it is shown that the depolarization develops in two phases which are affected differently by extrinsic currents. Finally, it is shown that by enhancing the differences in the responses of individual cells to a variety of stimuli, the interactions may facilitate a number of simple discriminations.

  7. Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting.

    Science.gov (United States)

    Liu, Jianfei; Jung, HaeWon; Dubra, Alfredo; Tam, Johnny

    2017-09-01

    Adaptive optics scanning light ophthalmoscopy (AOSLO) has enabled quantification of the photoreceptor mosaic in the living human eye using metrics such as cell density and average spacing. These rely on the identification of individual cells. Here, we demonstrate a novel approach for computer-aided identification of cone photoreceptors on nonconfocal split detection AOSLO images. Algorithms for identification of cone photoreceptors were developed, based on multiscale circular voting (MSCV) in combination with a priori knowledge that split detection images resemble Nomarski differential interference contrast images, in which dark and bright regions are present on the two sides of each cell. The proposed algorithm locates dark and bright region pairs, iteratively refining the identification across multiple scales. Identification accuracy was assessed in data from 10 subjects by comparing automated identifications with manual labeling, followed by computation of density and spacing metrics for comparison to histology and published data. There was good agreement between manual and automated cone identifications with overall recall, precision, and F1 score of 92.9%, 90.8%, and 91.8%, respectively. On average, computed density and spacing values using automated identification were within 10.7% and 11.2% of the expected histology values across eccentricities ranging from 0.5 to 6.2 mm. There was no statistically significant difference between MSCV-based and histology-based density measurements (P = 0.96, Kolmogorov-Smirnov 2-sample test). MSCV can accurately detect cone photoreceptors on split detection images across a range of eccentricities, enabling quick, objective estimation of photoreceptor mosaic metrics, which will be important for future clinical trials utilizing adaptive optics.

  8. Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa.

    Science.gov (United States)

    Petit, Lolita; Ma, Shan; Cipi, Joris; Cheng, Shun-Yun; Zieger, Marina; Hay, Nissim; Punzo, Claudio

    2018-05-29

    Aerobic glycolysis accounts for ∼80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic stress conditions such as those encountered in retinitis pigmentosa, where the loss of rods causes a nutrient shortage in cones. The data support a model where aerobic glycolysis in PRs is not a necessity but rather a metabolic choice that maximizes PR function and adaptability to nutrient stress conditions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Survival prediction of non-small cell lung cancer patients using radiomics analyses of cone-beam CT images

    DEFF Research Database (Denmark)

    van Timmeren, Janna E; Leijenaar, Ralph T H; van Elmpt, Wouter

    2017-01-01

    was validated. MATERIAL AND METHODS: One training dataset of 132 and two validation datasets of 62 and 94stage I-IV NSCLC patients were included. Interchangeability was assessed by performing a linear regression on CT and CBCT extracted features. A two-step correction was applied prior to model validation...... different between groups with high and low prognostic value for both modalities. Harrell's concordance index was 0.69 for CT and 0.66 for CBCT models for dataset 1. Conclusions The results show that a subset of radiomic features extracted from CT and CBCT images are interchangeable using simple linear...... regression. Moreover, a previously developed radiomics signature has prognostic value for overall survival in three CBCT cohorts, showing the potential of CBCT radiomics to be used as prognostic imaging biomarker....

  10. Ultrafast spectroscopy of biological photoreceptors

    NARCIS (Netherlands)

    Kennis, J.T.M.; Groot, M.L.

    2007-01-01

    We review recent new insights on reaction dynamics of photoreceptors proteins gained from ultrafast spectroscopy. In Blue Light sensing Using FAD (BLUF) domains, a hydrogen-bond rearrangement around the flavin chromophore proceeds through a radical-pair mechanism, by which light-induced electron and

  11. On Dispersion in Visual Photoreceptors

    NARCIS (Netherlands)

    Stavenga, D.G.; Barneveld, H.H. van

    1975-01-01

    An idealized visual pigment absorbance spectrum is used together with a Kramers-Kronig dispersion relation to calculate the contribution of the visual pigment to the refractive index of the fly photoreceptor. It appears that an absorption coefficient of 0.010 µm-1 results in a refractive index

  12. Three distinct roles for notch in Drosophila R7 photoreceptor specification.

    Directory of Open Access Journals (Sweden)

    Andrew Tomlinson

    2011-08-01

    Full Text Available Receptor tyrosine kinases (RTKs and Notch (N proteins are different types of transmembrane receptors that transduce extracellular signals and control cell fate. Here we examine cell fate specification in the Drosophila retina and ask how N acts together with the RTKs Sevenless (Sev and the EGF receptor (DER to specify the R7 photoreceptor. The retina is composed of many hundred ommatidia, each of which grows by recruiting surrounding, undifferentiated cells and directing them to particular fates. The R7 photoreceptor derives from a cohort of three cells that are incorporated together following specification of the R2-R5 and R8 photoreceptors. Two cells of the cohort are specified as the R1/6 photoreceptor type by DER activation. These cells then activate N in the third cell (the R7 precursor. By manipulation of N and RTK signaling in diverse combinations we establish three roles for N in specifying the R7 fate. The first role is to impose a block to photoreceptor differentiation; a block that DER activation cannot overcome. The second role, paradoxically, is to negate the first; Notch activation up-regulates Sev expression, enabling the presumptive R7 cell to receive an RTK signal from R8 that can override the block. The third role is to specify the cell as an R7 rather than an R1/6 once RTK signaling has specified the cells as a photoreceptor. We speculate why N acts both to block and to facilitate photoreceptor differentiation, and provide a model for how N and RTK signaling act combinatorially to specify the R1/6 and R7 photoreceptors as well as the surrounding non-neuronal cone cells.

  13. Shifts in Selective Pressures on Snake Phototransduction Genes Associated with Photoreceptor Transmutation and Dim-Light Ancestry.

    Science.gov (United States)

    Schott, Ryan K; Van Nynatten, Alexander; Card, Daren C; Castoe, Todd A; S W Chang, Belinda

    2018-06-01

    The visual systems of snakes are heavily modified relative to other squamates, a condition often thought to reflect their fossorial origins. Further modifications are seen in caenophidian snakes, where evolutionary transitions between rod and cone photoreceptors, termed photoreceptor transmutations, have occurred in many lineages. Little previous work, however, has focused on the molecular evolutionary underpinnings of these morphological changes. To address this, we sequenced seven snake eye transcriptomes and utilized new whole-genome and targeted capture sequencing data. We used these data to analyze gene loss and shifts in selection pressures in phototransduction genes that may be associated with snake evolutionary origins and photoreceptor transmutation. We identified the surprising loss of rhodopsin kinase (GRK1), despite a low degree of gene loss overall and a lack of relaxed selection early during snake evolution. These results provide some of the first evolutionary genomic corroboration for a dim-light ancestor that lacks strong fossorial adaptations. Our results also indicate that snakes with photoreceptor transmutation experienced significantly different selection pressures from other reptiles. Significant positive selection was found primarily in cone-specific genes, but not rod-specific genes, contrary to our expectations. These results reveal potential molecular adaptations associated with photoreceptor transmutation and also highlight unappreciated functional differences between rod- and cone-specific phototransduction proteins. This intriguing example of snake visual system evolution illustrates how the underlying molecular components of a complex system can be reshaped in response to changing selection pressures.

  14. Early photoreceptor outer segment loss and retinoschisis in Cohen syndrome.

    Science.gov (United States)

    Uyhazi, Katherine E; Binenbaum, Gil; Carducci, Nicholas; Zackai, Elaine H; Aleman, Tomas S

    2018-06-01

    To describe early structural and functional retinal changes in a patient with Cohen syndrome. A 13-month-old Caucasian girl of Irish and Spanish ancestry was noted to have micrognathia and laryngomalacia at birth, which prompted a genetic evaluation that revealed biallelic deletions in COH1 (VPS13B) (a maternally inherited 60-kb deletion involving exons 26-32 and a paternally inherited 3.5-kb deletion within exon 17) consistent with Cohen syndrome. She underwent a complete ophthalmic examination, full-field flash electroretinography and retinal imaging with spectral domain optical coherence tomography. Central vision was central, steady, and maintained. There was bilateral myopic astigmatic refractive error. Fundus exam was notable for dark foveolar pigmentation, but no obvious abnormalities of either eye. Spectral domain optical coherence tomography cross sections through the fovea revealed a normal appearing photoreceptor outer nuclear layer but loss of the interdigitation signal between the photoreceptor outer segments and the apical retinal pigment epithelium. Retinoschisis involving the inner nuclear layer of both eyes and possible ganglion cell layer thinning were also noted. There was a detectable electroretinogram with similarly reduced amplitudes of rod- (white, 0.01 cd.s.m -2 ) and cone-mediated (3 cd.s.m -2 , 30 Hz) responses. Photoreceptor outer segment abnormalities and retinoschisis may represent the earliest structural retinal change detected by spectral domain optical coherence tomography in patients with Cohen syndrome, suggesting a complex pathophysiology with primary involvement of the photoreceptor cilium and disorganization of the structural integrity of the inner retina.

  15. Salamander blue-sensitive cones lost during metamorphosis.

    NARCIS (Netherlands)

    Chen, Y.; Znoiko, S.; Grip, W.J. de; Crouch, R.K.; Ma, J.X.

    2008-01-01

    The tiger salamander lives in shallow water with bright light in the aquatic phase, and in dim tunnels or caves in the terrestrial phase. In the aquatic phase, there are five types of photoreceptors--two types of rods and three types of cones. Our previous studies showed that the green rods and

  16. Preservation of photoreceptors in dystrophic RCS rats following allo- and xenotransplantation of IPE cells.

    Science.gov (United States)

    Thumann, Gabriele; Salz, Anna Katharina; Walter, Peter; Johnen, Sandra

    2009-03-01

    To examine whether iris pigment epithelial (IPE) cells transplanted into the subretinal space of Royal College of Surgeons (RCS) rats have the ability to rescue photoreceptors. Rat IPE (rIPE) or human IPE (hIPE) cells were transplanted subretinally in 23-day-old RCS rats. Sham injection and transplantation of ARPE-19 cells served as controls. After 12 weeks, eyes were evaluated for photoreceptor survival by morphometric analysis and electron microscopy. Morphometric analysis showed photoreceptor rescue in all transplanted and sham-injected animals (number of photoreceptors/300 microm retina+/-sd: rIPE 41.67 +/- 28; hIPE 29.50 +/- 16; ARPE-19 36.12 +/- 21; sham 16.56 +/- 6) compared to age-matched, control rats (number of photoreceptors/300 microm retina+/-sd: 9.71 +/- 4). Photoreceptor rescue was prominent in IPE cell-transplanted rats and was significantly greater than sham-injected eyes (p = 0.02 for rIPE and p = 0.04 for hIPE). Since IPE cells transplanted into the subretinal space have the ability to rescue photoreceptors from degeneration in the RCS rat without any harmful effects, IPE cells may represent an ideal cell to genetically modify and thus carry essential genetic information for the repair of defects in the subretinal space.

  17. Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity.

    Science.gov (United States)

    Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Nakagawa, Atsushi; Furukawa, Takahisa

    2017-09-26

    Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7- null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7 -deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.

  18. Visual cycle and its metabolic support in gecko photoreceptors.

    Science.gov (United States)

    Kolesnikov, A V; Ala-Laurila, P; Shukolyukov, S A; Crouch, R K; Wiggert, B; Estevez, M E; Govardovskii, V I; Cornwall, M C

    2007-02-01

    Photoreceptors of nocturnal geckos are transmuted cones that acquired rod morphological and physiological properties but retained cone-type phototransduction proteins. We have used microspectrophotometry and microfluorometry of solitary isolated green-sensitive photoreceptors of Tokay gecko to study the initial stages of the visual cycle within these cells. These stages are the photolysis of the visual pigment, the reduction of all-trans retinal to all-trans retinol, and the clearance of all-trans retinol from the outer segment (OS) into the interphotoreceptor space. We show that the rates of decay of metaproducts (all-trans retinal release) and retinal-to-retinol reduction are intermediate between those of typical rods and cones. Clearance of retinol from the OS proceeds at a rate that is typical of rods and is greatly accelerated by exposure to interphotoreceptor retinoid-binding protein, IRBP. The rate of retinal release from metaproducts is independent of the position within the OS, while its conversion to retinol is strongly spatially non-uniform, being the fastest at the OS base and slowest at the tip. This spatial gradient of retinol production is abolished by dialysis of saponin-permeabilized OSs with exogenous NADPH or substrates for its production by the hexose monophosphate pathway (NADP+glucose-6-phosphate or 6-phosphogluconate, glucose-6-phosphate alone). Following dialysis by these agents, retinol production is accelerated by several-fold compared to the fastest rates observed in intact cells in standard Ringer solution. We propose that the speed of retinol production is set by the availability of NADPH which in turn depends on ATP supply within the outer segment. We also suggest that principal source of this ATP is from mitochondria located within the ellipsoid region of the inner segment.

  19. Cone dystrophy with "supernormal" rod ERG: psychophysical testing shows comparable rod and cone temporal sensitivity losses with no gain in rod function.

    Science.gov (United States)

    Stockman, Andrew; Henning, G Bruce; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Cammack, Jocelyn; Ripamonti, Caterina

    2014-02-10

    We report a psychophysical investigation of 5 observers with the retinal disorder "cone dystrophy with supernormal rod ERG," caused by mutations in the gene KCNV2 that encodes a voltage-gated potassium channel found in rod and cone photoreceptors. We compared losses for rod- and for cone-mediated vision to further investigate the disorder and to assess whether the supernormal ERG is associated with any visual benefit. L-cone, S-cone, and rod temporal acuity (critical flicker fusion frequency) were measured as a function of target irradiance; L-cone temporal contrast sensitivity was measured as a function of temporal frequency. Temporal acuity measures revealed that losses for vision mediated by rods, S-cones, and L-cones are roughly equivalent. Further, the gain in rod function implied by the supernormal ERG provides no apparent benefit to near-threshold rod-mediated visual performance. The L-cone temporal contrast sensitivity function in affected observers was similar in shape to the mean normal function but only after the mean function was compressed by halving the logarithmic sensitivities. The name of this disorder is potentially misleading because the comparable losses found across rod and cone vision suggest that the disorder is a generalized cone-rod dystrophy. Temporal acuity and temporal contrast sensitivity measures are broadly consistent with the defect in the voltage-gated potassium channel producing a nonlinear distortion of the photoreceptor response but after otherwise normal transduction processes.

  20. Simulating human photoreceptor optics using a liquid-filled photonic crystal fiber.

    Science.gov (United States)

    Rativa, Diego; Vohnsen, Brian

    2011-02-11

    We introduce a liquid-filled photonic crystal fiber to simulate a retinal cone photoreceptor mosaic and the directionality selective mechanism broadly known as the Stiles-Crawford effect. Experimental measurements are realized across the visible spectrum to study waveguide coupling and directionality at different managed waveguide parameters. The crystal fiber method is a hybrid tool between theory and a real biological sample and a valuable addition as a retina model for real eye simulations.

  1. Cone photopigment in older subjects: decreased optical density in early age-related macular degeneration

    Science.gov (United States)

    Elsner, Ann E.; Burns, Stephen A.; Weiter, John J.

    2002-01-01

    We measured changes to cone photoreceptors in patients with early age-related macular degeneration. The data of 53 patients were compared with normative data for color matching measurements of long- and middle-wavelength-sensitive cones in the central macula. A four-parameter model quantified cone photopigment optical density and kinetics. Cone photopigment optical density was on average less for the patients than for normal subjects and was uncorrelated with visual acuity. More light was needed to reduce the photopigment density by 50% in the steady state for patients. These results imply that cone photopigment optical density is reduced by factors other than slowed kinetics.

  2. Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

    KAUST Repository

    Busserolles, Fanny de

    2017-11-09

    Most vertebrates have a duplex retina comprising two photoreceptor types, rods for dim-light (scotopic) vision and cones for bright-light (photopic) and color vision. However, deep-sea fishes are only active in dim-light conditions; hence, most species have lost their cones in favor of a simplex retina composed exclusively of rods. Although the pearlsides, Maurolicus spp., have such a pure rod retina, their behavior is at odds with this simplex visual system. Contrary to other deep-sea fishes, pearlsides are mostly active during dusk and dawn close to the surface, where light levels are intermediate (twilight or mesopic) and require the use of both rod and cone photoreceptors. This study elucidates this paradox by demonstrating that the pearlside retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone phototransduction cascade to form a unique photoreceptor type, a rod-like cone, specifically tuned to the light conditions of the pearlsides\\' habitat (blue-shifted light at mesopic intensities). Combining properties of both rods and cones into a single cell type, instead of using two photoreceptor types that do not function at their full potential under mesopic conditions, is likely to be the most efficient and economical solution to optimize visual performance. These results challenge the standing paradigm of the function and evolution of the vertebrate duplex retina and emphasize the need for a more comprehensive evaluation of visual systems in general.

  3. Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment.

    Science.gov (United States)

    Schietroma, Cataldo; Parain, Karine; Estivalet, Amrit; Aghaie, Asadollah; Boutet de Monvel, Jacques; Picaud, Serge; Sahel, José-Alain; Perron, Muriel; El-Amraoui, Aziz; Petit, Christine

    2017-06-05

    Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis , these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23 , encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15-containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. © 2017 Schietroma et al.

  4. Usher syndrome type 1–associated cadherins shape the photoreceptor outer segment

    Science.gov (United States)

    Parain, Karine; Aghaie, Asadollah; Picaud, Serge

    2017-01-01

    Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. PMID:28495838

  5. The photocurrent response of human cones is fast and monophasic

    Directory of Open Access Journals (Sweden)

    Lamb TD

    2006-04-01

    Full Text Available Abstract Background The precise form of the light response of human cone photoreceptors in vivo has not been established with certainty. To investigate the response shape we compare the predictions of a recent model of transduction in primate cone photoreceptors with measurements extracted from human cones using the paired-flash electroretinogram method. As a check, we also compare the predictions with previous single-cell measurements of ground squirrel cone responses. Results The predictions of the model provide a good description of the measurements, using values of parameters within the range previously determined for primate retina. The dim-flash response peaks in about 20 ms, and flash responses at all intensities are essentially monophasic. Three time constants in the model are extremely short: the two time constants for inactivation (of visual pigment and of transducin/phosphodiesterase are around 3 and 10 ms, and the time constant for calcium equilibration lies in the same range. Conclusion The close correspondence between experiment and theory, using parameters previously derived for recordings from macaque retina, supports the notion that the electroretinogram approach and the modelling approach both provide an accurate estimate of the cone photoresponse in the living human eye. For reasons that remain unclear, the responses of isolated photoreceptors from the macaque retina, recorded previously using the suction pipette method, are considerably slower than found here, and display biphasic kinetics.

  6. CRALBP supports the mammalian retinal visual cycle and cone vision.

    Science.gov (United States)

    Xue, Yunlu; Shen, Susan Q; Jui, Jonathan; Rupp, Alan C; Byrne, Leah C; Hattar, Samer; Flannery, John G; Corbo, Joseph C; Kefalov, Vladimir J

    2015-02-01

    Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor-mediated vision loss in patients. It is not known how CRALBP supports cone function or how altered CRALBP leads to cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven visual behavior and light responses. Additionally, M-cone dark adaptation was largely suppressed in CRALBP-deficient animals. While rearing CRALBP-deficient mice in the dark prevented the deterioration of cone function, it did not rescue cone dark adaptation. Adeno-associated virus-mediated restoration of CRALBP expression specifically in Müller cells, but not retinal pigment epithelial (RPE) cells, rescued the retinal visual cycle and M-cone sensitivity in knockout mice. Our results identify Müller cell CRALBP as a key component of the retinal visual cycle and demonstrate that this pathway is important for maintaining normal cone-driven vision and accelerating cone dark adaptation.

  7. NMNAT1 variants cause cone and cone-rod dystrophy.

    Science.gov (United States)

    Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

    2018-03-01

    Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

  8. Cone visual pigments are present in gecko rod cells.

    Science.gov (United States)

    Kojima, D; Okano, T; Fukada, Y; Shichida, Y; Yoshizawa, T; Ebrey, T G

    1992-08-01

    The Tokay gecko (Gekko gekko), a nocturnal lizard, has two kinds of visual pigments, P467 and P521. In spite of the pure-rod morphology of the photoreceptor cells, the biochemical properties of P521 and P467 resemble those of iodopsin (the chicken red-sensitive cone visual pigment) and rhodopsin, respectively. We have found that the amino acid sequence of P521 deduced from the cDNA was very similar to that of iodopsin. In addition, P467 has the highest homology with the chicken green-sensitive cone visual pigment, although it also has a relatively high homology with rhodopsins. These results give additional strength to the transmutation theory of Walls [Walls, G. L. (1934) Am. J. Ophthalmol. 17, 892-915], who proposed that the rod-shaped photoreceptor cells of lizards have been derived from ancestral cone-like photoreceptors. Apparently amino acid sequences of visual pigments are less changeable than the morphology of the photoreceptor cells in the course of evolution.

  9. Photobiomodulation reduces photoreceptor death and regulates cytoprotection in early states of P23H retinal dystrophy

    Science.gov (United States)

    Kirk, Diana K.; Gopalakrishnan, Sandeep; Schmitt, Heather; Abroe, Betsy; Stoehr, Michele; Dubis, Adam; Carroll, Joseph; Stone, Jonathan; Valter, Krisztina; Eells, Janis

    2013-03-01

    Irradiation by light in the far-red to near-infrared (NIR) region of the spectrum (photobiomodulation, PBM) has been demonstrated to attenuate the severity of neurodegenerative disease in experimental and clinical studies. The purpose of this study was to test the hypothesis that 670 nm PBM would protect against the loss of retinal function and improve photoreceptor survival in a rodent model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated once per day with a 670 nm LED array (180 sec treatments at 50 mW/cm2; fluence 9 joules/cm2) (Quantum Devices Inc., Barneveld WI) from postnatal day (p) 16-20 or from p10-20. Sham-treated rats were restrained, but not exposed to NIR light. The status of the retina was determined at p22 by assessment of mitochondrial function, oxidative stress and cell death. In a second series of studies, retinal status was assessed at p30 by measuring photoreceptor function by ERG and retinal morphology by Spectral Domain Optical Coherence Tomography (SD-OCT). 670 nm PBM increased retinal mitochondrial cytochrome oxidase activity and upregulated the retina's production of the key mitochondrial antioxidant enzyme, MnSOD. PBM also attenuated photoreceptor cell loss and improved photoreceptor function. PBM protects photoreceptors in the developing P23H retina, by augmenting mitochondrial function and stimulating antioxidant protective pathways. Photobiomodulation may have therapeutic potential, where mitochondrial damage is a step in the death of photoreceptors.

  10. The influence of photoreceptor size and distribution on optical sensitivity in the eyes of lanternfishes (Myctophidae)

    KAUST Repository

    Busserolles, Fanny de

    2014-06-13

    The mesopelagic zone of the deep-sea (200-1000 m) is characterised by exponentially diminishing levels of downwelling sunlight and by the predominance of bioluminescence emissions. The ability of mesopelagic organisms to detect and behaviourally react to downwelling sunlight and/or bioluminescence will depend on the visual task and ultimately on the eyes and their capacity for detecting low levels of illumination and intermittent point sources of bioluminescent light. In this study, we investigate the diversity of the visual system of the lanternfish (Myctophidae). We focus specifically on the photoreceptor cells by examining their size, arrangement, topographic distribution and contribution to optical sensitivity in 53 different species from 18 genera. We also examine the influence(s) of both phylogeny and ecology on these photoreceptor variables using phylogenetic comparative analyses in order to understand the constraints placed on the visual systems of this large group of mesopelagic fishes at the first stage of retinal processing. We report great diversity in the visual system of the Myctophidae at the level of the photoreceptors. Photoreceptor distribution reveals clear interspecific differences in visual specialisations (areas of high rod photoreceptor density), indicating potential interspecific differences in interactions with prey, predators and/or mates. A great diversity in photoreceptor design (length and diameter) and density is also present. Overall, the myctophid eye is very sensitive compared to other teleosts and each species seems to be specialised for the detection of a specific signal (downwelling light or bioluminescence), potentially reflecting different visual demands for survival. Phylogenetic comparative analyses highlight several relationships between photoreceptor characteristics and the ecological variables tested (depth distribution and luminous tissue patterns). Depth distribution at night was a significant factor in most of the

  11. The influence of photoreceptor size and distribution on optical sensitivity in the eyes of lanternfishes (Myctophidae)

    KAUST Repository

    Busserolles, Fanny de; Fitzpatrick, John L.; Marshall, N. Justin; Collin, Shaun P.

    2014-01-01

    The mesopelagic zone of the deep-sea (200-1000 m) is characterised by exponentially diminishing levels of downwelling sunlight and by the predominance of bioluminescence emissions. The ability of mesopelagic organisms to detect and behaviourally react to downwelling sunlight and/or bioluminescence will depend on the visual task and ultimately on the eyes and their capacity for detecting low levels of illumination and intermittent point sources of bioluminescent light. In this study, we investigate the diversity of the visual system of the lanternfish (Myctophidae). We focus specifically on the photoreceptor cells by examining their size, arrangement, topographic distribution and contribution to optical sensitivity in 53 different species from 18 genera. We also examine the influence(s) of both phylogeny and ecology on these photoreceptor variables using phylogenetic comparative analyses in order to understand the constraints placed on the visual systems of this large group of mesopelagic fishes at the first stage of retinal processing. We report great diversity in the visual system of the Myctophidae at the level of the photoreceptors. Photoreceptor distribution reveals clear interspecific differences in visual specialisations (areas of high rod photoreceptor density), indicating potential interspecific differences in interactions with prey, predators and/or mates. A great diversity in photoreceptor design (length and diameter) and density is also present. Overall, the myctophid eye is very sensitive compared to other teleosts and each species seems to be specialised for the detection of a specific signal (downwelling light or bioluminescence), potentially reflecting different visual demands for survival. Phylogenetic comparative analyses highlight several relationships between photoreceptor characteristics and the ecological variables tested (depth distribution and luminous tissue patterns). Depth distribution at night was a significant factor in most of the

  12. Meaning of visualizing retinal cone mosaic on adaptive optics images.

    Science.gov (United States)

    Jacob, Julie; Paques, Michel; Krivosic, Valérie; Dupas, Bénédicte; Couturier, Aude; Kulcsar, Caroline; Tadayoni, Ramin; Massin, Pascale; Gaudric, Alain

    2015-01-01

    To explore the anatomic correlation of the retinal cone mosaic on adaptive optics images. Retrospective nonconsecutive observational case series. A retrospective review of the multimodal imaging charts of 6 patients with focal alteration of the cone mosaic on adaptive optics was performed. Retinal diseases included acute posterior multifocal placoid pigment epitheliopathy (n = 1), hydroxychloroquine retinopathy (n = 1), and macular telangiectasia type 2 (n = 4). High-resolution retinal images were obtained using a flood-illumination adaptive optics camera. Images were recorded using standard imaging modalities: color and red-free fundus camera photography; infrared reflectance scanning laser ophthalmoscopy, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography (OCT) images. On OCT, in the marginal zone of the lesions, a disappearance of the interdigitation zone was observed, while the ellipsoid zone was preserved. Image recording demonstrated that such attenuation of the interdigitation zone co-localized with the disappearance of the cone mosaic on adaptive optics images. In 1 case, the restoration of the interdigitation zone paralleled that of the cone mosaic after a 2-month follow-up. Our results suggest that the interdigitation zone could contribute substantially to the reflectance of the cone photoreceptor mosaic. The absence of cones on adaptive optics images does not necessarily mean photoreceptor cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Restoration of vision after transplantation of photoreceptors.

    Science.gov (United States)

    Pearson, R A; Barber, A C; Rizzi, M; Hippert, C; Xue, T; West, E L; Duran, Y; Smith, A J; Chuang, J Z; Azam, S A; Luhmann, U F O; Benucci, A; Sung, C H; Bainbridge, J W; Carandini, M; Yau, K-W; Sowden, J C; Ali, R R

    2012-05-03

    Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

  14. Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy

    Science.gov (United States)

    Hunter, Jennifer J.; Masella, Benjamin; Dubra, Alfredo; Sharma, Robin; Yin, Lu; Merigan, William H.; Palczewska, Grazyna; Palczewski, Krzysztof; Williams, David R.

    2011-01-01

    In vivo two-photon imaging through the pupil of the primate eye has the potential to become a useful tool for functional imaging of the retina. Two-photon excited fluorescence images of the macaque cone mosaic were obtained using a fluorescence adaptive optics scanning laser ophthalmoscope, overcoming the challenges of a low numerical aperture, imperfect optics of the eye, high required light levels, and eye motion. Although the specific fluorophores are as yet unknown, strong in vivo intrinsic fluorescence allowed images of the cone mosaic. Imaging intact ex vivo retina revealed that the strongest two-photon excited fluorescence signal comes from the cone inner segments. The fluorescence response increased following light stimulation, which could provide a functional measure of the effects of light on photoreceptors. PMID:21326644

  15. Photoreceptor Sensory Cilium: Traversing the Ciliary Gate

    Directory of Open Access Journals (Sweden)

    Hemant Khanna

    2015-10-01

    Full Text Available Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of technical limitations and the specific structural and functional modifications that cannot be modeled in vitro. With recent advances in microscopy techniques and molecular and biochemical approaches, we are now beginning to understand the molecular basis of photoreceptor ciliary architecture, ciliary function and its involvement in human diseases. Here, I will discuss the studies that have revealed new knowledge of how photoreceptor cilia regulate their identity and function while coping with high metabolic and trafficking demands associated with processing light signal.

  16. Machine learning approaches to supporting the identification of photoreceptor-enriched genes based on expression data

    Directory of Open Access Journals (Sweden)

    Simpson David

    2006-03-01

    Full Text Available Abstract Background Retinal photoreceptors are highly specialised cells, which detect light and are central to mammalian vision. Many retinal diseases occur as a result of inherited dysfunction of the rod and cone photoreceptor cells. Development and maintenance of photoreceptors requires appropriate regulation of the many genes specifically or highly expressed in these cells. Over the last decades, different experimental approaches have been developed to identify photoreceptor enriched genes. Recent progress in RNA analysis technology has generated large amounts of gene expression data relevant to retinal development. This paper assesses a machine learning methodology for supporting the identification of photoreceptor enriched genes based on expression data. Results Based on the analysis of publicly-available gene expression data from the developing mouse retina generated by serial analysis of gene expression (SAGE, this paper presents a predictive methodology comprising several in silico models for detecting key complex features and relationships encoded in the data, which may be useful to distinguish genes in terms of their functional roles. In order to understand temporal patterns of photoreceptor gene expression during retinal development, a two-way cluster analysis was firstly performed. By clustering SAGE libraries, a hierarchical tree reflecting relationships between developmental stages was obtained. By clustering SAGE tags, a more comprehensive expression profile for photoreceptor cells was revealed. To demonstrate the usefulness of machine learning-based models in predicting functional associations from the SAGE data, three supervised classification models were compared. The results indicated that a relatively simple instance-based model (KStar model performed significantly better than relatively more complex algorithms, e.g. neural networks. To deal with the problem of functional class imbalance occurring in the dataset, two data re

  17. Evolution, Development and Function of Vertebrate Cone Oil Droplets

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    Matthew B. Toomey

    2017-12-01

    Full Text Available To distinguish colors, the nervous system must compare the activity of distinct subtypes of photoreceptors that are maximally sensitive to different portions of the light spectrum. In vertebrates, a variety of adaptations have arisen to refine the spectral sensitivity of cone photoreceptors and improve color vision. In this review article, we focus on one such adaptation, the oil droplet, a unique optical organelle found within the inner segment of cone photoreceptors of a diverse array of vertebrate species, from fish to mammals. These droplets, which consist of neutral lipids and carotenoid pigments, are interposed in the path of light through the photoreceptor and modify the intensity and spectrum of light reaching the photosensitive outer segment. In the course of evolution, the optical function of oil droplets has been fine-tuned through changes in carotenoid content. Species active in dim light reduce or eliminate carotenoids to enhance sensitivity, whereas species active in bright light precisely modulate carotenoid double bond conjugation and concentration among cone subtypes to optimize color discrimination and color constancy. Cone oil droplets have sparked the curiosity of vision scientists for more than a century. Accordingly, we begin by briefly reviewing the history of research on oil droplets. We then discuss what is known about the developmental origins of oil droplets. Next, we describe recent advances in understanding the function of oil droplets based on biochemical and optical analyses. Finally, we survey the occurrence and properties of oil droplets across the diversity of vertebrate species and discuss what these patterns indicate about the evolutionary history and function of this intriguing organelle.

  18. FUNDUS AUTOFLUORESCENCE IN RUBELLA RETINOPATHY: Correlation With Photoreceptor Structure and Function.

    Science.gov (United States)

    Bukowska, Danuta M; Wan, Sue Ling; Chew, Avenell L; Chelva, Enid; Tang, Ivy; Mackey, David A; Chen, Fred K

    2017-01-01

    To illustrate altered fundus autofluorescence in rubella retinopathy and to investigate their relationships with photoreceptor structure and function using multimodal imaging. The authors report four cases of rubella retinopathy aged 8, 33, 42, and 50 years. All patients had dilated clinical fundus examination; wide-field color photography; blue, green, and near-infrared autofluorescence imaging and spectral domain optical coherence tomography. Two patients also underwent microperimetry and adaptive optics imaging. En face optical coherence tomography, cone mosaic, and microperimetry were coregistered with autofluorescence images. The authors explored the structure-function correlation. All four patients had a "salt-and-pepper" appearance on dilated fundus examination and wide-field color photography. There were variable-sized patches of hypoautofluorescence on both blue and near-infrared excitation in all four patients. Wave-guiding cones were visible and retinal sensitivity was intact over these regions. There was no correlation between hypoautofluorescence and regions of attenuated ellipsoid and interdigitation zones. Hyperautofluorescent lesions were also noted and some of these were pseudo-vitelliform lesions. Patchy hypoautofluorescence on near-infrared excitation can be a feature of rubella retinopathy. This may be due to abnormal melanin production or loss of melanin within retinal pigment epithelium cells harboring persistent rubella virus infection. Preservation of the ellipsoid zone, wave-guiding cones, and retinal sensitivity within hypoautofluorescent lesions suggest that these retinal pigment epithelium changes have only mild impact on photoreceptor cell function.

  19. THE STRUCTURE AND CONCENTRATION OF SOLIDS IN PHOTORECEPTOR CELLS STUDIED BY REFRACTOMETRY AND INTERFERENCE MICROSCOPY

    Science.gov (United States)

    Sidman, Richard L.

    1957-01-01

    Fragments of freshly obtained retinas of several vertebrate species were studied by refractometry, with reference to the structure of the rods and cones. The findings allowed a reassessment of previous descriptions based mainly on fixed material. The refractometric method was used also to measure the refractice indices and to calculate the concentrations of solids and water in the various cell segments. The main quantitative data were confirmed by interference microscopy. When examined by the method of refractometry the outer segments of freshly prepared retinal rods appear homogeneous. Within a few minutes a single eccentric longitudinal fiber appears, and transverse striations may develop. These changes are attributed to imbibition of water and swelling in structures normally too small for detection by light microscopy. The central "core" of outer segments and the chromophobic disc between outer and inner segments appear to be artifacts resulting from shrinkage during dehydration. The fresh outer segments of cones, and the inner segments of rods and cones also are described and illustrated. The volumes, refractive indices, concentrations of solids, and wet and dry weights of various segments of the photoreceptor cells were tabulated. Rod outer segments of the different species vary more than 100-fold in volume and mass but all have concentrations of solids of 40 to 43 per cent. Cone outer segments contain only about 30 per cent solids. The myoids, paraboloids, and ellipsoids of the inner segments likewise have characteristic refractive indices and concentrations of solids. Some of the limitations and particular virtues of refractometry as a method for quantitative analysis of living cells are discussed in comparison with more conventional biochemical techniques. Also the shapes and refractive indices of the various segments of photoreceptor cells are considered in relation to the absorption and transmission of light. The Stiles-Crawford effect can be accounted

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yoshihiro Omori

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

  2. Unidirectional photoreceptor-to-Müller glia coupling and unique K+ channel expression in Caiman retina.

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    Astrid Zayas-Santiago

    Full Text Available 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.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.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.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.

  3. Chloride equilibrium potential in salamander cones

    Directory of Open Access Journals (Sweden)

    Bryson Eric J

    2004-12-01

    Full Text Available Abstract Background GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl was determined in red-sensitive, large single cones from the tiger salamander retinal slice. Results Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current (ICl(Ca and then determined the reversal potential for the current component that was inhibited by the Cl- channel blocker, niflumic acid. With this method, ECl was found to average -46 mV. In a complementary approach, we used a Cl-sensitive dye, MEQ, to measure the Cl- flux produced by depolarization with elevated concentrations of K+. The membrane potentials produced by the various high K+ solutions were measured in separate current clamp experiments. Consistent with electrophysiological experiments, MEQ fluorescence measurements indicated that ECl was below -36 mV. Conclusions The results of this study indicate that ECl is close to the dark resting potential. This will minimize the impact of chloride-dependent presynaptic mechanisms in cone terminals involving GABAa receptors, glutamate transporters and ICl(Ca.

  4. An automated algorithm for photoreceptors counting in adaptive optics retinal images

    Science.gov (United States)

    Liu, Xu; Zhang, Yudong; Yun, Dai

    2012-10-01

    Eyes are important organs of humans that detect light and form spatial and color vision. Knowing the exact number of cones in retinal image has great importance in helping us understand the mechanism of eyes' function and the pathology of some eye disease. In order to analyze data in real time and process large-scale data, an automated algorithm is designed to label cone photoreceptors in adaptive optics (AO) retinal images. Images acquired by the flood-illuminated AO system are taken to test the efficiency of this algorithm. We labeled these images both automatically and manually, and compared the results of the two methods. A 94.1% to 96.5% agreement rate between the two methods is achieved in this experiment, which demonstrated the reliability and efficiency of the algorithm.

  5. Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1 alpha expression in photoreceptors.

    Science.gov (United States)

    Thiersch, Markus; Lange, Christina; Joly, Sandrine; Heynen, Severin; Le, Yun Zheng; Samardzija, Marijana; Grimm, Christian

    2009-06-01

    Hypoxic preconditioning stabilizes hypoxia-inducible factor (HIF) 1 alpha in the retina and protects photoreceptors against light-induced cell death. HIF-1 alpha is one of the major transcription factors responding to low oxygen tension and can differentially regulate a large number of target genes. To analyse whether photoreceptor-specific expression of HIF-1 alpha is essential to protect photoreceptors by hypoxic preconditioning, we knocked down expression of HIF-1 alpha specifically in photoreceptor cells, using the cyclization recombinase (Cre)-lox system. The Cre-mediated knockdown caused a 20-fold reduced expression of Hif-1 alpha in the photoreceptor cell layer. In the total retina, RNA expression was reduced by 65%, and hypoxic preconditioning led to only a small increase in HIF-1 alpha protein levels. Accordingly, HIF-1 target gene expression after hypoxia was significantly diminished. Retinas of Hif-1 alpha knockdown animals did not show any pathological alterations, and tolerated hypoxic exposure in a comparable way to wild-type retinas. Importantly, the strong neuroprotective effect of hypoxic preconditioning against light-induced photoreceptor degeneration persisted in knockdown mice, suggesting that hypoxia-mediated survival of light exposure does not depend on an autocrine action of HIF-1 alpha in photoreceptor cells. Hypoxia-mediated stabilization of HIF-2 alpha and phosphorylation of signal transducer and activator of transcription 3 (STAT 3) were not affected in the retinas of Hif-1 alpha knockdown mice. Thus, these factors are candidates for regulating the resistance of photoreceptors to light damage after hypoxic preconditioning, along with several potentially neuroprotective genes that were similarly induced in hypoxic knockdown and control mice.

  6. Photoreceptor inner segment ellipsoid band integrity on spectral domain optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Saxena S

    2014-12-01

    Full Text Available Sandeep Saxena,1 Khushboo Srivastav,1 Chui M Cheung,2 Joanne YW Ng,3 Timothy YY Lai3 1Retina Service, Department of Ophthalmology, King George’s Medical University Lucknow, India; 2Singapore National Eye Centre, Singapore; 3Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong Abstract: Spectral domain optical coherence tomography cross-sectional imaging of the macula has conventionally been resolved into four bands. However, some doubts were raised regarding authentication of the existence of these bands. Recently, a number of studies have suggested that the second band appeared to originate from the inner segment ellipsoids of the foveal cone photoreceptors, and therefore the previously called inner segment-outer segment junction is now referred to as inner segment ellipsoidband. Photoreceptor dysfunction may be a significant predictor of visual acuity in a spectrum of surgical and medical retinal diseases. This review aims to provide an overview and summarizes the role of the photoreceptor inner segment ellipsoid band in the management and prognostication of various vitreoretinal diseases. Keywords: spectral domain optical coherence tomography, inner segment-outer segment junction, external limiting membrane, macular hole, diabetic macular edema, age relate macular degeneration

  7. Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice

    Science.gov (United States)

    Sahly, Iman; Dufour, Eric; Schietroma, Cataldo; Michel, Vincent; Bahloul, Amel; Perfettini, Isabelle; Pepermans, Elise; Estivalet, Amrit; Carette, Diane; Aghaie, Asadollah; Ebermann, Inga; Lelli, Andrea; Iribarne, Maria; Hardelin, Jean-Pierre; Weil, Dominique; Sahel, José-Alain

    2012-01-01

    The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins—myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans—do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalized at membrane interfaces (i) between the inner and outer segments in rods and (ii) between the microvillus-like calyceal processes and the outer segment basolateral region in rods and cones. This pattern, conserved in humans and frogs, was mediated by the formation of an USH1 protein network, which was associated with the calyceal processes from the early embryonic stages of outer segment growth onwards. By contrast, mouse photoreceptors lacked calyceal processes and had no USH1 proteins at the inner–outer segment interface. We suggest that USH1 proteins form an adhesion belt around the basolateral region of the photoreceptor outer segment in humans, and that defects in this structure cause the retinal degeneration in USH1 patients. PMID:23045546

  8. Calcium homeostasis in fly photoreceptor cells

    NARCIS (Netherlands)

    Oberwinkler, J

    2002-01-01

    In fly photoreceptor cells, two processes dominate the Ca2+ homeostasis: light-induced Ca2+ influx through members of the TRP family of ion channels, and Ca2+ extrusion by Na+/Ca2+ exchange.Ca2+ release from intracellular stores is quantitatively insignificant. Both, the light-activated channels and

  9. The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

    Science.gov (United States)

    Wang, Feng-Yu; Fu, Wen-Chun; Wang, I-Li; Yan, Hong Young; Wang, Tzi-Yuan

    2014-01-01

    Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2) revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292) and four putative (S124, V189, V286, I290) tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

  10. The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

    Directory of Open Access Journals (Sweden)

    Feng-Yu Wang

    Full Text Available Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2 revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292 and four putative (S124, V189, V286, I290 tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

  11. RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations

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    Li eJiang

    2014-04-01

    Full Text Available RNA interference (RNAi knockdown is an efficacious therapeutic strategy for silencing genes causative for dominant retinal dystrophies. To test this, we used self-complementary (sc AAV2/8 vector to develop an RNAi-based therapy in two dominant retinal degeneration mouse models. The allele-specific model expresses transgenic bovine GCAP1(Y99C establishing a rapid RP-like phenotype, whereas the nonallele-specific model expresses mouse GCAP1(L151F producing a slowly progressing cone/rod dystrophy (CORD. The late onset GCAP1(L151F-CORD mimics the dystrophy observed in human GCAP1-CORD patients. Subretinal injection of scAAV2/8 carrying shRNA expression cassettes specific for bovine or mouse GCAP1 showed strong expression at one week post-injection. In both allele-specific (GCAP1(Y99C-RP and nonallele-specific (GCAP1(L151F-CORD models of dominant retinal dystrophy, RNAi-mediated gene silencing enhanced photoreceptor survival, delayed onset of degeneration and improved visual function. Such results provide a proof of concept toward effective RNAi-based gene therapy mediated by scAAV2/8 for dominant retinal disease based on GCAP1 mutation. Further, nonallele-specific RNAi knockdown of GCAP1 may prove generally applicable toward the rescue of any human GCAP1-based dominant cone-rod dystrophy.

  12. Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds.

    Science.gov (United States)

    Toomey, Matthew B; Lind, Olle; Frederiksen, Rikard; Curley, Robert W; Riedl, Ken M; Wilby, David; Schwartz, Steven J; Witt, Christopher C; Harrison, Earl H; Roberts, Nicholas W; Vorobyev, Misha; McGraw, Kevin J; Cornwall, M Carter; Kelber, Almut; Corbo, Joseph C

    2016-07-12

    Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (λmax) are evenly spaced across the light spectrum. In the course of avian evolution, the λmax of the most shortwave-sensitive cone, SWS1, has switched between violet (λmax > 400 nm) and ultraviolet (λmax < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11’,12’-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination.

  13. Material Exchange in Photoreceptor Transplantation: Updating Our Understanding of Donor/Host Communication and the Future of Cell Engraftment Science.

    Science.gov (United States)

    Nickerson, Philip E B; Ortin-Martinez, Arturo; Wallace, Valerie A

    2018-01-01

    Considerable research effort has been invested into the transplantation of mammalian photoreceptors into healthy and degenerating mouse eyes. Several platforms of rod and cone fluorescent reporting have been central to refining the isolation, purification and transplantation of photoreceptors. The tracking of engrafted cells, including identifying the position, morphology and degree of donor cell integration post-transplant is highly dependent on the use of fluorescent protein reporters. Improvements in imaging and analysis of transplant recipients have revealed that donor cell fluorescent reporters can transfer into host tissue though a process termed material exchange (ME). This recent discovery has chaperoned a new era of interpretation when reviewing the field's use of dissociated donor cell preparations, and has prompted scientists to re-examine how we use and interpret the information derived from fluorescence-based tracking tools. In this review, we describe the status of our understanding of ME in photoreceptor transplantation. In addition, we discuss the impact of this discovery on several aspects of historical rod and cone transplantation data, and provide insight into future standards and approaches to advance the field of cell engraftment.

  14. Material Exchange in Photoreceptor Transplantation: Updating Our Understanding of Donor/Host Communication and the Future of Cell Engraftment Science

    Directory of Open Access Journals (Sweden)

    Philip E. B. Nickerson

    2018-03-01

    Full Text Available Considerable research effort has been invested into the transplantation of mammalian photoreceptors into healthy and degenerating mouse eyes. Several platforms of rod and cone fluorescent reporting have been central to refining the isolation, purification and transplantation of photoreceptors. The tracking of engrafted cells, including identifying the position, morphology and degree of donor cell integration post-transplant is highly dependent on the use of fluorescent protein reporters. Improvements in imaging and analysis of transplant recipients have revealed that donor cell fluorescent reporters can transfer into host tissue though a process termed material exchange (ME. This recent discovery has chaperoned a new era of interpretation when reviewing the field’s use of dissociated donor cell preparations, and has prompted scientists to re-examine how we use and interpret the information derived from fluorescence-based tracking tools. In this review, we describe the status of our understanding of ME in photoreceptor transplantation. In addition, we discuss the impact of this discovery on several aspects of historical rod and cone transplantation data, and provide insight into future standards and approaches to advance the field of cell engraftment.

  15. Hypoxic preconditioning protects photoreceptors against light damage independently of hypoxia inducible transcription factors in rods.

    Science.gov (United States)

    Kast, Brigitte; Schori, Christian; Grimm, Christian

    2016-05-01

    Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Morphological characterization and topographic analysis of multiple photoreceptor types in the retinae of mesopelagic hatchetfishes with tubular eyes

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    Lauren Michelle Biagioni

    2016-03-01

    Full Text Available Marine hatchetfishes, Argyropelecus spp., are one of the 14 genera of mesopelagic teleosts, which possess tubular eyes. The tubular eyes are positioned dorsally on the head and consist of a main retina, which subtends a large dorsal binocular field, and an accessory retina, which subtends the lateral monocular visual field. The topographic distribution of photoreceptors in the retina of Argyropelecus sladeni, A. affinis and A. aculeatus was determined using a random, unbiased and systematic stereological approach, which consistently revealed a region of high density (area centralis in the central region of the main retina (up to a peak of 96,000 receptors per mm2 and a relatively homogeneous density of photoreceptors in the accessory retina (of approximately 20,000 receptors per mm2. The position of the area centralis in the main retina indicates this retinal region subserves greater spatial resolution in the centre of the dorsal binocular visual field. Light microscopy and transmission electron microscopy also revealed the presence of multiple photoreceptor types (two rod-like and one cone-like based on the size and shape of the inner and outer segments and ultrastructural differences in the ellipsoidal region. The presence of multiple photoreceptor types in these tubular-eyed, mesopelagic hatchetfishes may reflect the need for the visual system to function under different lighting conditions during vertical migratory behavior, especially given their unique dorsally-facing eyes.

  17. Quotient normed cones

    Indian Academy of Sciences (India)

    general setting of the space CL(X, Y ) of all continuous linear mappings from a normed cone (X, p) to a normed cone (Y, q), extending several well-known results related to open continuous linear mappings between normed linear spaces. Keywords. Normed cone; extended quasi-metric; continuous linear mapping; bicom-.

  18. Berkeley Lighting Cone

    Energy Technology Data Exchange (ETDEWEB)

    Lask, Kathleen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gadgil, Ashok [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-10-24

    A lighting cone is a simple metal cone placed on the fuel bed of a stove during ignition to act as a chimney, increasing the draft through the fuel bed. Many stoves tend to be difficult to light due to poor draft through the fuel bed, so lighting cones are used in various parts of the world as an inexpensive accessory to help with ignition.

  19. Cone and Rod Loss in Stargardt Disease Revealed by Adaptive Optics Scanning Light Ophthalmoscopy

    Science.gov (United States)

    Song, Hongxin; Rossi, Ethan A.; Latchney, Lisa; Bessette, Angela; Stone, Edwin; Hunter, Jennifer J.; Williams, David R.; Chung, Mina

    2015-01-01

    Importance Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. Observations Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1. PMID:26247787

  20. Correlated cone noise decreases rod signal contributions to the post-receptoral pathways.

    Science.gov (United States)

    Hathibelagal, Amithavikram R; Feigl, Beatrix; Zele, Andrew J

    2018-04-01

    This study investigated how invisible extrinsic temporal white noise that correlates with the activity of one of the three [magnocellular (MC), parvocellular (PC), or koniocellular (KC)] post-receptoral pathways alters mesopic rod signaling. A four-primary photostimulator provided independent control of the rod and three cone photoreceptor excitations. The rod contributions to the three post-receptoral pathways were estimated by perceptually matching a 20% contrast rod pulse by independently varying the LMS (MC pathway), +L-M (PC pathway), and S-cone (KC pathway) excitations. We show that extrinsic cone noise caused a predominant decrease in the overall magnitude and ratio of the rod contributions to each pathway. Thus, the relative cone activity in the post-receptoral pathways determines the relative mesopic rod inputs to each pathway.

  1. Domain requirements for the Dock adapter protein in growth- cone signaling.

    Science.gov (United States)

    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  2. Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells.

    Science.gov (United States)

    Ishikawa, Makoto; Sawada, Yu; Yoshitomi, Takeshi

    2015-04-01

    The interphotoreceptor matrix (IPM) is a highly organized structure with interconnected domains surrounding cone and rod photoreceptor cells and extends throughout the subretinal space. Based on known roles of the extracellular matrix in other tissues, the IPM is thought to have several prominent functions including serving as a receptor for growth factors, regulating retinoid transport, participating in cytoskeletal organization in surrounding cells, and regulation of oxygen and nutrient transport. In addition, a number of studies suggest that the IPM also may play a significant role in the etiology of retinal degenerative disorders. In this review, we describe the present knowledge concerning the structure and function of the IPM under physiological and pathological conditions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Visual pigment coexpression in all cones of two rodents, the Siberian hamster, and the pouched mouse.

    Science.gov (United States)

    Lukáts, Akos; Dkhissi-Benyahya, Ouria; Szepessy, Zsuzsanna; Röhlich, Pál; Vígh, Béla; Bennett, Nigel C; Cooper, Howard M; Szél, Agoston

    2002-07-01

    To decide whether the identical topography of short- and middle-wavelength cone photoreceptors in two species of rodents reflects the presence of both opsins in all cone cells. Double-label immunocytochemistry using antibodies directed against short-wavelength (S)-and middle- to long-wavelength (M/L)-sensitive opsin were used to determine the presence of visual pigments in cones of two species of rodents, the Siberian hamster (Phodopus sungorus) and the pouched mouse (Saccostomus campestris) from South Africa. Topographical distribution was determined from retinal whole-mounts, and the colocalization of visual pigments was examined using confocal laser scanning microscopy. Opsin colocalization was also confirmed in consecutive semithin tangential sections. The immunocytochemical results demonstrate that in both the Siberian hamster and the pouched mouse all retinal cones contain two visual pigments. No dorsoventral gradient in the differential expression of the two opsins is observed. The retina of the Siberian hamster and the pouched mouse is the first example to show a uniform coexpression of M and S cone opsins in all cones, without any topographical gradient in opsin expression. This finding makes these two species good models for the study of molecular control mechanisms in opsin coexpression in rodents, and renders them suitable as sources of dual cones for future investigations on the role and neural connections of this cone type.

  4. Extrafoveal Cone Packing in Eyes With a History of Retinopathy of Prematurity.

    Science.gov (United States)

    Ramamirtham, Ramkumar; Akula, James D; Soni, Garima; Swanson, Matthew J; Bush, Jennifer N; Moskowitz, Anne; Swanson, Emily A; Favazza, Tara L; Tavormina, Jena L; Mujat, Mircea; Ferguson, R Daniel; Hansen, Ronald M; Fulton, Anne B

    2016-02-01

    To study the density and packing geometry of the extrafoveal cone photoreceptors in eyes with a history of retinopathy of prematurity (ROP). We used a multimodal combination of adaptive optics (AO) scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT). Cones were identified in subjects (aged 14-26 years) with a history of ROP that was either severe and treated by laser ablation of avascular peripheral retina (TROP; n = 5) or mild and spontaneously resolved, untreated (UROP; n = 5), and in term-born controls (CT; n = 8). The AO-SLO images were obtained at temporal eccentricities 4.5°, 9°, 13.5°, and 18° using both confocal and offset apertures with simultaneous, colocal OCT images. Effects of group, eccentricity, and aperture were evaluated and the modalities compared. In the SLO images, cone density was lower and the packing pattern less regular in TROP, relative to CT and UROP retinae. Although SLO image quality appeared lower in TROP, root mean square (RMS) wavefront error did not differ among the groups. In TROP eyes, cone discrimination was easier in offset aperture images. There was no evidence of cone loss in the TROP OCT images. Low cone density in TROP confocal SLO images may have resulted from lower image quality. Since AO correction in these eyes was equivalent to that of the control group, and OCT imaging showed no significant cone loss, the optical properties of the inner retina or properties of the cones themselves are likely altered in a way that affects photoreceptor imaging.

  5. Luminescence- and nanoparticle-mediated increase of light absorption by photoreceptor cells: Converting UV light to visible light.

    Science.gov (United States)

    Li, Lei; Sahi, Sunil K; Peng, Mingying; Lee, Eric B; Ma, Lun; Wojtowicz, Jennifer L; Malin, John H; Chen, Wei

    2016-02-10

    We developed new optic devices - singly-doped luminescence glasses and nanoparticle-coated lenses that convert UV light to visible light - for improvement of visual system functions. Tb(3+) or Eu(3+) singly-doped borate glasses or CdS-quantum dot (CdS-QD) coated lenses efficiently convert UV light to 542 nm or 613 nm wavelength narrow-band green or red light, or wide-spectrum white light, and thereby provide extra visible light to the eye. In zebrafish (wild-type larvae and adult control animals, retinal degeneration mutants, and light-induced photoreceptor cell degeneration models), the use of Tb(3+) or Eu(3+) doped luminescence glass or CdS-QD coated glass lenses provide additional visible light to the rod and cone photoreceptor cells, and thereby improve the visual system functions. The data provide proof-of-concept for the future development of optic devices for improvement of visual system functions in patients who suffer from photoreceptor cell degeneration or related retinal diseases.

  6. Technical factors influencing cone packing density estimates in adaptive optics flood illuminated retinal images.

    Directory of Open Access Journals (Sweden)

    Marco Lombardo

    Full Text Available PURPOSE: To investigate the influence of various technical factors on the variation of cone packing density estimates in adaptive optics flood illuminated retinal images. METHODS: Adaptive optics images of the photoreceptor mosaic were obtained in fifteen healthy subjects. The cone density and Voronoi diagrams were assessed in sampling windows of 320×320 µm, 160×160 µm and 64×64 µm at 1.5 degree temporal and superior eccentricity from the preferred locus of fixation (PRL. The technical factors that have been analyzed included the sampling window size, the corrected retinal magnification factor (RMFcorr, the conversion from radial to linear distance from the PRL, the displacement between the PRL and foveal center and the manual checking of cone identification algorithm. Bland-Altman analysis was used to assess the agreement between cone density estimated within the different sampling window conditions. RESULTS: The cone density declined with decreasing sampling area and data between areas of different size showed low agreement. A high agreement was found between sampling areas of the same size when comparing density calculated with or without using individual RMFcorr. The agreement between cone density measured at radial and linear distances from the PRL and between data referred to the PRL or the foveal center was moderate. The percentage of Voronoi tiles with hexagonal packing arrangement was comparable between sampling areas of different size. The boundary effect, presence of any retinal vessels, and the manual selection of cones missed by the automated identification algorithm were identified as the factors influencing variation of cone packing arrangements in Voronoi diagrams. CONCLUSIONS: The sampling window size is the main technical factor that influences variation of cone density. Clear identification of each cone in the image and the use of a large buffer zone are necessary to minimize factors influencing variation of Voronoi

  7. A chick model of retinal detachment: cone rich and novel.

    Directory of Open Access Journals (Sweden)

    Colleen M Cebulla

    Full Text Available Development of retinal detachment models in small animals can be difficult and expensive. Here we create and characterize a novel, cone-rich retinal detachment (RD model in the chick.Retinal detachments were created in chicks between postnatal days 7 and 21 by subretinal injections of either saline (SA or hyaluronic acid (HA. Injections were performed through a dilated pupil with observation via surgical microscope, using the fellow eye as a control. Immunohistochemical analyses were performed at days 1, 3, 7, 10 and 14 after retinal detachment to evaluate the cellular responses of photoreceptors, Müller glia, microglia and nonastrocytic inner retinal glia (NIRG. Cell proliferation was detected with bromodeoxyuridine (BrdU-incorporation and by the expression of proliferating cell nuclear antigen (PCNA. Cell death was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL. As in mammalian models of RD, there is shortening of photoreceptor outer segments and mis-trafficking of photoreceptor opsins in areas of RD. Photoreceptor cell death was maximal 1 day after RD, but continued until 14 days after RD. Müller glia up-regulated glial fibriliary acidic protein (GFAP, proliferated, showed interkinetic nuclear migration, and migrated to the subretinal space in areas of detachment. Microglia became reactive; they up-regulated CD45, acquired amoeboid morphology, and migrated toward outer retina in areas of RD. Reactive NIRG cells accumulated in detached areas.Subretinal injections of SA or HA in the chick eye successfully produced retinal detachments and cellular responses similar to those seen in standard mammalian models. Given the relatively large eye size, and considering the low cost, the chick model of RD offers advantages for high-throughput studies.

  8. Modulation of recognition memory performance by light requires both melanopsin and classical photoreceptors

    Science.gov (United States)

    Tam, Shu K. E.; Hasan, Sibah; Hughes, Steven; Hankins, Mark W.; Foster, Russell G.; Bannerman, David M.

    2016-01-01

    Acute light exposure exerts various effects on physiology and behaviour. Although the effects of light on brain network activity in humans are well demonstrated, the effects of light on cognitive performance are inconclusive, with the size, as well as direction, of the effect depending on the nature of the task. Similarly, in nocturnal rodents, bright light can either facilitate or disrupt performance depending on the type of task employed. Crucially, it is unclear whether the effects of light on behavioural performance are mediated via the classical image-forming rods and cones or the melanopsin-expressing photosensitive retinal ganglion cells. Here, we investigate the modulatory effects of light on memory performance in mice using the spontaneous object recognition task. Importantly, we examine which photoreceptors are required to mediate the effects of light on memory performance. By using a cross-over design, we show that object recognition memory is disrupted when the test phase is conducted under a bright light (350 lux), regardless of the light level in the sample phase (10 or 350 lux), demonstrating that exposure to a bright light at the time of test, rather than at the time of encoding, impairs performance. Strikingly, the modulatory effect of light on memory performance is completely abolished in both melanopsin-deficient and rodless–coneless mice. Our findings provide direct evidence that melanopsin-driven and rod/cone-driven photoresponses are integrated in order to mediate the effect of light on memory performance. PMID:28003454

  9. Cone pigments in a North American marsupial, the opossum (Didelphis virginiana).

    Science.gov (United States)

    Jacobs, Gerald H; Williams, Gary A

    2010-05-01

    Only two of the four cone opsin gene families found in vertebrates are represented in contemporary eutherian and marsupial species. Recent genetic studies of two species of South American marsupial detected the presence of representatives from two of the classes of cone opsin genes and the structures of these genes predicted cone pigments with respective peaks in the ultraviolet and long-wavelength portions of the spectrum. The Virginia opossum (Didelphis virginiana), a profoundly nocturnal animal, is the only marsupial species found in North America. The prospects for cone-based vision in this species were examined through recordings of the electroretinogram (ERG), a commonly examined retinal response to photic stimulation. Recorded under flickering-light conditions that elicit signals from cone photoreceptors, the spectral sensitivity of the opossum eye is well accounted for by contributions from the presence of a single cone pigment having peak absorption at 561-562 nm. A series of additional experiments that employed various chromatic adaptation paradigms were conducted in a search for possible contributions from a second (short-wavelength sensitive) cone pigment. We found no evidence that such a mechanism contributes to the ERG in this marsupial.

  10. Axial length and cone density as assessed with adaptive optics in myopia

    Directory of Open Access Journals (Sweden)

    Supriya Dabir

    2015-01-01

    Full Text Available Aim: To assess the variations in cone mosaic in myopia and its correlation with axial length (AL. Subjects and Methods: Twenty-five healthy myopic volunteers underwent assessment of photoreceptors using adaptive optics retinal camera at 2° and 3° from the foveal center in four quadrants superior, inferior, temporal and nasal. Data was analyzed using SPSS version 17 (IBM. Multivariable regression analysis was conducted to study the relation between cone density and AL, quadrant around the fovea and eccentricity from the fovea. Results: The mean cone density was significantly lower as the eccentricity increased from 2° from the fovea to 3° (18,560 ± 5455-16,404 ± 4494/mm 2 respectively. There was also a statistically significant difference between four quadrants around the fovea. The correlation of cone density and spacing with AL showed that there was a significant inverse relation of AL with the cone density. Conclusion: In myopic patients with good visual acuity cone density around the fovea depends on the quadrant, distance from the fovea as well as the AL. The strength of the relation of AL with cone density depends on the quadrant and distance.

  11. Homeostatic Plasticity Mediated by Rod-Cone Gap Junction Coupling in Retinal Degenerative Dystrophic RCS Rats

    Science.gov (United States)

    Hou, Baoke; Fu, Yan; Weng, Chuanhuang; Liu, Weiping; Zhao, Congjian; Yin, Zheng Qin

    2017-01-01

    Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods. PMID:28473754

  12. Extracellular electrical activity from the photoreceptors of midge

    Indian Academy of Sciences (India)

    Unknown

    349. Keywords. Chironomus; electroretinogram; insect development; midge; photoreceptor ... ceran insects, only larval ocelli of mosquito (Family: Culi- cidae) have been ... and Ball (1995) studied the influence of light in Chiro- nomus tentans ...

  13. [Modification of retinal photoreceptor membranes and Ca ion binding].

    Science.gov (United States)

    Korchagin, V P; Berman, A L; Shukoliukov, S A; Rychkova, M P; Etingof, R N

    1978-10-01

    Calcium binding by modified photoreceptor membranes of cattle retina has been studied. Ca2+-binding the membranes significantly changes after C-phospholipase treatment, displaying the initial growth (less than 65% of lipid phosphorus removed) with subsequent decrease (more than 65% of phosphorus removed). Liposomes of the photoreceptor membranes lipids were found to bind more calcium than do the native photoreceptor membranes. Proteolytic enzymes (papaine, pronase) splitting some rhodopsin fragments do not affect the ability of the membrane to bind Ca2+. The increase of light-induced Ca-binding is observed only after the outer segments preincubation under conditions providing for rhodopsin phosphorylation. This effect was observed also after the splitting of the rhodopsin fragment by papaine. It is concluded that calcium binding in the photoreceptor membranes is mainly due to the phosphate groups of phospholipids.

  14. Progress in light cone physics

    International Nuclear Information System (INIS)

    Preparata, G.

    1973-01-01

    A very brief review is given of the progress made in the physics of the light cone in the past year. Included are the light cone expansion, gauge invariance and the consequences of precocious scaling near threshold, the light cone description of the muon pair experiment, light cone expansions, and the assessment and exploitation of analyticity properties in both mass and energy of light cone amplitudes. (U.S.)

  15. Cones for dental radiography

    Energy Technology Data Exchange (ETDEWEB)

    Butler, M J [National Radiological Protection Board, Harwell (UK)

    1977-04-01

    Dental radiographic techniques are summarized. The advantages and disadvantages of the use of both the conventional plastic pointer cone and the open-ended cylinders or divergent cones favoured both by the ICRP (Protection against Ionizing Radiation from External Sources, Oxford, Pergamon Press, 1973, ICRP Publication 15), and in the Code of Practice for the Protection of Persons against Ionizing Radiation arising from Medical and Dental Use (1972, 3rd edition, London, HMSO) are discussed. The use of the word 'should' in these recommendations to signify a desirable requirement, not an essential one, is noted. This wording is currently of interest both nationally and internationally in relation to regulations, standards and notes for guidance. The National Radiological Protection Board (NRPB) has been reviewing the position, and has concluded that open-ended cones have disadvantages which may sometimes outweigh their advantages. Although open-ended cones are preferable under some circumstances, the recommendation that they should be used ought not to be followed without an understanding of the issues involved. The hazards associated with the use of interchangeable cones are considered. The NRPB now proposes that the requirement for the replacement of pointer cones (for both new and existing equipment) should be withdrawn.

  16. Photoreceptor atrophy in acute zonal occult outer retinopathy

    DEFF Research Database (Denmark)

    Zibrandtsen, N.; Munch, I.C.; Klemp, K.

    2008-01-01

    appearance were examined using optical coherence tomography (OCT), automated perimetry and electroretinography (ERG). RESULTS: Both patients demonstrated photoreceptor atrophy corresponding to partial or complete scotomata with reduced or extinct electroretinographic responses. Attenuation or complete loss...... of all the segments composing the photoreceptor layer was found by OCT. Full-field ERG revealed affection of the 30 Hz flicker responses and subnormal photopic responses in both patients and subnormal scotopic responses in case 1. Multifocal electroretinography (mERG) revealed localized outer retinal...

  17. Photoreceptor atrophy in acute zonal occult outer retinopathy

    DEFF Research Database (Denmark)

    Zibrandtsen, N.; Munch, I.C.; Klemp, K.

    2008-01-01

    examined using optical coherence tomography (OCT), automated perimetry and electroretinography (ERG). Both patients demonstrated photoreceptor atrophy corresponding to partial or complete scotomata with reduced or extinct electroretinographic responses. Attenuation or complete loss of all the segments...... composing the photoreceptor layer was found by OCT. Full-field ERG revealed affection of the 30 Hz flicker responses and subnormal photopic responses in both patients and subnormal scotopic responses in case 1. Multifocal electroretinography (mERG) revealed localized outer retinal dysfunction. The field...

  18. Photoreceptor layer map using spectral-domain optical coherence tomography.

    Science.gov (United States)

    Lee, Ji Eun; Lim, Dae Won; Bae, Han Yong; Park, Hyun Jin

    2009-12-01

    To develop a novel method for analysis of the photoreceptor layer map (PLM) generated using spectral-domain optical coherence tomography (OCT). OCT scans were obtained from 20 eyes, 10 with macular holes (MH) and 10 with central serous chorioretinopathy (CSC) using the Macular Cube (512 x 128) protocol of the Cirrus HD-OCT (Carl Zeiss). The scanned data were processed using embedded tools of the advanced visualization. A partial thickness OCT fundus image of the photoreceptor layer was generated by setting the region of interest to a 50-microm thick layer that was parallel and adjacent to the retinal pigment epithelium. The resulting image depicted the photoreceptor layer as a map of the reflectivity in OCT. The PLM was compared with fundus photography, auto-fluorescence, tomography, and retinal thickness map. The signal from the photoreceptor layer of every OCT scan in each case was demonstrated as a single image of PLM in a fundus photograph fashion. In PLM images, detachment of the sensory retina is depicted as a hypo-reflective area, which represents the base of MH and serous detachment in CSC. Relative hypo-reflectivity, which was also noted at closed MH and at recently reattached retina in CSC, was associated with reduced signal from the junction between the inner and outer segments of photoreceptors in OCT images. Using PLM, changes in the area of detachment and reflectivity of the photoreceptor layer could be efficiently monitored. The photoreceptor layer can be analyzed as a map using spectral-domain OCT. In the treatment of both MH and CSC, PLM may provide new pathological information about the photoreceptor layer to expand our understanding of these diseases.

  19. Photoreceptor change and visual outcome after idiopathic epiretinal membrane removal with or without additional internal limiting membrane peeling.

    Science.gov (United States)

    Ahn, Seong Joon; Ahn, Jeeyun; Woo, Se Joon; Park, Kyu Hyung

    2014-01-01

    To compare the postoperative photoreceptor status and visual outcome after epiretinal membrane removal with or without additional internal limiting membrane (ILM) peeling. Medical records of 40 eyes from 37 patients undergoing epiretinal membrane removal with residual ILM peeling (additional ILM peeling group) and 69 eyes from 65 patients undergoing epiretinal membrane removal without additional ILM peeling (no additional peeling group) were reviewed. The length of defects in cone outer segment tips, inner segment/outer segment junction, and external limiting membrane line were measured using spectral domain optical coherence tomography images of the fovea before and at 1, 3, 6, and 12 months after the surgery. Cone outer segment tips and inner segment/outer segment junction line defects were most severe at postoperative 1 month and gradually restored at 12 months postoperatively. The cone outer segment tips line defect in the additional ILM peeling group was significantly greater than that in the no additional peeling group at postoperative 1 month (P = 0.006), and best-corrected visual acuity was significantly worse in the former group at the same month (P = 0.001). There was no significant difference in the defect size and best-corrected visual acuity at subsequent visits and recurrence rates between the two groups. Patients who received epiretinal membrane surgery without additional ILM peeling showed better visual and anatomical outcome than those with additional ILM peeling at postoperative 1 month. However, surgical outcomes were comparable between the two groups, thereafter. In terms of visual outcome and photoreceptor integrity, additional ILM peeling may not be an essential procedure.

  20. Modeling the Flexural Rigidity of Rod Photoreceptors

    Science.gov (United States)

    Haeri, Mohammad; Knox, Barry E.; Ahmadi, Aphrodite

    2013-01-01

    In vertebrate eyes, the rod photoreceptor has a modified cilium with an extended cylindrical structure specialized for phototransduction called the outer segment (OS). The OS has numerous stacked membrane disks and can bend or break when subjected to mechanical forces. The OS exhibits axial structural variation, with extended bands composed of a few hundred membrane disks whose thickness is diurnally modulated. Using high-resolution confocal microscopy, we have observed OS flexing and disruption in live transgenic Xenopus rods. Based on the experimental observations, we introduce a coarse-grained model of OS mechanical rigidity using elasticity theory, representing the axial OS banding explicitly via a spring-bead model. We calculate a bending stiffness of ∼105 nN⋅μm2, which is seven orders-of-magnitude larger than that of typical cilia and flagella. This bending stiffness has a quadratic relation to OS radius, so that thinner OS have lower fragility. Furthermore, we find that increasing the spatial frequency of axial OS banding decreases OS rigidity, reducing its fragility. Moreover, the model predicts a tendency for OS to break in bands with higher spring number density, analogous to the experimental observation that transgenic rods tended to break preferentially in bands of high fluorescence. We discuss how pathological alterations of disk membrane properties by mutant proteins may lead to increased OS rigidity and thus increased breakage, ultimately contributing to retinal degeneration. PMID:23442852

  1. Derivation of Traceable and Transplantable Photoreceptors from Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Sarah Decembrini

    2014-06-01

    Full Text Available Retinal degenerative diseases resulting in the loss of photoreceptors are one of the major causes of blindness. Photoreceptor replacement therapy is a promising treatment because the transplantation of retina-derived photoreceptors can be applied now to different murine retinopathies to restore visual function. To have an unlimited source of photoreceptors, we derived a transgenic embryonic stem cell (ESC line in which the Crx-GFP transgene is expressed in photoreceptors and assessed the capacity of a 3D culture protocol to produce integration-competent photoreceptors. This culture system allows the production of a large number of photoreceptors recapitulating the in vivo development. After transplantation, integrated cells showed the typical morphology of mature rods bearing external segments and ribbon synapses. We conclude that a 3D protocol coupled with ESCs provides a safe and renewable source of photoreceptors displaying a development and transplantation competence comparable to photoreceptors from age-matched retinas.

  2. The cone-dominant retina and the inner ear of zebrafish express the ortholog of CLRN1, the causative gene of human Usher syndrome type 3A.

    Science.gov (United States)

    Phillips, Jennifer B; Västinsalo, Hanna; Wegner, Jeremy; Clément, Aurélie; Sankila, Eeva-Marja; Westerfield, Monte

    2013-12-01

    Clarin-1 (CLRN1) is the causative gene in Usher syndrome type 3A, an autosomal recessive disorder characterized by progressive vision and hearing loss. CLRN1 encodes Clarin-1, a glycoprotein with homology to the tetraspanin family of proteins. Previous cell culture studies suggest that Clarin-1 localizes to the plasma membrane and interacts with the cytoskeleton. Mouse models demonstrate a role for the protein in mechanosensory hair bundle integrity, but the function of Clarin-1 in hearing remains unclear. Even less is known of its role in vision, because the Clrn1 knockout mouse does not exhibit a retinal phenotype and expression studies in murine retinas have provided conflicting results. Here, we describe cloning and expression analysis of the zebrafish clrn1 gene, and report protein localization of Clarin-1 in auditory and visual cells from embryonic through adult stages. We detect clrn1 transcripts as early as 24h post-fertilization, and expression is maintained through adulthood. In situ hybridization experiments show clrn1 transcripts enriched in mechanosensory hair cells and supporting cells of the inner ear and lateral line organ, photoreceptors, and cells of the inner retina. In mechanosensory hair cells, Clarin-1 is polarized to the apical cell body and the synapses. In the retina, Clarin-1 localizes to lateral cell contacts between photoreceptors and is associated with the outer limiting membrane and subapical processes emanating from Müller glial cells. We also find Clarin-1 protein in the outer plexiform, inner nuclear and ganglion cell layers of the retina. Given the importance of Clarin-1 function in the human retina, it is imperative to find an animal model with a comparable requirement. Our data provide a foundation for exploring the role of Clarin-1 in retinal cell function and survival in a diurnal, cone-dominant species. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Laser induced photoreceptor damage and recovery in the high numerical aperture eye of the garter snake.

    Science.gov (United States)

    Zwick, H; Edsall, P; Stuck, B E; Wood, E; Elliott, R; Cheramie, R; Hacker, H

    2008-02-01

    The garter snake provides a unique model for in-vivo imaging of photoreceptor damage induced by laser retinal exposure. Laser thermal/mechanical retinal injury induced alterations in photoreceptor structure and leukocyte cellular behavior. Photoreceptors turned white, lost mode structure, and swelled; leukocyte activity was observed in the vicinity of photoreceptor cells. Non-thermal alterations were identified with a bio-tag for oxidative stress. Mechanisms of photoreceptor recovery and replacement were observed and evaluated for active cytoskeletal systems by using an anti-actin tag that could detect the presence of active cytoskeletal systems resident in photoreceptors as well as other retinal systems.

  4. Partial reconstitution of photoreceptor cGMP phosphodiesterase characteristics in cGMP phosphodiesterase-5.

    Science.gov (United States)

    Granovsky, A E; Artemyev, N O

    2001-06-15

    Photoreceptor cGMP phosphodiesterases (PDE6) are uniquely qualified to serve as effector enzymes in the vertebrate visual transduction cascade. In the dark-adapted photoreceptors, the activity of PDE6 is blocked via tight association with the inhibitory gamma-subunits (Pgamma). The Pgamma block is removed in the light-activated PDE6 by the visual G protein, transducin. Transducin-activated PDE6 exhibits an exceptionally high catalytic rate of cGMP hydrolysis ensuring high signal amplification. To identify the structural determinants for the inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related cyclic GMP-specific, cGMP-binding PDE. PDE5 is insensitive to Pgamma and has a more than 100-fold lower k(cat) for cGMP hydrolysis. Our mutational analysis of chimeric PDE5/PDE6alpha' enzymes revealed that the inhibitory interaction of cone PDE6 catalytic subunits (PDE6alpha') with Pgamma is mediated primarily by three hydrophobic residues at the entry to the catalytic pocket, Met(758), Phe(777), and Phe(781). The maximal catalytic rate of PDE5 was enhanced by at least 10-fold with substitutions of PDE6alpha'-specific glycine residues for the corresponding PDE5 alanine residues, Ala(608) and Ala(612). The Gly residues are adjacent to the highly conserved metal binding motif His-Asn-X-X-His, which is essential for cGMP hydrolysis. Our results suggest that the unique Gly residues allow the PDE6 metal binding site to adopt a more favorable conformation for cGMP hydrolysis.

  5. Photoreceptor Outer Segment on Internal Limiting Membrane after Macular Hole Surgery: Implications for Pathogenesis.

    Science.gov (United States)

    Grinton, Michael E; Sandinha, Maria T; Steel, David H W

    2015-01-01

    This report presents a case, which highlights key principles in the pathophysiology of macular holes. It has been hypothesized that anteroposterior (AP) and tangential vitreous traction on the fovea are the primary underlying factors causing macular holes [Nischal and Pearson; in Kanski and Bowling: Clinical Ophthalmology: A Systemic Approach, 2011, pp 629-631]. Spectral domain optical coherence tomography (OCT) has subsequently corroborated this theory in part but shown that AP vitreofoveal traction is the more common scenario [Steel and Lotery: Eye 2013;27:1-21]. This study was conducted as a single case report. A 63-year old female presented to her optician with blurred and distorted vision in her left eye. OCT showed a macular hole with a minimum linear diameter of 370 µm, with persistent broad vitreofoveal attachment on both sides of the hole edges. The patient underwent combined left phacoemulsification and pars plana vitrectomy, internal limiting membrane (ILM) peel and gas injection. The ILM was examined by electron microscopy and showed the presence of a cone outer segment on the retinal side. Post-operative OCT at 11 weeks showed a closed hole with recovery of the foveal contour and good vision. Our case shows the presence of a photoreceptor outer segment on the retinal side of the ILM and reinforces the importance of tangential traction in the development of some macula holes. The case highlights the theory of transmission of inner retinal forces to the photoreceptors via Müller cells and how a full thickness macular hole defect can occur in the absence of AP vitreomacular traction.

  6. Photoreceptor spectral sensitivity in the bumblebee, Bombus impatiens (Hymenoptera: Apidae.

    Directory of Open Access Journals (Sweden)

    Peter Skorupski

    Full Text Available The bumblebee Bombus impatiens is increasingly used as a model in comparative studies of colour vision, or in behavioural studies relying on perceptual discrimination of colour. However, full spectral sensitivity data on the photoreceptor inputs underlying colour vision are not available for B. impatiens. Since most known bee species are trichromatic, with photoreceptor spectral sensitivity peaks in the UV, blue and green regions of the spectrum, data from a related species, where spectral sensitivity measurements have been made, are often applied to B impatiens. Nevertheless, species differences in spectral tuning of equivalent photoreceptor classes may result in peaks that differ by several nm, which may have small but significant effects on colour discrimination ability. We therefore used intracellular recording to measure photoreceptor spectral sensitivity in B. impatiens. Spectral peaks were estimated at 347, 424 and 539 nm for UV, blue and green receptors, respectively, suggesting that this species is a UV-blue-green trichromat. Photoreceptor spectral sensitivity peaks are similar to previous measurements from Bombus terrestris, although there is a significant difference in the peak sensitivity of the blue receptor, which is shifted in the short wave direction by 12-13 nm in B. impatiens compared to B. terrestris.

  7. Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.

    Science.gov (United States)

    Thomas, Biju B; Zhu, Danhong; Zhang, Li; Thomas, Padmaja B; Hu, Yuntao; Nazari, Hossein; Stefanini, Francisco; Falabella, Paulo; Clegg, Dennis O; Hinton, David R; Humayun, Mark S

    2016-05-01

    To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.

  8. CONE BIOPSY IN PREGNANCY*

    African Journals Online (AJOL)

    1 Mei 1971. S.-A. TYDSKRIF VIR OBSTETRIE EN GINEKOLOGIE. CONE BIOPSY ... of the abnormal cervix in pregnancy is also no longer in question following the .... the concept of cancer prophylaxis to the majority of women, many of whom ...

  9. Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses.

    Science.gov (United States)

    Johnson, Jerry E; Perkins, Guy A; Giddabasappa, Anand; Chaney, Shawntay; Xiao, Weimin; White, Andrew D; Brown, Joshua M; Waggoner, Jenna; Ellisman, Mark H; Fox, Donald A

    2007-06-15

    In conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles. Central retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted. Confocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes uniformly and intensely

  10. Usher protein functions in hair cells and photoreceptors.

    Science.gov (United States)

    Cosgrove, Dominic; Zallocchi, Marisa

    2014-01-01

    The 10 different genes associated with the deaf/blind disorder, Usher syndrome, encode a number of structurally and functionally distinct proteins, most expressed as multiple isoforms/protein variants. Functional characterization of these proteins suggests a role in stereocilia development in cochlear hair cells, likely owing to adhesive interactions in hair bundles. In mature hair cells, homodimers of the Usher cadherins, cadherin 23 and protocadherin 15, interact to form a structural fiber, the tip link, and the linkages that anchor the taller stereocilia's actin cytoskeleton core to the shorter adjacent stereocilia and the elusive mechanotransduction channels, explaining the deafness phenotype when these molecular interactions are perturbed. The conundrum is that photoreceptors lack a synonymous mechanotransduction apparatus, and so a common theory for Usher protein function in the two neurosensory cell types affected in Usher syndrome is lacking. Recent evidence linking photoreceptor cell dysfunction in the shaker 1 mouse model for Usher syndrome to light-induced protein translocation defects, combined with localization of an Usher protein interactome at the periciliary region of the photoreceptors suggests Usher proteins might regulate protein trafficking between the inner and outer segments of photoreceptors. A distinct Usher protein complex is trafficked to the ribbon synapses of hair cells, and synaptic defects have been reported in Usher mutants in both hair cells and photoreceptors. This review aims to clarify what is known about Usher protein function at the synaptic and apical poles of hair cells and photoreceptors and the prospects for identifying a unifying pathobiological mechanism to explain deaf/blindness in Usher syndrome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. The role of 11-cis-retinyl esters in vertebrate cone vision.

    Science.gov (United States)

    Babino, Darwin; Perkins, Brian D; Kindermann, Aljoscha; Oberhauser, Vitus; von Lintig, Johannes

    2015-01-01

    A cycle of cis-to-trans isomerization of the chromophore is intrinsic to vertebrate vision where rod and cone photoreceptors mediate dim- and bright-light vision, respectively. Daylight illumination can greatly exceed the rate at which the photoproduct can be recycled back to the chromophore by the canonical visual cycle. Thus, an additional supply pathway(s) must exist to sustain cone-dependent vision. Two-photon microscopy revealed that the eyes of the zebrafish (Danio rerio) contain high levels of 11-cis-retinyl esters (11-REs) within the retinal pigment epithelium. HPLC analyses demonstrate that 11-REs are bleached by bright light and regenerated in the dark. Pharmacologic treatment with all-trans-retinylamine (Ret-NH2), a potent and specific inhibitor of the trans-to-cis reisomerization reaction of the canonical visual cycle, impeded the regeneration of 11-REs. Intervention with 11-cis-retinol restored the regeneration of 11-REs in the presence of all-trans-Ret-NH2. We used the XOPS:mCFP transgenic zebrafish line with a functional cone-only retina to directly demonstrate that this 11-RE cycle is critical to maintain vision under bright-light conditions. Thus, our analyses reveal that a dark-generated pool of 11-REs helps to supply photoreceptors with the chromophore under the varying light conditions present in natural environments. © FASEB.

  12. Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress.

    Science.gov (United States)

    Barben, Maya; Ail, Divya; Storti, Federica; Klee, Katrin; Schori, Christian; Samardzija, Marijana; Michalakis, Stylianos; Biel, Martin; Meneau, Isabelle; Blaser, Frank; Barthelmes, Daniel; Grimm, Christian

    2018-04-17

    Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients.

  13. Idiopathic multifocal choroiditis/punctate inner choroidopathy with acute photoreceptor loss or dysfunction out of proportion to clinically visible lesions

    Science.gov (United States)

    Munk, Marion R.; Jung, Jesse J.; Biggee, Kristin; Tucker, William R.; Sen, H. Nida; Schmidt-Erfurth, Ursula; Fawzi, Amani A.; Jampol, Lee M.

    2014-01-01

    Purpose To report acute/subacute vision loss and paracentral scotomata in patients with idiopathic multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) due to large zones of acute photoreceptor attenuation surrounding the chorioretinal lesions. Methods Multimodal-imaging case-series Results Six females and 2 males were included (mean age 31.5±5.8 years). Vision ranged from 20/20-1 to hand motion (mean 20/364). SD-OCT demonstrated extensive attenuation of the external limiting membrane (ELM), ellipsoid and interdigitation zones, adjacent to the visible MFC/PIC lesions. The corresponding areas were hyperautofluorescent on fundus-autofluorescence (FAF), and were associated with corresponding visual field defects. Full-field ERG (available in 3 cases) showed markedly decreased cone/rod response and multifocal ERG revealed reduced amplitudes and increased implicit times in 2 cases. Three patients received no treatment, the remaining were treated with oral corticosteroids (n=4), oral acyclovir/valacyclovir (n=2), intravitreal/posterior subtenon triamcinolone-acetate (n=3) and anti-VEGF (n=2). Visual recovery occurred in only 3 cases, of whom 2 were treated. Varying morphological recovery was found in 6 cases, associated with decrease in hyperautofluorescence on FAF. Conclusions MFC/PIC can present with transient or permanent central photoreceptor attenuation/loss. This presentation is likely a variant of MFC/PIC with chorioretinal atrophy. Associated changes are best evaluated using multimodal imaging. PMID:25322466

  14. Ejecta evolution during cone impact

    KAUST Repository

    Marston, Jeremy

    2014-07-07

    We present findings from an experimental investigation into the impact of solid cone-shaped bodies onto liquid pools. Using a variety of cone angles and liquid physical properties, we show that the ejecta formed during the impact exhibits self-similarity for all impact speeds for very low surface tension liquids, whilst for high-surface tension liquids similarity is only achieved at high impact speeds. We find that the ejecta tip can detach from the cone and that this phenomenon can be attributed to the air entrainment phenomenon. We analyse of a range of cone angles, including some ogive cones, and impact speeds in terms of the spatiotemporal evolution of the ejecta tip. Using superhydrophobic cones, we also examine the entry of cones which entrain an air layer.

  15. Cone Algorithm of Spinning Vehicles under Dynamic Coning Environment

    Directory of Open Access Journals (Sweden)

    Shuang-biao Zhang

    2015-01-01

    Full Text Available Due to the fact that attitude error of vehicles has an intense trend of divergence when vehicles undergo worsening coning environment, in this paper, the model of dynamic coning environment is derived firstly. Then, through investigation of the effect on Euler attitude algorithm for the equivalency of traditional attitude algorithm, it is found that attitude error is actually the roll angle error including drifting error and oscillating error, which is induced directly by dynamic coning environment and further affects the pitch angle and yaw angle through transferring. Based on definition of the cone frame and cone attitude, a cone algorithm is proposed by rotation relationship to calculate cone attitude, and the relationship between cone attitude and Euler attitude of spinning vehicle is established. Through numerical simulations with different conditions of dynamic coning environment, it is shown that the induced error of Euler attitude fluctuates by the variation of precession and nutation, especially by that of nutation, and the oscillating frequency of roll angle error is twice that of pitch angle error and yaw angle error. In addition, the rotation angle is more competent to describe the spinning process of vehicles under coning environment than Euler angle gamma, and the real pitch angle and yaw angle are calculated finally.

  16. Lateral interactions in the photoreceptor membrane: a NMR study

    International Nuclear Information System (INIS)

    Mollevanger, L.C.P.J.

    1987-01-01

    The photoreceptor membrane has an exceptionally high content of polyunsaturated fatty acyl chains combined with a high amount of phosphatidyl ethanolamine. It is situated in a cell organelle, the rod outer segment, with a high biological activity in which controlable trans-membrane currents of different ions play an important role. These characteristics make it a very interesting biological membrane to search for the existence of non-bilayer structures. Therefore in this thesis a detailed study of the polymorphic phase behaviour of the rod outer segment photoreceptor lipids was undertaken, concerning modulation of the polymorphic phase behaviour of photoreceptor membrane lipids by divalent cations and temperature, polymorphism of the individual phospholipid classes phosphatidylethanolamine and phosphatidylserine and effects of cholesterol, bilayer stabilization by (rhod)opsin. Morphologically intact rod outer segment possesses a large magnetic anisotropy. This property is used to obtain 31 P-NMR of oriented photoreceptor membranes which allows spectral analysis and identification of individual phospholipid classes, and allows to study lateral lipid diffusion in intact disk membranes. The power of high resolution solid state 13 C-NMR to study the conformation of the chromophore in rhodopsin is demonstrated. (Auth.)

  17. Cubozoan genome illuminates functional diversification of opsins and photoreceptor evolution

    Czech Academy of Sciences Publication Activity Database

    Liegertová, Michaela; Pergner, Jiří; Kozmiková, Iryna; Fabian, Peter; Pombinho, António R.; Strnad, Hynek; Pačes, Jan; Vlček, Čestmír; Bartůněk, Petr; Kozmik, Zbyněk

    2015-01-01

    Roč. 5, Jul 8 (2015) ISSN 2045-2322 R&D Projects: GA ČR GAP305/10/2141; GA MŠk LO1220 Institutional support: RVO:68378050 Keywords : Cubozoan genome * opsins * photoreceptor * evolution Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.228, year: 2015

  18. Atypical retinal pigment epithelial defects with retained photoreceptor layers

    DEFF Research Database (Denmark)

    Giannakaki-Zimmermann, Helena; Querques, Giuseppe; Munch, Inger Christine

    2017-01-01

    BACKGROUND: To report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers. METHODS: Multimodal imaging case-series evaluating the course...

  19. Protein and signaling networks in vertebrate photoreceptor cells

    Directory of Open Access Journals (Sweden)

    Karl-Wilhelm eKoch

    2015-11-01

    Full Text Available Vertebrate photoreceptor cells are exquisite light detectors operating under very dim and bright illumination. The photoexcitation and adaptation machinery in photoreceptor cells consists of protein complexes that can form highly ordered supramolecular structures and control the homeostasis and mutual dependence of the secondary messengers cGMP and Ca2+. The visual pigment in rod photoreceptors, the G protein-coupled receptor rhodopsin is organized in tracks of dimers thereby providing a signaling platform for the dynamic scaffolding of the G protein transducin. Illuminated rhodopsin is turned off by phosphorylation catalyzed by rhodopsin kinase GRK1 under control of Ca2+-recoverin. The GRK1 protein complex partly assembles in lipid raft structures, where shutting off rhodopsin seems to be more effective. Re-synthesis of cGMP is another crucial step in the recovery of the photoresponse after illumination. It is catalyzed by membrane bound sensory guanylate cyclases and is regulated by specific neuronal Ca2+-sensor proteins called GCAPs. At least one guanylate cyclase (ROS-GC1 was shown to be part of a multiprotein complex having strong interactions with the cytoskeleton and being controlled in a multimodal Ca2+-dependent fashion. The final target of the cGMP signaling cascade is a cyclic nucleotide-gated channel that is a hetero-oligomeric protein located in the plasma membrane and interacting with accessory proteins in highly organized microdomains. We summarize results and interpretations of findings related to the inhomogeneous organization of signaling units in photoreceptor outer segments.

  20. Light cone thermodynamics

    Science.gov (United States)

    De Lorenzo, Tommaso; Perez, Alejandro

    2018-02-01

    We show that null surfaces defined by the outgoing and infalling wave fronts emanating from and arriving at a sphere in Minkowski spacetime have thermodynamical properties that are in strict formal correspondence with those of black hole horizons in curved spacetimes. Such null surfaces, made of pieces of light cones, are bifurcate conformal Killing horizons for suitable conformally stationary observers. They can be extremal and nonextremal depending on the radius of the shining sphere. Such conformal Killing horizons have a constant light cone (conformal) temperature, given by the standard expression in terms of the generalization of surface gravity for conformal Killing horizons. Exchanges of conformally invariant energy across the horizon are described by a first law where entropy changes are given by 1 /(4 ℓp2) of the changes of a geometric quantity with the meaning of horizon area in a suitable conformal frame. These conformal horizons satisfy the zeroth to the third laws of thermodynamics in an appropriate way. In the extremal case they become light cones associated with a single event; these have vanishing temperature as well as vanishing entropy.

  1. Pupillometer-based objective chromatic perimetry in normal eyes and patients with retinal photoreceptor dystrophies.

    Science.gov (United States)

    Skaat, Alon; Sher, Ifat; Kolker, Andrew; Elyasiv, Sivan; Rosenfeld, Elkana; Mhajna, Mohamad; Melamed, Shlomo; Belkin, Michael; Rotenstreich, Ygal

    2013-04-17

    To evaluate a novel objective perimetry using multifocal chromatic pupil light reflex in normal participants and patients with photoreceptor dysfunction, and to relate this new technique with subjective dark-adapted chromatic Goldmann perimetry. Thirty-two eyes of 17 retinitis pigmentosa (RP) or cone-rod dystrophy patients and 20 eyes of 12 healthy individuals were tested. A computerized infrared video pupillometer was used to record changes in pupil diameter in response to short- and long-wavelength stimuli (peak 485 and 640 nm, respectively; light intensity 40 cd/m(2)) at 13 different points of the 30° visual field (VF), under background illumination of 2.7 cd/m(2). The pupillary response (PR) of patients was compared with PR obtained from normal control participants. In 11 patients, the pupillary responses were also compared with their findings on dark-adapted chromatic Goldmann perimetry. Significantly reduced pupillary responses were obtained in RP patients in response to the short-wavelength stimulus in nearly all perimetric locations (P chromatic Goldmann perimetry. In all patients that were tested by the chromatic Goldmann, minimal PR was recorded in areas that were nondetected in the chromatic Goldmann perimetry. This study demonstrates the potential feasibility of using pupillometer-based chromatic perimetry for objectively assessing VF defects and retinal function in patients with retinal dystrophies. (ClinicalTrials.gov number, NCT01021982.).

  2. Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system.

    Science.gov (United States)

    Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

    2016-03-17

    The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.

  3. Fundus Autofluorescence and Photoreceptor Cell Rosettes in Mouse Models

    Science.gov (United States)

    Flynn, Erin; Ueda, Keiko; Auran, Emily; Sullivan, Jack M.; Sparrow, Janet R.

    2014-01-01

    Purpose. This study was conducted to study correlations among fundus autofluorescence (AF), RPE lipofuscin accumulation, and photoreceptor cell degeneration and to investigate the structural basis of fundus AF spots. Methods. Fundus AF images (55° lens; 488-nm excitation) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired in pigmented Rdh8−/−/Abca4−/− mice (ages 1–9 months) with a confocal scanning laser ophthalmoscope (cSLO). For quantitative fundus AF (qAF), gray levels (GLs) were calibrated to an internal fluorescence reference. Retinal bisretinoids were measured by quantitative HPLC. Histometric analysis of outer nuclear layer (ONL) thicknesses was performed, and cryostat sections of retina were examined by fluorescence microscopy. Results. Quantified A2E and qAF intensities increased until age 4 months in the Rdh8−/−/Abca4−/− mice. The A2E levels declined after 4 months of age, but qAF intensity values continued to rise. The decline in A2E levels in the Rdh8−/−/Abca4−/− mice paralleled reduced photoreceptor cell viability as reflected in ONL thinning. Hyperautofluorescent puncta in fundus AF images corresponded to photoreceptor cell rosettes in SD-OCT images and histological sections stained with hematoxylin and eosin. The inner segment/outer segment–containing core of the rosette emitted an autofluorescence detected by fluorescence microscopy. Conclusions. When neural retina is disordered, AF from photoreceptor cells can contribute to noninvasive fundus AF images. Hyperautofluorescent puncta in fundus AF images are attributable, in at least some cases, to photoreceptor cell rosettes. PMID:25015357

  4. Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig

    DEFF Research Database (Denmark)

    Klassen, H; Kiilgaard, Jens Folke; Warfvinge, K

    2012-01-01

    Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig....... Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression. Results. Results confirm the survival...

  5. Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells.

    Science.gov (United States)

    el-Amraoui, A; Sahly, I; Picaud, S; Sahel, J; Abitbol, M; Petit, C

    1996-08-01

    Usher syndrome type 1 (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepancy, the expression of myosin VIIA in retinal cells was analyzed in human and mouse during embryonic development and adult life. In the human embryo, myosin VIIA was present first in the pigment epithelium cells, and later in these cells as well as in the photoreceptor cells. In the adult human retina, myosin VIIA was present in both cell types. In contrast, in mouse, only pigment epithelium cells expressed the protein throughout development and adult life. Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expressed the protein in amphibians, avians and primates. These observations suggest that retinitis pigmentosa of USH1B results from a primary rod and cone defect. The USH1B/shaker-1 paradigm illustrates a species-specific cell pattern of gene expression as a possible cause for the discrepancy between phenotypes involving defective orthologous genes in man and mouse. Interestingly, in the photoreceptor cells, myosin VIIA is mainly localized in the inner and base of outer segments as well as in the synaptic ending region where it is co-localized with the synaptic vesicles. Therefore, we suggest that myosin VIIA might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks.

  6. Null cone superspace supergravity

    International Nuclear Information System (INIS)

    Downes-Martin, S.G.

    1980-03-01

    The null cone formalism is used to derive a 2(N-1) parameter family of constraints for O(N) extended superspace supergravity. The invariance groups of these constraints is analysed and is found to be [subgroup U submanifold] contains GL(4,R) for N = 1, the submanifold being eliminated for N > 1. The invariance group defines non-Weyl rotations on the superbein which combine to form Weyl transformations on the supertangent space metric. The invariance of the supergravity Lagrangian under these transformations is discussed. (Auth.)

  7. Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision.

    Science.gov (United States)

    Cao, Yan; Sarria, Ignacio; Fehlhaber, Katherine E; Kamasawa, Naomi; Orlandi, Cesare; James, Kiely N; Hazen, Jennifer L; Gardner, Matthew R; Farzan, Michael; Lee, Amy; Baker, Sheila; Baldwin, Kristin; Sampath, Alapakkam P; Martemyanov, Kirill A

    2015-09-23

    In the retina, rod and cone photoreceptors form distinct connections with different classes of downstream bipolar cells. However, the molecular mechanisms responsible for their selective connectivity are unknown. Here we identify a cell-adhesion protein, ELFN1, to be essential for the formation of synapses between rods and rod ON-bipolar cells in the primary rod pathway. ELFN1 is expressed selectively in rods where it is targeted to the axonal terminals by the synaptic release machinery. At the synapse, ELFN1 binds in trans to mGluR6, the postsynaptic receptor on rod ON-bipolar cells. Elimination of ELFN1 in mice prevents the formation of synaptic contacts involving rods, but not cones, allowing a dissection of the contributions of primary and secondary rod pathways to retinal circuit function and vision. We conclude that ELFN1 is necessary for the selective wiring of rods into the primary rod pathway and is required for high sensitivity of vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The holographic entropy cone

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Ning [Institute for Quantum Information and Matter, California Institute of Technology,Pasadena, CA 91125 (United States); Walter Burke Institute for Theoretical Physics, California Institute of Technology,452-48, Pasadena, CA 91125 (United States); Nezami, Sepehr [Stanford Institute for Theoretical Physics, Stanford University,Stanford, CA 94305 (United States); Ooguri, Hirosi [Walter Burke Institute for Theoretical Physics, California Institute of Technology,452-48, Pasadena, CA 91125 (United States); Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa 277-8583 (Japan); Stoica, Bogdan [Walter Burke Institute for Theoretical Physics, California Institute of Technology,452-48, Pasadena, CA 91125 (United States); Sully, James [Theory Group, SLAC National Accelerator Laboratory, Stanford University,Menlo Park, CA 94025 (United States); Walter, Michael [Stanford Institute for Theoretical Physics, Stanford University,Stanford, CA 94305 (United States)

    2015-09-21

    We initiate a systematic enumeration and classification of entropy inequalities satisfied by the Ryu-Takayanagi formula for conformal field theory states with smooth holographic dual geometries. For 2, 3, and 4 regions, we prove that the strong subadditivity and the monogamy of mutual information give the complete set of inequalities. This is in contrast to the situation for generic quantum systems, where a complete set of entropy inequalities is not known for 4 or more regions. We also find an infinite new family of inequalities applicable to 5 or more regions. The set of all holographic entropy inequalities bounds the phase space of Ryu-Takayanagi entropies, defining the holographic entropy cone. We characterize this entropy cone by reducing geometries to minimal graph models that encode the possible cutting and gluing relations of minimal surfaces. We find that, for a fixed number of regions, there are only finitely many independent entropy inequalities. To establish new holographic entropy inequalities, we introduce a combinatorial proof technique that may also be of independent interest in Riemannian geometry and graph theory.

  9. The holographic entropy cone

    International Nuclear Information System (INIS)

    Bao, Ning; Nezami, Sepehr; Ooguri, Hirosi; Stoica, Bogdan; Sully, James; Walter, Michael

    2015-01-01

    We initiate a systematic enumeration and classification of entropy inequalities satisfied by the Ryu-Takayanagi formula for conformal field theory states with smooth holographic dual geometries. For 2, 3, and 4 regions, we prove that the strong subadditivity and the monogamy of mutual information give the complete set of inequalities. This is in contrast to the situation for generic quantum systems, where a complete set of entropy inequalities is not known for 4 or more regions. We also find an infinite new family of inequalities applicable to 5 or more regions. The set of all holographic entropy inequalities bounds the phase space of Ryu-Takayanagi entropies, defining the holographic entropy cone. We characterize this entropy cone by reducing geometries to minimal graph models that encode the possible cutting and gluing relations of minimal surfaces. We find that, for a fixed number of regions, there are only finitely many independent entropy inequalities. To establish new holographic entropy inequalities, we introduce a combinatorial proof technique that may also be of independent interest in Riemannian geometry and graph theory.

  10. The Retinal Pigment Epithelium: a Convenient Source of New Photoreceptor cells?

    Directory of Open Access Journals (Sweden)

    Shu-Zhen Wang

    2014-01-01

    Full Text Available Recent success in restoring visual function through photoreceptor replacement in mouse models of photoreceptor degeneration intensifies the need to generate or regenerate photoreceptor cells for the ultimate goal of using cell replacement therapy for blindness caused by photoreceptor degeneration. Current research on deriving new photoreceptors for replacement, as regenerative medicine in general, focuses on the use of embryonic stem cells and induced pluripotent stem (iPS cells to generate transplantable cells. Nonetheless, naturally occurring regeneration, such as wound healing, involves awakening cells at or near a wound site to produce new cells needed to heal the wound. Here we discuss the possibility of tweaking an ocular tissue, the retinal pigment epithelium (RPE, to produce photoreceptor cells in situ in the eye. Unlike the neural retina, the RPE in adult mammals maintains cell proliferation capability. Furthermore, progeny cells from RPE proliferation may differentiate into cells other than RPE. The combination of proliferation and plasticity opens a question of whether they could be channeled by a regulatory gene with pro-photoreceptor activity towards photoreceptor production. Studies using embryonic chick and transgenic mouse showed that indeed photoreceptor-like cells were produced in culture and in vivo in the eye using genedirected reprogramming of RPE cells, supporting the feasibility of using the RPE as a convenient source of new photoreceptor cells for in situ retinal repair without involving cell transplantation.

  11. NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP).

    Science.gov (United States)

    Schorderet, Daniel F; Escher, Pascal

    2009-11-01

    NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the "blue" S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (www.LOVD.nl/eye), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes.

  12. Review on resonance cone fields

    International Nuclear Information System (INIS)

    Ohnuma, Toshiro.

    1980-02-01

    Resonance cone fields and lower hybrid heating are reviewed in this report. The resonance cone fields were reported by Fisher and Gould, and they proposed the use of the measurement of resonance cones and structure as a diagnostic tool to determine the plasma density and electron temperature in magnetoplasma. After the resonance cone, a wave-like disturbance persists. Ohnuma et al. have measured bending, reflection and ducting of resonance cones in detail. The thermal modes in inhomogeneous magnetoplasma were seen. The reflection of thermal mode near an electron plasma frequency layer and an insulating plate has been observed. The non-linear effects of resonance cones is reported. Monochromatic electron beam produces the noise of broad band whistler mode. Lower hybrid waves have been the subject of propagation from the edge of plasma to the lower hybrid layer. Linear lower hybrid waves were studied. The lower hybrid and ion acoustic waves radiated from a point source were observed. The parametric decay of finite-extent, cold electron plasma waves was studied. The lower hybrid cone radiated from a point source going along magnetic field lines was observed. Several experimental data on the lower hybrid heating in tokamak devices have been reported. The theories on resonance cones and lower hybrid waves are introduced in this report. (Kato, T.)

  13. Plate Tearing by a Cone

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1997-01-01

    The present paper is concerned with steady-state plate tearing by a cone. This is a scenario where a cone is forced through a ductile metal plate with a constant lateral tip penetration in a motion in the plane of the plate. The considered process could be an idealisaton of the damage, which...... as for the out-of-plane reaction force....

  14. Responses of crayfish photoreceptor cells following intense light adaptation.

    Science.gov (United States)

    Cummins, D R; Goldsmith, T H

    1986-01-01

    After intense orange adapting exposures that convert 80% of the rhodopsin in the eye to metarhodopsin, rhabdoms become covered with accessory pigment and appear to lose some microvillar order. Only after a delay of hours or even days is the metarhodopsin replaced by rhodopsin (Cronin and Goldsmith 1984). After 24 h of dark adaptation, when there has been little recovery of visual pigment, the photoreceptor cells have normal resting potentials and input resistances, and the reversal potential of the light response is 10-15 mV (inside positive), unchanged from controls. The log V vs log I curve is shifted about 0.6 log units to the right on the energy axis, quantitatively consistent with the decrease in the probability of quantum catch expected from the lowered concentration of rhodopsin in the rhabdoms. Furthermore, at 24 h the photoreceptors exhibit a broader spectral sensitivity than controls, which is also expected from accumulations of metarhodopsin in the rhabdoms. In three other respects, however, the transduction process appears to be light adapted: The voltage responses are more phasic than those of control photoreceptors. The relatively larger effect (compared to controls) of low extracellular Ca++ (1 mmol/l EGTA) in potentiating the photoresponses suggests that the photoreceptors may have elevated levels of free cytoplasmic Ca++. The saturating depolarization is only about 30% as large as the maximal receptor potentials of contralateral, dark controls, and by that measure the log V-log I curve is shifted downward by 0.54 log units.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Does Apoptosis Regulate the Function of Retinal Photoreceptors?

    OpenAIRE

    Halaby, Reginald

    2012-01-01

    Apoptosis, or programmed cell death, is an integral component of developmental biology, embryology, and anatomy. All eukaryotic cells possess the molecular machinery necessary to execute apoptosis. However, dysregulated apoptosis in the form of too much or too little cell death results in diseases such as Alzheimer’s disease, autoimmune disorders, and cancer. It is postulated that apoptosis of the photoreceptors in the retina plays a vital role in mediating vision, and evidence is presented h...

  16. QCD on the light cone

    International Nuclear Information System (INIS)

    Brodsky, S.J.

    1992-09-01

    The quantization of gauge theory at fixed light-cone time τ = t - z/c provides new perspectives for solving non-perturbative problems in quantum chromodynamics. The light-cone Fock state expansion provides both a precise definition of the relativistic wavefunctions of hadrons as bound-states of quarks and gluons and a general calculus for predicting QCD processes at the amplitude level. Applications to exclusive processes and weak decay amplitudes are discussed. The problem of computing the hadronic spectrum and the corresponding light-cone wavefunctions of QCD in one space and one time dimension has been successfully reduced to the diagonalization of a discrete representation of the light-cone Hamiltonian. The problems confronting the solution of gauge theories in 3 + 1 dimensions in the light-cone quantization formalism,, including zero modes and non-perturbative renormalization, are reviewed

  17. Chemically induced and light-independent cryptochrome photoreceptor activation.

    Science.gov (United States)

    Rosenfeldt, Gesa; Viana, Rafael Muñoz; Mootz, Henning D; von Arnim, Albrecht G; Batschauer, Alfred

    2008-01-01

    The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N-terminal photosensory domain mediates dimerization, and the unique C-terminal extension (CCT) mediates signaling. We made use of the human FK506-binding protein (FKBP) that binds with high affinity to rapamycin or rapamycin analogs (rapalogs). The FKBP-rapamycin complex is recognized by another protein, FRB, thus allowing rapamycin-induced dimerization of two target proteins. Here we demonstrate by bioluminescence resonance energy transfer (BRET) assays the applicability of this regulated dimerization system to plants. Furthermore, we show that fusion proteins consisting of the C-terminal domain of Arabidopsis cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells specifically induce the expression of cryptochrome-controlled reporter and endogenous genes in darkness upon incubation with the rapalog. These results demonstrate that the activation of cryptochrome signal transduction can be chemically induced in a dose-dependent fashion and uncoupled from the light signal, and provide the groundwork for gain-of-function experiments to study specifically the role of photoreceptors in darkness or in signaling cross-talk even under light conditions that activate members of all photoreceptor families.

  18. Retinal Photoreceptors and Microvascular Changes in Prediabetes Measured with Adaptive Optics (rtx1™: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Anna Zaleska-Żmijewska

    2017-01-01

    Full Text Available Background. Patients with prediabetes are at risk for diabetes, cardiovascular events, and microvascular complications. The rtx1 (Imagine Eyes, France permits early detection of changes in the retinal photoreceptors and vessels. Objective. Cone parameters and retinal microvasculature were analyzed with the rtx1 in 12 prediabetic patients and 22 healthy subjects. The analysis was based on cone density (DM, interphotoreceptor distance (SM, cone packing regularity, and retinal vessel parameters: wall thickness, lumen diameter (LD, wall-to-lumen ratio (WLR, and cross-sectional area of the vascular wall. Results. DM in the prediabetic group was not significantly lower than that in the control group (18,935 ± 1713 cells/mm2 and 19,900 ± 2375 cells/mm2, respectively; p=0.0928. The LD and WLR means differed significantly between the prediabetic and the control groups (LD 94.3 ± 10.9 versus 101.2 ± 15, p=0.022; WLR 0.29 ± 0.05 versus 0.22 ± 0.03, p<0.05. A multivariate regression analysis showed that the WLR was significantly correlated with BMI and total cholesterol. Conclusions. Abnormalities found in rtx1 examinations indicated early signs of arteriolar dysfunction, prior to impaired glucose tolerance progressing to diabetes. The rtx1 retinal image analysis offers noninvasive measurement of early changes in the vasculature that routine clinical examination cannot detect.

  19. Ordered cones and approximation

    CERN Document Server

    Keimel, Klaus

    1992-01-01

    This book presents a unified approach to Korovkin-type approximation theorems. It includes classical material on the approximation of real-valuedfunctions as well as recent and new results on set-valued functions and stochastic processes, and on weighted approximation. The results are notonly of qualitative nature, but include quantitative bounds on the order of approximation. The book is addressed to researchers in functional analysis and approximation theory as well as to those that want to applythese methods in other fields. It is largely self- contained, but the readershould have a solid background in abstract functional analysis. The unified approach is based on a new notion of locally convex ordered cones that are not embeddable in vector spaces but allow Hahn-Banach type separation and extension theorems. This concept seems to be of independent interest.

  20. The UVR8 UV-B Photoreceptor: Perception, Signaling and Response

    Science.gov (United States)

    Tilbrook, Kimberley; Arongaus, Adriana B.; Binkert, Melanie; Heijde, Marc; Yin, Ruohe; Ulm, Roman

    2013-01-01

    Ultraviolet-B radiation (UV-B) is an intrinsic part of sunlight that is accompanied by significant biological effects. Plants are able to perceive UV-B using the UV-B photoreceptor UVR8 which is linked to a specific molecular signaling pathway and leads to UV-B acclimation. Herein we review the biological process in plants from initial UV-B perception and signal transduction through to the known UV-B responses that promote survival in sunlight. The UVR8 UV-B photoreceptor exists as a homodimer that instantly monomerises upon UV-B absorption via specific intrinsic tryptophans which act as UV-B chromophores. The UVR8 monomer interacts with COP1, an E3 ubiquitin ligase, initiating a molecular signaling pathway that leads to gene expression changes. This signaling output leads to UVR8-dependent responses including UV-B-induced photomorphogenesis and the accumulation of UV-B-absorbing flavonols. Negative feedback regulation of the pathway is provided by the WD40-repeat proteins RUP1 and RUP2, which facilitate UVR8 redimerization, disrupting the UVR8-COP1 interaction. Despite rapid advancements in the field of recent years, further components of UVR8 UV-B signaling are constantly emerging, and the precise interplay of these and the established players UVR8, COP1, RUP1, RUP2 and HY5 needs to be defined. UVR8 UV-B signaling represents our further understanding of how plants are able to sense their light environment and adjust their growth accordingly. PMID:23864838

  1. Evidence for RPE65-independent vision in the cone-dominated zebrafish retina.

    Science.gov (United States)

    Schonthaler, Helia B; Lampert, Johanna M; Isken, Andrea; Rinner, Oliver; Mader, Andreas; Gesemann, Matthias; Oberhauser, Vitus; Golczak, Marcin; Biehlmaier, Oliver; Palczewski, Krzysztof; Neuhauss, Stephan C F; von Lintig, Johannes

    2007-10-01

    An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.

  2. Cone and Seed Maturation of Southern Pines

    Science.gov (United States)

    James P. Barnett

    1976-01-01

    If slightly reduced yields and viability are acceptable, loblolly and slash cone collections can begin 2 to 3 weeks before maturity if the cones are stored before processing. Longleaf(P. palestris Mill.) pine cones should be collected only when mature, as storage decreased germination of seeds from immature cones. Biochemical analyses to determine reducing sugar...

  3. Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in retina.

    Science.gov (United States)

    Suzuki-Kerr, Haruna; Iwagawa, Toshiro; Sagara, Hiroshi; Mizota, Atsushi; Suzuki, Yutaka; Watanabe, Sumiko

    2018-06-01

    During development of the retina, common retinal progenitor cells give rise to six classes of neurons that subsequently further diversify into more than 55 subtypes of neuronal subtypes. Here, we have investigated the expression and function of Fezf2, Fez zinc finger family of protein, in the developing mouse retina. Expression of Fezf2 transcripts was strongly observed in the embryonic retinal progenitors at E14.5 and declined quickly in subsequent development of retina. Then, in postnatal stage at around day 8, Fezf2 was transiently expressed then declined again. Loss-of-function analysis using retinas from mice in which Fezf2 coding region was substituted with β-galactosidase showed that Fezf2 is expressed in a subset of cone OFF bipolar cells and required for their differentiation. Using electroretinogram, we found that Fezf2 knockout retina exhibited significantly reduced photopic b-wave, suggesting functional abnormality of cone ON bipolar cells. Furthermore, reduced expression of synaptic protein Trpm1 and structural alteration of ON bipolar cell invagination, both of which affected cone photoreceptor terminal synaptic activity, was identified by transmission electron microscopy and immunohistochemistry, respectively. Taken together, our results show that Fezf2 is indispensable in differentiation of bipolar precursors into cone OFF bipolar cells and in functional maturation of cone ON bipolar cells during development of mouse retina. These results contribute to our understanding of how diversity of neuronal subtypes and hence specificity of neuronal connections are established in the retina by intrinsic cues. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. UV-sensitive photoreceptor protein OPN5 in humans and mice.

    Science.gov (United States)

    Kojima, Daisuke; Mori, Suguru; Torii, Masaki; Wada, Akimori; Morishita, Rika; Fukada, Yoshitaka

    2011-01-01

    A variety of animal species utilize the ultraviolet (UV) component of sunlight as their environmental cues, whereas physiological roles of UV photoreception in mammals, especially in human beings, remain open questions. Here we report that mouse neuropsin (OPN5) encoded by the Opn5 gene exhibited an absorption maximum (λmax) at 380 nm when reconstituted with 11-cis-retinal. Upon UV-light illumination, OPN5 was converted to a blue-absorbing photoproduct (λmax 470 nm), which was stable in the dark and reverted to the UV-absorbing state by the subsequent orange light illumination, indicating its bistable nature. Human OPN5 also had an absorption maximum at 380 nm with spectral properties similar to mouse OPN5, revealing that OPN5 is the first and hitherto unknown human opsin with peak sensitivity in the UV region. OPN5 was capable of activating heterotrimeric G protein Gi in a UV-dependent manner. Immuno-blotting analyses of mouse tissue extracts identified the retina, the brain and, unexpectedly, the outer ears as the major sites of OPN5 expression. In the tissue sections of mice, OPN5 immuno-reactivities were detected in a subset of non-rod/non-cone retinal neurons as well as in the epidermal and muscle cells of the outer ears. Most of these OPN5-immuno-reactivities in mice were co-localized with positive signals for the alpha-subunit of Gi. These results demonstrate the first example of UV photoreceptor in human beings and strongly suggest that OPN5 triggers a UV-sensitive Gi-mediated signaling pathway in the mammalian tissues.

  5. In silico modeling of epigenetic-induced changes in photoreceptor cis-regulatory elements.

    Science.gov (United States)

    Hossain, Reafa A; Dunham, Nicholas R; Enke, Raymond A; Berndsen, Christopher E

    2018-01-01

    DNA methylation is a well-characterized epigenetic repressor of mRNA transcription in many plant and vertebrate systems. However, the mechanism of this repression is not fully understood. The process of transcription is controlled by proteins that regulate recruitment and activity of RNA polymerase by binding to specific cis-regulatory sequences. Cone-rod homeobox (CRX) is a well-characterized mammalian transcription factor that controls photoreceptor cell-specific gene expression. Although much is known about the functions and DNA binding specificity of CRX, little is known about how DNA methylation modulates CRX binding affinity to genomic cis-regulatory elements. We used bisulfite pyrosequencing of human ocular tissues to measure DNA methylation levels of the regulatory regions of RHO , PDE6B, PAX6 , and LINE1 retrotransposon repeats. To describe the molecular mechanism of repression, we used molecular modeling to illustrate the effect of DNA methylation on human RHO regulatory sequences. In this study, we demonstrate an inverse correlation between DNA methylation in regulatory regions adjacent to the human RHO and PDE6B genes and their subsequent transcription in human ocular tissues. Docking of CRX to the DNA models shows that CRX interacts with the grooves of these sequences, suggesting changes in groove structure could regulate binding. Molecular dynamics simulations of the RHO promoter and enhancer regions show changes in the flexibility and groove width upon epigenetic modification. Models also demonstrate changes in the local dynamics of CRX binding sites within RHO regulatory sequences which may account for the repression of CRX-dependent transcription. Collectively, these data demonstrate epigenetic regulation of CRX binding sites in human retinal tissue and provide insight into the mechanism of this mode of epigenetic regulation to be tested in future experiments.

  6. Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

    Science.gov (United States)

    Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

    2016-09-01

    Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Plate Tearing by a Cone

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1998-01-01

    The present paper is concerned with steady-state plate tearing by a cone. This is a scenario where a cone is forced through a ductile metal plate with a constant lateral tip penetration in a motion in the plane of the plate. The considered process could be an idealisation of the damage, which...... as for the out-of-plane reaction force. (C) 1998 Elsevier Science Ltd. All rights reserved....

  8. Role of kinesin heavy chain in Crumbs localization along the rhabdomere elongation in Drosophila photoreceptor.

    Directory of Open Access Journals (Sweden)

    Garrett P League

    Full Text Available BACKGROUND: Crumbs (Crb, a cell polarity gene, has been shown to provide a positional cue for the extension of the apical membrane domain, adherens junction (AJ, and rhabdomere along the growing proximal-distal axis during Drosophila photoreceptor morphogenesis. In developing Drosophila photoreceptors, a stabilized microtubule structure was discovered and its presence was linked to polarity protein localization. It was therefore hypothesized that the microtubules may provide trafficking routes for the polarity proteins during photoreceptor morphogenesis. This study has examined whether Kinesin heavy chain (Khc, a subunit of the microtubule-based motor Kinesin-1, is essential in polarity protein localization in developing photoreceptors. METHODOLOGY/PRINCIPAL FINDINGS: Because a genetic interaction was found between crb and khc, Crb localization was examined in the developing photoreceptors of khc mutants. khc was dispensable during early eye differentiation and development. However, khc mutant photoreceptors showed a range of abnormalities in the apical membrane domain depending on the position along the proximal-distal axis in pupal photoreceptors. The khc mutant showed a progressive mislocalization in the apical domain along the distal-proximal axis during rhabdomere elongation. The khc mutation also led to a similar progressive defect in the stabilized microtubule structures, strongly suggesting that Khc is essential for microtubule structure and Crb localization during distal to proximal rhabdomere elongation in pupal morphogenesis. This role of Khc in apical domain control was further supported by khc's gain-of-function phenotype. Khc overexpression in photoreceptors caused disruption of the apical membrane domain and the stabilized microtubules in the developing photoreceptors. CONCLUSIONS/SIGNIFICANCE: In summary, we examined the role of khc in the regulation of the apical Crb domain in developing photoreceptors. Since the rhabdomeres in

  9. Light cone approach

    International Nuclear Information System (INIS)

    Brodsky, Stan

    1993-01-01

    One of the most challenging problems in theoretical high energy physics is to compute the bound state structure of the proton and other hadrons from quantum chromodynamics (QCD), the field theory of quarks and gluons. The goal is not only to calculate the spectrum of hadrons masses from first principles, but also to derive the momentum and spin distributions of the quarks and gluons which control high energy hadron interactions. One approach to these difficult calculations is to simulate QCD on an artificial lattice. Recently, several new methods based on ''light-cone'' quantization have been proposed as alternatives to lattice theory for solving non-perturbative problems in QCD and other field theories. The basic idea is a generalization of Heisenberg's pioneer matrix formulation of quantum mechanics: if one could numerically diagonalize the matrix of the Hamiltonian representing the underlying QCD interaction, then the resulting eigenvalues would give the hadron spectrum, while the corresponding eigenstates would describe each hadron in terms of its quark and gluon degrees of freedom

  10. Mutations in the ABCA4 (ABCR) Gene Are the Major Cause of Autosomal Recessive Cone-Rod Dystrophy

    OpenAIRE

    Maugeri, Alessandra; Klevering, B. Jeroen; Rohrschneider, Klaus; Blankenagel, Anita; Brunner, Han G.; Deutman, August F.; Hoyng, Carel B.; Cremers, Frans P. M.

    2000-01-01

    The photoreceptor cell–specific ATP-binding cassette transporter gene (ABCA4; previously denoted “ABCR”) is mutated in most patients with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients with isolated CRD, all fro...

  11. Evidence for dynamic network regulation of Drosophila photoreceptor function from mutants lacking the neurotransmitter histamine

    Directory of Open Access Journals (Sweden)

    An eDau

    2016-03-01

    Full Text Available Synaptic feedback from interneurons to photoreceptors can help to optimize visual information flow by balancing its allocation on retinal pathways under changing light conditions. But little is known about how this critical network operation is regulated dynamically. Here, we investigate this question by comparing signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors to those of the hdcJK910 mutant, which lacks the neurotransmitter histamine and therefore cannot transmit information to interneurons. Recordings show that hdcJK910 photoreceptors sample similar amounts of information from naturalistic stimulation to wild-type photoreceptors, but this information is packaged in smaller responses, especially under bright illumination. Analyses reveal how these altered dynamics primarily resulted from network overload that affected hdcJK910 photoreceptors in two ways. First, the missing inhibitory histamine input to interneurons almost certainly depolarized them irrevocably, which in turn increased their excitatory feedback to hdcJK910 R1-R6s. This tonic excitation depolarized the photoreceptors to artificially high potentials, reducing their operational range. Second, rescuing histamine input to interneurons in hdcJK910 mutant also restored their normal phasic feedback modulation to R1-R6s, causing photoreceptor output to accentuate dynamic intensity differences at bright illumination, similar to the wild-type. These results provide mechanistic explanations of how synaptic feedback connections optimize information packaging in photoreceptor output and novel insight into the operation and design of dynamic network regulation of sensory neurons.

  12. Cellular elements for seeing in the dark: voltage-dependent conductances in cockroach photoreceptors

    Directory of Open Access Journals (Sweden)

    Salmela Iikka

    2012-08-01

    Full Text Available Abstract Background The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana, a nocturnal insect with a visual system adapted for dim light. Results Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR and a fast transient inactivating type (KA. Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role. Conclusions The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.

  13. Photoreceptor processing speed and input resistance changes during light adaptation correlate with spectral class in the bumblebee, Bombus impatiens.

    Directory of Open Access Journals (Sweden)

    Peter Skorupski

    Full Text Available Colour vision depends on comparison of signals from photoreceptors with different spectral sensitivities. However, response properties of photoreceptor cells may differ in ways other than spectral tuning. In insects, for example, broadband photoreceptors, with a major sensitivity peak in the green region of the spectrum (>500 nm, drive fast visual processes, which are largely blind to chromatic signals from more narrowly-tuned photoreceptors with peak sensitivities in the blue and UV regions of the spectrum. In addition, electrophysiological properties of the photoreceptor membrane may result in differences in response dynamics of photoreceptors of similar spectral class between species, and different spectral classes within a species. We used intracellular electrophysiological techniques to investigate response dynamics of the three spectral classes of photoreceptor underlying trichromatic colour vision in the bumblebee, Bombus impatiens, and we compare these with previously published data from a related species, Bombus terrestris. In both species, we found significantly faster responses in green, compared with blue- or UV-sensitive photoreceptors, although all 3 photoreceptor types are slower in B. impatiens than in B. terrestris. Integration times for light-adapted B. impatiens photoreceptors (estimated from impulse response half-width were 11.3 ± 1.6 ms for green photoreceptors compared with 18.6 ± 4.4 ms and 15.6 ± 4.4 for blue and UV, respectively. We also measured photoreceptor input resistance in dark- and light-adapted conditions. All photoreceptors showed a decrease in input resistance during light adaptation, but this decrease was considerably larger (declining to about 22% of the dark value in green photoreceptors, compared to blue and UV (41% and 49%, respectively. Our results suggest that the conductances associated with light adaptation are largest in green photoreceptors, contributing to their greater temporal processing speed

  14. Response Function of the Crayfish Caudal Photoreceptor to Hydrodynamic Stimuli

    Science.gov (United States)

    Breite, Sally; Bahar, Sonya; Neiman, Alexander; Moss, Frank

    2002-03-01

    In its abdominal 6th ganglion the crayfish houses 2 light-sensitive neurons (caudal photoreceptors, or CPRs). It is known that these neurons work in tandem with a mechanosensory system of tiny hairs spread across the tailfan, which make synaptic contact with the photoreceptors. A stochastic resonance effect has been shown in this system in which light enhances the transduction of a weak, periodic mechanosensory (hydrodynamic) stimulus. It is not known, however, whether an optimal response from the CPR is induced by a single sine wave cycle or some other waveform. We have experimentally investigated this favorable waveform by driving a tailfan preparation with mechanical 10 Hz correlated Ornstein-Uhlenbeck noise and calculating the response function from the spike-triggered average of the applied noise waveform. We will discuss differences in the shape of the optimal waveform under dark and light conditions, as well as what seems to be a noticeable difference in the magnitude of the animals' response to a noisy stimulus in comparison with a periodic stimulus.

  15. Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity

    DEFF Research Database (Denmark)

    Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

    2016-01-01

    The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer...... marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm2). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly...... synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells...

  16. Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

    Science.gov (United States)

    Marcos, S; Tornow, R P; Elsner, A E; Navarro, R

    1997-07-01

    Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.

  17. Knock-in strategy at 3'-end of Crx gene by CRISPR/Cas9 system shows the gene expression profiles during human photoreceptor differentiation.

    Science.gov (United States)

    Homma, Kohei; Usui, Sumiko; Kaneda, Makoto

    2017-03-01

    Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus. We found that the fluorescence intensity was positively correlated with the expression levels of Crx mRNA and that fluorescent cells expressed rod photoreceptor-specific genes in the later stage of differentiation. Finally, we treated the fluorescent cells with DAPT, a Notch inhibitor, and found that DAPT-enhanced retinal differentiation was associated with up-regulation of Crx, Otx2 and NeuroD1, and down-regulation of Hes5 and Ngn2. These suggest that this knock-in strategy at the 3'-end of the target gene, combined with the 2A peptide linked to fluorescent proteins, offers a useful tool for labeling specific cell lineages or monitoring expression of any marker genes without affecting the function of the target gene. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  18. X-box binding protein 1 is essential for the anti-oxidant defense and cell survival in the retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Yimin Zhong

    Full Text Available Damage to the retinal pigment epithelium (RPE is an early event in the pathogenesis of age-related macular degeneration (AMD. X-box binding protein 1 (XBP1 is a key transcription factor that regulates endoplasmic reticulum (ER homeostasis and cell survival. This study aimed to delineate the role of endogenous XBP1 in the RPE. Our results show that in a rat model of light-induced retinal degeneration, XBP1 activation was suppressed in the RPE/choroid complex, accompanied by decreased anti-oxidant genes and increased oxidative stress. Knockdown of XBP1 by siRNA resulted in reduced expression of SOD1, SOD2, catalase, and glutathione synthase and sensitized RPE cells to oxidative damage. Using Cre/LoxP system, we generated a mouse line that lacks XBP1 only in RPE cells. Compared to wildtype littermates, RPE-XBP1 KO mice expressed less SOD1, SOD2, and catalase in the RPE, and had increased oxidative stress. At age 3 months and older, these mice exhibited apoptosis of RPE cells, decreased number of cone photoreceptors, shortened photoreceptor outer segment, reduced ONL thickness, and deficit in retinal function. Electron microscopy showed abnormal ultrastructure, Bruch's membrane thickening, and disrupted basal membrane infolding in XBP1-deficient RPE. These results indicate that XBP1 is an important gene involved in regulation of the anti-oxidant defense in the RPE, and that impaired activation of XBP1 may contribute to RPE dysfunction and cell death during retinal degeneration and AMD.

  19. Differentiation of retinal ganglion cells and photoreceptor precursors from mouse induced pluripotent stem cells carrying an Atoh7/Math5 lineage reporter.

    Directory of Open Access Journals (Sweden)

    Bin-Bin Xie

    Full Text Available The neural retina is a critical component of the visual system, which provides the majority of sensory input in humans. Various retinal degenerative diseases can result in the permanent loss of retinal neurons, especially the light-sensing photoreceptors and the centrally projecting retinal ganglion cells (RGCs. The replenishment of lost RGCs and the repair of optic nerve damage are particularly challenging, as both RGC specification and their subsequent axonal growth and projection involve complex and precise regulation. To explore the developmental potential of pluripotent stem cell-derived neural progenitors, we have established mouse iPS cells that allow cell lineage tracing of progenitors that have expressed Atoh7/Math5, a bHLH transcription factor required for RGC production. These Atoh7 lineage reporter iPS cells encode Cre to replace one copy of the endogenous Atoh7 gene and a Cre-dependent YFP reporter in the ROSA locus. In addition, they express pluripotent markers and are capable of generating teratomas in vivo. Under anterior neural induction and neurogenic conditions in vitro, the Atoh7-Cre/ROSA-YFP iPS cells differentiate into neurons that co-express various RGC markers and YFP, indicating that these neurons are derived from Atoh7-expressing progenitors. Consistent with previous in vivo cell lineage studies, the Atoh7-Cre/ROSA-YFP iPS cells also give rise to a subset of Crx-positive photoreceptor precursors. Furthermore, inhibition of Notch signaling in the iPSC cultures results in a significant increase of YFP-positive RGCs and photoreceptor precursors. Together, these results show that Atoh7-Cre/ROSA-YFP iPS cells can be used to monitor the development and survival of RGCs and photoreceptors from pluripotent stem cells.

  20. Loss of ift122, a Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Due to Inefficient Opsin Transport*

    Science.gov (United States)

    Boubakri, Meriam; Chaya, Taro; Hirata, Hiromi; Kajimura, Naoko; Kuwahara, Ryusuke; Ueno, Akiko; Malicki, Jarema; Furukawa, Takahisa; Omori, Yoshihiro

    2016-01-01

    In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system that mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A. ift122 mutant larvae show unexpectedly mild phenotypes, compared with those of mutants defective in IFT-B. ift122 mutants exhibit a slow onset of progressive photoreceptor degeneration mainly after 7 days post-fertilization. ift122 mutant larvae also develop cystic kidney but not curly body, both of which are typically observed in various ciliary mutants. ift122 mutants display a loss of cilia in the inner ear hair cells and nasal pit epithelia. Loss of ift122 causes disorganization of outer segment discs. Ectopic accumulation of an IFT-B component, ift88, is observed in the ift122 mutant photoreceptor cilia. In addition, pulse-chase experiments using GFP-opsin fusion proteins revealed that ift122 is required for the efficient transport of opsin and the distal elongation of outer segments. These results show that IFT-A is essential for the efficient transport of outer segment proteins, including opsin, and for the survival of retinal photoreceptor cells, rendering the ift122 mutant a unique model for human retinal degenerative diseases. PMID:27681595

  1. Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening.

    Science.gov (United States)

    Sobacı, Güngör; Ozge, Gökhan; Gündoğan, Fatih Ç

    2012-01-01

    To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port(®) system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = -0.55, P = 0.004, r = 0.68, P = 0.001, r = -0.65, P = 0.001, and r = -0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system.

  2. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Deepak A Lamba

    2010-01-01

    Full Text Available Inherited and acquired retinal degenerations are frequent causes of visual impairment and photoreceptor cell replacement therapy may restore visual function to these individuals. To provide a source of new retinal neurons for cell based therapies, we developed methods to derive retinal progenitors from human ES cells.In this report we have used a similar method to direct induced pluripotent stem cells (iPS from human fibroblasts to a retinal progenitor fate, competent to generate photoreceptors. We also found we could purify the photoreceptors derived from the iPS cells using fluorescence activated cell sorting (FACS after labeling photoreceptors with a lentivirus driving GFP from the IRBP cis-regulatory sequences. Moreover, we found that when we transplanted the FACS purified iPSC derived photoreceptors, they were able to integrate into a normal mouse retina and express photoreceptor markers.This report provides evidence that enriched populations of human photoreceptors can be derived from iPS cells.

  3. A new photosensory function for simple photoreceptors, the intrinsically photoresponsive neurons of the sea slug Onchidium

    Directory of Open Access Journals (Sweden)

    Tsukasa Gotow

    2009-12-01

    Full Text Available Simple photoreceptors, namely intrinsically light-sensitive neurons without microvilli and/or cilia, have long been known to exist in the central ganglia of crayfish, Aplysia, Onchidium, and Helix. These simple photoreceptors are not only first-order photosensory cells, but also second-order neurons (interneurons, relaying several kinds of sensory synaptic inputs. Another important issue is that the photoresponses of these simple photoreceptors show very slow kinetics and little adaptation. These characteristics suggest that the simple photoreceptors of the Onchidium have a function in non-image-forming vision, different from classical eye photoreceptors used for cording dynamic images of vision. The cited literature provides evidence that the depolarizing and hyperpolarizing photoresponses of simple photoreceptors play a role in the long-lasting potentiation of synaptic transmission of excitatory and inhibitory sensory inputs, and as well as in the potentiation and the suppression of the subsequent behavioral outputs. In short, we suggest that simple photoreceptors operate in the general potentiation of synaptic transmission and subsequent motor output; i.e., they perform a new photosensory function.

  4. Generation of a genetically encoded marker of rod photoreceptor outer segment growth and renewal

    Directory of Open Access Journals (Sweden)

    John J. Willoughby

    2011-10-01

    Vertebrate photoreceptors are specialized light sensing neurons. The photoreceptor outer segment is a highly modified cilium where photons of light are transduced into a chemical and electrical signal. The outer segment has the typical cilary axoneme but, in addition, it has a large number of densely packed, stacked, intramembranous discs. The molecular and cellular mechanisms that contribute to vertebrate photoreceptor outer segment morphogenesis are still largely unknown. Unlike typical cilia, the outer segment is continuously regenerated or renewed throughout the life of the animal through the combined process of distal outer segment shedding and proximal outer segment growth. The process of outer segment renewal was discovered over forty years ago, but we still lack an understanding of how photoreceptors renew their outer segments and few, if any, molecular mechanisms that regulate outer segment growth or shedding have been described. Our lack of progress in understanding how photoreceptors renew their outer segments has been hampered by the difficulty in measuring rates of renewal. We have created a new method that uses heat-shock induction of a fluorescent protein that can be used to rapidly measure outer segment growth rates. We describe this method, the stable transgenic line we created, and the growth rates observed in larval and adult rod photoreceptors using this new method. This new method will allow us to begin to define the genetic and molecular mechanisms that regulate rod outer segment renewal, a crucial aspect of photoreceptor function and, possibly, viability.

  5. Intraocular gene transfer of ciliary neurotrophic factor rescues photoreceptor degeneration in RCS rats.

    Science.gov (United States)

    Huang, Shun-Ping; Lin, Po-Kang; Liu, Jorn-Hon; Khor, Chin-Ni; Lee, Yih-Jing

    2004-01-01

    Ciliary neurotrophic factor (CNTF) is known as an important factor in the regulation of retinal cell growth. We used both recombinant CNTF and an adenovirus carrying the CNTF gene to regulate retinal photoreceptor expression in a retinal degenerative animal, Royal College of Surgeons (RCS) rats. Cells in the outer nuclear layer of the retinae from recombinant-CNTF-treated, adenoviral-CNTF-treated, saline-operated, and contralateral untreated preparations were examined for those exhibiting CNTF photoreceptor protective effects. Cell apoptosis in the outer nuclear layer of the retinae was also detected. It was found that CNTF had a potent effect on delaying the photoreceptor degeneration process in RCS rats. Furthermore, adenovirus CNTF gene transfer was proven to be better at rescuing photoreceptors than that when using recombinant CNTF, since adenoviral CNTF prolonged the photoreceptor protection effect. The function of the photoreceptors was also examined by taking electroretinograms of different animals. Adenoviral-CNTF-treated eyes showed better retinal function than did the contralateral control eyes. This study indicates that adenoviral CNTF effectively rescues degenerating photoreceptors in RCS rats. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

  6. High-Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy Using Adaptive Optics Fundus Camera.

    Directory of Open Access Journals (Sweden)

    Mohamed Kamel Soliman

    Full Text Available To assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus.An adaptive optics (AO retinal camera (rtx1™; Imagine Eyes, Orsay, France was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors.Ten healthy participants (20 eyes and 25 patients (29 eyes with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD] age of the healthy participants (Control group, patients with diabetes without retinopathy (No DR group, and patients with diabetic retinopathy (DR group was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05. No correlation was found between cone density and the level of hemoglobin A1c (HbA1c or the duration of diabetes.The extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.

  7. Coping with 'Dark Sides of the Sun' through Photoreceptor Signaling.

    Science.gov (United States)

    Demarsy, Emilie; Goldschmidt-Clermont, Michel; Ulm, Roman

    2018-03-01

    Plants grow in constantly changing environments, including highly variable light intensities. Sunlight provides the energy that drives photosynthesis and is thus of the utmost importance for plant growth and the generation of oxygen, which the majority of life on Earth depends on. However, exposure to either insufficient or excess levels of light can have detrimental effects and cause light stress. Whereas exposure to insufficient light limits photosynthetic activity, resulting in 'energy starvation', exposure to excess light can damage the photosynthetic apparatus. Furthermore, strong sunlight is associated with high levels of potentially damaging UV-B radiation. Different classes of photoreceptors play important roles in coping with the negative aspects of sunlight, for which specific mechanisms are emerging that are reviewed here. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Blue and ultraviolet-B light photoreceptors in parsley cells

    International Nuclear Information System (INIS)

    Ensminger, P.A.; Schaefer, E.

    1992-01-01

    The authors studied UV-B photoreception in parsley cell cultures with physiological experiments involving temperature shifts and examined the possible role of flavin in blue and UV-B light photo-reception. Cells irradiated with UV-B light (0.5-15 min) at 2 o C have the same fluence requirement for chalcone synthase and flavonoid induction as controls irradiated at 25 o C. This is indicative of a purely photochemical reaction. Cells fed with riboflavin and irradiated with 6 h of UV-containing white light synthesize higher levels of chalcone synthase and flavonoid than unfed controls. This effect did not occur with blue light. These results indicate that flavin-sensitization requires excitation of flavin and the UV-B light photoreceptor. (author)

  9. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  10. DOS cones along atomic chains

    Science.gov (United States)

    Kwapiński, Tomasz

    2017-03-01

    The electron transport properties of a linear atomic chain are studied theoretically within the tight-binding Hamiltonian and the Green’s function method. Variations of the local density of states (DOS) along the chain are investigated. They are crucial in scanning tunnelling experiments and give important insight into the electron transport mechanism and charge distribution inside chains. It is found that depending on the chain parity the local DOS at the Fermi level can form cone-like structures (DOS cones) along the chain. The general condition for the local DOS oscillations is obtained and the linear behaviour of the local density function is confirmed analytically. DOS cones are characterized by a linear decay towards the chain which is in contrast to the propagation properties of charge density waves, end states and Friedel oscillations in one-dimensional systems. We find that DOS cones can appear due to non-resonant electron transport, the spin-orbit scattering or for chains fabricated on a substrate with localized electrons. It is also shown that for imperfect chains (e.g. with a reduced coupling strength between two neighboring sites) a diamond-like structure of the local DOS along the chain appears.

  11. DOS cones along atomic chains

    International Nuclear Information System (INIS)

    Kwapiński, Tomasz

    2017-01-01

    The electron transport properties of a linear atomic chain are studied theoretically within the tight-binding Hamiltonian and the Green’s function method. Variations of the local density of states (DOS) along the chain are investigated. They are crucial in scanning tunnelling experiments and give important insight into the electron transport mechanism and charge distribution inside chains. It is found that depending on the chain parity the local DOS at the Fermi level can form cone-like structures (DOS cones) along the chain. The general condition for the local DOS oscillations is obtained and the linear behaviour of the local density function is confirmed analytically. DOS cones are characterized by a linear decay towards the chain which is in contrast to the propagation properties of charge density waves, end states and Friedel oscillations in one-dimensional systems. We find that DOS cones can appear due to non-resonant electron transport, the spin–orbit scattering or for chains fabricated on a substrate with localized electrons. It is also shown that for imperfect chains (e.g. with a reduced coupling strength between two neighboring sites) a diamond-like structure of the local DOS along the chain appears. (paper)

  12. Ejecta evolution during cone impact

    KAUST Repository

    Marston, Jeremy; Thoroddsen, Sigurdur T

    2014-01-01

    -similarity for all impact speeds for very low surface tension liquids, whilst for high-surface tension liquids similarity is only achieved at high impact speeds. We find that the ejecta tip can detach from the cone and that this phenomenon can be attributed

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

    Directory of Open Access Journals (Sweden)

    Tracy Ho

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

  14. Hanford waste tank cone penetrometer

    International Nuclear Information System (INIS)

    Seda, R.Y.

    1995-12-01

    A new tool is being developed to characterize tank waste at the Hanford Reservation. This tool, known as the cone penetrometer, is capable of obtaining chemical and physical properties in situ. For the past 50 years, this tool has been used extensively in soil applications and now has been modified for usage in Hanford Underground Storage tanks. These modifications include development of new ''waste'' data models as well as hardware design changes to accommodate the hazardous and radioactive environment of the tanks. The modified cone penetrometer is scheduled to be deployed at Hanford by Fall 1996. At Hanford, the cone penetrometer will be used as an instrumented pipe which measures chemical and physical properties as it pushes through tank waste. Physical data, such as tank waste stratification and mechanical properties, is obtained through three sensors measuring tip pressure, sleeve friction and pore pressure. Chemical data, such as chemical speciation, is measured using a Raman spectroscopy sensor. The sensor package contains other instrumentation as well, including a tip and side temperature sensor, tank bottom detection and an inclinometer. Once the cone penetrometer has reached the bottom of the tank, a moisture probe will be inserted into the pipe. This probe is used to measure waste moisture content, water level, waste surface moisture and tank temperature. This paper discusses the development of this new measurement system. Data from the cone penetrometer will aid in the selection of sampling tools, waste tank retrieval process, and addressing various tank safety issues. This paper will explore various waste models as well as the challenges associated with tank environment

  15. Ultrastructural and ERG findings in progressive rod-cone dystrophy in a litter of Labrador retrievers.

    Science.gov (United States)

    Raitta, C; Kommonen, B; Ulshafer, R; Karhunen, U

    1991-02-01

    Early ultrastructural findings of a progressive photoreceptor dystrophy and corresponding ERG findings are reported in 3 Labrador Retrievers from a litter of 7 pups bred from 2 dogs clinically and electroretinographically affected with generalized progressive retinal dystrophy. The pups were euthanized at 5, 11 and 15 months post partum. The most prominent ultrastructural finding was photoreceptor dystrophy. At 5 months the outer nuclear layer (ONL) consisted of 8-10 layers and seemed reduced in thickness, pyknotic nuclei were seen in this layer. The receptor outer segments (OS) were short and swollen. Some disorientation of OS discs occurred. In the 11-months specimen 7-8 ONL layers were identified. Overall thinning of the neuro-retina had occurred and fewer receptors compared to the 5-months specimen were present. By 15 months the ONL was further reduced to about 4 layers. Enlarged internuclear spaces were present in the ONL as well as around inner segments (IS). Phagocytic cells were frequent among remains of OS. The pigment epithelium appeared normal. The dark adapted ERG b-wave amplitudes and photopic 30 Hz flicker responses were low in comparison to controls of the same breed, and decreased with age. The condition represents a progressive rod-cone dystrophy which shares similarities with primary receptor dystrophy in man such as retinitis pigmentosa.

  16. Characterization of Multiple Light Damage Paradigms Reveals Regional Differences in Photoreceptor Loss

    OpenAIRE

    Thomas, Jennifer L.; Nelson, Craig M.; Luo, Xixia; Hyde, David R.; Thummel, Ryan

    2012-01-01

    Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether th...

  17. LONGITUDINAL QUANTITATIVE EVALUATION OF PHOTORECEPTOR VOLUME FOLLOWING REPAIR OF MACULA-OFF RETINAL DETACHMENT.

    Science.gov (United States)

    Narala, Ramsudha; Scarinci, Fabio; Shaarawy, Amr; Simonett, Joseph M; Flaxel, Christina J; Fawzi, Amani A

    2016-08-01

    To quantify photoreceptor volume changes after successful surgical repair of macula-off retinal detachment and to correlate these volumetric changes to postoperative best-corrected visual acuity (BCVA). Retrospective study of 15 eyes of 15 patients with macula-off retinal detachment who underwent successful surgical repair. A minimum of 4 optical coherence tomography scans that straddled the foveal center was used to quantify the central photoreceptor volume (central 1 mm). Mean photoreceptor volume at the first postoperative visit was 0.451 mm, increasing to 0.523 mm at the final postoperative visit (P = 0.004). Mean BCVA improved from 1.13 ± 0.59 logarithm of the minimum angle of resolution units (∼20/270) preoperatively to 0.52 ± 0.42 logarithm of the minimum angle of resolution units (∼20/66) at the final postoperative visit (P = 0.001). Mean photoreceptor volume at either the initial or final visit demonstrated significant correlations with final postoperative BCVA (r = -0.670, P = 0.017 and r = -0.753, P = 0.005, respectively). Shorter time interval from diagnosis to surgery was significantly associated with greater mean final postoperative photoreceptor volume (r = -0.588, P = 0.021) and better mean final postoperative BCVA (r = 0.709, P = 0.003). We observed a significant increase in photoreceptor volume after successful retinal detachment repair; photoreceptor volume was positively associated with BCVA and time to surgery. Our series emphasizes the importance of prompt surgical repair and shows that photoreceptor recovery and volumetric improvement correlate significantly with BCVA.

  18. Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells.

    Science.gov (United States)

    Omori, Yoshihiro; Araki, Fumiyuki; Chaya, Taro; Kajimura, Naoko; Irie, Shoichi; Terada, Koji; Muranishi, Yuki; Tsujii, Toshinori; Ueno, Shinji; Koyasu, Toshiyuki; Tamaki, Yasuhiro; Kondo, Mineo; Amano, Shiro; Furukawa, Takahisa

    2012-05-02

    Dystroglycan (DG) is a key component of the dystrophin-glycoprotein complex (DGC) at the neuromuscular junction postsynapse. In the mouse retina, the DGC is localized at the presynapse of photoreceptor cells, however, the function of presynaptic DGC is poorly understood. Here, we developed and analyzed retinal photoreceptor-specific DG conditional knock-out (DG CKO) mice. We found that the DG CKO retina showed a reduced amplitude and a prolonged implicit time of the ERG b-wave. Electron microscopic analysis revealed that bipolar dendrite invagination into the photoreceptor terminus is perturbed in the DG CKO retina. In the DG CKO retina, pikachurin, a DG ligand in the retina, is markedly decreased at photoreceptor synapses. Interestingly, in the Pikachurin(-/-) retina, the DG signal at the ribbon synaptic terminus was severely reduced, suggesting that pikachurin is required for the presynaptic accumulation of DG at the photoreceptor synaptic terminus, and conversely DG is required for pikachurin accumulation. Furthermore, we found that overexpression of pikachurin induces formation and clustering of a DG-pikachurin complex on the cell surface. The Laminin G repeats of pikachurin, which are critical for its oligomerization and interaction with DG, were essential for the clustering of the DG-pikachurin complex as well. These results suggest that oligomerization of pikachurin and its interaction with DG causes DG assembly on the synapse surface of the photoreceptor synaptic terminals. Our results reveal that the presynaptic interaction of pikachurin with DG at photoreceptor terminals is essential for both the formation of proper photoreceptor ribbon synaptic structures and normal retinal electrophysiology.

  19. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus.

    Science.gov (United States)

    Flannery, J G; Zolotukhin, S; Vaquero, M I; LaVail, M M; Muzyczka, N; Hauswirth, W W

    1997-06-24

    We describe a general approach for achieving efficient and cell type-specific expression of exogenous genes in photoreceptor cells of the mammalian retina. Recombinant adeno-associated virus (rAAV) vectors were used to transfer the bacterial lacZ gene or a synthetic green fluorescent protein gene (gfp) to mouse or rat retinas after injection into the subretinal space. Using a proximal murine rod opsin promoter (+86 to -385) to drive expression, reporter gene product was found exclusively in photoreceptors, not in any other retinal cell type or in the adjacent retinal pigment epithelium. GFP-expressing photoreceptors typically encompassed 10-20% of the total retinal area after a single 2-microl injection. Photoreceptors were transduced with nearly 100% efficiency in the region directly surrounding the injection site. We estimate approximately 2.5 million photoreceptors were transduced as a result of the single subretinal inoculation. This level of gene transfer and expression suggests the feasibility of genetic therapy for retinal disease. The gfp-containing rAAV stock was substantially free of both adenovirus and wild-type AAV, as judged by plaque assay and infectious center assay, respectively. Thus, highly purified, helper virus-free rAAV vectors can achieve high-frequency tissue-specific transduction of terminally differentiated, postmitotic photoreceptor cells.

  20. Polyhedral combinatorics of UPGMA cones

    OpenAIRE

    Davidson, Ruth; Sullivant, Seth

    2013-01-01

    Distance-based methods such as UPGMA (Unweighted Pair Group Method with Arithmetic Mean) continue to play a significant role in phylogenetic research. We use polyhedral combinatorics to analyze the natural subdivision of the positive orthant induced by classifying the input vectors according to tree topologies returned by the algorithm. The partition lattice informs the study of UPGMA trees. We give a closed form for the extreme rays of UPGMA cones on n taxa, and compute the normalized volume...

  1. Liouville action in cone gauge

    International Nuclear Information System (INIS)

    Zamolodchikov, A.B.

    1989-01-01

    The effective action of the conformally invariant field theory in the curved background space is considered in the light cone gauge. The effective potential in the classical background stress is defined as the Legendre transform of the Liouville action. This potential is tightly connected with the sl(2) current algebra. The series of the covariant differential operators is constructed and the anomalies of their determinants are reduced to this effective potential. 7 refs

  2. Cardiac cone-beam CT

    International Nuclear Information System (INIS)

    Manzke, Robert

    2005-01-01

    This doctoral thesis addresses imaging of the heart with retrospectively gated helical cone-beam computed tomography (CT). A thorough review of the CT reconstruction literature is presented in combination with a historic overview of cardiac CT imaging and a brief introduction to other cardiac imaging modalities. The thesis includes a comprehensive chapter about the theory of CT reconstruction, familiarizing the reader with the problem of cone-beam reconstruction. The anatomic and dynamic properties of the heart are outlined and techniques to derive the gating information are reviewed. With the extended cardiac reconstruction (ECR) framework, a new approach is presented for the heart-rate-adaptive gated helical cardiac cone-beam CT reconstruction. Reconstruction assessment criteria such as the temporal resolution, the homogeneity in terms of the cardiac phase, and the smoothness at cycle-to-cycle transitions are developed. Several reconstruction optimization approaches are described: An approach for the heart-rate-adaptive optimization of the temporal resolution is presented. Streak artifacts at cycle-to-cycle transitions can be minimized by using an improved cardiac weighting scheme. The optimal quiescent cardiac phase for the reconstruction can be determined automatically with the motion map technique. Results for all optimization procedures applied to ECR are presented and discussed based on patient and phantom data. The ECR algorithm is analyzed for larger detector arrays of future cone-beam systems throughout an extensive simulation study based on a four-dimensional cardiac CT phantom. The results of the scientific work are summarized and an outlook proposing future directions is given. The presented thesis is available for public download at www.cardiac-ct.net

  3. Prescriptionless light-cone integrals

    International Nuclear Information System (INIS)

    Suzuki, A.T.; Schmidt, A.G.M.

    2000-01-01

    Perturbative quantum gauge field theory as seen within the perspective of physical gauge choices such as the light-cone gauge entails the emergence of troublesome poles of the type (k.n) -α in the Feynman integrals. These come from the boson field propagator, where α=1,2,.. and n μ is the external arbitrary four-vector that defines the gauge properly. This becomes an additional hurdle in the computation of Feynman diagrams, since any graph containing internal boson lines will inevitably produce integrands with denominators bearing the characteristic gauge-fixing factor. How one deals with them has been the subject of research over decades, and several prescriptions have been suggested and tried in the course of time, with failures and successes. However, a more recent development at this fronteer which applies the negative dimensional technique to compute light-cone Feynman integrals shows that we can altogether dispense with prescriptions to perform the calculations. An additional bonus comes to us attached to this new technique, in that not only it renders the light-cone prescriptionless but, by the very nature of it, it can also dispense with decomposition formulas or partial fractioning tricks used in the standard approach to separate pole products of the type (k.n) -α [(k-p).n] -β (β=1,2,..). In this work we demonstrate how all this can be done. (orig.)

  4. Light-cone quantization of quantum chromodynamics

    International Nuclear Information System (INIS)

    Brodsky, S.J.; Pauli, H.C.

    1991-06-01

    We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, ''discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism

  5. Light-cone quantization of quantum chromodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, S.J. (Stanford Linear Accelerator Center, Menlo Park, CA (USA)); Pauli, H.C. (Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany, F.R.))

    1991-06-01

    We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism.

  6. A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

    2010-01-01

    The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...... melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx(-/-) mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse....

  7. Non-directional photoreceptors in the pluteus of Strongylocentrotus purpuratus

    Directory of Open Access Journals (Sweden)

    Alberto Valero-Gracia

    2016-11-01

    Full Text Available In comparison to complex visual systems, non-directional photoreception – the most primitive form of biological photodetection – has been poorly investigated, although it is essential to many biological processes such as circadian and seasonal rhythms. Here we describe the spatiotemporal expression pattern of the major molecular actors mediating light reception – opsins – localized in the Strongylocentrotus purpuratus larva. In contrast to other zooplanktonic larvae, the echinopluteus lacks photoreceptor cells with observable shading pigments involved in directional visual tasks. Nonetheless, the echinopluteus expresses two distinct classes of opsins: a Go-opsin and a rhabdomeric opsin. The Go-opsin, Sp-opsin3.2, is detectable at early (3 days post fertilization and four armed pluteus stages (4 days post fertilization in two cells that flank the apical organ. To rule out the presence of shading pigments involved in directional photoreception, we used electron microscopy to explore the expression domain of Go-opsin Sp-opsin3.2 positive cells. The rhabdomeric opsin Sp-Opsin4 expression is detectable in clusters of cells located around the primary podia at the five-fold ectoderm pentagonal disc stage (day 18-21 and thereafter, thus indicating that Sp-Opsin4 may not be involved in the photoreception mechanism of the larva, but only of the juvenile. We discuss the putative function of the relevant cells in their neural context, and propose a model for understanding simple photodetection in marine larvae.

  8. Geomorphometric variability of "monogenetic" volcanic cones: Evidence from Mauna Kea, Lanzarote and experimental cones

    Science.gov (United States)

    Kervyn, M.; Ernst, G. G. J.; Carracedo, J.-C.; Jacobs, P.

    2012-01-01

    Volcanic cones are the most common volcanic constructs on Earth. Their shape can be quantified using two morphometric ratios: the crater/cone base ratio (W cr/W co) and the cone height/width ratio (H co/W co). The average values for these ratios obtained over entire cone fields have been explained by the repose angle of loose granular material (i.e. scoria) controlling cone slopes. The observed variability in these ratios between individual cones has been attributed to the effect of erosional processes or contrasting eruptive conditions on cone morphometry. Using a GIS-based approach, high spatial resolution Digital Elevation Models and airphotos, two new geomorphometry datasets for cone fields at Mauna Kea (Hawaii, USA) and Lanzarote (Canary Islands, Spain) are extracted and analyzed here. The key observation in these datasets is the great variability in morphometric ratios, even for simple-shape and well-preserved cones. Simple analog experiments are presented to analyze factors influencing the morphometric ratios. The formation of a crater is simulated within an analog cone (i.e. a sand pile) by opening a drainage conduit at the cone base. Results from experiments show that variability in the morphometric ratios can be attributed to variations in the width, height and horizontal offset of the drainage point relative to the cone symmetry axis, to the dip of the underlying slope or to the influence of a small proportion of fine cohesive material. GIS analysis and analog experiments, together with specific examples of cones documented in the field, suggest that the morphometric ratios for well-preserved volcanic cones are controlled by a combination of 1) the intrinsic cone material properties, 2) time-dependent eruption conditions, 3) the local setting, and 4) the method used to estimate the cone height. Implications for interpreting cone morphometry solely as either an age or as an eruption condition indicator are highlighted.

  9. BMI1 loss delays photoreceptor degeneration in Rd1 mice. Bmi1 loss and neuroprotection in Rd1 mice.

    Science.gov (United States)

    Zencak, Dusan; Crippa, Sylvain V; Tekaya, Meriem; Tanger, Ellen; Schorderet, Daniel E; Munier, Francis L; van Lohuizen, Maarten; Arsenijevic, Yvan

    2006-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of genetic disorders leading to blindness, which remain untreatable at present. Rd1 mice represent a recognized model of RP, and so far only GDNF treatment provided a slight delay in the retinal degeneration in these mice. Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell (NSC) renewal in the brain, with an increased appearance of glial cells in vivo in Bmi1 knockout (Bmi1-/-) mice. One of the roles of glial cells is to sustain neuronal function and survival. In the view of a role of the retinal Miller glia as a source of neural protection in the retina, the increased astrocytic population in the Bmi1-/- brain led us to investigate the effect of Bmi1 loss in Rd1 mice. We observed an increase of Müller glial cells in Rd1-Bmi1-/- retinas compared to Rd1. Moreover, Rd1-Bmi1-/- mice showed 7-8 rows of photoreceptors at 30 days of age (P30), while in Rd1 littermates there was a complete disruption of the outer nuclear layer (ONL). Preliminary ERG results showed a responsiveness of Rd1-Bmi1-/- mice in scotopic vision at P35. In conclusion, Bmi1 loss prevented, or rescued, photoreceptors from degeneration to an unanticipated extent in Rd1 mice. In this chapter, we will first provide a brief review of our work on the cortical NSCs and introduce the Bmi1 oncogene, thus offering a rational to our observations on the retina.

  10. g-Weak Contraction in Ordered Cone Rectangular Metric Spaces

    Directory of Open Access Journals (Sweden)

    S. K. Malhotra

    2013-01-01

    Full Text Available We prove some common fixed-point theorems for the ordered g-weak contractions in cone rectangular metric spaces without assuming the normality of cone. Our results generalize some recent results from cone metric and cone rectangular metric spaces into ordered cone rectangular metric spaces. Examples are provided which illustrate the results.

  11. Temporal and spatial characteristics of male cone development in Metasequoia glyptostroboides Hu et Cheng.

    Science.gov (United States)

    Jin, Biao; Tang, Liang; Lu, Yan; Wang, Di; Zhang, Min; Ma, Jiuxia

    2012-12-01

    Metasequoia glyptostroboides, a famous relic species of conifer that survived in China, has been successfully planted in large numbers across the world. However, limited information on male cone development in the species is available. In this study, we observed the morphological and anatomical changes that occur during male cone development in M. glyptostroboides using semi-thin sections and scanning electron microscopy. The male cones were borne oppositely on one-year-old twigs that were mainly located around the outer and sunlit parts of crown. Male cones were initiated from early September and shed pollen in the following February. Each cone consisted of spirally arranged microsporophylls subtended by decussate sterile scales, and each microsporophyll commonly consisted of three microsporangia and a phylloclade. The microsporangial wall was composed of an epidermis, endothecium, and tapetum. In mid-February, the endothecium and tapetum layers disintegrated, and in the epidermal layer the cell walls were thickened with inner protrusions. Subsequently, dehiscence of the microsporangia occurred through rupturing of the microsporangial wall along the dehiscence line. These results suggest that the structure, morphology, architecture and arrangement of male cones of M. glyptostroboides are mainly associated with the production, protection and dispersal of pollen for optimization of wind pollination.

  12. Energy integration in south cone

    International Nuclear Information System (INIS)

    Ribeiro, M.A.K.

    1990-01-01

    The economic development of a geo-political region is directly related to the energy resources available to its productive system. The analysis carried out in this paper focus a region limited by Paraguay, Uruguay, the Argentina north and the Brazilian south, the core of the so called South Cone. The region has a diversified energy matrix that assures strong connections between the countries. The main resources available are hydroelectric but the approach gives a strong emphasis in coal and natural gas. The outlined model of a self sustained development of the region can be used as the foundation of the independent economic development of South America. (author)

  13. Seawave Slot-Cone Generator

    DEFF Research Database (Denmark)

    Vicinanza, Diego; Margheritini, Lucia; Contestabile, Pasquale

    2009-01-01

    This paper discusses a new type of Wave Energy Converter (WEC) named Seawave Slot-Cone Generator (SSG). The SSG is a WEC of the overtopping type. The structure consists of a number of reservoirs one on the top of each others above the mean water level in which the water of incoming waves is store...... on sloping walls constituting the structure. The research is intended to be of direct use to engineers analyzing design and stability of this peculiar kind of coastal structure....

  14. In vitro transdifferentiation of human peripheral blood mononuclear cells to photoreceptor-like cells

    Directory of Open Access Journals (Sweden)

    Yukari Komuta

    2016-06-01

    Full Text Available Direct reprogramming is a promising, simple and low-cost approach to generate target cells from somatic cells without using induced pluripotent stem cells. Recently, peripheral blood mononuclear cells (PBMCs have attracted considerable attention as a somatic cell source for reprogramming. As a cell source, PBMCs have an advantage over dermal fibroblasts with respect to the ease of collecting tissues. Based on our studies involving generation of photosensitive photoreceptor cells from human iris cells and human dermal fibroblasts by transduction of photoreceptor-related transcription factors via retrovirus vectors, we transduced these transcription factors into PBMCs via Sendai virus vectors. We found that retinal disease-related genes were efficiently detected in CRX-transduced cells, most of which are crucial to photoreceptor functions. In functional studies, a light-induced inward current was detected in some CRX-transduced cells. Moreover, by modification of the culture conditions including additional transduction of RAX1 and NEUROD1, we found a greater variety of retinal disease-related genes than that observed in CRX-transduced PBMCs. These data suggest that CRX acts as a master control gene for reprogramming PBMCs into photoreceptor-like cells and that our induced photoreceptor-like cells might contribute to individualized drug screening and disease modeling of inherited retinal degeneration.

  15. PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration.

    Science.gov (United States)

    Pichaud, Franck

    2018-01-01

    The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb) are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM) and zonula adherens (ZA) , thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1) gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.

  16. PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration

    Directory of Open Access Journals (Sweden)

    Franck Pichaud

    2018-03-01

    Full Text Available The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM and zonula adherens (ZA, thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1 gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.

  17. Rod and cone function in patients with KCNV2 retinopathy.

    Directory of Open Access Journals (Sweden)

    Ditta Zobor

    Full Text Available BACKGROUND: To investigate rod and cone function and disease mechanisms in patients with KCNV2 retinopathy. METHODOLOGY/PRINCIPAL FINDINGS: Psychophysical examinations as well as detailed electrophysiological examinations with Ganzfeld and multifocal electroretinogram (ERG were performed to study response dynamics. Additionally, fundus photography, autofluorescence imaging and spectral domain OCTs were carried out for morphological characterization. Molecular genetic analysis revealed compound heterozygosity in five patients and homozygosity for the KCNV2 gene in one patient. The mutations resulted in complete absence of Kv8.2 subunits in three patients (no protein group, NOP, while the other three patients expressed mutant Kv8.2 subunits resulting in altered Kv2.1/Kv8.2 heteromeric or residual Kv2.1 homomeric potassium channel function (altered protein group, ALP. Although more advanced morphological changes were visible in the NOP group, a clear functional difference between the two groups could not be observed. All patients showed characteristic dynamics of the b-wave intensity-response function, however, scotopic b-wave response amplitudes were within normal limits. We also observed severely reduced oscillatory potentials. CONCLUSIONS/SIGNIFICANCE: A specific genotype-phenotype correlation in retinal function could not be demonstrated. KCNV2 mutations cause a unique form of retinal disorder illustrating the importance of K(+-channels for the resting potential, activation and deactivation of photoreceptors, while phototransduction remains unchanged. The reduced oscillatory potentials further suggest an altered function of the inner retina. Besides the characteristically steep amplitude-versus-intensity relationship, flicker responses at intermediate frequencies (5-15 Hz are significantly reduced and shifted in phase.

  18. Identification of the gamma subunit-interacting residues on photoreceptor cGMP phosphodiesterase, PDE6alpha '.

    Science.gov (United States)

    Granovsky, A E; Artemyev, N O

    2000-12-29

    Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the G protein-mediated visual transduction cascade. In the dark, the activity of PDE6 is shut off by the inhibitory gamma subunit (Pgamma). Chimeric proteins between cone PDE6alpha' and cGMP-binding and cGMP-specific PDE (PDE5) have been constructed and expressed in Sf9 cells to study the mechanism of inhibition of PDE6 catalytic activity by Pgamma. Substitution of the segment PDE5-(773-820) by the corresponding PDE6alpha'-(737-784) sequence in the wild-type PDE5 or in a PDE5/PDE6alpha' chimera containing the catalytic domain of PDE5 results in chimeric enzymes capable of inhibitory interaction with Pgamma. The catalytic properties of the chimeric PDEs remained similar to those of PDE5. Ala-scanning mutational analysis of the Pgamma-binding region, PDE6alpha'-(750-760), revealed PDE6alpha' residues essential for the interaction. The M758A mutation markedly impaired and the Q752A mutation moderately impaired the inhibition of chimeric PDE by Pgamma. The analysis of the catalytic properties of mutant PDEs and a model of the PDE6 catalytic domain suggest that residues Met(758) and Gln(752) directly bind Pgamma. A model of the PDE6 catalytic site shows that PDE6alpha'-(750-760) forms a loop at the entrance to the cGMP-binding pocket. Binding of Pgamma to Met(758) would effectively block access of cGMP to the catalytic cavity, providing a structural basis for the mechanism of PDE6 inhibition.

  19. N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR).

    Science.gov (United States)

    Beharry, Seelochan; Zhong, Ming; Molday, Robert S

    2004-12-24

    ABCA4, a member of the family of ATP binding cassette (ABC) proteins found in rod and cone photoreceptors, has been implicated in the transport of retinoid compounds across the outer segment disk membrane following the photoactivation of rhodopsin. Mutations in the ABCA4 gene are responsible for Stargardt macular dystrophy and related retinal degenerative diseases that cause a loss in vision. To identify the retinoid substrate that interacts with ABCA4, we have isolated ABCA4 from rod outer segment disk membranes on an immunoaffinity matrix and analyzed retinoid compounds that bind to ABCA4 using high performance liquid chromatography and radiolabeling methods. When all-trans-retinal was added to ABCA4 in the presence of phosphatidylethanolamine, approximately 0.9 mol of N-retinylidene-phosphatidylethanolamine and 0.3 mol of all-trans-retinal were bound per mol of ABCA4 with an apparent K(d) of 2-5 microm. ATP and GTP released these retinoids from ABCA4, whereas ADP, GDP, and nonhydrolyzable derivatives, adenosine 5'-(beta,gamma-imido)triphosphate and guanosine 5'-(beta,gamma-imido)triphosphate, were ineffective. One mole of N-retinyl-phosphatidylethanolamine, the reduced form of N-retinylidene-phosphatidylethanolamine, bound per mol of ABCA4, whereas 0.3 mol of all-trans-retinal were bound in the absence of phosphatidylethanolamine. No binding of all-trans-retinol to ABCA4 was observed. Our results indicate that ABCA4 preferentially binds N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP. Our studies further suggest that ATP binding and hydrolysis induces a protein conformational change that causes N-retinylidene-phosphatidylethanolamine to dissociate from ABCA4.

  20. Mapping of the human cone transducin {alpha} subunit (GNAT2) gene to 1p13 and mutation analysis in patients with Stargardt`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Magovcevic, I.; Weremowicz, S.; Morton, C.C. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    Transducin {alpha} subunits are members of a large family of G-proteins and play an important role in phototransduction in rod and cone photoreceptors. We report the localization of the human cone {alpha} transducin (GNAT2) gene using fluorescence in situ hybridization (FISH) on chromosome 1 in band p13. The recent assignment of a gene for Stargardt`s disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNAT2 in the pathogenesis of this disease. Stargardt`s disease is characterized by degeneration in late childhood or early adulthood of the macula of the retina, a region rich in cones. We screened patients with Stargardt`s disease, with or without peripheral cone involvement as monitored by the full-field ERG, for mutations in this gene. We investigated 66 unrelated patients including 22 with peripheral cone dysfunction for mutations in the coding region of the GNAT2 gene using polymerase chain reaction-single strand conformation polymorphism analysis (SSCP) and direct sequencing. One patient (034-16) was heterozygous for a silent change in exon VI, Asp238Asp (GAT to GAC). Two patients, one (035-005) with peripheral cone involvement and one (071-001) without peripheral cone involvement, were heterozygous for the missense change Val124Met (GTG to ATG) in exon IV. A subsequent screen of 96 unrelated, unaffected controls revealed one individual (N10) who was also heterozygous for the Val124Met alteration. We concluded that Asp238Asp and Val124Met are rare variants not causing Stargardt`s disease. Hence, no disease-specific mutations were found indicating that GNAT2 is probably not involved in the pathogenesis of most cases of Stargardt`s disease.

  1. Release from the cone ribbon synapse under bright light conditions can be controlled by the opening of only a few Ca(2+) channels.

    Science.gov (United States)

    Bartoletti, Theodore M; Jackman, Skyler L; Babai, Norbert; Mercer, Aaron J; Kramer, Richard H; Thoreson, Wallace B

    2011-12-01

    Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca(2+) channels to open infrequently. To understand neurotransmission under these conditions, we determined the number of L-type Ca(2+) channel openings necessary for vesicle fusion at the cone ribbon synapse. Ca(2+) currents (I(Ca)) were activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs) were recorded from horizontal cells in the salamander retina slice preparation. Ca(2+) channel number and single-channel current amplitude were calculated by mean-variance analysis of I(Ca). Two different comparisons-one comparing average numbers of release events to average I(Ca) amplitude and the other involving deconvolution of both EPSCs and simultaneously recorded cone I(Ca)-suggested that fewer than three Ca(2+) channel openings accompanied fusion of each vesicle at the peak of release during the first few milliseconds of stimulation. Opening fewer Ca(2+) channels did not enhance fusion efficiency, suggesting that few unnecessary channel openings occurred during strong depolarization. We simulated release at the cone synapse, using empirically determined synaptic dimensions, vesicle pool size, Ca(2+) dependence of release, Ca(2+) channel number, and Ca(2+) channel properties. The model replicated observations when a barrier was added to slow Ca(2+) diffusion. Consistent with the presence of a diffusion barrier, dialyzing cones with diffusible Ca(2+) buffers did not affect release efficiency. The tight clustering of Ca(2+) channels, along with a high-Ca(2+) affinity release mechanism and diffusion barrier, promotes a linear coupling between Ca(2+) influx and vesicle fusion. This may improve detection of small light decrements when cones are hyperpolarized by bright light.

  2. Micro-calibration of space and motion by photoreceptors synchronized in parallel with cortical oscillations: A unified theory of visual perception.

    Science.gov (United States)

    Jerath, Ravinder; Cearley, Shannon M; Barnes, Vernon A; Jensen, Mike

    2018-01-01

    A fundamental function of the visual system is detecting motion, yet visual perception is poorly understood. Current research has determined that the retina and ganglion cells elicit responses for motion detection; however, the underlying mechanism for this is incompletely understood. Previously we proposed that retinogeniculo-cortical oscillations and photoreceptors work in parallel to process vision. Here we propose that motion could also be processed within the retina, and not in the brain as current theory suggests. In this paper, we discuss: 1) internal neural space formation; 2) primary, secondary, and tertiary roles of vision; 3) gamma as the secondary role; and 4) synchronization and coherence. Movement within the external field is instantly detected by primary processing within the space formed by the retina, providing a unified view of the world from an internal point of view. Our new theory begins to answer questions about: 1) perception of space, erect images, and motion, 2) purpose of lateral inhibition, 3) speed of visual perception, and 4) how peripheral color vision occurs without a large population of cones located peripherally in the retina. We explain that strong oscillatory activity influences on brain activity and is necessary for: 1) visual processing, and 2) formation of the internal visuospatial area necessary for visual consciousness, which could allow rods to receive precise visual and visuospatial information, while retinal waves could link the lateral geniculate body with the cortex to form a neural space formed by membrane potential-based oscillations and photoreceptors. We propose that vision is tripartite, with three components that allow a person to make sense of the world, terming them "primary, secondary, and tertiary roles" of vision. Finally, we propose that Gamma waves that are higher in strength and volume allow communication among the retina, thalamus, and various areas of the cortex, and synchronization brings cortical

  3. Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function.

    Science.gov (United States)

    Nishiguchi, Koji M; Friedman, James S; Sandberg, Michael A; Swaroop, Anand; Berson, Eliot L; Dryja, Thaddeus P

    2004-12-21

    Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition. In vitro luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL.

  4. Cone calorimeter tests of wood composites

    Science.gov (United States)

    Robert H. White; Kuma Sumathipala

    2013-01-01

    The cone calorimeter is widely used for the determination of the heat release rate (HRR) of building products and other materials. As part of an effort to increase the availability of cone calorimeter data on wood products, the U.S. Forest Products Laboratory and the American Wood Council conducted this study on composite wood products in cooperation with the Composite...

  5. Cone Penetrometer N Factor Determination Testing Results

    Energy Technology Data Exchange (ETDEWEB)

    Follett, Jordan R.

    2014-03-05

    This document contains the results of testing activities to determine the empirical 'N Factor' for the cone penetrometer in kaolin clay simulant. The N Factor is used to releate resistance measurements taken with the cone penetrometer to shear strength.

  6. Cone penetrometer demonstration standard startup review checklist

    International Nuclear Information System (INIS)

    KRIEG, S.A.

    1998-01-01

    Startup readiness for the Cone Penetrometer Demonstration in AX Tank Farm will be verified through the application of a Standard Startup Review Checklist. This is a listing of those items essential to demonstrating readiness to start the Cone Penetrometer Demonstration in AX Tank Farm

  7. Shaggy Photoreceptors with Subfoveal Fluid Associated with a Distant Choroidal Melanoma

    Directory of Open Access Journals (Sweden)

    Ann Q. Tran

    2015-01-01

    Full Text Available Purpose. To describe the enhanced depth imaging optical coherence tomography (EDI-OCT findings in a patient with an extra macula choroidal melanoma before and after treatment. Methods. Observational case report. Results. A 45 year-old Caucasian male patient was referred to retina clinic for management of choroidal melanoma. Examination revealed a nasal choroidal melanoma while EDI-OCT illustrated subfoveal fluid pocket with elongated shaggy photoreceptors distant and separate from the tumor. The patient was treated with plaque brachytherapy and intravitreal bevacizumab. One week after plaque removal, there was a dramatic reduction in the shaggy photoreceptors. Conclusion. Choroidal melanomas have effects that are not localized to the area of the tumor. This loculated pocket of subretinal fluid and coinciding changes to photoreceptor morphology may be related to global changes in choroidal function or release of tumor related cytokines.

  8. Double Dirac cones in phononic crystals

    KAUST Repository

    Li, Yan

    2014-07-07

    A double Dirac cone is realized at the center of the Brillouin zone of a two-dimensional phononic crystal (PC) consisting of a triangular array of core-shell-structure cylinders in water. The double Dirac cone is induced by the accidental degeneracy of two double-degenerate Bloch states. Using a perturbation method, we demonstrate that the double Dirac cone is composed of two identical and overlapping Dirac cones whose linear slopes can also be accurately predicted from the method. Because the double Dirac cone occurs at a relatively low frequency, a slab of the PC can be mapped onto a slab of zero refractive index material by using a standard retrieval method. Total transmission without phase change and energy tunneling at the double Dirac point frequency are unambiguously demonstrated by two examples. Potential applications can be expected in diverse fields such as acoustic wave manipulations and energy flow control.

  9. Double Dirac cones in phononic crystals

    KAUST Repository

    Li, Yan; Wu, Ying; Mei, Jun

    2014-01-01

    A double Dirac cone is realized at the center of the Brillouin zone of a two-dimensional phononic crystal (PC) consisting of a triangular array of core-shell-structure cylinders in water. The double Dirac cone is induced by the accidental degeneracy of two double-degenerate Bloch states. Using a perturbation method, we demonstrate that the double Dirac cone is composed of two identical and overlapping Dirac cones whose linear slopes can also be accurately predicted from the method. Because the double Dirac cone occurs at a relatively low frequency, a slab of the PC can be mapped onto a slab of zero refractive index material by using a standard retrieval method. Total transmission without phase change and energy tunneling at the double Dirac point frequency are unambiguously demonstrated by two examples. Potential applications can be expected in diverse fields such as acoustic wave manipulations and energy flow control.

  10. Edaravone, an ROS Scavenger, Ameliorates Photoreceptor Cell Death after Experimental Retinal Detachment

    Science.gov (United States)

    Roh, Mi In; Murakami, Yusuke; Thanos, Aristomenis; Miller, Joan W.

    2011-01-01

    Purpose. To investigate whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, would be neuroprotective against photoreceptor cell death in a rat model of retinal detachment (RD). Methods. RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3, 5, or 10 mg/kg) or physiologic saline was administered intraperitoneally once a day until death on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness. Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively. Results. RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced the ROS level, along with a decrease in TUNEL-positive cells in the photoreceptor layer. A caspase assay also confirmed decreased activation of caspase-3, -8, and -9 in RD treated with edaravone. The level of the antiapoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. In addition, edaravone treatment resulted in a significant decrease in the levels of TNF-α, MCP-1, and macrophage infiltration. Conclusions. Oxidative stress plays an important role in photoreceptor cell death after RD. Edaravone treatment may aid in preventing photoreceptor cell death after RD by suppressing ROS-induced photoreceptor damage. PMID:21310909

  11. Photoreceptor cells with profound structural deficits can support useful vision in mice.

    Science.gov (United States)

    Thompson, Stewart; Blodi, Frederick R; Lee, Swan; Welder, Chris R; Mullins, Robert F; Tucker, Budd A; Stasheff, Steven F; Stone, Edwin M

    2014-03-25

    In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting stem cell-derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer segments, considered critical for photoreceptor cell function. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (Rds(P90)). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Rds(P90) mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that Rds(P90) mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m(2)). Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision.

  12. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

  13. Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: electron microscopy, tomography and oxygen consumption.

    Science.gov (United States)

    Perkins, Guy A; Scott, Ray; Perez, Alex; Ellisman, Mark H; Johnson, Jerry E; Fox, Donald A

    2012-01-01

    Postnatal lead exposure produces rod-selective and Bax-mediated apoptosis, decreased scotopic electroretinograms (ERGs), and scotopic and mesopic vision deficits in humans and/or experimental animals. Rod, but not cone, inner segment mitochondria were considered the primary site of action. However, photoreceptor synaptic mitochondria were not examined. Thus, our experiments investigated the structural and functional effects of environmentally relevant postnatal lead exposure on rod spherule and cone pedicle mitochondria and whether Bcl-xL overexpression provided neuroprotection. C57BL/6N mice pups were exposed to lead only during lactation via dams drinking water containing lead acetate. The blood [Pb] at weaning was 20.6±4.7 µg/dl, which decreased to the control value by 2 months. To assess synaptic mitochondrial structural differences and vulnerability to lead exposure, wild-type and transgenic mice overexpressing Bcl-xL in photoreceptors were used. Electron microscopy, three-dimensional electron tomography, and retinal and photoreceptor synaptic terminal oxygen consumption (QO(2)) studies were conducted in adult control, Bcl-xL, lead, and Bcl-xL/lead mice. The spherule and pedicle mitochondria in lead-treated mice were swollen, and the cristae structure was markedly changed. In the lead-treated mice, the mitochondrial cristae surface area and volume (abundance: measure correlated with ATP (ATP) synthesis) were decreased in the spherules and increased in the pedicles. Pedicles also had an increased number of crista segments per volume. In the lead-treated mice, the number of segments/crista and fraction of cristae with multiple segments (branching) similarly increased in spherule and pedicle mitochondria. Lead-induced remodeling of spherule mitochondria produced smaller cristae with more branching, whereas pedicle mitochondria had larger cristae with more branching and increased crista junction (CJ) diameter. Lead decreased dark- and light-adapted photoreceptor

  14. Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging.

    Science.gov (United States)

    Song, Hongxin; Rossi, Ethan A; Stone, Edwin; Latchney, Lisa; Williams, David; Dubra, Alfredo; Chung, Mina

    2018-01-01

    Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A . This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  16. Interaction of two photoreceptors in the regulation of bacterial photosynthesis genes

    OpenAIRE

    Metz, Sebastian; Haberzettl, Kerstin; Frühwirth, Sebastian; Teich, Kristin; Hasewinkel, Christian; Klug, Gabriele

    2012-01-01

    The expression of photosynthesis genes in the facultatively photosynthetic bacterium Rhodobacter sphaeroides is controlled by the oxygen tension and by light quantity. Two photoreceptor proteins, AppA and CryB, have been identified in the past, which are involved in this regulation. AppA senses light by its N-terminal BLUF domain, its C-terminal part binds heme and is redox-responsive. Through its interaction to the transcriptional repressor PpsR the AppA photoreceptor controls expression of ...

  17. No evidence for a genetic blueprint: The case of the "complex" mammalian photoreceptor

    Directory of Open Access Journals (Sweden)

    G Kumaramanickavel

    2015-01-01

    Full Text Available Despite the intensity of the search for genes causing inherited retinal degenerations over the past 3 decades, of the approximately 200 disease genes identified to date, all appear to be ordinary housekeeping genes specifying proteins playing basic structural and functional roles in the mature photoreceptor cells. No genes or genetic elements have been identified which can be construed as having a specific morphogenic role, directing the development of the cytoarchitecture of any particular retinal cell. The evidence suggests that the cytoarchitecture of the retinal photoreceptors, although enormously complex, arises from the self-organization of the cells constituents without any regulation or direction from an external genetic blueprint.

  18. Chemically-induced photoreceptor degeneration and protection in mouse iPSC-derived three-dimensional retinal organoids

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Ito

    2017-10-01

    Full Text Available Induced pluripotent stem cells (iPSCs, which can be differentiated into various tissues and cell types, have been used for clinical research and disease modeling. Self-organizing three-dimensional (3D tissue engineering has been established within the past decade and enables researchers to obtain tissues and cells that almost mimic in vivo development. However, there are no reports of practical experimental procedures that reproduce photoreceptor degeneration. In this study, we induced photoreceptor cell death in mouse iPSC-derived 3D retinal organoids (3D-retinas by 4-hydroxytamoxifen (4-OHT, which induces photoreceptor degeneration in mouse retinal explants, and then established a live-cell imaging system to measure degeneration-related properties. Furthermore, we quantified the protective effects of representative ophthalmic supplements for treating the photoreceptor degeneration. This drug evaluation system enables us to monitor drug effects in photoreceptor cells and could be useful for drug screening.

  19. Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

    Science.gov (United States)

    Dryja, Thaddeus P.; McGee, Terri L.; Berson, Eliot L.; Fishman, Gerald A.; Sandberg, Michael A.; Alexander, Kenneth R.; Derlacki, Deborah J.; Rajagopalan, Aruna S.

    2005-01-01

    We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform. PMID:15781871

  20. The southern cone petroleum market

    International Nuclear Information System (INIS)

    Pisani, W.

    1992-01-01

    The Argentine oil sector has been moving strongly toward complete deregulation since 1989. Price controls on byproducts has been lifted, old petroleum contracts became into concessions, and the state oil company, YPF, is under process of privatization. In this context, the international companies scouting for opportunities can find an important menu of potential investments But here remain some problems connected with this deregulation, too. The lack of a reference crude and product market price is one of them. This paper focuses how to overcome this trouble with the establishment of an institutional market for crude and products, not only for Argentina but also for the entire Southern Cone Region (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay), inquiring into the benefits of its creation

  1. Parafoveal retinal cone mosaic imaging in children with ultra-compact switchable SLO/OCT handheld probe (Conference Presentation)

    Science.gov (United States)

    LaRocca, Francesco; Nankivil, Derek; DuBose, Theodore B.; Toth, Cynthia A.; Farsiu, Sina; Izatt, Joseph A.

    2016-03-01

    In vivo photoreceptor imaging has enhanced the way vision scientists and ophthalmologists understand the retinal structure, function, and etiology of numerous retinal pathologies. However, the complexity and large footprint of current systems capable of resolving photoreceptors has limited imaging to patients who are able to sit in an upright position and fixate for several minutes. Unfortunately, this excludes an important fraction of patients including bedridden patients, small children, and infants. Here, we show that our dual-modality, high-resolution handheld probe with a weight of only 94 g is capable of visualizing photoreceptors in supine children. Our device utilizes a microelectromechanical systems (MEMS) scanner and a novel telescope design to achieve over an order of magnitude reduction in size compared to similar systems. The probe has a 7° field of view and a lateral resolution of 8 µm. The optical coherence tomography (OCT) system has an axial resolution of 7 µm and a sensitivity of 101 dB. High definition scanning laser ophthalmoscopy (SLO) and OCT images were acquired from children ranging from 14 months to 12 years of age with and without pathology during examination under anesthesia in the operating room. Parafoveal cone imaging was shown using the SLO arm of this device without adaptive optics using a 3° FOV for the first time in children under 4 years old. This work lays the foundation for pediatric research, which will improve understanding of retinal development, maldevelopment and early onset of diseases at the cellular level during the beginning stages of human growth.

  2. Dirac cones in isogonal hexagonal metallic structures

    Science.gov (United States)

    Wang, Kang

    2018-03-01

    A honeycomb hexagonal metallic lattice is equivalent to a triangular atomic one and cannot create Dirac cones in its electromagnetic wave spectrum. We study in this work the low-frequency electromagnetic band structures in isogonal hexagonal metallic lattices that are directly related to the honeycomb one and show that such structures can create Dirac cones. The band formation can be described by a tight-binding model that allows investigating, in terms of correlations between local resonance modes, the condition for the Dirac cones and the consequence of the third structure tile sustaining an extra resonance mode in the unit cell that induces band shifts and thus nonlinear deformation of the Dirac cones following the wave vectors departing from the Dirac points. We show further that, under structure deformation, the deformations of the Dirac cones result from two different correlation mechanisms, both reinforced by the lattice's metallic nature, which directly affects the resonance mode correlations. The isogonal structures provide new degrees of freedom for tuning the Dirac cones, allowing adjustment of the cone shape by modulating the structure tiles at the local scale without modifying the lattice periodicity and symmetry.

  3. Cone penetrometer moisture probe acceptance test report

    International Nuclear Information System (INIS)

    Barnes, G.A.

    1996-01-01

    This Acceptance Test Report (ATR) documents the results of WHC-SD-WM-ATP-146 (Prototype Cone Penetrometer Moisture Probe Acceptance Test Procedure) and WHC-SD-WM-ATP-145 (Cone Penetrometer Moisture Probe Acceptance Test Procedure). The master copy of WHC-SD-WM-ATP-145 can be found in Appendix A and the master copy of WHC-SD-WM-ATP-146 can be found in Appendix B. Also included with this report is a matrix showing design criteria of the cone penetrometer moisture probe and the verification method used (Appendix C)

  4. Demise of light cone field theory

    International Nuclear Information System (INIS)

    Hagen, C.R.

    1977-01-01

    It is shown that the massive spin one-half field is noncovariant in two dimensional light cone coordinates. It is shown that spin one-half is noncovariant in four dimensions as well. It is concluded that since the case of the spin one-half field is an absolute necessity if one is to build a world containing fermions. It seems safe to infer that light cone quantization cannot be useful in the quark binding problem as currently conceived. It is suggested that further work on light cone quantization be focused solely upon the questions of consistency as discussed rather than on applications to model building. 9 references

  5. Correlation Between Cone Penetration Rate And Measured Cone Penetration Parameters In Silty Soils

    DEFF Research Database (Denmark)

    Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

    2013-01-01

    This paper shows, how a change in cone penetration rate affects the cone penetration measurements, hence the cone resistance, pore pressure, and sleeve friction in silty soil. The standard rate of penetration is 20 mm/s, and it is generally accepted that undrained penetration occurs in clay while...... drained penetration occurs in sand. When lowering the penetration rate, the soil pore water starts to dissipate and a change in the drainage condition is seen. In intermediate soils such as silty soils, the standard cone penetration rate may result in a drainage condition that could be undrained......, partially or fully drained. However, lowering the penetration rate in silty soils has a great significance because of the soil permeability, and only a small change in penetration rate will result in changed cone penetration measurements. In this paper, analyses will be done on data from 15 field cone...

  6. The xanthopsins : a new family of eubacterial blue-light photoreceptors

    NARCIS (Netherlands)

    Kort, R; Hoff, W.D.; West, M.E.; Kroon, A R; Hoffer, S.M.; Vlieg, K H; Crielaand, W; van Beeumen, J.; Hellingwerf, K J

    1996-01-01

    Photoactive yellow protein (PYP) is a photoreceptor that has been isolated from three halophilic phototrophic purple bacteria. The PYP from Ectothiorhodospira halophila BN9626 is the only member for which the sequence has been reported at the DNA level. Here we describe the cloning and sequencing of

  7. The Xanthopsins: a new family of eubacterial blue-light photoreceptors

    NARCIS (Netherlands)

    Kort, R.; Hoff, W.D.; van West, W.S.; Kroon, A.R.; Hoffer, S.M.; Vlieg, K.H.; Crielaard, W.; van Beeumen, J.J.; Hellingwerf, K.J.

    1996-01-01

    Photoactive yellow protein (PYP) is a photoreceptor that has been isolated from three halophilic phototrophic purple bacteria. The PYP from Ectothiorhodospira halophila BN9626 is the only member for which the sequence has been reported at the DNA level. Here we describe the cloning and sequencing of

  8. Melanopsin-expressing amphioxus photoreceptors transduce light via a phospholipase C signaling cascade.

    Directory of Open Access Journals (Sweden)

    Juan Manuel Angueyra

    Full Text Available Melanopsin, the receptor molecule that underlies light sensitivity in mammalian 'circadian' receptors, is homologous to invertebrate rhodopsins and has been proposed to operate via a similar signaling pathway. Its downstream effectors, however, remain elusive. Melanopsin also expresses in two distinct light-sensitive cell types in the neural tube of amphioxus. This organism is the most basal extant chordate and can help outline the evolutionary history of different photoreceptor lineages and their transduction mechanisms; moreover, isolated amphioxus photoreceptors offer unique advantages, because they are unambiguously identifiable and amenable to single-cell physiological assays. In the present study whole-cell patch clamp recording, pharmacological manipulations, and immunodetection were utilized to investigate light transduction in amphioxus photoreceptors. A G(q was identified and selectively localized to the photosensitive microvillar membrane, while the pivotal role of phospholipase C was established pharmacologically. The photocurrent was profoundly depressed by IP₃ receptor antagonists, highlighting the importance of IP₃ receptors in light signaling. By contrast, surrogates of diacylglycerol (DAG, as well as poly-unsaturated fatty acids failed to activate a membrane conductance or to alter the light response. The results strengthen the notion that calcium released from the ER via IP₃-sensitive channels may fulfill a key role in conveying--directly or indirectly--the melanopsin-initiated light signal to the photoconductance; moreover, they challenge the dogma that microvillar photoreceptors and phoshoinositide-based light transduction are a prerogative of invertebrate eyes.

  9. Temperature Dependence of Receptor Potential and Noise in Fly (Calliphora erythrocephala) Photoreceptor Cells

    NARCIS (Netherlands)

    Roebroek, J.G.H.; Tjonger, M. van; Stavenga, D.G.

    1990-01-01

    We investigated the effect of temperature on the response to light of photoreceptors of the blowfly Calliphora erythrocephala. The latency and the time-to-peak of the responses become shorter as the temperature increases; Q10 = 2.8 ± 0.6. The response amplitude is independent of the temperature in

  10. Moderate Light-Induced Degeneration of Rod Photoreceptors with Delayed Transducin Translocation in shaker1 Mice

    Science.gov (United States)

    Zallocchi, Marisa; Wang, Wei-Min; Delimont, Duane; Cosgrove, Dominic

    2011-01-01

    Purpose. Usher syndrome is characterized by congenital deafness associated with retinitis pigmentosa (RP). Mutations in the myosin VIIa gene (MYO7A) cause a common and severe subtype of Usher syndrome (USH1B). Shaker1 mice have mutant MYO7A. They are deaf and have vestibular dysfunction but do not develop photoreceptor degeneration. The goal of this study was to investigate abnormalities of photoreceptors in shaker1 mice. Methods. Immunocytochemistry and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated. Results. In shaker1 mice, the rod transducin translocation is delayed because of a shift of its light activation threshold to a higher level. Even moderate light exposure can induce oxidative damage and significant rod degeneration in shaker1 mice. Shaker1 mice reared under a moderate light/dark cycle develop severe retinal degeneration in less than 6 months. Conclusions. These findings show that, contrary to earlier studies, shaker1 mice possess a robust retinal phenotype that may link to defective rod protein translocation. Importantly, USH1B animal models are likely vulnerable to light-induced photoreceptor damage, even under moderate light. PMID:21447681

  11. Effective delivery of recombinant proteins to rod photoreceptors via lipid nanovesicles

    Energy Technology Data Exchange (ETDEWEB)

    Asteriti, Sabrina [Dept. of Translational Research, University of Pisa, Pisa (Italy); Dal Cortivo, Giuditta [Dept. of Life Sciences and Reproduction, University of Verona, Strada Le Grazie 8, Verona (Italy); Pontelli, Valeria [Dept. of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, Verona (Italy); Cangiano, Lorenzo [Dept. of Translational Research, University of Pisa, Pisa (Italy); Buffelli, Mario, E-mail: mario.buffelli@univr.it [Dept. of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, Verona (Italy); Center for Biomedical Computing, University of Verona, Strada le Grazie 8, 37134 Verona (Italy); Dell’Orco, Daniele, E-mail: daniele.dellorco@univr.it [Dept. of Life Sciences and Reproduction, University of Verona, Strada Le Grazie 8, Verona (Italy); Center for Biomedical Computing, University of Verona, Strada le Grazie 8, 37134 Verona (Italy)

    2015-06-12

    The potential of liposomes to deliver functional proteins in retinal photoreceptors and modulate their physiological response was investigated by two experimental approaches. First, we treated isolated mouse retinas with liposomes encapsulating either recoverin, an important endogenous protein operating in visual phototransduction, or antibodies against recoverin. We then intravitrally injected in vivo liposomes encapsulating either rhodamin B or recoverin and we investigated the distribution in retina sections by confocal microscopy. The content of liposomes was found to be released in higher amount in the photoreceptor layer than in the other regions of the retina and the functional effects of the release were in line with the current model of phototransduction. Our study sets the basis for quantitative investigations aimed at assessing the potential of intraocular protein delivery via biocompatible nanovesicles, with promising implications for the treatment of retinal diseases affecting the photoreceptor layer. - Highlights: • Recombinant proteins encapsulated in nano-sized liposomes injected intravitreally reach retinal photoreceptors. • The phototransduction cascade in rods is modulated by the liposome content. • Mathematical modeling predicts the alteration of the photoresponses following liposome fusion.

  12. Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats.

    Science.gov (United States)

    Schraermeyer, U; Thumann, G; Luther, T; Kociok, N; Armhold, S; Kruttwig, K; Andressen, C; Addicks, K; Bartz-Schmidt, K U

    2001-01-01

    The Royal College of Surgeons (RCS) rat is an animal model for retinal degeneration such as the age-related macular degeneration. The RCS rat undergoes a progressive retinal degeneration during the early postnatal period. A potential treatment to prevent this retinal degeneration is the transplantation into the subretinal space of cells that would replace functions of the degenerating retinal pigment epithelium (RPE) cells or may form neurotrophic factors. In this study we have investigated the potential of subretinally transplanted embryonic stem cells to prevent the genetically determined photoreceptor cell degeneration in the RCS rat. Embryonic stem cells from the inner cell mass of the mouse blastocyst were allowed to differentiate to neural precursor cells in vitro and were then transplanted into the subretinal space of 20-day-old RCS rats. Transplanted and sham-operated rats were sacrificed 2 months following cell transplantation. The eyes were enucleated and photoreceptor degeneration was quantified by analyzing and determining the thickness of the outer nuclear layer by light and electron microscopy. In the eyes transplanted with embryonic cells up to 8 rows of photoreceptor cell nuclei were observed, whereas in nontreated control eyes the outer nuclear layer had degenerated completely. Transplantation of embryonic stem cells appears to delay photoreceptor cell degeneration in RCS rats.

  13. Is the photoactive yellow protein a UV-B/blue light photoreceptor?

    NARCIS (Netherlands)

    Carroll, E. C.; Hospes, M.; Valladares, C.; Hellingwerf, K.J.; Larsen, D.S.

    2011-01-01

    UV light below 300 nm is shown to generate the first photocycle intermediate in the blue light photoreceptor Photoactive Yellow Protein. Fluorescence and ultrafast transient absorption measurements indicate two excitation pathways: UV-B absorption by the chromophore and Fluorescence Resonant Energy

  14. The genetics of some planthormones and photoreceptors in Arabidopsis thaliana (L.) Heynh.

    NARCIS (Netherlands)

    Koornneef, M.

    1982-01-01

    This thesis describes the isolation and characterization in Arabidopsis thaliana (L.) Heynh. of induced mutants, deficient for gibberellins (GA's), abscisic acid (ABA) and photoreceptors.

    These compounds are known to regulate various facets of plant growth and

  15. Simple explant culture of the embryonic chicken retina with long-term preservation of photoreceptors.

    Science.gov (United States)

    Thangaraj, Gopenath; Greif, Alexander; Layer, Paul G

    2011-10-01

    Structurally stable in vitro-model systems are indispensible to analyse neural development during embryogenesis, follow cellular differentiation and evaluate neurotoxicological or growth factor effects. Here we describe a three-dimensional, long-term in vitro-culture system of the embryonic chick retina which supports photoreceptor development. Retinal tissue was isolated from E6 chick eye, and cultured as explants by continuous orbital rotation to allow free floatation without any supporting materials. Young stage (E6) immature retinas were cultured for various time periods in order to follow the differentiation of cell types and plexiform layers by immunocytochemical methods. These explants could be cultured for at least 2-3 weeks with remarkable retention of retinal architecture. Interestingly, photoreceptors developed in the absence of pigment epithelium. Electron microscopic studies revealed formation of structures resembling photoreceptor outer segments, a feature not reported previously. Thus, the verification of photoreceptors, Müller cells, inner retinal cells and the inner plexiform layer described in our study establishes this explant culture as a valuable in vivo-like model system. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  16. Chemical Excitation and Inactivation in Photoreceptors of the Fly Mutants trp and nss

    NARCIS (Netherlands)

    Suss, E.; Barash, S.; Stavenga, D.G.; Stieve, H.; Selinger, Z.; Minke, B.

    1989-01-01

    The Drosophila and Lucilia photoreceptor mutants, trp and nss, respond like wild-type flies to a short pulse of intense light or prolonged dim light; however, upon continuous intense illumination, the trp and nss mutants are unable to maintain persistent excitation. This defect manifests itself by a

  17. Photoreceptor spectral sensitivities of the Small White butterfly Pieris rapae crucivora interpreted with optical modeling

    NARCIS (Netherlands)

    Stavenga, Doekele G.; Arikawa, Kentaro

    The compound eye of the Small White butterfly, Pieris rapae crucivora, has four classes of visual pigments, with peak absorption in the ultraviolet, violet, blue and green, but electrophysiological recordings yielded eight photoreceptors classes: an ultraviolet, violet, blue, double-peaked blue,

  18. Sexual dimorphism of short-wavelength photoreceptors in the small white butterfly, Pieris rapae crucivora

    NARCIS (Netherlands)

    Arikawa, K; Wakakuwa, M; Qiu, XD; Kurasawa, M; Stavenga, DG; Qiu, Xudong

    2005-01-01

    The eyes of the female small white butterfly, Pieris rapae crucivora, are furnished with three classes of short-wavelength photoreceptors, with sensitivity peaks in the ultraviolet (UV) (lambda(max) = 360 nm), violet (V) (lambda max = 425 nm), and blue (B) (lambda(max) = 453 nm) wavelength range.

  19. Xbp1-Independent Ire1 Signaling Is Required for Photoreceptor Differentiation and Rhabdomere Morphogenesis in Drosophila

    Directory of Open Access Journals (Sweden)

    Dina S. Coelho

    2013-11-01

    Full Text Available The unfolded protein response (UPR is composed by homeostatic signaling pathways that are activated by excessive protein misfolding in the endoplasmic reticulum. Ire1 signaling is an important mediator of the UPR, leading to the activation of the transcription factor Xbp1. Here, we show that Drosophila Ire1 mutant photoreceptors have defects in the delivery of rhodopsin-1 to the rhabdomere and in the secretion of Spacemaker/Eyes Shut into the interrhabdomeral space. However, these defects are not observed in Xbp1 mutant photoreceptors. Ire1 mutant retinas have higher mRNA levels for targets of regulated Ire1-dependent decay (RIDD, including for the fatty acid transport protein (fatp. Importantly, the downregulation of fatp by RNAi rescues the rhodopsin-1 delivery defects observed in Ire1 mutant photoreceptors. Our results show that the role of Ire1 during photoreceptor differentiation is independent of Xbp1 function and demonstrate the physiological relevance of the RIDD mechanism in this specific paradigm.

  20. Mach cones in space and laboratory dusty magnetoplasmas

    International Nuclear Information System (INIS)

    Mamun, A.A.; Shukla, P.K

    2004-07-01

    We present a rigorous theoretical investigation on the possibility for the formation of Mach cones in both space and laboratory dusty magnetoplasmas. We find the parametric regimes for which different types of Mach cones, such as dust acoustic Mach cones, dust magneto-acoustic Mach cones, oscillonic Mach cones, etc. are formed in space and laboratory dusty magnetoplasmas. We also identify the basic features of such different classes of Mach cones (viz. dust- acoustic, dust magneto-acoustic, oscillonic Mach cones, etc.), and clearly explain how they are relevant to space and laboratory dusty manetoplasmas. (author)

  1. Perturbation theory in light-cone gauge

    International Nuclear Information System (INIS)

    Vianello, Eliana

    2000-01-01

    Perturbation calculations are presented for the light-cone gauge Schwinger model. Eigenstates can be calculated perturbatively but the perturbation theory is nonstandard. We hope to extend the work to QCD 2 to resolve some outstanding issues in those theories

  2. Gibberellin and auxin influence the diurnal transcription pattern of photoreceptor genes via CRY1a in tomato.

    Directory of Open Access Journals (Sweden)

    Paolo Facella

    Full Text Available Plant photoreceptors, phytochromes and cryptochromes, regulate many aspects of development and growth, such as seed germination, stem elongation, seedling de-etiolation, cotyledon opening, flower induction and circadian rhythms. There are several pieces of evidence of interaction between photoreceptors and phyto-hormones in all of these physiological processes, but little is known about molecular and genetic mechanisms underlying hormone-photoreceptor crosstalk.In this work, we investigated the molecular effects of exogenous phyto-hormones to photoreceptor gene transcripts of tomato wt, as well as transgenic and mutant lines with altered cryptochromes, by monitoring day/night transcript oscillations. GA and auxin alter the diurnal expression level of different photoreceptor genes in tomato, especially in mutants that lack a working form of cryptochrome 1a: in those mutants the expression of some (IAA or most (GA photoreceptor genes is down regulated by these hormones.Our results highlight the presence of molecular relationships among cryptochrome 1a protein, hormones, and photoreceptors' gene expression in tomato, suggesting that manipulation of cryptochromes could represent a good strategy to understand in greater depth the role of phyto-hormones in the plant photoperceptive mechanism.

  3. Modified superstring in light cone gauge

    International Nuclear Information System (INIS)

    Kamimura, Kiyoshi; Tatewaki, Machiko.

    1988-01-01

    We analyze the covariant superstring theory proposed by Siegel in light cone gauge. The physical states are the direct product of those of Green-Schwarz Superstring and the additional internal space spanned by light cone spinors. At clasical level, there is no difference among observables in Siegel's modified Superstring theory (SMST) and Green-Schwarz's one (GSST). However SMST can not be quantized with additional constraints as the physical state conditions. (author)

  4. Design of a trichromatic cone array.

    Directory of Open Access Journals (Sweden)

    Patrick Garrigan

    2010-02-01

    Full Text Available Cones with peak sensitivity to light at long (L, medium (M and short (S wavelengths are unequal in number on the human retina: S cones are rare (<10% while increasing in fraction from center to periphery, and the L/M cone proportions are highly variable between individuals. What optical properties of the eye, and statistical properties of natural scenes, might drive this organization? We found that the spatial-chromatic structure of natural scenes was largely symmetric between the L, M and S sensitivity bands. Given this symmetry, short wavelength attenuation by ocular media gave L/M cones a modest signal-to-noise advantage, which was amplified, especially in the denser central retina, by long-wavelength accommodation of the lens. Meanwhile, total information represented by the cone mosaic remained relatively insensitive to L/M proportions. Thus, the observed cone array design along with a long-wavelength accommodated lens provides a selective advantage: it is maximally informative.

  5. Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

    Science.gov (United States)

    Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

    2012-01-01

    In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance between excitation and inhibition in the outer retina needs to be adaptable. How this is achieved is unknown. Using electrophysiological techniques in the isolated retina of the goldfish, it was found that opening Ca2+-dependent Cl− channels in recorded cones reduced the size of feedback responses measured in both cones and HCs. Furthermore, we show that cones express Cl− channels that are gated by GABA released from HCs. Similar to activation of ICl(Ca), opening of these GABA-gated Cl− channels reduced the size of light-induced feedback responses both in cones and HCs. Conversely, application of picrotoxin, a blocker of GABAA and GABAC receptors, had the opposite effect. In addition, reducing GABA release from HCs by blocking GABA transporters also led to an increase in the size of feedback. Because the independent manipulation of Ca2+-dependent Cl− currents in individual cones yielded results comparable to bath-applied GABA, it was concluded that activation of either Cl− current by itself is sufficient to reduce the size of HC feedback. However, additional effects of GABA on outer retinal processing cannot be excluded. These results can be accounted for by an ephaptic feedback model in which a cone Cl− current shunts the current flow in the synaptic cleft. The Ca2+-dependent Cl− current might be essential to set the initial balance between the feedforward and the feedback signals active in the cone HC synapse. It prevents that strong feedback from HCs to cones flood the cone with Ca2+. Modulation of the feedback strength by GABA might play a role during light/dark adaptation, adjusting the amount of negative feedback to the signal to noise ratio of the

  6. Spectral characteristics of light sources for S-cone stimulation.

    Science.gov (United States)

    Schlegelmilch, F; Nolte, R; Schellhorn, K; Husar, P; Henning, G; Tornow, R P

    2002-11-01

    Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

  7. Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats.

    Science.gov (United States)

    Pinilla, I; Lund, R D; Sauvé, Y

    2005-01-01

    The Royal College of Surgeons (RCS) rat has a primary defect in retinal pigment epithelial cells that leads to the progressive loss of photoreceptors and central visual responsiveness. While most rods are lost by 90 days of age (P90), cones degenerate more slowly, and can be detected anatomically up to 2 years of age, despite massive neuronal death and retinal remodelling. To examine how this progressive degenerative process impacts on cone function, we recorded the electroretingram to white light flashes (1.37 log cd s m(-2)) presented at frequencies ranging from 3 to 50 Hz, under light adapted conditions (29.8 cd m(-2)). Pigmented dystrophic and congenic non-dystrophic RCS rats aged from 18 to 300 days were studied. In all responsive animals at all ages, maximal amplitudes were obtained at 3 Hz. In both non-dystrophic and dystrophic rats, there was an increase from P18 to P21 in response amplitude and critical fusion frequency. After P21, these two parameters declined progressively with age in dystrophic rats. Other changes included prolongation in latency, which was first detected prior to the initiation of amplitude reduction. While phase shifts were also detected in dystrophic RCS rats, they appeared at later degenerative stages. The latest age at which responses could be elicited in dystrophic rats was at P200, with positive waves being replaced by negative deflections. The effect of increments in the intensity of background illumination was tested at P50 in both groups. This caused a diminution in flicker response amplitude and critical fusion frequencies in non-dystrophics, while in dystrophic animals, response amplitudes were reduced only at low frequencies and critical fusion frequencies were unaltered. In conclusion, although dystrophic RCS rats undergo a progressive decline in cone function with age, the flicker responsiveness at P21 is comparable to that of non-dystrophic congenic rats, suggesting normal developmental maturation of the cone system in

  8. Clinical Course, Genetic Etiology, and Visual Outcome in Cone and Cone-Rod Dystrophy

    NARCIS (Netherlands)

    Thiadens, Alberta A. H. J.; Phan, T. My Lan; Zekveld-Vroon, Renate C.; Leroy, Bart P.; van den Born, L. Ingeborgh; Hoyng, Carel B.; Klaver, Caroline C. W.; Roosing, Susanne; Pott, Jan-Willem R.; van Schooneveld, Mary J.; van Moll-Ramirez, Norka; van Genderen, Maria M.; Boon, Camiel J. F.; den Hollander, Anneke I.; Bergen, Arthur A. B.; De Baere, Elfride; Cremers, Frans P. M.; Lotery, Andrew J.

    Objective: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD). Design: Clinic-based, longitudinal, multicenter study. Participants: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N =

  9. Universal enveloping algebras of Toda field theories and the light-cone asymmetry parameter

    International Nuclear Information System (INIS)

    Itoyama, H.; Moxhay, P.

    1990-01-01

    The generators of the universal enveloping algebras in Toda field theories associated with Lie algebras are constructed. These form spectrum-generating algebras of the system which survive the constraints acting on the larger current algebra structure. It is found that the same generators fail to be a symmetry in the case of affine Toda field theory despite their close relationship with Mandelstam's soliton operators. We introduce the light-cone asymmetry parameter; its significance and utility are demonstrated. (orig.)

  10. OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models.

    Directory of Open Access Journals (Sweden)

    Juan Wang

    Full Text Available Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP, a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N-methyl-N-nitrosourea (MNU-induced rats and Royal College of Surgeons (RCS rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC. Reactive oxygen species (ROS were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS. Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up-regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor

  11. Activin Signals through SMAD2/3 to Increase Photoreceptor Precursor Yield during Embryonic Stem Cell Differentiation.

    Science.gov (United States)

    Lu, Amy Q; Popova, Evgenya Y; Barnstable, Colin J

    2017-09-12

    In vitro differentiation of mouse embryonic stem cells (ESCs) into retinal fates can be used to study the roles of exogenous factors acting through multiple signaling pathways during retina development. Application of activin A during a specific time frame that corresponds to early embryonic retinogenesis caused increased generation of CRX + photoreceptor precursors and decreased PAX6 + retinal progenitor cells (RPCs). Following activin A treatment, SMAD2/3 was activated in RPCs and bound to promoter regions of key RPC and photoreceptor genes. The effect of activin on CRX expression was repressed by pharmacological inhibition of SMAD2/3 phosphorylation. Activin signaling through SMAD2/3 in RPCs regulates expression of transcription factors involved in cell type determination and promotes photoreceptor lineage specification. Our findings can contribute to the production of photoreceptors for cell replacement therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. NINL and DZANK1 Co-function in Vesicle Transport and Are Essential for Photoreceptor Development in Zebrafish

    NARCIS (Netherlands)

    Dona, M.; Bachmann-Gagescu, R.; Texier, Y.; Toedt, G.; Hetterschijt, L.; Tonnaer, E.L.; Peters, T.A.; Beersum, S.E.C. van; Bergboer, J.G.M.; Horn, N.; Vrieze, E. de; Slijkerman, R.W.N.; Reeuwijk, J. van; Flik, G.; Keunen, J.E.E.; Ueffing, M.; Gibson, T.J.; Roepman, R.; Boldt, K.; Kremer, H.; Wijk, E. van

    2015-01-01

    Ciliopathies are Mendelian disorders caused by dysfunction of cilia, ubiquitous organelles involved in fluid propulsion (motile cilia) or signal transduction (primary cilia). Retinal dystrophy is a common phenotypic characteristic of ciliopathies since photoreceptor outer segments are specialized

  13. Optical coherence tomography of the photoreceptor layer in the healthy eye and in eyes with hereditary macular dystrophy

    International Nuclear Information System (INIS)

    Stur, M.; Hermann, B.; Drexler, W.; Unterhuber, A.; Sattmann, H.; Ergun, E.; Wirtitsch, M.

    2007-01-01

    Optical coherence tomography is primarily used for the evaluation of pronounced alterations of the retinal architecture, such as in macular holes, epiretinal gliosis, intra- and subretinal fluid accumulation as well as retinal atrophy. Ultrahigh resolution OCT devices also allow the assessment of discrete alterations of the photoreceptor layer and the retinal pigment epithelium. On the basis of cases from two different macular dystrophies, the importance of the evaluation of the photoreceptor layer and its correlation with visual acuity is demonstrated.(author) [de

  14. Strain engineering of Dirac cones in graphyne

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Gaoxue; Kumar, Ashok; Pandey, Ravindra, E-mail: pandey@mtu.edu [Department of Physics, Michigan Technological University, Houghton, Michigan 49931 (United States); Si, Mingsu [Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Lanzhou 730000 (China)

    2014-05-26

    6,6,12-graphyne, one of the two-dimensional carbon allotropes with the rectangular lattice structure, has two kinds of non-equivalent anisotropic Dirac cones in the first Brillouin zone. We show that Dirac cones can be tuned independently by the uniaxial compressive strain applied to graphyne, which induces n-type and p-type self-doping effect, by shifting the energy of the Dirac cones in the opposite directions. On the other hand, application of the tensile strain results into a transition from gapless to finite gap system for the monolayer. For the AB-stacked bilayer, the results predict tunability of Dirac-cones by in-plane strains as well as the strain applied perpendicular to the plane. The group velocities of the Dirac cones show enhancement in the resistance anisotropy for bilayer relative to the case of monolayer. Such tunable and direction-dependent electronic properties predicted for 6,6,12-graphyne make it to be competitive for the next-generation electronic devices at nanoscale.

  15. Automated detection of photoreceptor disruption in mild diabetic retinopathy on volumetric optical coherence tomography.

    Science.gov (United States)

    Wang, Zhuo; Camino, Acner; Zhang, Miao; Wang, Jie; Hwang, Thomas S; Wilson, David J; Huang, David; Li, Dengwang; Jia, Yali

    2017-12-01

    Diabetic retinopathy is a pathology where microvascular circulation abnormalities ultimately result in photoreceptor disruption and, consequently, permanent loss of vision. Here, we developed a method that automatically detects photoreceptor disruption in mild diabetic retinopathy by mapping ellipsoid zone reflectance abnormalities from en face optical coherence tomography images. The algorithm uses a fuzzy c-means scheme with a redefined membership function to assign a defect severity level on each pixel and generate a probability map of defect category affiliation. A novel scheme of unsupervised clustering optimization allows accurate detection of the affected area. The achieved accuracy, sensitivity and specificity were about 90% on a population of thirteen diseased subjects. This method shows potential for accurate and fast detection of early biomarkers in diabetic retinopathy evolution.

  16. Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD.

    Directory of Open Access Journals (Sweden)

    Yuko Seko

    Full Text Available Examples of direct differentiation by defined transcription factors have been provided for beta-cells, cardiomyocytes and neurons. In the human visual system, there are four kinds of photoreceptors in the retina. Neural retina and iris-pigmented epithelium (IPE share a common developmental origin, leading us to test whether human iris cells could differentiate to retinal neurons. We here define the transcription factor combinations that can determine human photoreceptor cell fate. Expression of rhodopsin, blue opsin and green/red opsin in induced photoreceptor cells were dependent on combinations of transcription factors: A combination of CRX and NEUROD induced rhodopsin and blue opsin, but did not induce green opsin; a combination of CRX and RX induced blue opsin and green/red opsin, but did not induce rhodopsin. Phototransduction-related genes as well as opsin genes were up-regulated in those cells. Functional analysis; i.e. patch clamp recordings, clearly revealed that generated photoreceptor cells, induced by CRX, RX and NEUROD, responded to light. The response was an inward current instead of the typical outward current. These data suggest that photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. These findings contribute substantially to a major advance toward eventual cell-based therapy for retinal degenerative diseases.

  17. Short-term psychosocial stress protects photoreceptors from damage via corticosterone-mediated activation of the AKT pathway.

    Science.gov (United States)

    Forkwa, Tembei K; Neumann, Inga D; Tamm, Ernst R; Ohlmann, Andreas; Reber, Stefan O

    2014-02-01

    Apoptotic death of photoreceptors in hereditary retinal degenerations can be prevented by neuroprotective molecules. Here, we report that adrenal glucocorticoids (GC) released during psychosocial stress protect photoreceptors from apoptosis after light damage. Psychosocial stress is known to be the main type of stressor humans are exposed to and was induced here in mice by 10h of chronic subordinate colony housing (CSC). Photoreceptor damage was generated by subsequent exposure to white light. Short-term psychosocial stress prior to illumination significantly reduced the number of apoptotic photoreceptors, an effect that was absent in adrenalectomized (ADX) mice. The neuroprotective effect was completely restored in ADX mice substituted with GC. Moreover, phosphorylation of retinal AKT increased following CSC or exogenous GC treatment, an effect that was again absent in ADX mice exposed to CSC. Finally, inhibition of AKT signaling with triciribine blocked the stress- and GC-mediated neuroprotective effects on photoreceptors. In summary, we provide evidence that 1) short-term psychosocial stress protects photoreceptors from light-induced damage and 2) the protective effect is most likely mediated by GC-induced activation of the AKT signaling pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Photoreceptor dysplasia (pd) in miniature schnauzer dogs: evaluation of candidate genes by molecular genetic analysis.

    Science.gov (United States)

    Zhang, Q; Baldwin, V J; Acland, G M; Parshall, C J; Haskel, J; Aguirre, G D; Ray, K

    1999-01-01

    Photoreceptor dysplasia (pd) is one of a group of at least six distinct autosomal and one X-linked retinal disorders identified in dogs which are collectively known as progressive retinal atrophy (PRA). It is an early onset retinal disease identified in miniature schnauzer dogs, and pedigree analysis and breeding studies have established autosomal recessive inheritance of the disease. Using a gene-based approach, a number of retina-expressed genes, including some members of the phototransduction pathway, have been causally implicated in retinal diseases of humans and other animals. Here we examined seven such potential candidate genes (opsin, RDS/peripherin, ROM1, rod cGMP-gated cation channel alpha-subunit, and three subunits of transducin) for their causal association with the pd locus by testing segregation of intragenic markers with the disease locus, or, in the absence of informative polymorphisms, sequencing of the coding regions of the genes. Based on these results, we have conclusively excluded four photoreceptor-specific genes as candidates for pd by linkage analysis. For three other photoreceptor-specific genes, we did not find any mutation in the coding sequences of the genes and have excluded them provisionally. Formal exclusion would require investigation of the levels of expression of the candidate genes in pd-affected dogs relative to age-matched controls. At present we are building suitable informative pedigrees for the disease locus with a sufficient number of meiosis to be useful for genomewide screening. This should identify markers linked to the disease locus and eventually permit progress toward the identification of the photoreceptor dysplasia gene and the disease-causing mutation.

  19. The role of carcinine in signaling at the Drosophila photoreceptor synapse.

    Directory of Open Access Journals (Sweden)

    Brendan A Gavin

    2007-12-01

    Full Text Available The Drosophila melanogaster photoreceptor cell has long served as a model system for researchers focusing on how animal sensory neurons receive information from their surroundings and translate this information into chemical and electrical messages. Electroretinograph (ERG analysis of Drosophila mutants has helped to elucidate some of the genes involved in the visual transduction pathway downstream of the photoreceptor cell, and it is now clear that photoreceptor cell signaling is dependent upon the proper release and recycling of the neurotransmitter histamine. While the neurotransmitter transporters responsible for clearing histamine, and its metabolite carcinine, from the synaptic cleft have remained unknown, a strong candidate for a transporter of either substrate is the uncharacterized inebriated protein. The inebriated gene (ine encodes a putative neurotransmitter transporter that has been localized to photoreceptor cells in Drosophila and mutations in ine result in an abnormal ERG phenotype in Drosophila. Loss-of-function mutations in ebony, a gene required for the synthesis of carcinine in Drosophila, suppress components of the mutant ine ERG phenotype, while loss-of-function mutations in tan, a gene necessary for the hydrolysis of carcinine in Drosophila, have no effect on the ERG phenotype in ine mutants. We also show that by feeding wild-type flies carcinine, we can duplicate components of mutant ine ERGs. Finally, we demonstrate that treatment with H(3 receptor agonists or inverse agonists rescue several components of the mutant ine ERG phenotype. Here, we provide pharmacological and genetic epistatic evidence that ine encodes a carcinine neurotransmitter transporter. We also speculate that the oscillations observed in mutant ine ERG traces are the result of the aberrant activity of a putative H(3 receptor.

  20. Random Photon Absorption Model Elucidates How Early Gain Control in Fly Photoreceptors Arises from Quantal Sampling

    Science.gov (United States)

    Song, Zhuoyi; Zhou, Yu; Juusola, Mikko

    2016-01-01

    Many diurnal photoreceptors encode vast real-world light changes effectively, but how this performance originates from photon sampling is unclear. A 4-module biophysically-realistic fly photoreceptor model, in which information capture is limited by the number of its sampling units (microvilli) and their photon-hit recovery time (refractoriness), can accurately simulate real recordings and their information content. However, sublinear summation in quantum bump production (quantum-gain-nonlinearity) may also cause adaptation by reducing the bump/photon gain when multiple photons hit the same microvillus simultaneously. Here, we use a Random Photon Absorption Model (RandPAM), which is the 1st module of the 4-module fly photoreceptor model, to quantify the contribution of quantum-gain-nonlinearity in light adaptation. We show how quantum-gain-nonlinearity already results from photon sampling alone. In the extreme case, when two or more simultaneous photon-hits reduce to a single sublinear value, quantum-gain-nonlinearity is preset before the phototransduction reactions adapt the quantum bump waveform. However, the contribution of quantum-gain-nonlinearity in light adaptation depends upon the likelihood of multi-photon-hits, which is strictly determined by the number of microvilli and light intensity. Specifically, its contribution to light-adaptation is marginal (≤ 1%) in fly photoreceptors with many thousands of microvilli, because the probability of simultaneous multi-photon-hits on any one microvillus is low even during daylight conditions. However, in cells with fewer sampling units, the impact of quantum-gain-nonlinearity increases with brightening light. PMID:27445779

  1. NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

    Science.gov (United States)

    Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Wu, Zhijian; Sieving, Paul A.

    2016-01-01

    Purpose The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1. Methods Transgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP. Results Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas. Conclusions Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway. PMID:27233035

  2. Studying of Phototransformation of Light Signal by Photoreceptor Pigments - Rhodopsin, Iodopsin and Bacteriorhodopsin

    OpenAIRE

    Ignat Ignatov; Oleg Mosin

    2014-01-01

    This review article views predominately the structure and function of animal and bacterial photoreceptor pigments (rhodopsin, iodopsin, bacteriorhodopsin) and their aspects of nano- and biotechnological usage. On an example of bacteriorhodopsin is described the method of its isolation from purple membranes of photo-organotrophic halobacterium Halobacterium halobium by cellular autolysis by distilled water, processing of bacterial biomass by ultrasound at 22 KHz, alcohol extraction of low and ...

  3. The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse

    Science.gov (United States)

    Gavin, Brendan A; Arruda, Susan E; Dolph, Patrick J

    2007-01-01

    The Drosophila melanogaster photoreceptor cell has long served as a model system for researchers focusing on how animal sensory neurons receive information from their surroundings and translate this information into chemical and electrical messages. Electroretinograph (ERG) analysis of Drosophila mutants has helped to elucidate some of the genes involved in the visual transduction pathway downstream of the photoreceptor cell, and it is now clear that photoreceptor cell signaling is dependent upon the proper release and recycling of the neurotransmitter histamine. While the neurotransmitter transporters responsible for clearing histamine, and its metabolite carcinine, from the synaptic cleft have remained unknown, a strong candidate for a transporter of either substrate is the uncharacterized inebriated protein. The inebriated gene (ine) encodes a putative neurotransmitter transporter that has been localized to photoreceptor cells in Drosophila and mutations in ine result in an abnormal ERG phenotype in Drosophila. Loss-of-function mutations in ebony, a gene required for the synthesis of carcinine in Drosophila, suppress components of the mutant ine ERG phenotype, while loss-of-function mutations in tan, a gene necessary for the hydrolysis of carcinine in Drosophila, have no effect on the ERG phenotype in ine mutants. We also show that by feeding wild-type flies carcinine, we can duplicate components of mutant ine ERGs. Finally, we demonstrate that treatment with H3 receptor agonists or inverse agonists rescue several components of the mutant ine ERG phenotype. Here, we provide pharmacological and genetic epistatic evidence that ine encodes a carcinine neurotransmitter transporter. We also speculate that the oscillations observed in mutant ine ERG traces are the result of the aberrant activity of a putative H3 receptor. PMID:18069895

  4. Amphioxus photoreceptors insights into the evolution of vertebrate opsins, vision and circadian rhythmicity

    Czech Academy of Sciences Publication Activity Database

    Pergner, Jiří; Kozmik, Zbyněk

    2017-01-01

    Roč. 61, č. 10-12 (2017), s. 665-681 ISSN 0214-6282 R&D Projects: GA ČR GA17-15374S; GA MŠk(CZ) LM2015062; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : chordate * opsin evolution * photoreceptor * eye evolution * phototransduction Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 1.981, year: 2016

  5. Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina.

    Science.gov (United States)

    White, David T; Sengupta, Sumitra; Saxena, Meera T; Xu, Qingguo; Hanes, Justin; Ding, Ding; Ji, Hongkai; Mumm, Jeff S

    2017-05-02

    Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of ( i ) rod cell clearance, ( ii ) MG/progenitor cell proliferation, and ( iii ) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions.

  6. Respiratory correlated cone beam CT

    International Nuclear Information System (INIS)

    Sonke, Jan-Jakob; Zijp, Lambert; Remeijer, Peter; Herk, Marcel van

    2005-01-01

    A cone beam computed tomography (CBCT) scanner integrated with a linear accelerator is a powerful tool for image guided radiotherapy. Respiratory motion, however, induces artifacts in CBCT, while the respiratory correlated procedures, developed to reduce motion artifacts in axial and helical CT are not suitable for such CBCT scanners. We have developed an alternative respiratory correlated procedure for CBCT and evaluated its performance. This respiratory correlated CBCT procedure consists of retrospective sorting in projection space, yielding subsets of projections that each corresponds to a certain breathing phase. Subsequently, these subsets are reconstructed into a four-dimensional (4D) CBCT dataset. The breathing signal, required for respiratory correlation, was directly extracted from the 2D projection data, removing the need for an additional respiratory monitor system. Due to the reduced number of projections per phase, the contrast-to-noise ratio in a 4D scan reduced by a factor 2.6-3.7 compared to a 3D scan based on all projections. Projection data of a spherical phantom moving with a 3 and 5 s period with and without simulated breathing irregularities were acquired and reconstructed into 3D and 4D CBCT datasets. The positional deviations of the phantoms center of gravity between 4D CBCT and fluoroscopy were small: 0.13±0.09 mm for the regular motion and 0.39±0.24 mm for the irregular motion. Motion artifacts, clearly present in the 3D CBCT datasets, were substantially reduced in the 4D datasets, even in the presence of breathing irregularities, such that the shape of the moving structures could be identified more accurately. Moreover, the 4D CBCT dataset provided information on the 3D trajectory of the moving structures, absent in the 3D data. Considerable breathing irregularities, however, substantially reduces the image quality. Data presented for three different lung cancer patients were in line with the results obtained from the phantom study. In

  7. RPGR: Its role in photoreceptor physiology, human disease, and future therapies.

    Science.gov (United States)

    Megaw, Roly D; Soares, Dinesh C; Wright, Alan F

    2015-09-01

    Mammalian photoreceptors contain specialised connecting cilia that connect the inner (IS) to the outer segments (OS). Dysfunction of the connecting cilia due to mutations in ciliary proteins are a common cause of the inherited retinal dystrophy retinitis pigmentosa (RP). Mutations affecting the Retinitis Pigmentosa GTPase Regulator (RPGR) protein is one such cause, affecting 10-20% of all people with RP and the majority of those with X-linked RP. RPGR is located in photoreceptor connecting cilia. It interacts with a wide variety of ciliary proteins, but its exact function is unknown. Recently, there have been important advances both in our understanding of RPGR function and towards the development of a therapy. This review summarises the existing literature on human RPGR function and dysfunction, and suggests that RPGR plays a role in the function of the ciliary gate, which controls access of both membrane and soluble proteins to the photoreceptor outer segment. We discuss key models used to investigate and treat RPGR disease and suggest that gene augmentation therapy offers a realistic therapeutic approach, although important questions still remain to be answered, while cell replacement therapy based on retinal progenitor cells represents a more distant prospect. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Variation in LOV Photoreceptor Activation Dynamics Probed by Time Resolved Infrared Spectroscopy

    KAUST Repository

    Iuliano, James N.

    2017-12-14

    The light, oxygen, voltage (LOV) domain proteins are blue light photoreceptors that utilize a non-covalently bound flavin mononucleotide (FMN) cofactor as the chromophore. The modular nature of these proteins has led to their wide adoption in the emerging fields of optogenetics and optobiology, where the LOV domain has been fused to a variety of output domains leading to novel light-controlled applications. In the present work, we extend our studies of the sub-picosecond to several hundred microsecond transient infrared spectroscopy of the isolated LOV domain AsLOV2 to three full-length photoreceptors in which the LOV domain is fused to an output domain: the LOV-STAS protein, YtvA, the LOV-HTH transcription factor, EL222, and the LOV-histidine kinase, LovK. Despite differences in tertiary structure, the overall pathway leading to cysteine adduct formation from the FMN triplet state is highly conserved, although there are slight variations in rate. However significant differences are observed in the vibrational spectra and kinetics after adduct formation, which are directly linked to the specific output function of the LOV domain. While the rate of adduct formation varies by only 3.6-fold amongst the proteins, the subsequent large-scale structural changes in the full-length LOV photoreceptors occur over the micro- to sub-millisecond timescales and vary by orders of magnitude depending on the different output function of each LOV domain.

  9. An Unexpected Diversity of Photoreceptor Classes in the Longfin Squid, Doryteuthis pealeii.

    Science.gov (United States)

    Kingston, Alexandra C N; Wardill, Trevor J; Hanlon, Roger T; Cronin, Thomas W

    2015-01-01

    Cephalopods are famous for their ability to change color and pattern rapidly for signaling and camouflage. They have keen eyes and remarkable vision, made possible by photoreceptors in their retinas. External to the eyes, photoreceptors also exist in parolfactory vesicles and some light organs, where they function using a rhodopsin protein that is identical to that expressed in the retina. Furthermore, dermal chromatophore organs contain rhodopsin and other components of phototransduction (including retinochrome, a photoisomerase first found in the retina), suggesting that they are photoreceptive. In this study, we used a modified whole-mount immunohistochemical technique to explore rhodopsin and retinochrome expression in a number of tissues and organs in the longfin squid, Doryteuthis pealeii. We found that fin central muscles, hair cells (epithelial primary sensory neurons), arm axial ganglia, and sucker peduncle nerves all express rhodopsin and retinochrome proteins. Our findings indicate that these animals possess an unexpected diversity of extraocular photoreceptors and suggest that extraocular photoreception using visual opsins and visual phototransduction machinery is far more widespread throughout cephalopod tissues than previously recognized.

  10. An Unexpected Diversity of Photoreceptor Classes in the Longfin Squid, Doryteuthis pealeii.

    Directory of Open Access Journals (Sweden)

    Alexandra C N Kingston

    Full Text Available Cephalopods are famous for their ability to change color and pattern rapidly for signaling and camouflage. They have keen eyes and remarkable vision, made possible by photoreceptors in their retinas. External to the eyes, photoreceptors also exist in parolfactory vesicles and some light organs, where they function using a rhodopsin protein that is identical to that expressed in the retina. Furthermore, dermal chromatophore organs contain rhodopsin and other components of phototransduction (including retinochrome, a photoisomerase first found in the retina, suggesting that they are photoreceptive. In this study, we used a modified whole-mount immunohistochemical technique to explore rhodopsin and retinochrome expression in a number of tissues and organs in the longfin squid, Doryteuthis pealeii. We found that fin central muscles, hair cells (epithelial primary sensory neurons, arm axial ganglia, and sucker peduncle nerves all express rhodopsin and retinochrome proteins. Our findings indicate that these animals possess an unexpected diversity of extraocular photoreceptors and suggest that extraocular photoreception using visual opsins and visual phototransduction machinery is far more widespread throughout cephalopod tissues than previously recognized.

  11. Autofluorescence Lifetimes in Patients With Choroideremia Identify Photoreceptors in Areas With Retinal Pigment Epithelium Atrophy.

    Science.gov (United States)

    Dysli, Chantal; Wolf, Sebastian; Tran, Hoai Viet; Zinkernagel, Martin S

    2016-12-01

    The purpose of this study was to investigate fundus autofluorescence lifetimes in patients with choroideremia and to identify tissue-specific lifetime characteristics and potential prognostic markers. Autofluorescence lifetimes of the retina were measured in two spectral channels (498-560 nm and 560-720 nm) in patients with choroideremia and age-matched healthy controls. Furthermore, autofluorescence intensities and spectral-domain optical coherence tomography (OCT) data were acquired and compared to fundus autofluorescence lifetime data. Sixteen eyes from 8 patients with advanced choroideremia (mean ± SD age, 55 ± 13 years) were included in this study and compared with 10 age-matched healthy participants. Whereas fundus autofluorescence intensity measurement identified areas of remaining retinal pigment epithelium (RPE), autofluorescence lifetime maps identified areas with remaining photoreceptor layers in OCT but RPE atrophy. In these areas, mean (±SEM) lifetimes were 567 ± 59 ps in the short and 603 ± 49 ps in the long spectral channels (+98% and +88% compared to controls). In areas of combined RPE atrophy and loss of photoreceptors, autofluorescence lifetimes were significantly prolonged by 1116 ± 63 ps (+364%) in the short and by 915 ± 52 ps (+270%) in the long spectral channels compared with controls. Because autofluorescence lifetimes identify areas of remaining photoreceptors in the absence of RPE, this imaging modality may be useful to monitor disease progression in the natural course of disease and in context of potential future therapeutic interventions.

  12. Lack of protein-tyrosine sulfation disrupts photoreceptor outer segment morphogenesis, retinal function and retinal anatomy.

    Science.gov (United States)

    Sherry, David M; Murray, Anne R; Kanan, Yogita; Arbogast, Kelsey L; Hamilton, Robert A; Fliesler, Steven J; Burns, Marie E; Moore, Kevin L; Al-Ubaidi, Muayyad R

    2010-11-01

    To investigate the role(s) of protein-tyrosine sulfation in the retina, we examined retinal function and structure in mice lacking tyrosylprotein sulfotransferases (TPST) 1 and 2. Tpst double knockout (DKO; Tpst1(-/-) /Tpst2 (-/-) ) retinas had drastically reduced electroretinographic responses, although their photoreceptors exhibited normal responses in single cell recordings. These retinas appeared normal histologically; however, the rod photoreceptors had ultrastructurally abnormal outer segments, with membrane evulsions into the extracellular space, irregular disc membrane spacing and expanded intradiscal space. Photoreceptor synaptic terminals were disorganized in Tpst DKO retinas, but established ultrastructurally normal synapses, as did bipolar and amacrine cells; however, the morphology and organization of neuronal processes in the inner retina were abnormal. These results indicate that protein-tyrosine sulfation is essential for proper outer segment morphogenesis and synaptic function, but is not critical for overall retinal structure or synapse formation, and may serve broader functions in neuronal development and maintenance. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  13. Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors.

    Directory of Open Access Journals (Sweden)

    Patrick Vancura

    Full Text Available The mammalian retina harbors a circadian clockwork that regulates vision and promotes healthiness of retinal neurons, mainly through directing the rhythmic release of the neurohormones dopamine-acting on dopamine D4 receptors-and melatonin-acting on MT1 and MT2 receptors. The gene Gnaz-a unique Gi/o subfamily member-was seen in the present study to be expressed in photoreceptors where its protein product Gαz shows a daily rhythm in its subcellular localization. Apart from subcellular localization, Gnaz displays a daily rhythm in expression-with peak values at night-in preparations of the whole retina, microdissected photoreceptors and photoreceptor-related pinealocytes. In retina, Gnaz rhythmicity was observed to persist under constant darkness and to be abolished in retina deficient for Clock or dopamine D4 receptors. Furthermore, circadian regulation of Gnaz was disturbed in the db/db mouse, a model of diabetic retinopathy. The data of the present study suggest that Gnaz links the circadian clockwork-via dopamine acting on D4 receptors-to G protein-mediated signaling in intact but not diabetic retina.

  14. Variation in LOV Photoreceptor Activation Dynamics Probed by Time Resolved Infrared Spectroscopy

    KAUST Repository

    Iuliano, James N.; Gil, Agnieszka A.; Laptenok, Sergey P.; Hall, Christopher R.; Tolentino Collado, Jinnette; Lukacs, Andras; Hag Ahmed, Safaa A; Abyad, Jenna; Daryaee, Taraneh; Greetham, Gregory M.; Sazanovich, Igor V.; Illarionov, Boris; Bacher, Adelbert; Fischer, Markus; Towrie, Michael; French, Jarrod B.; Meech, Stephen R.; Tonge, Peter J

    2017-01-01

    The light, oxygen, voltage (LOV) domain proteins are blue light photoreceptors that utilize a non-covalently bound flavin mononucleotide (FMN) cofactor as the chromophore. The modular nature of these proteins has led to their wide adoption in the emerging fields of optogenetics and optobiology, where the LOV domain has been fused to a variety of output domains leading to novel light-controlled applications. In the present work, we extend our studies of the sub-picosecond to several hundred microsecond transient infrared spectroscopy of the isolated LOV domain AsLOV2 to three full-length photoreceptors in which the LOV domain is fused to an output domain: the LOV-STAS protein, YtvA, the LOV-HTH transcription factor, EL222, and the LOV-histidine kinase, LovK. Despite differences in tertiary structure, the overall pathway leading to cysteine adduct formation from the FMN triplet state is highly conserved, although there are slight variations in rate. However significant differences are observed in the vibrational spectra and kinetics after adduct formation, which are directly linked to the specific output function of the LOV domain. While the rate of adduct formation varies by only 3.6-fold amongst the proteins, the subsequent large-scale structural changes in the full-length LOV photoreceptors occur over the micro- to sub-millisecond timescales and vary by orders of magnitude depending on the different output function of each LOV domain.

  15. Restoration of outer segments of foveal photoreceptors after resolution of central serous chorioretinopathy.

    Science.gov (United States)

    Ojima, Yumiko; Tsujikawa, Akitaka; Yamashiro, Kenji; Ooto, Sotaro; Tamura, Hiroshi; Yoshimura, Nagahisa

    2010-01-01

    To study morphologically and functionally the prognosis of damaged outer segments of the foveal photoreceptor layer in eyes with resolved central serous chorioretinopathy (CSC). We studied retrospectively the medical records of 70 patients (74 eyes) with resolved CSC. Optical coherence tomography was used to detect the junctions between inner and outer segments of the photoreceptors (IS/OS) as a hallmark of the integrity of the outer photoreceptor layer. In 53 eyes (71.6%), the IS/OS line was clearly detected beneath the fovea immediately after resolution of the retinal detachment, with good visual acuity (VA). In the remaining 21 eyes (28.4%), however, the foveal IS/OS line could not be detected shortly after resolution of CSC, and VA was variable, ranging from 0.1 to 1.5 (median, 0.9). Of these 21 eyes, 15 had a follow-up examination with OCT, and in four the foveal IS/OS line was not detected at the follow-up and vision in these eyes remained poor. However, nine eyes showed recovery of the foveal IS/OS line during follow-up, and these eyes had substantial visual recovery. Immediately after resolution of active CSC, although the IS/OS line cannot be detected beneath the fovea, it often shows restoration over time, with visual recovery, though in some eyes no restoration takes place and the prognosis remains poor.

  16. Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis.

    Science.gov (United States)

    Dörken, Veit Martin; Rudall, Paula J

    2018-01-01

    Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales). The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

  17. Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis

    Directory of Open Access Journals (Sweden)

    Veit Martin Dörken

    2018-06-01

    Full Text Available Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales. The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

  18. Resonance in a Cone-Topped Tube

    Directory of Open Access Journals (Sweden)

    Angus Cheng-Huan Chia

    2011-06-01

    Full Text Available The relationship between ratio of the upper opening diameter of a cone-topped cylinder to the cylinder diameter,and the ratio of the length of the air column to resonant period was examined. Plastic cones with upper openings ranging from 1.3 cm to 3.6 cm and tuning forks with frequencies ranging from 261.6 Hz to 523.3 Hz were used. The transition from a standing wave in a cylindrical column to a Helmholtz-type resonance in a resonant cavity with a narrow opening was observed.

  19. Cone-based Electrical Resistivity Tomography

    Science.gov (United States)

    Pidlisecky, A.; Knight, R.; Haber, E.

    2005-05-01

    Determining the 3D spatial distribution of subsurface properties is a critical part of managing the clean-up of contaminated sites. Most standard hydrologic methods sample small regions immediately adjacent to wells or testing devices. This provides data which are not representative of the entire region of interest. Furthermore, at many contaminated sites invasive methods are not acceptable, due to the risks associated with contacting and spreading the contaminants. To address these issues, we have developed a minimally invasive technology that provides information about the 3D distribution of electrical conductivity. This new technique, cone-based electrical resistivity tomography (C-bert), involves placing several permanent current electrodes in the subsurface and using electrodes mounted on a cone penetrometer to measure the resultant potential field while advancing the cone into the subsurface. In addition to potential field measurements, we obtain the standard suite of cone-penetration measurements, including high resolution resistivity logs; these data can then be used to constrain the inversion of the potential field data. A major challenge of working with these data is that the cone penetrometer is highly conductive, and thus presents a large local perturbation around the measurement location. As the cone is very small (approximately 30mm in diameter) with respect to the total model space, explicitly modeling the cone is computationally demanding. We developed a method for solving the forward model that reduces computational time by an order of magnitude. This solution method, iteratively determined boundary conditions, makes it possible to correct for the cone effect before inversion of the data. Results from synthetic experiments suggest that the C-bert method of data acquisition can result in high quality electrical conductivity images of the subsurface. We tested the practicality of this technique by performing a field test of the C-bert system to image

  20. Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.

    Science.gov (United States)

    Klevering, B Jeroen; Yzer, Suzanne; Rohrschneider, Klaus; Zonneveld, Marijke; Allikmets, Rando; van den Born, L Ingeborgh; Maugeri, Alessandra; Hoyng, Carel B; Cremers, Frans P M

    2004-12-01

    Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or autosomal recessive CRD (54 cases) or RP (90 cases). We performed detailed ophthalmologic examinations and identified at least one ABCA4 mutation in 18 patients (33%) with CRD and in five patients (5.6%) with RP. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing revealed four novel missense mutations (R24C, E161K, P597S, G618E) and a novel 1-bp deletion (5888delG). Ophthalmoscopic abnormalities in CRD patients ranged from minor granular pigmentary changes in the posterior pole to widespread atrophy. In 12 patients with recordable electroretinogram (ERG) tracings, a cone-rod pattern was detected. Three patients demonstrated progression from a retinal dystrophy resembling STGD1 to a more widespread degeneration, and were subsequently diagnosed as CRD. In addition to a variable degree of atrophy, all RP patients displayed ophthalmologic characteristics of classic RP. When detectable, ERG recordings in these patients demonstrated rod-cone patterns of photoreceptor degeneration. In conclusion, in this study, we show that the ABCA4 mutation chip is an efficient first screening tool for arCRD.

  1. Critical condition for the transformation from Taylor cone to cone-jet

    International Nuclear Information System (INIS)

    Wei Cheng; Zhao Yang; Gang Tie-Qiang; Chen Li-Jie

    2014-01-01

    An energy method is proposed to investigate the critical transformation condition from a Taylor cone to a cone-jet. Based on the kinetic theorem, the system power allocation and the electrohydrodynamics stability are discussed. The numerical results indicate that the energy of the liquid cone tip experiences a maximum value during the transformation. With the proposed jetting energy, we give the critical transformation condition under which the derivative of jetting energy with respect to the surface area is greater than or equal to the energy required to form a unit of new liquid surface

  2. Direct estimation of human trabecular bone stiffness using cone beam computed tomography.

    Science.gov (United States)

    Klintström, Eva; Klintström, Benjamin; Pahr, Dieter; Brismar, Torkel B; Smedby, Örjan; Moreno, Rodrigo

    2018-04-10

    The aim of this study was to evaluate the possibility of estimating the biomechanical properties of trabecular bone through finite element simulations by using dental cone beam computed tomography data. Fourteen human radius specimens were scanned in 3 cone beam computed tomography devices: 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan), NewTom 5 G (QR Verona, Verona, Italy), and Verity (Planmed, Helsinki, Finland). The imaging data were segmented by using 2 different methods. Stiffness (Young modulus), shear moduli, and the size and shape of the stiffness tensor were studied. Corresponding evaluations by using micro-CT were regarded as the reference standard. The 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan) showed good performance in estimating stiffness and shear moduli but was sensitive to the choice of segmentation method. NewTom 5 G (QR Verona, Verona, Italy) and Verity (Planmed, Helsinki, Finland) yielded good correlations, but they were not as strong as Accuitomo 80 (J. Morita MFG., Kyoto, Japan). The cone beam computed tomography devices overestimated both stiffness and shear compared with the micro-CT estimations. Finite element-based calculations of biomechanics from cone beam computed tomography data are feasible, with strong correlations for the Accuitomo 80 scanner (J. Morita MFG., Kyoto, Japan) combined with an appropriate segmentation method. Such measurements might be useful for predicting implant survival by in vivo estimations of bone properties. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Jordan's algebra of a facially homogeneous autopolar cone

    International Nuclear Information System (INIS)

    Bellissard, Jean; Iochum, Bruno

    1979-01-01

    It is shown that a Jordan-Banach algebra with predual may be canonically associated with a facially homogeneous autopolar cone. This construction generalizes the case where a trace vector exists in the cone [fr

  4. Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin-deficient mouse.

    Science.gov (United States)

    Janssen, Andreas; Min, Seok H; Molday, Laurie L; Tanimoto, Naoyuki; Seeliger, Mathias W; Hauswirth, William W; Molday, Robert S; Weber, Bernhard H F

    2008-06-01

    Proof-of-concept for a successful adeno-associated virus serotype 5 (AAV5)-mediated gene therapy in X-linked juvenile retinoschisis (XLRS) has been demonstrated in an established mouse model for this condition. The initial studies concentrated on early time-points of treatment. In this study, we aimed to explore the consequences of single subretinal injections administered at various stages of more advanced disease. By electroretinogram (ERG), functional improvement in treated versus untreated eyes is found to be significant in retinoschisin-deficient mice injected at the time-points of 15 days (P15), 1 month (PM1), and 2 months (PM2) after birth. In mice treated at 7 months after birth (PM7), an age previously shown to exhibit advanced retinal disease, ERG responses reveal no beneficial effects of vector treatment. Generally, functional rescue is paralleled by sustained retinoschisin expression and significant photoreceptor survival relative to untreated eyes. Quantitative measures of photoreceptors and peanut agglutinin-labeled ribbon synapses demonstrate rescue effects even in mice injected as late as PM7. Taken together, AAV5-mediated gene replacement is beneficial in slowing disease progression in murine XLRS. In addition, we show the effectiveness of rescue efforts even if treatment is delayed until advanced signs of disease have developed. Human XLRS patients might benefit from these findings, which suggest that the effectiveness of treatment appears not to be restricted to the early stages of the disease, and that treatment may prove to be valuable even when administered at more advanced stages.

  5. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  6. Analog Experiment for rootless cone eruption

    Science.gov (United States)

    Noguchi, R.; Hamada, A.; Suzuki, A.; Kurita, K.

    2017-09-01

    Rootless cone is a unique geomorphological landmark to specify igneous origin of investigated terrane, which is formed by magma-water interaction. To understand its formation mechanism we conducted analog experiment for heat-induced vesiculation by using hot syrup and sodium bicarbonate solution.

  7. Cone beam computed tomography in veterinary dentistry

    NARCIS (Netherlands)

    van Thielen, B.; Siguenza, F.; Hassan, B.

    2012-01-01

    The purpose of this study was to assess the feasibility of cone beam computed tomography (CBCT) in imaging dogs and cats for diagnostic dental veterinary applications. CBCT scans of heads of six dogs and two cats were made. Dental panoramic and multi-planar reformatted (MPR) para-sagittal

  8. Case of Unilateral Peripheral Cone Dysfunction

    Directory of Open Access Journals (Sweden)

    Yujin Mochizuki

    2012-05-01

    Full Text Available Purpose: Peripheral cone dystrophy is a subgroup of cone dystrophy, and only 4 cases have been reported. We present a patient with unilateral peripheral cone dysfunction and report the functional changes determined by electrophysiological tests and ultrastructural changes determined by spectral domain optical coherence tomography (SD-OCT. Case: A 34-year-old woman complained of blurred vision in both eyes. Our examination showed that her visual acuity was 0.05 OD and 0.2 OS. A relative afferent pupillary defect was present in her right eye. The results of slit-lamp examination, ophthalmoscopy, and fluorescein angiography were normal except for pallor of the right optic disc. SD-OCT showed a diffuse thinning of the retina in the posterior pole of the right eye. A severe constriction of the visual fields was found in both eyes but more in the right eye. The photopic full-field electroretinograms (ERGs were reduced in the right eye but normal in the left eye. The multifocal ERGs were severely reduced throughout the visual field except in the central area of the right eye. The multifocal ERGs from the left eye were normal. The pattern visual evoked responses were within the normal range in both eyes. She had a 5-year history of sniffing paint thinner. Results: Although the visual dysfunction was initially suspected to be due to psychological problems from the results of subjective tests, objective tests indicated a peripheral cone dysfunction in the right eye. The pathophysiological mechanism and the relationship with thinner sniffing were not determined. Conclusions: Our findings indicate that peripheral cone dysfunction can occur unilaterally. Electrophysiology and SD-OCT are valuable tests to perform to determine the pathogenesis of unusual ocular findings objectively.

  9. Dysregulation of Ca(v)1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2.

    Science.gov (United States)

    Liu, Xiaoni; Kerov, Vasily; Haeseleer, Françoise; Majumder, Anurima; Artemyev, Nikolai; Baker, Sheila A; Lee, Amy

    2013-01-01

    Mutations in the gene encoding Cav 1.4, CACNA1F, are associated with visual disorders including X-linked incomplete congenital stationary night blindness type 2 (CSNB2). In mice lacking Cav 1.4 channels, there are defects in the development of "ribbon" synapses formed between photoreceptors (PRs) and second-order neurons. However, many CSNB2 mutations disrupt the function rather than expression of Cav 1.4 channels. Whether defects in PR synapse development due to altered Cav 1.4 function are common features contributing to the pathogenesis of CSNB2 is unknown. To resolve this issue, we profiled changes in the subcellular distribution of Cav 1.4 channels and synapse morphology during development in wild-type (WT) mice and mouse models of CSNB2. Using Cav 1.4-selective antibodies, we found that Cav 1.4 channels associate with ribbon precursors early in development and are concentrated at both rod and cone PR synapses in the mature retina. In mouse models of CSNB2 in which the voltage-dependence of Cav 1.4 activation is either enhanced (Cav 1.4I756T) or inhibited (CaBP4 KO), the initial stages of PR synaptic ribbon formation are largely unaffected. However, after postnatal day 13, many PR ribbons retain the immature morphology. This synaptic abnormality corresponds in severity to the defect in synaptic transmission in the adult mutant mice, suggesting that lack of sufficient mature synapses contributes to vision impairment in Cav 1.4I756T and CaBP4 KO mice. Our results demonstrate the importance of proper Cav 1.4 function for efficient PR synapse maturation, and that dysregulation of Cav 1.4 channels in CSNB2 may have synaptopathic consequences.

  10. Use of RI-cone penetrometer in clay foundations

    International Nuclear Information System (INIS)

    Mimura, Mamoru; Shibata, Toru; Shrivastava, A.K.

    1993-01-01

    RI cone penetrometer tests are carried out at four different sites. The foundation grounds discussed here mainly consist of clayey materials. The measured results by RI cone penetrometers are shown for Kyobashi, Hachirougata, Kurihama and Kinkai Bay site. According to comparison of water content and density profiles by RI cone measurement with the conventional testing results, RI cone penetrometers are proved to be versatile tools for site investigation. Settlement assessment by RI cone penetrometer is also discussed by exemplifying the embankment at Kinkai Bay site. Elasto-vis-coplastic finite element analysis correspondingly performed strongly supports the RI cone based assessment. Repeated use of RI cone penetrometer with the advance of construction enables us to assess the consolidation process of the clay foundation. (author)

  11. Diurnal and circadian rhythms in the tomato transcriptome and their modulation by cryptochrome photoreceptors.

    Directory of Open Access Journals (Sweden)

    Paolo Facella

    Full Text Available BACKGROUND: Circadian clocks are internal molecular time-keeping mechanisms that provide living organisms with the ability to adjust their growth and physiology and to anticipate diurnal environmental changes. Circadian clocks, without exception, respond to light and, in plants, light is the most potent and best characterized entraining stimulus. The capacity of plants to respond to light is achieved through a number of photo-perceptive proteins including cryptochromes and phytochromes. There is considerable experimental evidence demonstrating the roles of photoreceptors in providing light input to the clock. METHODOLOGY: In order to identify genes regulated by diurnal and circadian rhythms, and to establish possible functional relations between photoreceptors and the circadian clock in tomato, we monitored the temporal transcription pattern in plants entrained to long-day conditions, either by large scale comparative profiling, or using a focused approach over a number of photosensory and clock-related genes by QRT-PCR. In parallel, focused transcription analyses were performed in cry1a- and in CRY2-OX tomato genotypes. CONCLUSIONS: We report a large series of transcript oscillations that shed light on the complex network of interactions among tomato photoreceptors and clock-related genes. Alteration of cryptochrome gene expression induced major changes in the rhythmic oscillations of several other gene transcripts. In particular, over-expression of CRY2 had an impact not only on day/night fluctuations but also on rhythmicity under constant light conditions. Evidence was found for widespread diurnal oscillations of transcripts encoding specific enzyme classes (e.g. carotenoid biosynthesis enzymes as well as for post-transcriptional diurnal and circadian regulation of the CRY2 transcript.

  12. Light- and GTP-activated hydrolysis of phosphatidylinositol bisphosphate in squid photoreceptor membranes

    International Nuclear Information System (INIS)

    Baer, K.M.; Saibil, H.R.

    1988-01-01

    Light stimulates the hydrolysis of exogenous, [ 3 H]inositol-labeled phosphatidylinositol bisphosphate (PtdInsP2) added to squid photoreceptor membranes, releasing inositol trisphosphate (InsP3). At free calcium levels of 0.05 microM or greater, hydrolysis of the labeled lipid is stimulated up to 4-fold by GTP and light together, but not separately. This activity is the biochemical counterpart of observations on intact retina showing that a rhodopsin-activated GTP-binding protein is involved in visual transduction in invertebrates, and that InsP3 release is correlated with visual excitation and adaptation. Using an in vitro assay, we investigated the calcium and GTP dependence of the phospholipase activity. At calcium concentrations between 0.1 and 0.5 microM, some hydrolysis occurs independently of GTP and light, with a light- and GTP-activated component superimposed. At 1 microM calcium there is no background activity, and hydrolysis absolutely requires both GTP and light. Ion exchange chromatography on Dowex 1 (formate form) of the water-soluble products released at 1 microM calcium reveals that the product is almost entirely InsP3. Invertebrate rhodopsin is homologous in sequence and function to vertebrate visual pigment, which modulates the concentration of cyclic GMP through the mediation of the GTP-binding protein transducin. While there is some evidence that light also modulates PtdInsP2 content in vertebrate photoreceptors, the case for its involvement in phototransduction is stronger for the invertebrate systems. The results reported here support the scheme of rhodopsin----GTP-binding protein----phospholipase C activation in invertebrate photoreceptors

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

    Directory of Open Access Journals (Sweden)

    Aurélie Cubizolle

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

  14. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Delyfer

    Full Text Available BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

  15. RDH13L, an enzyme responsible for the aldehyde-alcohol redox coupling reaction (AL-OL coupling reaction) to supply 11-cis retinal in the carp cone retinoid cycle.

    Science.gov (United States)

    Sato, Shinya; Miyazono, Sadaharu; Tachibanaki, Shuji; Kawamura, Satoru

    2015-01-30

    Cone photoreceptors require effective pigment regeneration mechanisms to maintain their sensitivity in the light. Our previous studies in carp cones suggested the presence of an unconventional and very effective mechanism to produce 11-cis retinal, the necessary component in pigment regeneration. In this reaction (aldehyde-alcohol redox coupling reaction, AL-OL coupling reaction), formation of 11-cis retinal, i.e. oxidation of 11-cis retinol is coupled to reduction of an aldehyde at a 1:1 molar ratio without exogenous NADP(H) which is usually required in this kind of reaction. Here, we identified carp retinol dehydrogenase 13-like (RDH13L) as an enzyme catalyzing the AL-OL coupling reaction. RDH13L was partially purified from purified carp cones, identified as a candidate protein, and its AL-OL coupling activity was confirmed using recombinant RDH13L. We further examined the substrate specificity, subcellular localization, and expression level of RDH13L. Based on these results, we concluded that RDH13L contributes to a significant part, but not all, of the AL-OL coupling activity in carp cones. RDH13L contained tightly bound NADP(+) which presumably functions as a cofactor in the reaction. Mouse RDH14, a mouse homolog of carp RDH13L, also showed the AL-OL coupling activity. Interestingly, although carp cone membranes, carp RDH13L and mouse RDH14 all showed the coupling activity at 15-37 °C, they also showed a conventional NADP(+)-dependent 11-cis retinol oxidation activity above 25 °C without addition of aldehydes. This dual mechanism of 11-cis retinal synthesis attained by carp RDH13L and mouse RDH14 probably contribute to effective pigment regeneration in cones that function in the light. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Correlated evolution of short wavelength sensitive photoreceptor sensitivity and color pattern in Lake Malawi cichlids

    Directory of Open Access Journals (Sweden)

    Michael J. Pauers

    2016-02-01

    Full Text Available For evolutionary ecologists, the holy grail of visual ecology is to establish an unambiguous link between photoreceptor sensitivity, the spectral environment, and the perception of specific visual stimuli (e.g., mates, food, predators, etc.. Due to the bright nuptial colors of the males, and the role female mate choice plays in their evolution, the haplochromine cichlid fishes of the African great lakes are favorite research subjects for such investigations. Despite this attention, current evidence is equivocal; while distinct correlations among photoreceptor sensitivity, photic environment, and male coloration exist in Lake Victorian haplochromines, attempts to find such correlations in Lake Malawian cichlids have failed. Lake Malawi haplochromines have a wide variability in their short-wavelength-sensitive photoreceptors, especially compared to their mid- and long-wavelength-sensitive photoreceptors; these cichlids also vary in the degree to which they express one of three basic color patterns (vertical bars, horizontal stripes, and solid patches of colors, each of which is likely used in a different form of communication. Thus, we hypothesize that, in these fishes, spectral sensitivity and color pattern have evolved in a correlated fashion to maximize visual communication; specifically, ultraviolet sensitivity should be found in vertically-barred species to promote ‘private’ communication, while striped species should be less likely to have ultraviolet sensitivity, since their color pattern carries ‘public’ information. Using phylogenetic independent contrasts, we found that barred species had strong sensitivity to ultraviolet wavelengths, but that striped species typically lacked sensitivity to ultraviolet light. Further, the only variable, even when environmental variables were simultaneously considered, that could predict ultraviolet sensitivity was color pattern. We also found that, using models of correlated evolution, color

  17. Overexpression of retinal degeneration slow (RDS protein adversely affects rods in the rd7 model of enhanced S-cone syndrome.

    Directory of Open Access Journals (Sweden)

    Dibyendu Chakraborty

    Full Text Available The nuclear receptor NR2E3 promotes expression of rod photoreceptor genes while repressing cone genes. Mice lacking NR2E3 (Nr2e3(rd7/rd7 referred to here as rd7 are a model for enhanced S-cone syndrome, a disease associated with increased sensitivity to blue light and night blindness. Rd7 retinas have reduced levels of the outer segment (OS structural protein retinal degeneration slow (RDS. We test the hypothesis that increasing RDS levels would improve the Rd7 phenotype. Transgenic mice over-expressing normal mouse peripherin/RDS (NMP in rods and cones were crossed onto the rd7 background. Disease phenotypes were assessed in NMP/rd7 eyes and compared to wild-type (WT and rd7 eyes at postnatal day 30. NMP/rd7 retinas expressed total RDS (transgenic and endogenous message at WT levels, and NMP protein was correctly localized to the OS. NMP/rd7 retinas have shorter OSs compared to rd7 and WT and significantly reduced number of rosettes. NMP/rd7 mice also exhibited significant deficits in scotopic ERG amplitudes compared to rd7 while photopic amplitudes remained unaffected. Protein levels of rhodopsin, RDS, and the RDS homologue ROM-1 were significantly reduced in the NMP/rd7 retinas compared to rd7. We show that correcting the levels of RDS gene expression does not improve the phenotype of the rd7 suggesting that RDS deficiency is not responsible for the defect in this model. We suggest that the specific rod defect in the NMP/rd7 is likely associated with ongoing problems in the rd7 that are related to the expression of cone genes in rod cells, a characteristic of the model.

  18. On Krasnoselskii's Cone Fixed Point Theorem

    Directory of Open Access Journals (Sweden)

    Man Kam Kwong

    2008-04-01

    Full Text Available In recent years, the Krasnoselskii fixed point theorem for cone maps and its many generalizations have been successfully applied to establish the existence of multiple solutions in the study of boundary value problems of various types. In the first part of this paper, we revisit the Krasnoselskii theorem, in a more topological perspective, and show that it can be deduced in an elementary way from the classical Brouwer-Schauder theorem. This viewpoint also leads to a topology-theoretic generalization of the theorem. In the second part of the paper, we extend the cone theorem in a different direction using the notion of retraction and show that a stronger form of the often cited Leggett-Williams theorem is a special case of this extension.

  19. Basic principle of cone beam computed tomography

    International Nuclear Information System (INIS)

    Choi, Yong Suk; Kim, Gyu Tae; Hwang, Eui Hwan

    2006-01-01

    The use of computed tomography for dental procedures has increased recently. Cone beam computed tomography(CBCT) systems have been designed for imaging hard tissues of the dentomaxillofacial region. CBCT is capable of providing high resolution in images of high diagnostic quality. This technology allows for 3-dimensional representation of the dentomaxillofacial skeleton with minimal distortion, but at lower equipment cost, simpler image acquisition and lower patient dose. Because this technology produces images with isotropic sub-millimeter spatial resolution, it is ideally suited for dedicated dentomaxillofacial imaging. In this paper, we provide a brief overview of cone beam scanning technology and compare it with the fan beam scanning used in conventional CT and the basic principles of currently available CBCT systems

  20. Hadronic wavefunctions in light-cone quantization

    International Nuclear Information System (INIS)

    Hyer, T.

    1994-05-01

    The analysis of light-cone wavefunctions seems the most promising theoretical approach to a detailed understanding of the structure of relativistic bound states, particularly hadrons. However, there are numerous complications in this approach. Most importantly, the light-cone approach sacrifices manifest rotational invariance in exchange for the elimination of negative-energy states. The requirement of rotational invariance of the full theory places important constraints on proposed light-cone wavefunctions, whether they are modelled or extracted from some numerical procedure. A formulation of the consequences of the hidden rotational symmetry has been sought for some time; it is presented in Chapter 2. In lattice gauge theory or heavy-quark effective theory, much of the focus is on the extraction of numerical values of operators which are related to the hadronic wavefunction. These operators are to some extent interdependent, with relations induced by fundamental constraints on the underlying wavefunction. The consequences of the requirement of unitarity are explored in Chapter 3, and are found to have startling phenomenological relevance. To test model light-cone wavefunctions, experimental predictions must be made. The reliability of perturbative QCD as a tool for making such predictions has been questioned. In Chapter 4, the author presents a computation of the rates for nucleon-antinucleon annihilation, improving the reliability of the perturbative computation by taking into account the Sudakov suppression of exclusive processes at large transverse impact parameter. In Chapter 5, he develops the analysis of semiexclusive production. This work focuses on processes in which a single isolated meson is produced perturbatively and recoils against a wide hadronizing system. At energies above about 10 GeV, semiexclusive processes are shown to be the most sensitive experimental probes of hadronic structure

  1. Development of a Motorized Digital Cone Penetrometer

    OpenAIRE

    Chung, Sun–Ok; Cho, Jin–Woong; Yamakawa, Takeo; 山川, 武夫

    2012-01-01

    Quantification and management of variability in soil strength, or soil compaction, is an important issue in countries such as Korea and Japan where typical field sizes are small, but tractor mounted on–the–go sensors that have been developed in USA and European countries are not practical. Therefore, hand–operated digital penetrometers have been widely used in Asian countries, but maintaining standard penetration rate and angle would be difficult. In this study, a motorized digital cone penet...

  2. Variability of silver fir (Abies alba Mill. cones – variability of cone parameters

    Directory of Open Access Journals (Sweden)

    Aniszewska Monika

    2016-09-01

    Full Text Available This study aimed at determining the shape of closed silver fir cones from the Jawor Forest District (Wroclaw, based purely on measurements of their length and thickness. Using these two parameters, the most accurate estimations were achieved with a fourth-degree polynomial fitting function. We then calculated the cones’ surface area and volume in three different ways: 1 Using the fourth-degree polynomial shape estimation, 2 Introducing indicators of compliance (k1, k2, k3 to calculate the volume and then comparing it to its actual value as measured in a pitcher filled with water, 3 Comparing the surface area of the cones as calculated with the polynomial function to the value obtained from ratios of indicators of compliance (ratios k4 and k5. We found that the calculated surface area and volume were substantially higher than the corresponding measured values. Test values of cone volume and surface area as calculated by our model were 8% and 5% lower, respectively, compared to direct measurements. We also determined the fir cones apparent density to be 0.8 g·cm-3on average. The gathered data on cone surface area, volume and bulk density is a valuable tool for optimizing the thermal peeling process in mill cabinets to acquire high quality seeds.

  3. The NLO jet vertex in the small-cone approximation for kt and cone algorithms

    International Nuclear Information System (INIS)

    Colferai, D.; Niccoli, A.

    2015-01-01

    We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

  4. The NLO jet vertex in the small-cone approximation for kt and cone algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Colferai, D.; Niccoli, A. [Dipartimento di Fisica e Astronomia, Università di Firenze and INFN, Sezione di Firenze, 50019 Sesto Fiorentino (Italy)

    2015-04-15

    We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

  5. Different effects of valproic acid on photoreceptor loss in Rd1 and Rd10 retinal degeneration mice.

    Science.gov (United States)

    Mitton, Kenneth P; Guzman, Alvaro E; Deshpande, Mrinalini; Byrd, David; DeLooff, Camryn; Mkoyan, Kristina; Zlojutro, Paul; Wallace, Adrianne; Metcalf, Brandon; Laux, Kirsten; Sotzen, Jason; Tran, Trung

    2014-01-01

    The histone-deacetylase inhibitor activity of valproic acid (VPA) was discovered after VPA's adoption as an anticonvulsant. This generated speculation for VPA's potential to increase the expression of neuroprotective genes. Clinical trials for retinitis pigmentosa (RP) are currently active, testing VPA's potential to reduce photoreceptor loss; however, we lack information regarding the effects of VPA on available mammalian models of retinal degeneration, nor do we know if retinal gene expression is perturbed by VPA in a predictable way. Thus, we examined the effects of systemic VPA on neurotrophic factor and Nrl-related gene expression in the mouse retina and compared VPA's effects on the rate of photoreceptor loss in two strains of mice, Pde6b(rd1/rd1) and Pde6b(rd10/rd10) . The expression of Bdnf, Gdnf, Cntf, and Fgf2 was measured by quantitative PCR after single and multiple doses of VPA (intraperitoneal) in wild-type and Pde6b(rd1/rd1) mice. Pde6b(rd1/rd1) mice were treated with daily doses of VPA during the period of rapid photoreceptor loss. Pde6b(rd10/rd10) mice were also treated with systemic VPA to compare in a partial loss-of-function model. Retinal morphology was assessed by virtual microscopy or spectral-domain optical coherence tomography (SD-OCT). Full-field and focal electroretinography (ERG) analysis were employed with Pde6b(rd10/rd10) mice to measure retinal function. In wild-type postnatal mice, a single VPA dose increased the expression of Bdnf and Gdnf in the neural retina after 18 h, while the expression of Cntf was reduced by 70%. Daily dosing of wild-type mice from postnatal day P17 to P28 resulted in smaller increases in Bdnf and Gdnf expression, normal Cntf expression, and reduced Fgf2 expression (25%). Nrl gene expression was decreased by 50%, while Crx gene expression was not affected. Rod-specific expression of Mef2c and Nr2e3 was decreased substantially by VPA treatment, while Rhodopsin and Pde6b gene expression was normal at P28. Daily

  6. Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress.

    Science.gov (United States)

    Hu, Qi-Di; Xu, Ling-Li; Gong, Yan; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun; Zhang, Zhe; Mao, Wei; Zhou, Yu-Sheng; Li, Qin-Bo; Yuan, Jian-Shu

    2018-01-19

    Lysergic acid diethylamide (LSD), a classical hallucinogen, was used as a popular and notorious substance of abuse in various parts of the world. Its abuse could result in long-lasting abnormalities in retina and little is known about the exact mechanism. This study was to investigate the effect of LSD on macrophage activation state at non-toxic concentration and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by LSD on 661 W cells after co-culturing with RAW264.7 cells. Treatment with LSD-induced RAW264.7 cells to the M1 phenotype, releasing more pro-inflammatory cytokines, and increasing the M1-related gene expression. Moreover, after co-culturing with RAW264.7 cells, significant oxidative stress in 661 W cells treated with LSD was observed, by increasing the level of malondialdehyde (MDA) and reactive oxygen species (ROS), and decreasing the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). Our study demonstrated that LSD caused photoreceptor cell damage by inducing inflammatory response and resultant oxidative stress, providing the scientific rationale for the toxicity of LSD to retina.

  7. In vivo imaging of human photoreceptor mosaic with wavefront sensorless adaptive optics optical coherence tomography.

    Science.gov (United States)

    Wong, Kevin S K; Jian, Yifan; Cua, Michelle; Bonora, Stefano; Zawadzki, Robert J; Sarunic, Marinko V

    2015-02-01

    Wavefront sensorless adaptive optics optical coherence tomography (WSAO-OCT) is a novel imaging technique for in vivo high-resolution depth-resolved imaging that mitigates some of the challenges encountered with the use of sensor-based adaptive optics designs. This technique replaces the Hartmann Shack wavefront sensor used to measure aberrations with a depth-resolved image-driven optimization algorithm, with the metric based on the OCT volumes acquired in real-time. The custom-built ultrahigh-speed GPU processing platform and fast modal optimization algorithm presented in this paper was essential in enabling real-time, in vivo imaging of human retinas with wavefront sensorless AO correction. WSAO-OCT is especially advantageous for developing a clinical high-resolution retinal imaging system as it enables the use of a compact, low-cost and robust lens-based adaptive optics design. In this report, we describe our WSAO-OCT system for imaging the human photoreceptor mosaic in vivo. We validated our system performance by imaging the retina at several eccentricities, and demonstrated the improvement in photoreceptor visibility with WSAO compensation.

  8. Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

    Directory of Open Access Journals (Sweden)

    Narsing A Rao

    Full Text Available The small heat shock protein, αA-crystallin null (αA-/- mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU. In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB, a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice, which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ, both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

  9. Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

    Science.gov (United States)

    Rao, Narsing A; Saraswathy, Sindhu; Pararajasegaram, Geeta; Bhat, Suraj P

    2012-01-01

    The small heat shock protein, αA-crystallin null (αA-/-) mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice), which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ), both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

  10. Low-resolution characterization of the 3D structure of the Euglena gracilis photoreceptor

    International Nuclear Information System (INIS)

    Barsanti, Laura; Coltelli, Primo; Evangelista, Valtere; Passarelli, Vincenzo; Frassanito, Anna Maria; Vesentini, Nicoletta; Gualtieri, Paolo

    2008-01-01

    This paper deals with the first characterization of the structure of the photoreceptive organelle of the unicellular alga Euglena gracilis (Euglenophyta). This organelle has a three-dimensional organization consisting of up to 50 closely stacked membrane lamellae. Ionically induced unstacking of the photoreceptor lamellae revealed ordered arrays well suited to structural analysis by electron microscopy and image analysis, which ultimately yielded a low-resolution picture of the structure. Each lamella is formed by the photoreceptive membrane protein of the cell assembled within the membrane layer in a hexagonal lattice. The first order diffraction spots in the calculated Fourier transform reveals the presence of 6-fold symmetrized topography (better resolution about 90 A). The 2D and 3D structural data are very similar with those recently published on proteorodopsin, a membrane protein used by marine bacterio-plankton as light-driven proton pump. In our opinion these similarity indicate that a photoreceptive protein belonging to the same superfamily of proteorodopsin could form the Euglena photoreceptor

  11. UV-B photoreceptor-mediated protection of the photosynthetic machinery in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Allorent, Guillaume; Lefebvre-Legendre, Linnka; Chappuis, Richard; Kuntz, Marcel; Truong, Thuy B; Niyogi, Krishna K; Ulm, Roman; Goldschmidt-Clermont, Michel

    2016-12-20

    Life on earth is dependent on the photosynthetic conversion of light energy into chemical energy. However, absorption of excess sunlight can damage the photosynthetic machinery and limit photosynthetic activity, thereby affecting growth and productivity. Photosynthetic light harvesting can be down-regulated by nonphotochemical quenching (NPQ). A major component of NPQ is qE (energy-dependent nonphotochemical quenching), which allows dissipation of light energy as heat. Photodamage peaks in the UV-B part of the spectrum, but whether and how UV-B induces qE are unknown. Plants are responsive to UV-B via the UVR8 photoreceptor. Here, we report in the green alga Chlamydomonas reinhardtii that UVR8 induces accumulation of specific members of the light-harvesting complex (LHC) superfamily that contribute to qE, in particular LHC Stress-Related 1 (LHCSR1) and Photosystem II Subunit S (PSBS). The capacity for qE is strongly induced by UV-B, although the patterns of qE-related proteins accumulating in response to UV-B or to high light are clearly different. The competence for qE induced by acclimation to UV-B markedly contributes to photoprotection upon subsequent exposure to high light. Our study reveals an anterograde link between photoreceptor-mediated signaling in the nucleocytosolic compartment and the photoprotective regulation of photosynthetic activity in the chloroplast.

  12. Interaction of two photoreceptors in the regulation of bacterial photosynthesis genes.

    Science.gov (United States)

    Metz, Sebastian; Haberzettl, Kerstin; Frühwirth, Sebastian; Teich, Kristin; Hasewinkel, Christian; Klug, Gabriele

    2012-07-01

    The expression of photosynthesis genes in the facultatively photosynthetic bacterium Rhodobacter sphaeroides is controlled by the oxygen tension and by light quantity. Two photoreceptor proteins, AppA and CryB, have been identified in the past, which are involved in this regulation. AppA senses light by its N-terminal BLUF domain, its C-terminal part binds heme and is redox-responsive. Through its interaction to the transcriptional repressor PpsR the AppA photoreceptor controls expression of photosynthesis genes. The cryptochrome-like protein CryB was shown to affect regulation of photosynthesis genes, but the underlying signal chain remained unknown. Here we show that CryB interacts with the C-terminal domain of AppA and modulates the binding of AppA to the transcriptional repressor PpsR in a light-dependent manner. Consequently, binding of the transcription factor PpsR to its DNA target is affected by CryB. In agreement with this, all genes of the PpsR regulon showed altered expression levels in a CryB deletion strain after blue-light illumination. These results elucidate for the first time how a bacterial cryptochrome affects gene expression.

  13. UV-B photoreceptor-mediated protection of the photosynthetic machinery in Chlamydomonas reinhardtii

    Science.gov (United States)

    Allorent, Guillaume; Lefebvre-Legendre, Linnka; Chappuis, Richard; Kuntz, Marcel; Truong, Thuy B.; Niyogi, Krishna K.; Goldschmidt-Clermont, Michel

    2016-01-01

    Life on earth is dependent on the photosynthetic conversion of light energy into chemical energy. However, absorption of excess sunlight can damage the photosynthetic machinery and limit photosynthetic activity, thereby affecting growth and productivity. Photosynthetic light harvesting can be down-regulated by nonphotochemical quenching (NPQ). A major component of NPQ is qE (energy-dependent nonphotochemical quenching), which allows dissipation of light energy as heat. Photodamage peaks in the UV-B part of the spectrum, but whether and how UV-B induces qE are unknown. Plants are responsive to UV-B via the UVR8 photoreceptor. Here, we report in the green alga Chlamydomonas reinhardtii that UVR8 induces accumulation of specific members of the light-harvesting complex (LHC) superfamily that contribute to qE, in particular LHC Stress-Related 1 (LHCSR1) and Photosystem II Subunit S (PSBS). The capacity for qE is strongly induced by UV-B, although the patterns of qE-related proteins accumulating in response to UV-B or to high light are clearly different. The competence for qE induced by acclimation to UV-B markedly contributes to photoprotection upon subsequent exposure to high light. Our study reveals an anterograde link between photoreceptor-mediated signaling in the nucleocytosolic compartment and the photoprotective regulation of photosynthetic activity in the chloroplast. PMID:27930292

  14. Cryptochrome photoreceptors in green algae: Unexpected versatility of mechanisms and functions.

    Science.gov (United States)

    Kottke, Tilman; Oldemeyer, Sabine; Wenzel, Sandra; Zou, Yong; Mittag, Maria

    2017-10-01

    Green algae have a highly complex and diverse set of cryptochrome photoreceptor candidates including members of the following subfamilies: plant, plant-like, animal-like, DASH and cryptochrome photolyase family 1 (CPF1). While some green algae encode most or all of them, others lack certain members. Here we present an overview about functional analyses of so far investigated cryptochrome photoreceptors from the green algae Chlamydomonas reinhardtii (plant and animal-like cryptochromes) and Ostreococcus tauri (CPF1) with regard to their biological significance and spectroscopic properties. Cryptochromes of both algae have been demonstrated recently to be involved to various extents in circadian clock regulation and in Chlamydomonas additionally in life cycle control. Moreover, CPF1 even performs light-driven DNA repair. The plant cryptochrome and CPF1 are UVA/blue light receptors, whereas the animal-like cryptochrome responds to almost the whole visible spectrum including red light. Accordingly, plant cryptochrome, animal-like cryptochrome and CPF1 differ fundamentally in their structural response to light as revealed by their visible and infrared spectroscopic signatures, and in the role of the flavin neutral radical acting as dark form or signaling state. Copyright © 2017 Elsevier GmbH. All rights reserved.

  15. Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration.

    Science.gov (United States)

    Zhang, Qian; Zhang, Zuo-Ming

    2014-04-25

    It is reported that retinal neovascularization seems to rarely co-exist with retinitis pigmentosa in patients and in some mouse models; however, it is not widely acknowledged as a universal phenomenon in all strains of all animal species. We aimed to further explore this phenomenon with an oxygen-induced retinopathy model in mice with retinal photoreceptor cell degeneration. Oxygen-induced retinopathy of colored and albino mice with rapid retinal degeneration were compared to homologous wild-type mice. The retinas were analyzed using high-molecular-weight FITC-dextran stained flat-mount preparation, hematoxylin and eosin (H&E) stained cross-sections, an immunohistochemical test for vascular endothelial growth factor (VEGF) distribution and Western blotting for VEGF expression after exposure to hyperoxia between postnatal days 17 (P17) and 21. Leakage and areas of non-perfusion of the retinal blood vessels were alleviated in the retinal degeneration mice. The number of preretinal vascular endothelial cell nuclei in the retinal degeneration mice was smaller than that in the homologous wild-type mice after exposure to hyperoxia (Poxygen-induced retinopathy was positively correlated with the VEGF expression level. However, the VEGF expression level was lower in the retinal degeneration mice. Proliferative retinopathy occurred in mice with rapid retinal degeneration, but retinal photoreceptor cell degeneration could partially restrain the retinal neovascularization in this rapid retinal degeneration mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Structural aspects of the antioxidant activity of lutein in a model of photoreceptor membranes

    Science.gov (United States)

    Wisniewska-Becker, Anna; Nawrocki, Grzegorz; Duda, Mariusz; Subczynski, Witold K.

    2014-01-01

    It was shown that in membranes containing raft domains, the macular xanthophylls lutein and zeaxanthin are not distributed uniformly, but are excluded from saturated raft domains and about ten times more concentrated in unsaturated bulk lipids. The selective accumulation of lutein and zeaxanthin in direct proximity to unsaturated lipids, which are especially susceptible to lipid peroxidation, could be very important as far as their antioxidant activity is concerned. Therefore, the protective role of lutein against lipid peroxidation was investigated in membranes made of raft-forming mixtures and in models of photoreceptor outer segment membranes and compared with their antioxidant activity in homogeneous membranes composed of unsaturated lipids. Lipid peroxidation was induced by photosensitized reactions using rose Bengal and monitored by an MDA-TBA test, an iodometric assay, and oxygen consumption (using EPR spectroscopy and the mHCTPO spin label as an oxygen probe). The results show that lutein protects unsaturated lipids more effectively in membranes made of raft-forming mixtures than in homogeneous membranes. This suggests that the selective accumulation of macular xanthophylls in the most vulnerable regions of photoreceptor membranes may play an important role in enhancing their antioxidant properties and ability to prevent age-related macular diseases (such as age-related macular degeneration [AMD]). PMID:22428148

  17. Light-cone observables and gauge-invariance in the geodesic light-cone formalism

    Energy Technology Data Exchange (ETDEWEB)

    Scaccabarozzi, Fulvio; Yoo, Jaiyul, E-mail: fulvio@physik.uzh.ch, E-mail: jyoo@physik.uzh.ch [Center for Theoretical Astrophysics and Cosmology, Institute for Computational Science, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich (Switzerland)

    2017-06-01

    The remarkable properties of the geodesic light-cone (GLC) coordinates allow analytic expressions for the light-cone observables, providing a new non-perturbative way for calculating the effects of inhomogeneities in our Universe. However, the gauge-invariance of these expressions in the GLC formalism has not been shown explicitly. Here we provide this missing part of the GLC formalism by proving the gauge-invariance of the GLC expressions for the light-cone observables, such as the observed redshift, the luminosity distance, and the physical area and volume of the observed sources. Our study provides a new insight on the properties of the GLC coordinates and it complements the previous work by the GLC collaboration, leading to a comprehensive description of light propagation in the GLC representation.

  18. A cone-beam reconstruction algorithm using shift-variant filtering and cone-beam backprojection

    International Nuclear Information System (INIS)

    Defrise, M.; Clack, R.

    1994-01-01

    An exact inversion formula written in the form of shift-variant filtered-backprojection (FBP) is given for reconstruction from cone-beam data taken from any orbit satisfying Tuy's sufficiency conditions. The method is based on a result of Grangeat, involving the derivative of the three-dimensional (3-D) Radon transform, but unlike Grangeat's algorithm, no 3D rebinning step is required. Data redundancy, which occurs when several cone-beam projections supply the same values in the Radon domain, is handled using an elegant weighting function and without discarding data. The algorithm is expressed in a convenient cone-beam detector reference frame, and a specific example for the case of a dual orthogonal circular orbit is presented. When the method is applied to a single circular orbit, it is shown to be equivalent to the well-known algorithm of Feldkamp et al

  19. Techniques for optimizing nanotips derived from frozen taylor cones

    Science.gov (United States)

    Hirsch, Gregory

    2017-12-05

    Optimization techniques are disclosed for producing sharp and stable tips/nanotips relying on liquid Taylor cones created from electrically conductive materials with high melting points. A wire substrate of such a material with a preform end in the shape of a regular or concave cone, is first melted with a focused laser beam. Under the influence of a high positive potential, a Taylor cone in a liquid/molten state is formed at that end. The cone is then quenched upon cessation of the laser power, thus freezing the Taylor cone. The tip of the frozen Taylor cone is reheated by the laser to allow its precise localized melting and shaping. Tips thus obtained yield desirable end-forms suitable as electron field emission sources for a variety of applications. In-situ regeneration of the tip is readily accomplished. These tips can also be employed as regenerable bright ion sources using field ionization/desorption of introduced chemical species.

  20. JWFront: Wavefronts and Light Cones for Kerr Spacetimes

    Science.gov (United States)

    Frutos Alfaro, Francisco; Grave, Frank; Müller, Thomas; Adis, Daria

    2015-04-01

    JWFront visualizes wavefronts and light cones in general relativity. The interactive front-end allows users to enter the initial position values and choose the values for mass and angular momentum per unit mass. The wavefront animations are available in 2D and 3D; the light cones are visualized using the coordinate systems (t, x, y) or (t, z, x). JWFront can be easily modified to simulate wavefronts and light cones for other spacetime by providing the Christoffel symbols in the program.

  1. Preparation of Au cone for fast ignition target

    International Nuclear Information System (INIS)

    Du Kai; Zhou Lan; Zhang Lin; Wan Xiaobo; Xiao Jiang

    2005-01-01

    Cone-shell target is typically used for the fast ignition experiments of inertial confinement fusion. In order to fabricate cone-shell target the Au cones with different angles were produced by electroplating and precise machining. The Au electroplating process was introduced in the paper, and the dependence of coating quality on the parameters, such as composition, temperature, pH of electroplating bath, current density and tip effect, were discussed. (author)

  2. Plasma microinstabilities driven by loss-cone distributions

    International Nuclear Information System (INIS)

    Summers, D.; Thorne, R.M.

    1995-01-01

    Electromagnetic and electrostatic instabilities driven by loss-cone particle distributions have been invoked to explain a variety of plasma phenomena observed in space and in the laboratory. In this paper we analyse how the loss-cone feature (as determined by the loss-cone index or indices) influences the growth of such instabilities in a fully ionized, homogeneous, hot plasma in a uniform magnetic field. Specifically, we consider three loss-cone distributions: a generalized Lorentzian (kappa) loss-cone distribution, the Dory-Guest-Harris distribution and the Ashour-Abdalla-Kennel distribution (involving a subtracted Maxwellian). Our findings are common to all three distributions. We find that, for parallel propagation, electromagnetic instabilities are only affected by the loss-cone indices in terms of their occurrence in the temperature anisotropy. However, for oblique propagation, even including propagation at small angles to the ambient magnetic field, the loss-cone indices do independently affect the growth of instabilities for electromagnetic waves, in contrast to certain claims in the literature. For electrostatic waves such that 1/2(κ perpendicular to ρ L σ 2 L σ is the Larmor radius for particle species σ, we find that the loss-cone indices only enter the dispersion equation via the temperature anisotropy, and so in this case the loss-cone feature and perpendicular effective thermal speed do not independently affect wave growth. (Author)

  3. Identifying Dirac cones in carbon allotropes with square symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jinying [College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Huang, Huaqing; Duan, Wenhui [Department of Physics, Tsinghua University, Beijing 100084 (China); Liu, Zhirong, E-mail: LiuZhiRong@pku.edu.cn [College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); State Key Laboratory for Structural Chemistry of Unstable and Stable Species and Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing 100871 (China)

    2013-11-14

    A theoretical study is conducted to search for Dirac cones in two-dimensional carbon allotropes with square symmetry. By enumerating the carbon atoms in a unit cell up to 12, an allotrope with octatomic rings is recognized to possess Dirac cones under a simple tight-binding approach. The obtained Dirac cones are accompanied by flat bands at the Fermi level, and the resulting massless Dirac-Weyl fermions are chiral particles with a pseudospin of S = 1, rather than the conventional S = 1/2 of graphene. The spin-1 Dirac cones are also predicted to exist in hexagonal graphene antidot lattices.

  4. Conical Refraction: new observations and a dual cone model.

    Science.gov (United States)

    Sokolovskii, G S; Carnegie, D J; Kalkandjiev, T K; Rafailov, E U

    2013-05-06

    We propose a paraxial dual-cone model of conical refraction involving the interference of two cones of light behind the exit face of the crystal. The supporting experiment is based on beam selecting elements breaking down the conically refracted beam into two separate hollow cones which are symmetrical with one another. The shape of these cones of light is a product of a 'competition' between the divergence caused by the conical refraction and the convergence due to the focusing by the lens. The developed mathematical description of the conical refraction demonstrates an excellent agreement with experiment.

  5. Use of cone beam computed tomography in implant dentistry: current concepts, indications and limitations for clinical practice and research.

    Science.gov (United States)

    Bornstein, Michael M; Horner, Keith; Jacobs, Reinhilde

    2017-02-01

    Diagnostic radiology is an essential component of treatment planning in the field of implant dentistry. This narrative review will present current concepts for the use of cone beam computed tomography imaging, before and after implant placement, in daily clinical practice and research. Guidelines for the selection of three-dimensional imaging will be discussed, and limitations will be highlighted. Current concepts of radiation dose optimization, including novel imaging modalities using low-dose protocols, will be presented. For preoperative cross-sectional imaging, data are still not available which demonstrate that cone beam computed tomography results in fewer intraoperative complications such as nerve damage or bleeding incidents, or that implants inserted using preoperative cone beam computed tomography data sets for planning purposes will exhibit higher survival or success rates. The use of cone beam computed tomography following the insertion of dental implants should be restricted to specific postoperative complications, such as damage of neurovascular structures or postoperative infections in relation to the maxillary sinus. Regarding peri-implantitis, the diagnosis and severity of the disease should be evaluated primarily based on clinical parameters and on radiological findings based on periapical radiographs (two dimensional). The use of cone beam computed tomography scans in clinical research might not yield any evident beneficial effect for the patient included. As many of the cone beam computed tomography scans performed for research have no direct therapeutic consequence, dose optimization measures should be implemented by using appropriate exposure parameters and by reducing the field of view to the actual region of interest. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Integrating Topographic Measures to Explore the Protective Effects of Peonidin Against the N-Methyl-N-Nitrosourea Induced Photoreceptor Degeneration

    Directory of Open Access Journals (Sweden)

    Ye Tao

    2016-02-01

    Full Text Available Background/Aims: The pathphysiological properties of N-Methyl -N -nitrosourea (MNU induced photoreceptor degeneration are similar to the hereditary retinitis pigmentosa (RP. The present study sought to explore the beneficial effects of the peonidin, a common aglycone form of anthocyanin, on the MNU induced photoreceptor degeneration via topographic measurements. Methods: The MNU administrated mouse received peonidin or vehicle injections, and then they were examined by electroretinography (ERG, multi electrode array (MEA, histological and immunohistochemistry studies. Results: The protective effects of peonidin on the MNU administrated retinas were systematically verified and quantified by topographic measures. The peonidin treatment could protect the photoreceptor against the MNU toxicity both functionally and morphologicaly. The most sensitive zone to peonidin therapy was sorted out, indicating that different rescuing kinetics existed between the retinal hemispheres and retinal quadrants. Moreover, the hyperactive spontaneous firing response and the debilitated light induced response in MNU administrated retinas could be partially reversed by peonidin treatment. To our knowledge, this was the first study to explore the pharmacological effects of peonidin on the electrophysiological properties of inner visual signal pathways. Conclusion: The peonidin could ameliorate the MNU induced photoreceptors degeneration and rectify the abnormities in the inner visual signal pathways. Future refinements of the knowledge cast insights into the discovery of a novel treatment for human RP.

  7. Na+/K(+)pump activity in photoreceptors of the blowfly Calliphora : A model analysis based on membrane potential measurements

    NARCIS (Netherlands)

    Gerster, U; Stavenga, DG; Backhaus, W

    Na+/K+-pump activity and intracellular Na+ and K+ concentration changes in blowfly photoreceptors are derived from intracellular potential measurements in vivo with a model based on the Goldman-Hodgkin-Katz theory for membrane currents. The relation between the intracellular Na+ concentration and

  8. Photocycle of the flavin-binding photoreceptor AppA, a bacterial transcriptional antirepressor of photosynthesis genes

    NARCIS (Netherlands)

    Gauden, M.L.; Yeremenko, S.; Laan, W.; van Stokkum, I.H.M.; Ihalainen, J.A.; van Grondelle, R.; Hellingwerf, K.J.; Kennis, J.T.M.

    2005-01-01

    The flavoprotein AppA from Rhodobacter sphaeroides contains an N-terminal domain belonging to a new class of photoreceptors designated BLUF domains. AppA was shown to control photosynthesis gene expression in response to blue light and oxygen tension. We have investigated the photocycle of the AppA

  9. Metarhodopsin control by arrestin, light-filtering screening pigments, and visual pigment turnover in invertebrate microvillar photoreceptors

    NARCIS (Netherlands)

    Stavenga, Doekele G.; Hardie, Roger C.

    The visual pigments of most invertebrate photoreceptors have two thermostable photo-interconvertible states, the ground state rhodopsin and photo-activated metarhodopsin, which triggers the phototransduction cascade until it binds arrestin. The ratio of the two states in photoequilibrium is

  10. Surviving Sengstaken.

    Science.gov (United States)

    Jayakumar, S; Odulaja, A; Patel, S; Davenport, M; Ade-Ajayi, N

    2015-07-01

    To report the outcomes of children who underwent Sengstaken-Blakemore tube (SBT) insertion for life-threatening haemetemesis. Single institution retrospective review (1997-2012) of children managed with SBT insertion. Patient demographics, diagnosis and outcomes were noted. Data are expressed as median (range). 19 children [10 male, age 1 (0.4-16) yr] were identified; 18 had gastro-oesophageal varices and 1 aorto-oesophageal fistula. Varices were secondary to: biliary atresia (n=8), portal vein thrombosis (n=5), alpha-1-anti-trypsin deficiency (n=1), cystic fibrosis (n=1), intrahepatic cholestasis (n=1), sclerosing cholangitis (n=1) and nodular hyperplasia with arterio-portal shunt (n=1). Three children deteriorated rapidly and did not survive to have post-SBT endoscopy. The child with an aortooesophageal fistula underwent aortic stent insertion and subsequently oesophageal replacement. Complications included gastric mucosal ulceration (n=3, 16%), pressure necrosis at lips and cheeks (n=6, 31%) and SBT dislodgment (n=1, 6%). Six (31%) children died. The remaining 13 have been followed up for 62 (2-165) months; five required liver transplantation, two underwent a mesocaval shunt procedure and 6 have completed endoscopic variceal obliteration and are under surveillance. SBT can be an effective, albeit temporary, life-saving manoeuvre in children with catastrophic haematemesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema.

    Science.gov (United States)

    Forooghian, Farzin; Stetson, Paul F; Meyer, Scott A; Chew, Emily Y; Wong, Wai T; Cukras, Catherine; Meyerle, Catherine B; Ferris, Frederick L

    2010-01-01

    The purpose of this study was to quantify photoreceptor outer segment (PROS) length in 27 consecutive patients (30 eyes) with diabetic macular edema using spectral domain optical coherence tomography and to describe the correlation between PROS length and visual acuity. Three spectral domain-optical coherence tomography scans were performed on all eyes during each session using Cirrus HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for 3 parameters: macular grid (6 x 6 mm), central subfield (1 mm), and center foveal point (0.33 mm). Intrasession repeatability was assessed using coefficient of variation and intraclass correlation coefficient. The association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses. The main outcome measures include intrasession repeatability of macular parameters and correlation of these parameters with visual acuity. Mean retinal thickness and PROS length were 298 mum to 381 microm and 30 microm to 32 mum, respectively, for macular parameters assessed in this study. Coefficient of variation values were 0.75% to 4.13% for retinal thickness and 1.97% to 14.01% for PROS length. Intraclass correlation coefficient values were 0.96 to 0.99 and 0.73 to 0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from 0 (P > 0.20), whereas the slopes of PROS length and visual acuity were significantly different from 0 (P < 0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, whereas coefficients for PROS length and visual acuity ranged from -0.61 to -0.81. Photoreceptor outer segment length can be quantitatively assessed using Cirrus HD-OCT. Although the intrasession repeatability of PROS

  12. Light-cone quantization and QCD phenomenology

    International Nuclear Information System (INIS)

    Brodsky, S.J.; Robertson, D.G.

    1995-01-01

    In principle, quantum chromodynamics provides a fundamental description of hadronic and nuclear structure and dynamics in terms of their elementary quark and gluon degrees of freedom. In practice, the direct application of QCD to reactions involving the structure of hadrons is extremely complex because of the interplay of nonperturbative effects such as color confinement and multi-quark coherence. A crucial tool in analyzing such phenomena is the use of relativistic light-cone quantum mechanics and Fock state methods to provide tractable and consistent treatments of relativistic many-body systems. In this article we present an overview of this formalism applied to QCD, focusing in particular on applications to the final states in deep inelastic lepton scattering that will be relevant for the proposed European Laboratory for Electrons (ELFE), HERMES, HERA, SLAC, and CEBAF. We begin with a brief introduction to light-cone field theory, stressing how it many allow the derivation of a constituent picture, analogous to the constituent quark model, from QCD. We then discuss several applications of the light-cone Fock state formalism to QCD phenomenology. The Fock state representation includes all quantum fluctuations of the hadron wavefunction, including far off-shell configurations such as intrinsic charm and, in the case of nuclei, hidden color. In some applications, such as exclusive processes at large momentum transfer, one can make first-principle predictions using factorization theorems which separate the hard perturbative dynamics from the nonpertubative physics associated with hadron binding. The Fock state components of the hadron with small transverse size, which dominate hard exclusive reactions, have small color dipole moments and thus diminished hadronic interactions. Thus QCD predicts minimal absorptive corrections, i.e., color transparency for quasi-elastic exclusive reactions in nuclear targets at large momentum transfer

  13. Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

    NARCIS (Netherlands)

    Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

    2012-01-01

    In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance

  14. Basic principles of cone beam computed tomography.

    Science.gov (United States)

    Abramovitch, Kenneth; Rice, Dwight D

    2014-07-01

    At the end of the millennium, cone-beam computed tomography (CBCT) heralded a new dental technology for the next century. Owing to the dramatic and positive impact of CBCT on implant dentistry and orthognathic/orthodontic patient care, additional applications for this technology soon evolved. New software programs were developed to improve the applicability of, and access to, CBCT for dental patients. Improved, rapid, and cost-effective computer technology, combined with the ability of software engineers to develop multiple dental imaging applications for CBCT with broad diagnostic capability, have played a large part in the rapid incorporation of CBCT technology into dentistry. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Cone penetrometer: Innovative technology summary report

    International Nuclear Information System (INIS)

    1996-04-01

    Cone penetrometer technology (CPT) provides cost-effective, real-time data for use in the characterization of the subsurface. Recent innovations in this baseline technology allow for improved access to the subsurface for environmental restoration applications. The technology has been improved by both industry and government agencies and is constantly advancing due to research efforts. The U.S. Department of Energy (DOE) Office of Science and Technology (formerly Technology Development) has contributed significantly to these efforts. This report focuses on the advancements made in conjunction with DOE's support but recognizes Department of Defense (DOD) and industry efforts

  16. CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family.

    Science.gov (United States)

    Kubota, Daiki; Gocho, Kiyoko; Kikuchi, Sachiko; Akeo, Keiichiro; Miura, Masahiro; Yamaki, Kunihiko; Takahashi, Hiroshi; Kameya, Shuhei

    2018-05-02

    CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins. C-Nap1 has been reported to be expressed in the photoreceptor cilia and is known to interact with other ciliary proteins. Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa. This study tested the hypothesis that the mild cone-rod dystrophy (CRD) and SNHL in a non-consanguineous Japanese family was caused by CEP250 mutations. Detailed ophthalmic and auditory examinations were performed on the proband and her family members. Whole exome sequencing (WES) was used on the DNA obtained from the proband. Electrophysiological analysis revealed a mild CRD in two family members. Adaptive optics (AO) imaging showed reduced cone density around the fovea. Auditory examinations showed a slight SNHL in both patients. WES of the proband identified compound heterozygous variants c.361C>T, p.R121*, and c.562C>T, p.R188* in CEP250. The variants were found to co-segregate with the disease in five members of the family. The variants of CEP250 are both null variants and according to American College of Medical Genetics and Genomics (ACMG) standards and guideline, these variants are classified into the very strong category (PVS1). The criteria for both alleles will be pathogenic. Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease.

  17. Gene Correction Reverses Ciliopathy and Photoreceptor Loss in iPSC-Derived Retinal Organoids from Retinitis Pigmentosa Patients

    Directory of Open Access Journals (Sweden)

    Wen-Li Deng

    2018-04-01

    Full Text Available Summary: Retinitis pigmentosa (RP is an irreversible, inherited retinopathy in which early-onset nyctalopia is observed. Despite the genetic heterogeneity of RP, RPGR mutations are the most common causes of this disease. Here, we generated induced pluripotent stem cells (iPSCs from three RP patients with different frameshift mutations in the RPGR gene, which were then differentiated into retinal pigment epithelium (RPE cells and well-structured retinal organoids possessing electrophysiological properties. We observed significant defects in photoreceptor in terms of morphology, localization, transcriptional profiling, and electrophysiological activity. Furthermore, shorted cilium was found in patient iPSCs, RPE cells, and three-dimensional retinal organoids. CRISPR-Cas9-mediated correction of RPGR mutation rescued photoreceptor structure and electrophysiological property, reversed the observed ciliopathy, and restored gene expression to a level in accordance with that in the control using transcriptome-based analysis. This study recapitulated the pathogenesis of RPGR using patient-specific organoids and achieved targeted gene therapy of RPGR mutations in a dish as proof-of-concept evidence. : Jin and colleagues demonstrate that patient-specific iPSC-derived 3D retinae can recapitulate disease progress of retinitis pigmentosa through presenting defects in photoreceptor morphology, gene profile, and electrophysiology, as well as the defective ciliogenesis in iPSCs, iPSC-RPE, and 3D retinae. CRISPR/Cas9-mediated gene correction can rescue not only photoreceptor structure and electrophysiological property but also observed ciliopathy. Keywords: RPGR, photoreceptor, electrophysiology, retinitis pigmentosa, patient-derived iPSCs, retinal organoid, RPE cells, cilium, ciliopathy, disease modeling

  18. Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution.

    Science.gov (United States)

    Solovei, Irina; Kreysing, Moritz; Lanctôt, Christian; Kösem, Süleyman; Peichl, Leo; Cremer, Thomas; Guck, Jochen; Joffe, Boris

    2009-04-17

    We show that the nuclear architecture of rod photoreceptor cells differs fundamentally in nocturnal and diurnal mammals. The rods of diurnal retinas possess the conventional architecture found in nearly all eukaryotic cells, with most heterochromatin situated at the nuclear periphery and euchromatin residing toward the nuclear interior. The rods of nocturnal retinas have a unique inverted pattern, where heterochromatin localizes in the nuclear center, whereas euchromatin, as well as nascent transcripts and splicing machinery, line the nuclear border. The inverted pattern forms by remodeling of the conventional one during terminal differentiation of rods. The inverted rod nuclei act as collecting lenses, and computer simulations indicate that columns of such nuclei channel light efficiently toward the light-sensing rod outer segments. Comparison of the two patterns suggests that the conventional architecture prevails in eukaryotic nuclei because it results in more flexible chromosome arrangements, facilitating positional regulation of nuclear functions.

  19. The UV-B Photoreceptor UVR8: From Structure to Physiology

    Science.gov (United States)

    Jenkins, Gareth I.

    2014-01-01

    Low doses of UV-B light (280 to 315 nm) elicit photomorphogenic responses in plants that modify biochemical composition, photosynthetic competence, morphogenesis, and defense. UV RESISTANCE LOCUS8 (UVR8) mediates photomorphogenic responses to UV-B by regulating transcription of a set of target genes. UVR8 differs from other known photoreceptors in that it uses specific Trp amino acids instead of a prosthetic chromophore for light absorption during UV-B photoreception. Absorption of UV-B dissociates the UVR8 dimer into monomers, initiating signal transduction through interaction with CONSTITUTIVELY PHOTOMORPHOGENIC1. However, much remains to be learned about the physiological role of UVR8 and its interaction with other signaling pathways, the molecular mechanism of UVR8 photoreception, how the UVR8 protein initiates signaling, how it is regulated, and how UVR8 regulates transcription of its target genes. PMID:24481075

  20. Circadian locomotor rhythms in the cricket, Gryllodes sigillatus. I. Localization of the pacemaker and the photoreceptor.

    Science.gov (United States)

    Abe, Y; Ushirogawa, H; Tomioka, K

    1997-10-01

    Circadian locomotor rhythm and its underlying mechanism were investigated in the cricket, Gryllodes sigillatus. Adult male crickets showed a nocturnal locomotor rhythm peaking early in the dark phase of a light to dark cycle. This rhythm persisted under constant darkness (DD) with a free-running period averaging 23.1 +/- 0.3 hr. Although constant bright light made most animals arrhythmic, about 40% of the animals showed free-running rhythms with a period longer than 24 hr under constant dim light condition. On transfer to DD, all arrhythmic animals restored the locomotor rhythm. Bilateral optic nerve severance resulted in free-running of the rhythm even under light-dark cycles. The free-running period of the optic nerve severed animals was significantly longer than sham operated crickets in DD, suggesting that the compound eye plays some role in determining the free-running period. Removal of bilateral lamina-medulla portion of the optic lobe abolished the rhythm under DD. These results demonstrate that the photoreceptor for entrainment is the compound eye and the optic lobe is indispensable for persistence of the rhythm. However, 75% and 54% of the optic lobeless animals showed aberrant rhythms with a period very close to 24 hr under light and temperature cycles, respectively, suggesting that there are neural and/or humoral mechanisms for the aberrant rhythms outside of the optic lobe. Since ocelli removal did not affect the photoperiodically induced rhythm, it is likely that the photoreception for the rhythm is performed through an extraretinal photoreceptor.

  1. Regulatory arrestin cycle secures the fidelity and maintenance of the fly photoreceptor cell.

    Science.gov (United States)

    Byk, T; Bar-Yaacov, M; Doza, Y N; Minke, B; Selinger, Z

    1993-01-01

    Excitation of fly photoreceptor cells is initiated by photoisomerization of rhodopsin to the active form of metarhodopsin. Fly metarhodopsin is thermostable, does not bleach, and does not regenerate spontaneously to rhodopsin. For this reason, the activity of metarhodopsin must be stopped by an effective termination reaction. On the other hand, there is also a need to restore the inactivated photopigment to an excitable state in order to keep a sufficient number of photopigment molecules available for excitation. The following findings reveal how these demands are met. The photopigment undergoes rapid phosphorylation upon photoconversion of rhodopsin to metarhodopsin and an efficient Ca2+ dependent dephosphorylation upon regeneration of metarhodopsin to rhodopsin. Phosphorylation decreases the ability of metarhodopsin to activate the guanine nucleotide-binding protein. Binding of 49-kDa arrestin further quenches the activity of metarhodopsin and protects it from dephosphorylation. Light-dependent binding and release of 49-kDa arrestin from metarhodopsin- and rhodopsin-containing membranes, respectively, directs the dephosphorylation reaction toward rhodopsin. This ensures the return of phosphorylated metarhodopsin to the rhodopsin pool without initiating transduction in the dark. Assays of rhodopsin dephosphorylation in the Drosophila retinal degeneration C (rdgC) mutant, a mutant in a gene previously cloned and predicted to encode a serine/threonine protein phosphatase, reveal that phosphorylated rhodopsin is a major substrate for the rdgC phosphatase. We propose that mutations resulting in either a decrease or an improper regulation of rhodopsin phosphatase activity bring about degeneration of the fly photoreceptor cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8446607

  2. Role of the mouse retinal photoreceptor ribbon synapse in visual motion processing for optokinetic responses.

    Science.gov (United States)

    Sugita, Yuko; Araki, Fumiyuki; Chaya, Taro; Kawano, Kenji; Furukawa, Takahisa; Miura, Kenichiro

    2015-01-01

    The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs). The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz) that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz). The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz) were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz). These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated.

  3. Role of the mouse retinal photoreceptor ribbon synapse in visual motion processing for optokinetic responses.

    Directory of Open Access Journals (Sweden)

    Yuko Sugita

    Full Text Available The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs. The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz. The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz. These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated.

  4. Light-cone quantization and hadron structure

    International Nuclear Information System (INIS)

    Brodsky, S.J.

    1996-04-01

    Quantum chromodynamics provides a fundamental description of hadronic and nuclear structure and dynamics in terms of elementary quark and gluon degrees of freedom. In practice, the direct application of QCD to reactions involving the structure of hadrons is extremely complex because of the interplay of nonperturbative effects such as color confinement and multi-quark coherence. In this talk, the author will discuss light-cone quantization and the light-cone Fock expansion as a tractable and consistent representation of relativistic many-body systems and bound states in quantum field theory. The Fock state representation in QCD includes all quantum fluctuations of the hadron wavefunction, including fax off-shell configurations such as intrinsic strangeness and charm and, in the case of nuclei, hidden color. The Fock state components of the hadron with small transverse size, which dominate hard exclusive reactions, have small color dipole moments and thus diminished hadronic interactions. Thus QCD predicts minimal absorptive corrections, i.e., color transparency for quasi-elastic exclusive reactions in nuclear targets at large momentum transfer. In other applications, such as the calculation of the axial, magnetic, and quadrupole moments of light nuclei, the QCD relativistic Fock state description provides new insights which go well beyond the usual assumptions of traditional hadronic and nuclear physics

  5. Insectos de cones y semillas de las coniferas de Mexico

    Science.gov (United States)

    David Cibrián-Tovar; Bernard H. Ebel; Harry O. Yates; José Tulio Mhdez-Montiel

    1986-01-01

    The hosts, description, damage, life cycle, habits, and importance of 54 known cone and seed destroying insects attacking Mexican conifer trees are discussed. Distribution maps and color photos are provided. New species described are three species of Cydia (seedworm), four species of Dioryctria (coneworm), and four species of cone...

  6. Polynomial Primal-Dual Cone Affine Scaling for Semidefinite Programming

    NARCIS (Netherlands)

    A.B. Berkelaar (Arjan); J.F. Sturm; S. Zhang (Shuzhong)

    1996-01-01

    textabstractIn this paper we generalize the primal--dual cone affine scaling algorithm of Sturm and Zhang to semidefinite programming. We show in this paper that the underlying ideas of the cone affine scaling algorithm can be naturely applied to semidefinite programming, resulting in a new

  7. Fan-beam and cone-beam image reconstruction via filtering the backprojection image of differentiated projection data

    International Nuclear Information System (INIS)

    Zhuang Tingliang; Leng Shuai; Nett, Brian E; Chen Guanghong

    2004-01-01

    In this paper, a new image reconstruction scheme is presented based on Tuy's cone-beam inversion scheme and its fan-beam counterpart. It is demonstrated that Tuy's inversion scheme may be used to derive a new framework for fan-beam and cone-beam image reconstruction. In this new framework, images are reconstructed via filtering the backprojection image of differentiated projection data. The new framework is mathematically exact and is applicable to a general source trajectory provided the Tuy data sufficiency condition is satisfied. By choosing a piece-wise constant function for one of the components in the factorized weighting function, the filtering kernel is one dimensional, viz. the filtering process is along a straight line. Thus, the derived image reconstruction algorithm is mathematically exact and efficient. In the cone-beam case, the derived reconstruction algorithm is applicable to a large class of source trajectories where the pi-lines or the generalized pi-lines exist. In addition, the new reconstruction scheme survives the super-short scan mode in both the fan-beam and cone-beam cases provided the data are not transversely truncated. Numerical simulations were conducted to validate the new reconstruction scheme for the fan-beam case

  8. Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

    Science.gov (United States)

    Maugeri, A; Klevering, B J; Rohrschneider, K; Blankenagel, A; Brunner, H G; Deutman, A F; Hoyng, C B; Cremers, F P

    2000-10-01

    The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.

  9. Derivation of the gauge link in light cone gauge

    International Nuclear Information System (INIS)

    Gao Jianhua

    2010-01-01

    In light cone gauge, a gauge link at light cone infinity is necessary for transverse momentum-dependent parton distribution to restore the gauge invariance in some specific boundary conditions. We derive such transverse gauge link in a more regular and general method. We find the gauge link at light cone infinity naturally arises from the contribution of the pinched poles: one is from the quark propagator and the other is hidden in the gauge vector field in light cone gauge. Actually, in the amplitude level, we have obtained a more general gauge link over the hypersurface at light cone infinity which is beyond the transverse direction. The difference of such gauge link between semi-inclusive deep inelastic scattering and Drell-Yan processes can also be obtained directly and clearly in our derivation.

  10. Conceptual Design of Deployment Structure of Morphing Nose Cone

    Directory of Open Access Journals (Sweden)

    Junlan Li

    2013-01-01

    Full Text Available For a reusable space vehicle or a missile, the shape of the nose cone has a significant effect on the drag of the vehicle. In this paper, the concept of morphing nose cone is proposed to reduce the drag when the reentry vehicle flies back into the atmosphere. The conceptual design of the structure of morphing nose cone is conducted. Mechanical design and optimization approach are developed by employing genetic algorithm to find the optimal geometric parameters of the morphing structure. An example is analyzed by using the proposed method. The results show that optimal solution supplies the minimum position error. The concept of morphing nose cone will provide a novel way for the drag reduction of reentry vehicle. The proposed method could be practically used for the design and optimization of the deployable structure of morphing nose cone.

  11. Implementation of Tuy's cone-beam inversion formula

    International Nuclear Information System (INIS)

    Zeng, G.L.; Clack, R.; Gullberg, G.T.

    1994-01-01

    Tuy's cone-beam inversion formula was modified to develop a cone-beam reconstruction algorithm. The algorithm was implemented for a cone-beam vertex orbit consisting of a circle and two orthogonal lines. This orbit geometry satisfies the cone-beam data sufficiency condition and is easy to implement on commercial single photon emission computed tomography (SPECT) systems. The algorithm which consists of two derivative steps, one rebinning step, and one three-dimensional backprojection step, was verified by computer simulations and by reconstructing physical phantom data collected on a clinical SPECT system. The proposed algorithm gives equivalent results and is as efficient as other analytical cone-beam reconstruction algorithms. (Author)

  12. The Ste20 kinase misshapen regulates both photoreceptor axon targeting and dorsal closure, acting downstream of distinct signals.

    Science.gov (United States)

    Su, Y C; Maurel-Zaffran, C; Treisman, J E; Skolnik, E Y

    2000-07-01

    We have previously shown that the Ste20 kinase encoded by misshapen (msn) functions upstream of the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase module in Drosophila. msn is required to activate the Drosophila JNK, Basket (Bsk), to promote dorsal closure of the embryo. A mammalian homolog of Msn, Nck interacting kinase, interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We now show that Msn likewise interacts with Dreadlocks (Dock), the Drosophila homolog of Nck. dock is required for the correct targeting of photoreceptor axons. We have performed a structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to determine whether msn, like dock, is required for the correct targeting of photoreceptor axons. We show that Msn requires both a functional kinase and a C-terminal regulatory domain to activate JNK in vivo in Drosophila. A mutation in a PXXP motif on Msn that prevents it from binding to the SH3 domains of Dock does not affect its ability to rescue the dorsal closure defect in msn embryos, suggesting that Dock is not an upstream regulator of msn in dorsal closure. Larvae with only this mutated form of Msn show a marked disruption in photoreceptor axon targeting, implicating an SH3 domain protein in this process; however, an activated form of Msn is not sufficient to rescue the dock mutant phenotype. Mosaic analysis reveals that msn expression is required in photoreceptors in order for their axons to project correctly. The data presented here genetically link msn to two distinct biological events, dorsal closure and photoreceptor axon pathfinding, and thus provide the first evidence that Ste20 kinases of the germinal center kinase family play a role in axonal pathfinding. The ability of Msn to interact with distinct classes of adapter molecules in dorsal closure and photoreceptor axon pathfinding may provide the flexibility that allows it to link to distinct

  13. Handling data redundancy in helical cone beam reconstruction with a cone-angle-based window function and its asymptotic approximation

    International Nuclear Information System (INIS)

    Tang Xiangyang; Hsieh Jiang

    2007-01-01

    A cone-angle-based window function is defined in this manuscript for image reconstruction using helical cone beam filtered backprojection (CB-FBP) algorithms. Rather than defining the window boundaries in a two-dimensional detector acquiring projection data for computed tomographic imaging, the cone-angle-based window function deals with data redundancy by selecting rays with the smallest cone angle relative to the reconstruction plane. To be computationally efficient, an asymptotic approximation of the cone-angle-based window function is also given and analyzed in this paper. The benefit of using such an asymptotic approximation also includes the avoidance of functional discontinuities that cause artifacts in reconstructed tomographic images. The cone-angle-based window function and its asymptotic approximation provide a way, equivalent to the Tam-Danielsson-window, for helical CB-FBP reconstruction algorithms to deal with data redundancy, regardless of where the helical pitch is constant or dynamically variable during a scan. By taking the cone-parallel geometry as an example, a computer simulation study is conducted to evaluate the proposed window function and its asymptotic approximation for helical CB-FBP reconstruction algorithm to handle data redundancy. The computer simulated Forbild head and thorax phantoms are utilized in the performance evaluation, showing that the proposed cone-angle-based window function and its asymptotic approximation can deal with data redundancy very well in cone beam image reconstruction from projection data acquired along helical source trajectories. Moreover, a numerical study carried out in this paper reveals that the proposed cone-angle-based window function is actually equivalent to the Tam-Danielsson-window, and rigorous mathematical proofs are being investigated

  14. Cone beam computed tomography in endodontic

    Energy Technology Data Exchange (ETDEWEB)

    Durack, Conor; Patel, Shanon [Unit of Endodontology, Department of Conservative Dentistry, King' s College London, London (United Kingdom)

    2012-07-01

    Cone beam computed tomography (CBCT) is a contemporary, radiological imaging system designed specifically for use on the maxillofacial skeleton. The system overcomes many of the limitations of conventional radiography by producing undistorted, three-dimensional images of the area under examination. These properties make this form of imaging particularly suitable for use in endodontic. The clinician can obtain an enhanced appreciation of the anatomy being assessed, leading to an improvement in the detection of endodontic disease and resulting in more effective treatment planning. In addition, CBCT operates with a significantly lower effective radiation dose when compared with conventional computed tomography (CT). The purpose of this paper is to review the current literature relating to the limitations and potential applications of CBCT in endodontic practice. (author)

  15. Cone beam computed tomography in endodontic

    International Nuclear Information System (INIS)

    Durack, Conor; Patel, Shanon

    2012-01-01

    Cone beam computed tomography (CBCT) is a contemporary, radiological imaging system designed specifically for use on the maxillofacial skeleton. The system overcomes many of the limitations of conventional radiography by producing undistorted, three-dimensional images of the area under examination. These properties make this form of imaging particularly suitable for use in endodontic. The clinician can obtain an enhanced appreciation of the anatomy being assessed, leading to an improvement in the detection of endodontic disease and resulting in more effective treatment planning. In addition, CBCT operates with a significantly lower effective radiation dose when compared with conventional computed tomography (CT). The purpose of this paper is to review the current literature relating to the limitations and potential applications of CBCT in endodontic practice. (author)

  16. Chemical profile of Taxodium distichum winter cones

    Directory of Open Access Journals (Sweden)

    Đapić Nina M.

    2017-01-01

    Full Text Available This work is concerned with the chemical profile of Taxodium distichum winter cones. The extract obtained after maceration in absolute ethanol was subjected to qualitative analysis by gas chromatography/mass spectrometry and quantification was done by gas chromatography/ flame ionization detector. The chromatogram revealed the presence of 53 compounds, of which 33 compounds were identified. The extract contained oxygenated monoterpenes (12.42%, sesquiterpenes (5.18%, oxygenated sesquiterpenes (17.41%, diterpenes (1.15%, and oxygenated diterpenes (30.87%, while the amount of retinoic acid was 0.32%. Monoacylglycerols were detected in the amount of 4.32%. The most abundant compounds were: caryophyllene oxide (14.27%, 6,7-dehydro-ferruginol (12.49%, bornyl acetate (10.96%, 6- deoxy-taxodione (9.50% and trans-caryophyllene (4.20%.

  17. Cone penetrometer testing (CPT) for groundwater contamination

    International Nuclear Information System (INIS)

    Jordan, J.E.; Van Pelt, R.S.

    1993-01-01

    Over the past decade, researchers at the Savannah River Site (SRS) and elsewhere have greatly advanced the knowledge of waste site characterization technologies. As a result, many of the techniques used in the past to investigate waste sites have been replaced by newer technologies, designed to provide greater protection for human health and the environment, greater access to suspected zones of contamination, and more accurate information of subsurface conditions. Determining the most environmentally sound method of assessing a waste unit is a major component of the SRS environmental restoration program. In an effort to understand the distribution and migration of contaminants in the groundwater system, the cone penetrometer investigation of the A/M-Area Southern Sector was implemented. The program incorporated a phased approach toward characterization by first using the CPT to delineate the plume boundary, followed by installing groundwater monitoring wells. The study provided the additional hydrogeologic information necessary to better understand the nature and extent of the contaminant plume (Fig. 1) and the hydrogeologic system in the Southem Sector. This data is essential for the optimal layout of the planned groundwater monitoring well network and recovery system to remediate the aquifers in the area. A number of other test locations were selected in the area during this study for lithologic calibration of the tool and to collect confirmation water samples from the aquifer. Cone penetrometer testing and hydrocone sampling, were performed at 17 sites (Fig. 2). The hydrocone, a tool modification to the CPT, was used to collect four groundwater samples from confined aquifers. These samples were analyzed by SRS laboratories. Elevated levels of chlorinated compounds were detected from these samples and have aided in further delineating the southern sector contaminant plume

  18. Cadmium Removal from Aqueous Solutions by Ground Pine Cone

    Directory of Open Access Journals (Sweden)

    H Izanloo, S Nasseri

    2005-01-01

    Full Text Available A study on the removal of cadmium ions from aqueous solutions by pine cone was conducted in batch conditions. Kinetic data and equilibrium removal isotherms were obtained. The influence of different experimental parameters such as contact time, initial concentration of cadmium, pine cone mass and particle size, and temperature on the kinetics of cadmium removal was studied. Results showed that the main parameters that played an important role in removal phenomenon were initial cadmium concentration, particle size and pine cone mass. The necessary time to reach equilibrium was between 4 and 7 hours based on the initial concentration of cadmium. The capacity of cadmium adsorption at equilibrium increased with the decrease of pine cone particle size. The capacity of cadmium adsorption at equilibrium by pine cone increased with the quantity of pine cone introduced (1–4 g/L. Temperature in the range of 20-30°C showed a restricted effect on the removal kinetics (13.56 mg/g at 20°C and a low capacity of adsorption about 11.48 mg/g at 30°C. The process followed pseudo second-order kinetics. The cadmium uptake of pine cone was quantitatively evaluated using adsorption isotherms. Results indicated that the Langmuir model gave a better fit to the experimental data in comparison with the Freundlich equation.

  19. Topology-optimized dual-polarization Dirac cones

    Science.gov (United States)

    Lin, Zin; Christakis, Lysander; Li, Yang; Mazur, Eric; Rodriguez, Alejandro W.; Lončar, Marko

    2018-02-01

    We apply a large-scale computational technique, known as topology optimization, to the inverse design of photonic Dirac cones. In particular, we report on a variety of photonic crystal geometries, realizable in simple isotropic dielectric materials, which exhibit dual-polarization Dirac cones. We present photonic crystals of different symmetry types, such as fourfold and sixfold rotational symmetries, with Dirac cones at different points within the Brillouin zone. The demonstrated and related optimization techniques open avenues to band-structure engineering and manipulating the propagation of light in periodic media, with possible applications to exotic optical phenomena such as effective zero-index media and topological photonics.

  20. Instantaneous interactions of hadrons on the light cone

    International Nuclear Information System (INIS)

    Hyer, T.

    1994-01-01

    Hadron wave functions are most naturally defined in the framework of light-cone quantization, a Hamiltonian formulation quantized at equal light-cone ''time'' τ≡t+z. One feature of the light-cone perturbation theory is the presence of instantaneous interactions, which complicate the consideration of processes involving bound states. We show that these interactions can be written in a simple and general form, parametrized by an instantaneous contribution ψ to the hadronic wave function. We use the rotational invariance of Feynman diagrams to relate this instantaneous piece of the meson wave function to the propagating part, and to obtain constraints relating wave functions and quark fragmentation amplitudes

  1. Light-cone averaging in cosmology: formalism and applications

    International Nuclear Information System (INIS)

    Gasperini, M.; Marozzi, G.; Veneziano, G.; Nugier, F.

    2011-01-01

    We present a general gauge invariant formalism for defining cosmological averages that are relevant for observations based on light-like signals. Such averages involve either null hypersurfaces corresponding to a family of past light-cones or compact surfaces given by their intersection with timelike hypersurfaces. Generalized Buchert-Ehlers commutation rules for derivatives of these light-cone averages are given. After introducing some adapted ''geodesic light-cone'' coordinates, we give explicit expressions for averaging the redshift to luminosity-distance relation and the so-called ''redshift drift'' in a generic inhomogeneous Universe

  2. Compensation of deformations in 3D cone beam tomography

    International Nuclear Information System (INIS)

    Desbat, L.; Roux, S.; Roux, S.; Grangeat, P.

    2006-01-01

    In dynamic tomography, the measured objects or organs are no-longer supposed to be static in the scanner during the acquisition but are supposed to move or to be deformed. Our approach is the analytic deformation compensation during the reconstruction. Our work concentrates on 3-dimensional cone beam tomography. We introduce a new large class of deformations preserving the 3-dimensional cone beam geometry. We show that deformations from this class can be analytically compensated. We present numerical experiments on phantoms showing the compensation of these deformations in 3-dimensional cone beam tomography. (authors)

  3. Alopecia associated with unexpected leakage from electron cone

    Energy Technology Data Exchange (ETDEWEB)

    Wen, B.C.; Pennington, E.C.; Hussey, D.H.; Jani, S.K.

    1989-06-01

    Excessive irradiation due to unexpected leakage was found on a patient receiving electron beam therapy. The cause of this leakage was analyzed and the amount of leakage was measured for different electron beam energies. The highest leakage occurred with a 6 x 6 cm cone using a 12 MeV electron beam. The leakage dose measured along the side of the cone could be as great as 40%. Until the cones are modified or redesigned, it is advised that all patient setups be carefully reviewed to assure that no significant patient areas are in the side scatter region.

  4. Applications of hydrogen deuterium exchange (HDX for the characterization of conformational dynamics in light-activated photoreceptors

    Directory of Open Access Journals (Sweden)

    Robert eLindner

    2015-06-01

    Full Text Available Rational design of optogenetic tools is inherently linked to the understanding of photoreceptor function. Structural analysis of elements involved in signal integration in individual sensor domains provides an initial idea of their mode of operation, but understanding how local structural rearrangements eventually affect signal transmission to output domains requires inclusion of the effector regions in the characterization. However, the dynamic nature of these assemblies renders their structural analysis challenging and therefore a combination of high- and low-resolution techniques is required to appreciate functional aspects of photoreceptors.This review focuses on the potential of Hydrogen-Deuterium exchange coupled to mass spectrometry (HDX-MS for complementing the structural characterization of photoreceptors. In this respect, the ability of HDX-MS to provide information on the conformational dynamics and the possibility to address multiple functionally relevant states in solution render this methodology ideally suitable. We highlight recent examples demonstrating the potential of HDX-MS and discuss how these results can help to improve existing optogenetic systems or guide the design of novel optogenetic tools.

  5. Blockage of NOX2/MAPK/NF-κB Pathway Protects Photoreceptors against Glucose Deprivation-Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Bin Fan

    2017-01-01

    Full Text Available Acute energy failure is one of the critical factors contributing to the pathogenic mechanisms of retinal ischemia. Our previous study demonstrated that glucose deprivation can lead to a caspase-dependent cell death of photoreceptors. The aim of this study was to decipher the upstream signal pathway in glucose deprivation- (GD- induced cell death. We mimicked acute energy failure by using glucose deprivation in photoreceptor cells (661W cells. GD-induced oxidative stress was evaluated by measuring ROS with the DCFH-DA assay and HO-1 expression by Western blot analysis. The activation of NOX2/MAPK/NF-κB signal was assessed by Western blot and immunohistochemical assays. The roles of these signals in GD-induced cell death were measured by using their specific inhibitors. Inhibition of Rac-1 and NOX2 suppressed GD-induced oxidative stress and protected photoreceptors against GD-induced cell death. NOX2 was an upstream signal in the caspase-dependent cell death cascade, yet the downstream MAPK pathways were activated and blocking MAPK signals rescued 661W cells from GD-induced death. In addition, GD caused the activation of NF-κB signal and inhibiting NF-κB significantly protected 661W cells. These observations may provide insights for treating retinal ischemic diseases and protecting retinal neurons from ischemia-induced cell death.

  6. Revision total knee arthroplasty with the use of trabecular metal cones

    DEFF Research Database (Denmark)

    Jensen, Claus L; Petersen, Michael Mygind; Schrøder, Henrik

    2012-01-01

    "Trabecular Metal Cone" (TM Cone) (Zimmer, Inc, Warsaw, Ind) for reconstruction of bone loss in the proximal tibia during revision total knee arthroplasty is now optional. Forty patients were randomized to receive revision total knee arthroplasty with or without TM Cone (No TM Cone). The Anderson...

  7. Simulation analysis of the effects of an initial cone position and opening angle on a cone-guided implosion

    Energy Technology Data Exchange (ETDEWEB)

    Yanagawa, T. [Department of Physics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602 (Japan); Sakagami, H. [Fundamental Physics Simulation Division, National Institute for Fusion Science, Oroshi-cho, Toki, Gifu 509-5292 (Japan); Nagatomo, H. [Institute of Laser Engineering, Osaka University, Suita, Osaka 565-0871 (Japan)

    2013-10-15

    In inertial confinement fusion, the implosion process is important in forming a high-density plasma core. In the case of a fast ignition scheme using a cone-guided target, the fuel target is imploded with a cone inserted. This scheme is advantageous for efficiently heating the imploded fuel core; however, asymmetric implosion is essentially inevitable. Moreover, the effect of cone position and opening angle on implosion also becomes critical. Focusing on these problems, the effect of the asymmetric implosion, the initial position, and the opening angle on the compression rate of the fuel is investigated using a three-dimensional pure hydrodynamic code.

  8. Multiple photoreceptor systems control the swim pacemaker activity in box jellyfish

    DEFF Research Database (Denmark)

    Garm, Anders Lydik; Mori, S.

    2009-01-01

    Like all other cnidarian medusae, box jellyfish propel themselves through the water by contracting their bell-shaped body in discrete swim pulses. These pulses are controlled by a swim pacemaker system situated in their sensory structures, the rhopalia. Each medusa has four rhopalia each with a s......Like all other cnidarian medusae, box jellyfish propel themselves through the water by contracting their bell-shaped body in discrete swim pulses. These pulses are controlled by a swim pacemaker system situated in their sensory structures, the rhopalia. Each medusa has four rhopalia each...... with a similar set of six eyes of four morphologically different types. We have examined how each of the four eye types influences the swim pacemaker. Multiple photoreceptor systems, three of the four eye types, plus the rhopalial neuropil, affect the swim pacemaker. The lower lens eye inhibits the pacemaker...... when stimulated and provokes a strong increase in the pacemaker frequency upon light-off. The upper lens eye, the pit eyes and the rhopalial neuropil all have close to the opposite effect. When these responses are compared with all-eye stimulations it is seen that some advanced integration must take...

  9. How can EPR spectroscopy help to unravel molecular mechanisms of flavin-dependent photoreceptors?

    Directory of Open Access Journals (Sweden)

    Daniel eNohr

    2015-09-01

    Full Text Available Electron paramagnetic resonance (EPR spectroscopy is a well-established spectroscopic method for the examination of paramagnetic molecules. Proteins can contain paramagnetic moieties in form of stable cofactors, transiently formed intermediates, or spin labels artificially introduced to cysteine sites. The focus of this review is to evaluate potential scopes of application of EPR to the emerging field of optogenetics. The main objective for EPR spectroscopy in this context is to unravel the complex mechanisms of light-active proteins, from their primary photoreaction to downstream signal transduction. An overview of recent results from the family of flavin-containing, blue-light dependent photoreceptors is given. In detail, mechanistic similarities and differences are condensed from the three classes of flavoproteins, the cryptochromes, LOV (Light-oxygen-voltage, and BLUF (blue-light using FAD domains. Additionally, a concept that includes spin-labeled proteins and examination using modern pulsed EPR is introduced, which allows for a precise mapping of light-induced conformational changes.

  10. How can EPR spectroscopy help to unravel molecular mechanisms of flavin-dependent photoreceptors?

    Science.gov (United States)

    Nohr, Daniel; Rodriguez, Ryan; Weber, Stefan; Schleicher, Erik

    2015-01-01

    Electron paramagnetic resonance (EPR) spectroscopy is a well-established spectroscopic method for the examination of paramagnetic molecules. Proteins can contain paramagnetic moieties in form of stable cofactors, transiently formed intermediates, or spin labels artificially introduced to cysteine sites. The focus of this review is to evaluate potential scopes of application of EPR to the emerging field of optogenetics. The main objective for EPR spectroscopy in this context is to unravel the complex mechanisms of light-active proteins, from their primary photoreaction to downstream signal transduction. An overview of recent results from the family of flavin-containing, blue-light dependent photoreceptors is given. In detail, mechanistic similarities and differences are condensed from the three classes of flavoproteins, the cryptochromes, LOV (Light-oxygen-voltage), and BLUF (blue-light using FAD) domains. Additionally, a concept that includes spin-labeled proteins and examination using modern pulsed EPR is introduced, which allows for a precise mapping of light-induced conformational changes.

  11. Effect of hydroxylamine on photon-like events during dark adaptation in toad rod photoreceptors.

    Science.gov (United States)

    Leibrock, C S; Lamb, T D

    1997-01-01

    1. The suction pipette technique was used to investigate the recovery of toad rod photoreceptors following small bleaches of 0.2-3% of the rhodopsin. 2. The reduction in sensitivity and the increase in noise elicited by bleaches were measured, and from these measurements the underlying rate of occurrence of photon-like events was calculated as a function of time after the bleach. 3. Exposure to hydroxylamine solution was used to hasten the decomposition of the metarhodopsin photoproducts. The outer segment was exposed to 110 mM hydroxylamine in a low-Ca2+ Ringer solution for a period of 10-50 s beginning 10-17 min after the bleaching exposure. 4. By the time of the hydroxylamine exposure, the flash sensitivity and response kinetics had returned almost to normal, and were not significantly altered by the exposure. 5. Following hydroxylamine exposure, the rate of spontaneous photon-like events in the rods declined rapidly to near pre-bleach levels. 6. We conclude that hydroxylamine reduces the rate of occurrence of photon-like events induced by a bleach, and we postulate that this reduction results from the removal of metarhodopsin (most likely metarhodopsin II) from the outer segment. 7. Our results are consistent with a model in which photon-like events result from reversal of the reactions (phosphorylation and capping by arrestin) that lead to inactivation of the activated form of rhodopsin, Rh*. PMID:9174997

  12. Knocking Down Snrnp200 Initiates Demorphogenesis of Rod Photoreceptors in Zebrafish

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2015-01-01

    Full Text Available Purpose. The small nuclear ribonucleoprotein 200 kDa (SNRNP200 gene is a fundamental component for precursor message RNA (pre-mRNA splicing and has been implicated in the etiology of autosomal dominant retinitis pigmentosa (adRP. This study aims to determine the consequences of knocking down Snrnp200 in zebrafish. Methods. Expression of the Snrnp200 transcript in zebrafish was determined via whole mount in situ hybridization. Morpholino oligonucleotide (MO aiming to knock down the expression of Snrnp200 was injected into zebrafish embryos, followed by analyses of aberrant splicing and expression of the U4/U6-U5 tri-small nuclear ribonucleoproteins (snRNPs components and retina-specific transcripts. Systemic changes and retinal phenotypes were further characterized by histological study and immunofluorescence staining. Results. Snrnp200 was ubiquitously expressed in zebrafish. Knocking down Snrnp200 in zebrafish triggered aberrant splicing of the cbln1 gene, upregulation of other U4/U6-U5 tri-snRNP components, and downregulation of a panel of retina-specific transcripts. Systemic defects were found correlated with knockdown of Snrnp200 in zebrafish. Only demorphogenesis of rod photoreceptors was detected in the initial stage, mimicking the disease characteristics of RP. Conclusions. We conclude that knocking down Snrnp200 in zebrafish could alter regular splicing and expression of a panel of genes, which may eventually trigger rod defects.

  13. Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina.

    Science.gov (United States)

    López-Begines, Santiago; Plana-Bonamaisó, Anna; Méndez, Ana

    2018-02-13

    Retinal guanylate cyclase (RetGC) and guanylate cyclase activating proteins (GCAPs) play an important role during the light response in photoreceptor cells. Mutations in these proteins are linked to distinct forms of blindness. RetGC and GCAPs exert their role at the ciliary outer segment where phototransduction takes place. We investigated the mechanisms governing GCAP1 and GCAP2 distribution to rod outer segments by expressing selected GCAP1 and GCAP2 mutants as transient transgenes in the rods of GCAP1/2 double knockout mice. We show that precluding GCAP1 direct binding to RetGC (K23D/GCAP1) prevented its distribution to rod outer segments, while preventing GCAP1 activation of RetGC post-binding (W94A/GCAP1) did not. We infer that GCAP1 translocation to the outer segment strongly depends on GCAP1 binding affinity for RetGC, which points to GCAP1 requirement to bind to RetGC to be transported. We gain further insight into the distinctive regulatory steps of GCAP2 distribution, by showing that a phosphomimic at position 201 is sufficient to retain GCAP2 at proximal compartments; and that the bovine equivalent to blindness-causative mutation G157R/GCAP2 results in enhanced phosphorylation in vitro and significant retention at the inner segment in vivo, as likely contributing factors to the pathophysiology.

  14. Induction of the unfolded protein response by constitutive G-protein signaling in rod photoreceptor cells.

    Science.gov (United States)

    Wang, Tian; Chen, Jeannie

    2014-10-17

    Phototransduction is a G-protein signal transduction cascade that converts photon absorption to a change in current at the plasma membrane. Certain genetic mutations affecting the proteins in the phototransduction cascade cause blinding disorders in humans. Some of these mutations serve as a genetic source of "equivalent light" that activates the cascade, whereas other mutations lead to amplification of the light response. How constitutive phototransduction causes photoreceptor cell death is poorly understood. We showed that persistent G-protein signaling, which occurs in rod arrestin and rhodopsin kinase knock-out mice, caused a rapid and specific induction of the PERK pathway of the unfolded protein response. These changes were not observed in the cGMP-gated channel knock-out rods, an equivalent light condition that mimics light-stimulated channel closure. Thus transducin signaling, but not channel closure, triggers rapid cell death in light damage caused by constitutive phototransduction. Additionally, we show that in the albino light damage model cell death was not associated with increase in global protein ubiquitination or unfolded protein response induction. Taken together, these observations provide novel mechanistic insights into the cell death pathway caused by constitutive phototransduction and identify the unfolded protein response as a potential target for therapeutic intervention. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. [Restoring vision in blind patients following photoreceptor degeneration: clinical results and future challenges].

    Science.gov (United States)

    Bendali, Amel; Lorach, Henri; Djilas, Milan; Marre, Olivier; Bensoman, Ryad; Rousseau, Lionel; Lissorgues, Gaëlle; Scorsone, Emmanuel; Bergonzo, Philippe; Garrido, Jose A; Sahel, José Alain; Picaud, Serge

    2013-01-01

    Retinal prostheses aim at restoring vision in patients blind from photoreceptor degeneration by electrically stimulating the residual retinal tissue. Currently, the most efficient implants are either inserted in the subretinal space or on the vitreal side of the retina (epi-retinal). Although the residual tissue can partly degenerate, it was shown that acute stimulation of residual neurones can induce visual percepts. Recently, a clinical trial with the epiretinal Argus2 device (60 electrodes) from the company 2nd Sight enabled most patients to orient and find light targets, some even reading words. This device has received a CE mark. Surprisingly, when the subretinal implant from the company Retina Implant AG displaying many more electrodes (1500 electrodes) was evaluated in clinical trials, the patient visual performances were fairly similar. The restored visual performances of the patients demonstrate that blind patients can recover some visual function when their residual retina is properly stimulated. However, the resolution is not yet sufficient to perform complex tasks such as autonomous locomotion, face identification or text reading. Several challenges remain to generate an increase in pixel density corresponding to the increase in electrode number and density. These challenges include the stimulation modality, the tissue/implant interface design, the electrode materials, and the visual information encoder. This review will discuss these great challenges after introducing the major clinical results. © Société de Biologie, 2013.

  16. Fasudil, a Clinically Used ROCK Inhibitor, Stabilizes Rod Photoreceptor Synapses after Retinal Detachment.

    Science.gov (United States)

    Townes-Anderson, Ellen; Wang, Jianfeng; Halász, Éva; Sugino, Ilene; Pitler, Amy; Whitehead, Ian; Zarbin, Marco

    2017-06-01

    Retinal detachment disrupts the rod-bipolar synapse in the outer plexiform layer by retraction of rod axons. We showed that breakage is due to RhoA activation whereas inhibition of Rho kinase (ROCK), using Y27632, reduces synaptic damage. We test whether the ROCK inhibitor fasudil, used for other clinical applications, can prevent synaptic injury after detachment. Detachments were made in pigs by subretinal injection of balanced salt solution (BSS) or fasudil (1, 10 mM). In some animals, fasudil was injected intravitreally after BSS-induced detachment. After 2 to 4 hours, retinae were fixed for immunocytochemistry and confocal microscopy. Axon retraction was quantified by imaging synaptic vesicle label in the outer nuclear layer. Apoptosis was analyzed using propidium iodide staining. For biochemical analysis by Western blotting, retinal explants, detached from retinal pigmented epithelium, were cultured for 2 hours. Subretinal injection of fasudil (10 mM) reduced retraction of rod spherules by 51.3% compared to control detachments ( n = 3 pigs, P = 0.002). Intravitreal injection of 10 mM fasudil, a more clinically feasible route of administration, also reduced retraction (28.7%, n = 5, P ROCK, was decreased with 30 μM fasudil ( n = 8-10 explants, P ROCK signaling with fasudil reduced photoreceptor degeneration and preserved the rod-bipolar synapse after retinal detachment. These results support the possibility, previously tested with Y27632, that ROCK inhibition may attenuate synaptic damage in iatrogenic detachments.

  17. Photoreceptor PhyB Involved in Arabidopsis Temperature Perception and Heat-Tolerance Formation.

    Science.gov (United States)

    Song, Junyi; Liu, Qijun; Hu, Biru; Wu, Wenjian

    2017-06-05

    The influence of temperature on plants is essential. However, our knowledge on the intricate regulation process underlying heat stress (HS) response in plants is limited. Recently, information about thermal sensors in vivo has begun to emerge. In this study, another primary environmental stimulus, light, was verified once again to work with temperature synergistically on plants, through the modulation of numerous biological processes. With the application of transcriptomic analysis, a substantial number of heat-responsive genes were detected involved in both light- and phytohormone-mediated pathways in Arabidopsis. During this process, phytoreceptor phyB acts as a molecular switch to turn on or turn off several other genes HS response, under different light conditions. Furthermore, a morphological study showed the afunction of phyB enhanced plants thermal tolerance, confirming the important role of this phytochrome in temperature perception and response in plants. This study adds data to the picture of light and temperature signaling cross-talk in plants, which is important for the exploration of complicated HS responses or light-mediated mechanisms. Furthermore, based on its influence on Arabidopsis thermal response in both morphological and physiological levels, phyB is a photoreceptor, as revealed before, as well as an essential thermal sensor in plants.

  18. The two parallel photocycles of the Chlamydomonas sensory photoreceptor histidine kinase rhodopsin 1.

    Science.gov (United States)

    Luck, Meike; Hegemann, Peter

    2017-10-01

    Histidine kinase rhodopsins (HKRs) belong to a class of unexplored sensory photoreceptors that share a similar modular architecture. The light sensing rhodopsin domain is covalently linked to signal-transducing modules and in some cases to a C-terminal guanylyl-cyclase effector. In spite of their wide distribution in unicellular organisms, very little is known about their physiological role and mechanistic functioning. We investigated the photochemical properties of the recombinant rhodopsin-fragment of Cr-HKR1 originating from Chlamydomonas reinhardtii. Our spectroscopic studies revealed an unusual thermal stability of the photoproducts with the deprotonated retinal Schiff base (RSB). Upon UV-irradiation these Rh-UV states with maximal absorbance in the UVA-region (Rh-UV) photochemically convert to stable blue light absorbing rhodopsin (Rh-Bl) with protonated chromophore. The heterogeneity of the sample is based on two parallel photocycles with the chromophore in C 15 =N-syn- or -anti-configuration. This report represents an attempt to decipher the underlying reaction schemes and interconversions of the two coexisting photocycles. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Distribution of macular xanthophylls between domains in a model of photoreceptor outer segment membranes.

    Science.gov (United States)

    Wisniewska, Anna; Subczynski, Witold K

    2006-10-15

    A model of photoreceptor outer segment (POS) membranes has been proposed, consisting of an equimolar ternary mixture of 1-palmitoyl-2-docosahexaenoylphosphatidylcholine/distearoylphosphatidylcholine/cholesterol. It was shown that, as in membranes made from the raft-forming mixture, in the model of POS membranes, two domains are formed: the raft domain (detergent resistant membranes, DRM), and the bulk domain (detergent soluble membranes, DSM). Saturation-recovery EPR discrimination by oxygen transport method also demonstrated the presence of two domains in this model system in situ at a wide range of temperatures (10-55 degrees C), showing additionally that neither lutein nor zeaxanthin at 1 mol% affect the formation of these domains. These membrane domains have been separated using cold Triton X-100 extraction from a model of POS membranes containing 1 mol% of either lutein or zeaxanthin. The results indicated that the macular xanthophylls lutein and zeaxanthin are substantially excluded from DRM and remain concentrated in DSM, a domain enriched in highly unsaturated docosahexaenoyl acid which is abundant in retina membranes. The concentration of xanthophylls in DRM and DSM calculated as the mol ratio of either xanthophyll to total lipid (phospholipid+cholesterol) was 0.0028 and 0.0391, respectively. Thus, xanthophylls are about 14 times more concentrated in DSM than in DRM. No significant difference in the distribution of lutein and zeaxanthin was found. The obtained results suggest that in POS membranes macular xanthophylls should also be concentrated in domains enriched in polyunsaturated chains.

  20. Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes.

    Science.gov (United States)

    Subczynski, Witold K; Wisniewska, Anna; Widomska, Justyna

    2010-12-01

    Lutein and zeaxanthin are two dietary carotenoids that compose the macular pigment of the primate retina. Another carotenoid, meso-zeaxanthin, is formed from lutein in the retina. A membrane location is one possible site where these dipolar, terminally dihydroxylated carotenoids, named macular xanthophylls, are accumulated in the nerve fibers and photoreceptor outer segments. Macular xanthophylls are oriented perpendicular to the membrane surface, which ensures their high solubility, stability, and significant effects on membrane properties. It was recently shown that they are selectively accumulated in membrane domains that contain unsaturated phospholipids, and thus are located in the most vulnerable regions of the membrane. This location is ideal if they are to act as lipid antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect the retina from age-related macular degeneration. In this mini-review, we examine published data on carotenoid-membrane interactions and present our hypothesis that the specific orientation and location of macular xanthophylls maximize their protective action in membranes of the eye retina. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Protein kinase C activation induces conductance changes in Hermissenda photoreceptors like those seen in associative learning.

    Science.gov (United States)

    Farley, J; Auerbach, S

    Phosphorylation of ion channels has been suggested as one molecular mechanism responsible for learning-produced long-term changes in neuronal excitability. Persistent training-produced changes in two distinct K+ currents (IA (ref. 2), IK-Ca (refs 3,4)) and a voltage-dependent calcium current (ICa; refs 3,4) have previously been shown to occur in type B photoreceptors of Hermissenda, as a result of associative learning. But the identity of the phosphorylation pathway(s) responsible for these changes has not as yet been determined. Injections of cyclic AMP-dependent protein kinase reduce a K+ current (IK) in B cells which is different from those changed by training, but fails to reduce IA and IK-Ca. Phosphorylase b kinase (an exogenous calcium/calmodulin-dependent kinase) reduces IA, but whether IK-Ca and ICa are changed in the manner of associative training is not yet known. Another protein kinase present in high concentrations in both mammalian brain and molluscan nervous systems is protein kinase C, which is both calcium- and phospholipid-sensitive. We now present evidence that activation of protein kinase C by the tumour promoter phorbol ester (PDB) and intracellular injection of the enzyme induce conductance changes similar to those caused by associative training in Hermissenda B cells (that is a reduction of IA and IK-Ca, and enhancement of ICa). These results represent the first direct demonstration that protein kinase C affects membrane K+ ion conductance mechanisms.

  2. Role of fractalkine/CX3CR1 interaction in light-induced photoreceptor degeneration through regulating retinal microglial activation and migration.

    Directory of Open Access Journals (Sweden)

    Meng Zhang

    Full Text Available BACKGROUND: Excessive exposure to light enhances the progression and severity of some human retinal degenerative diseases. While retinal microglia are likely to be important in neuron damage associated with these diseases, the relationship between photoreceptor damage and microglial activation remains poorly understood. Some recent studies have indicated that the chemokine fractalkine is involved in the pathogenesis of many neurodegenerative diseases. The present study was performed to investigate the cross-talk between injured photoreceptors and activated retinal microglia, focusing on the role of fractalkine and its receptor CX3CR1 in light-induced photoreceptor degeneration. METHODOLOGY/PRINCIPAL FINDINGS: Both in vivo and in vitro experiments were involved in the research. In vivo, Sprague-Dawley rats were exposed to blue light for 24 hours. In vitro, the co-culture of primary retinal microglia and a photoreceptor cell line (661W cell was exposed to blue light for five hours. Some cultures were pretreated by the addition of anti-CX3CR1 neutralizing antibody or recombinant fractalkine. Expression of fractalkine/CX3CR1 and inflammatory cytokines was detected by immunofluorescence, real-time PCR, Western immunoblot analysis, and ELISA assay. TUNEL method was used to detect cell apoptosis. In addition, chemotaxis assay was performed to evaluate the impact of soluble fractalkine on microglial migration. Our results showed that the expression of fractalkine that was significantly upregulated after exposure to light, located mainly at the photoreceptors. The extent of photoreceptor degeneration and microglial migration paralleled the increased level of fractalkine/CX3CR1. Compared with the control, the expression of inflammatory cytokines was significantly downregulated in the anti-CX3CR1 neutralizing antibody-treated group, and the number of photoreceptors was also well preserved. The addition of recombinant full-length fractalkine or soluble

  3. Propagation characteristics of resonance cone in a nonuniform magnetic field

    International Nuclear Information System (INIS)

    Ohnuma, T.; Sanuki, H.

    1984-01-01

    Propagation characteristics of resonance cone field for frequencies below the electron cyclotron frequency are described in a mirror magnetic field on the basis of fluid equation. Theoretical results are compared qualitatively with those of experiment

  4. Shape measurement and vibration analysis of moving speaker cone

    Science.gov (United States)

    Zhang, Qican; Liu, Yuankun; Lehtonen, Petri

    2014-06-01

    Surface three-dimensional (3-D) shape information is needed for many fast processes such as structural testing of material, standing waves on loudspeaker cone, etc. Usually measurement is done from limited number of points using electrical sensors or laser distance meters. Fourier Transform Profilometry (FTP) enables fast shape measurement of the whole surface. Method is based on angled sinusoidal fringe pattern projection and image capturing. FTP requires only one image of the deformed fringe pattern to restore the 3-D shape of the measured object, which makes real-time or dynamic data processing possible. In our experiment the method was used for loudspeaker cone distortion measurement in dynamic conditions. For sound quality issues it is important that the whole cone moves in same phase and there are no partial waves. Our imaging resolution was 1280x1024 pixels and frame rate was 200 fps. Using our setup we found unwanted spatial waves in our sample cone.

  5. Accessibility analysis in manufacturing processes using visibility cones

    Institute of Scientific and Technical Information of China (English)

    尹周平; 丁汉; 熊有伦

    2002-01-01

    Accessibility is a kind of important design feature of products,and accessibility analysis has been acknowledged as a powerful tool for solving computational manufacturing problems arising from different manufacturing processes.After exploring the relations among approachability,accessibility and visibility,a general method for accessibility analysis using visibility cones (VC) is proposed.With the definition of VC of a point,three kinds of visibility of a feature,namely complete visibility cone (CVC),partial visibility cone (PVC) and local visibility cone (LVC),are defined.A novel approach to computing VCs is formulated by identifying C-obstacles in the C-space,for which a general and efficient algorithm is proposed and implemented by making use of visibility culling.Lastly,we discuss briefly how to realize accessibility analysis in numerically controlled (NC) machining planning,coordinate measuring machines (CMMs) inspection planning and assembly sequence planning with the proposed methods.

  6. Effect of loss cone on confinement in toroidal helical device

    International Nuclear Information System (INIS)

    Itoh, K.; Itoh, S.-I.; Fukuyama, A.; Hanatani, K.

    1988-12-01

    Analytical estimation is given on the loss cone in the toroidal helical devices in the presence of the radial electric field and the modulation of the helical ripple. The minimum energy of particles entering the loss cone is calculated. The modulation is not always effective in reducing the loss in the presence of the radial electric field. The plasma loss due to the loss cone is estimated in the collisionless limit. The radial electric field is estimated in the presence of the loss cone. It is found that the transition to the solution with positive radial electric field, which is necessary to achieve the high-ion-temperature mode, becomes difficult. This difficulty is large for the systems with the small helical ripple. (author)

  7. Development of pits and cones on ion bombarded copper

    International Nuclear Information System (INIS)

    Tanovic, L.A.; Carter, G.; Nobes, M.J.; Whitton, I.L.; Williams, J.S.

    1980-01-01

    The formation of pits and cones on Ar ion bombarded copper has been studied. Carefully polished surfaces of large grained 99.999% pure copper crystals have been bombarded at normal incidence with 40 keV argon ions. The cone formation has been investigated for annealed and non-annealed crystals at room temperature and at 30 K and in the case of monocrystal and polycrystal samples. Although in the most other studies the presence of impurities is as a necessary condition for generation of cones and pits the obtained experimental results show that under certain conditions these features are formed on clean surfaces. It is shown that the dominant parameter in the production of cones on copper is the crystal orientation [ru

  8. Holographic entanglement entropy for hollow cones and banana shaped regions

    Energy Technology Data Exchange (ETDEWEB)

    Dorn, Harald [Institut für Physik und IRIS Adlershof, Humboldt-Universität zu Berlin,Zum Großen Windkanal 6, D-12489 Berlin (Germany)

    2016-06-09

    We consider banana shaped regions as examples of compact regions, whose boundary has two conical singularities. Their regularised holographic entropy is calculated with all divergent as well as finite terms. The coefficient of the squared logarithmic divergence, also in such a case with internally curved boundary, agrees with that calculated in the literature for infinite circular cones with their internally flat boundary. For the otherwise conformally invariant coefficient of the ordinary logarithmic divergence an anomaly under exceptional conformal transformations is observed. The construction of minimal submanifolds, needed for the entanglement entropy of cones, requires fine-tuning of Cauchy data. Perturbations of such fine-tuning leads to solutions relevant for hollow cones. The divergent parts for the entanglement entropy of hollow cones are calculated. Increasing the difference between the opening angles of their outer and inner boundary, one finds a transition between connected solutions for small differences to disconnected solutions for larger ones.

  9. Spray Modeling for Outwardly-Opening Hollow-Cone Injector

    KAUST Repository

    Sim, Jaeheon; Badra, Jihad; Elwardani, Ahmed Elsaid; Im, Hong G.

    2016-01-01

    linear instability sheet atomization (LISA) model was originally developed for pressure swirl hollow-cone injectors with moderate spray angle and toroidal ligament breakups. Therefore, it is not appropriate for the outwardly-opening injectors having wide

  10. Measurement of light-cone wave functions by diffractive dissociation

    Energy Technology Data Exchange (ETDEWEB)

    Asheri, D. [Tel Aviv Univ., School of Physics and Astronomy, Sackler Faculty of Exact Science (Israel)

    2005-07-01

    The measurement of the pion light-cone wave function is revisited and results for the Gegenbauer coefficients are presented. Measurements of the photon electromagnetic and hadronic wave functions are described and results are presented. (authors)

  11. QCD string with quarks. 2. Light cone Hamiltonian

    International Nuclear Information System (INIS)

    Dubin, A.Yu.; Kaidalov, A.B.; Simonov, Yu.A.

    1994-01-01

    The light-cone Hamiltonian is derived from the general gauge - and Lorentz - invariant expression for the qq-bar Green function. The resulting Hamiltonian contains in a non-additive way contributions from quark and string degrees of freedom

  12. New fixed and periodic point results on cone metric spaces

    Directory of Open Access Journals (Sweden)

    Ghasem Soleimani Rad

    2014-05-01

    Full Text Available In this paper, several xed point theorems for T-contraction of two maps on cone metric spaces under normality condition are proved. Obtained results extend and generalize well-known comparable results in the literature.

  13. Direct cone beam SPECT reconstruction with camera tilt

    International Nuclear Information System (INIS)

    Jianying Li; Jaszczak, R.J.; Greer, K.L.; Coleman, R.E.; Zongjian Cao; Tsui, B.M.W.

    1993-01-01

    A filtered backprojection (FBP) algorithm is derived to perform cone beam (CB) single-photon emission computed tomography (SPECT) reconstruction with camera tilt using circular orbits. This algorithm reconstructs the tilted angle CB projection data directly by incorporating the tilt angle into it. When the tilt angle becomes zero, this algorithm reduces to that of Feldkamp. Experimentally acquired phantom studies using both a two-point source and the three-dimensional Hoffman brain phantom have been performed. The transaxial tilted cone beam brain images and profiles obtained using the new algorithm are compared with those without camera tilt. For those slices which have approximately the same distance from the detector in both tilt and non-tilt set-ups, the two transaxial reconstructions have similar profiles. The two-point source images reconstructed from this new algorithm and the tilted cone beam brain images are also compared with those reconstructed from the existing tilted cone beam algorithm. (author)

  14. Testing the reliability of ice-cream cone model

    Science.gov (United States)

    Pan, Zonghao; Shen, Chenglong; Wang, Chuanbing; Liu, Kai; Xue, Xianghui; Wang, Yuming; Wang, Shui

    2015-04-01

    Coronal Mass Ejections (CME)'s properties are important to not only the physical scene itself but space-weather prediction. Several models (such as cone model, GCS model, and so on) have been raised to get rid of the projection effects within the properties observed by spacecraft. According to SOHO/ LASCO observations, we obtain the 'real' 3D parameters of all the FFHCMEs (front-side full halo Coronal Mass Ejections) within the 24th solar cycle till July 2012, by the ice-cream cone model. Considering that the method to obtain 3D parameters from the CME observations by multi-satellite and multi-angle has higher accuracy, we use the GCS model to obtain the real propagation parameters of these CMEs in 3D space and compare the results with which by ice-cream cone model. Then we could discuss the reliability of the ice-cream cone model.

  15. Light cone sum rules in nonabelian gauge field theory

    Energy Technology Data Exchange (ETDEWEB)

    Mallik, S [Bern Univ. (Switzerland). Inst. fuer Theoretische Physik

    1981-03-24

    The author examines, in the context of nonabelian gauge field theory, the derivation of the light cone sum rules which were obtained earlier on the assumption of dominance of canonical singularity in the current commutator on the light cone. The retarded scaling functions appearing in the sum rules are numbers known in terms of the charges of the quarks and the number of quarks and gluons in the theory. Possible applications of the sum rules are suggested.

  16. Cinder cones of Mount Slamet, Central Java, Indonesia

    Directory of Open Access Journals (Sweden)

    Igan S. SutawIdjaja

    2014-06-01

    Full Text Available http://dx.doi.org/10.17014/ijog.vol4no1.20096The Mount Slamet volcanic field in Central Java, Indonesia, contains thirty five cinder cones within an area of 90 sq. km in the east flank of the volcano. The cinder cones occur singly or in small groups, with diameter of the base ranges from 130 - 750 m and the height is around 250 m. Within the volcanic field, the cinder cones are spread over the volcanic area at the distance of 4 to 14 km from the eruption center of the Slamet Volcano. They are concentrated within latitudes 7°11’00” - 7°16’00” S,, and longitudes 109°15’00” - 109°18’00” E. The density of the cinder cones is about 1.5 cones/km2. Most of the cinder cones lie on the Tertiary sedimentary rocks along the NW-trending fault system and on radial fractures. The structural pattern may be related to the radial faults in this region. The cone surfaces are commonly blanketed by Slamet air-falls and lava flows. The deposits consist of poorly bedded, very coarse-grained, occasionally overlain by oxidized scoria, and large-sized of ballistic bombs and blocks. There are various kind of volcanic bombs originating from scoriae ballistic rock fragments. The other kind of volcanic bombs are breadcrust bomb, almond seed or contorted shape. All of the cinder cones have undergone degradation, which can be observed from the characters of gully density and surface morphology. By using Porter parameters, Hco is equal to 0.25 Wco, whilst Wcr is equal to 0.40 Wco. The Hco/Wco ratio is higher than Hco = 0.2 Wco reference line. A radiometric dating using K-Ar method carried out on a scoria bomb yields the age of 0.042 + 0.020 Ma.  

  17. Weather effects on the success of longleaf pine cone crops

    Science.gov (United States)

    Daniel J. Leduc; Shi-Jean Susana Sung; Dale G. Brockway; Mary Anne Sword Sayer

    2016-01-01

    We used National Oceanic and Atmospheric Administration weather data and historical records of cone crops from across the South to relate weather conditions to the yield of cones in 10 longleaf pine (Pinus palustris Mill.) stands. Seed development in this species occurs over a three-year time period and weather conditions during any part of this...

  18. Tracking blue cone signals in the primate brain.

    Science.gov (United States)

    Jayakumar, Jaikishan; Dreher, Bogdan; Vidyasagar, Trichur R

    2013-05-01

    In this paper, we review the path taken by signals originating from the short wavelength sensitive cones (S-cones) in Old World and New World primates. Two types of retinal ganglion cells (RGCs) carrying S-cone signals (blue-On and blue-Off cells) project to the dorsal lateral geniculate nucleus (dLGN) in the thalamus. In all primates, these S-cone signals are relayed through the 'dust-like' (konis in classical Greek) dLGN cells. In New World primates such as common marmoset, these very small cells are known to form distinct and spatially extensive, koniocellular layers. Although in Old World primates, such as macaques, koniocellular layers tend to be very thin, the adjacent parvocellular layers contain distinct koniocellular extensions. It appears that all S-cone signals are relayed through such konio cells, whether they are in the main koniocellular layers or in their colonies within the parvocellular layers of the dLGN. In the primary visual cortex, these signals begin to merge with the signals carried by the other two principal parallel channels, namely the magnocellular and parvocellular channels. This article will also review the possible routes taken by the S-cone signals to reach one of the topographically organised extrastriate visual cortical areas, the middle temporal area (area MT). This area is the major conduit for signals reaching the parietal cortex. Alternative visual inputs to area MT not relayed via the primary visual cortex area (V1) may provide the neurological basis for the phenomenon of 'blindsight' observed in human and non-human primates, who have partial or complete damage to the primary visual cortex. Short wavelength sensitive cone (S-cone) signals to area MT may also play a role in directing visual attention with possible implications for understanding the pathology in dyslexia and some of its treatment options. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

  19. Scattering of wedges and cones with impedance boundary conditions

    CERN Document Server

    Lyalinov, Mikhail

    2012-01-01

    This book is a systematic and detailed exposition of different analytical techniques used in studying two of the canonical problems, the wave scattering by wedges or cones with impedance boundary conditions. It is the first reference on novel, highly efficient analytical-numerical approaches for wave diffraction by impedance wedges or cones. The applicability of the reported solution procedures and formulae to existing software packages designed for real-world high-frequency problems encountered in antenna, wave propagation, and radar cross section.

  20. The generalized back projection theorem for cone beam reconstruction

    International Nuclear Information System (INIS)

    Peyrin, F.C.

    1985-01-01

    The use of cone beam scanners raises the problem of three dimensional reconstruction from divergent projections. After a survey on bidimensional analytical reconstruction methods we examine their application to the 3D problem. Finally, it is shown that the back projection theorem can be generalized to cone beam projections. This allows to state a new inversion formula suitable for both the 4 π parallel and divergent geometries. It leads to the generalization of the ''rho-filtered back projection'' algorithm which is outlined

  1. A Clinical Evaluation Of Cone Beam Computed Tomography

    Science.gov (United States)

    2016-06-01

    A CLINICAL EVALUATION OF CONE BEAM COMPUTED TOMOGRAPHY by Bryan James Behm, D.D.S. Lieutenant, Dental Corps United States Navy A thesis... COMPUTED TOMOGRAPHY " is appropriately acknowledged and, beyond brief excerpts, is with the permission of the copyright owner. ~mes Behm Endodontic...printed without the expressed written permission of the author. IV ABSTRACT A CLINICAL EVALUATION OF CONE BEAM COMPUTED TOMOGRAPHY BRYAN JAMES

  2. Enhanced photon production rate on the light-cone

    International Nuclear Information System (INIS)

    Aurenche, P.; Grenoble-1 Univ., 74 - Annecy; Gelis, F.; Kobes, R.; Petitgirard, E.

    1996-01-01

    Recent studies of the high temperature soft photon production rate on the light cone using Braaten-Pisarski resummation techniques have found collinear divergences present. It is shown that there exist a class of terms outside the Braaten-Pisarski framework which, although also divergent, dominate over these previously considered terms. The divergences in these new terms may be alleviated by application of a recently developed resummation scheme for processes sensitive to the light-cone. (author)

  3. Full utilization of semi-Dirac cones in photonics

    Science.gov (United States)

    Yasa, Utku G.; Turduev, Mirbek; Giden, Ibrahim H.; Kurt, Hamza

    2018-05-01

    In this study, realization and applications of anisotropic zero-refractive-index materials are proposed by exposing the unit cells of photonic crystals that exhibit Dirac-like cone dispersion to rotational symmetry reduction. Accidental degeneracy of two Bloch modes in the Brillouin zone center of two-dimensional C2-symmetric photonic crystals gives rise to the semi-Dirac cone dispersion. The proposed C2-symmetric photonic crystals behave as epsilon-and-mu-near-zero materials (ɛeff≈ 0 , μeff≈ 0 ) along one propagation direction, but behave as epsilon-near-zero material (ɛeff≈ 0 , μeff≠ 0 ) for the perpendicular direction at semi-Dirac frequency. By extracting the effective medium parameters of the proposed C4- and C2-symmetric periodic media that exhibit Dirac-like and semi-Dirac cone dispersions, intrinsic differences between isotropic and anisotropic materials are investigated. Furthermore, advantages of utilizing semi-Dirac cone materials instead of Dirac-like cone materials in photonic applications are demonstrated in both frequency and time domains. By using anisotropic transmission behavior of the semi-Dirac materials, photonic application concepts such as beam deflectors, beam splitters, and light focusing are proposed. Furthermore, to the best of our knowledge, semi-Dirac cone dispersion is also experimentally demonstrated for the first time by including negative, zero, and positive refraction states of the given material.

  4. CRYOVOLCANISM AND THE MYSTERY OF THE PATOM CONE

    Directory of Open Access Journals (Sweden)

    Vladimir R. Alekseyev

    2012-01-01

    Full Text Available In the Earth’s regions with cold climate, cryovolcanism is widespread. This phenomena is manifested as eruptions of material due to freezing of closed-type or open-type water-bearing systems which is accompanied by generation of effusive topographic forms, such as «pingo». The Patom cone is a typical structure created by cryovolcanism in fractured bedrocksof the Proterozoic age. The cone was shaped a result of the long-term, possibly multistage freezing of the hydrogeological structure during continuous and complicated phase of cryo- and speleo-genesis. The ice-saturated breccia containing limestone, sandstone and shale, which composed the cone, was subject to slow spreading due to its plastic properties; the top of the mound developed into a subsidence cone bordered by ring-shaped ramparts and a knoll in the middle, while thelongitudinal profile took on an asymmetric form. The absence of soil and vegetation cover on the surface of the cone, and a relatively weak degree of weathering of the rudaceous deposits bear no evidence that the geological object is young. The question as to the age of the cone is still open.

  5. Heavy-to-light correlators beyond the light cone

    International Nuclear Information System (INIS)

    Lucha, W.; Melikhov, D. I.; Simula, S.

    2008-01-01

    We present the first systematic analysis of the off-light-cone effects in correlators relevant for the extraction of the heavy-to-light form factors within the method of light-cone sum rules. In a model with scalar constituents, the correlator is calculated in two different ways: (i) by performing the expansion of the Bethe-Salpeter amplitude of the light meson near the light cone x 2 = 0 and (ii) by adopting the known solution for the Bethe-Salpeter amplitude which allows one to calculate the correlator without invoking any expansion. We demonstrate that the contributions to the correlator from the off-light-cone terms x 2 ≠ 0 are not suppressed by any large parameter compared to the contribution of the light-cone term x 2 0. For decays of heavy particles of mass in the range 1.5-5 GeV, the light-cone correlator is shown to systematically overestimate the full correlator, numerically the difference being 10-20%

  6. Heavy-to-light correlators beyond the light cone

    International Nuclear Information System (INIS)

    Lucha, W.; Melikhov, D. I.; Simula, S.

    2008-01-01

    We present the first systematic analysis of the off-light-cone effects in correlators relevant for the extraction of the heavy-to-light form factors within the method of light-cone sum rules. In a model with scalar constituents, the correlator is calculated in two different ways: (i) by performing the expansion of the Bethe-Salpeter amplitude of the light meson near the light cone x 2 = 0 and (ii) by adopting the known solution for the Bethe-Salpeter amplitude which allows one to calculate the correlator without invoking any expansion. We demonstrate that the contributions to the correlator from the off-light-cone terms x 2 ≠ 0 are not suppressed by any large parameter compared to the contribution of the light-cone term x 2 = 0. For decays of heavy particles of mass in the range 1.5–5 GeV, the light-cone correlator is shown to systematically overestimate the full correlator, numerically the difference being 10–20%.

  7. A reconstruction algorithms for helical cone-beam SPECT

    International Nuclear Information System (INIS)

    Weng, Y.; Zeng, G.L.; Gullberg, G.T.

    1993-01-01

    Cone-beam SPECT provides improved sensitivity for imaging small organs like the brain and heart. However, current cone-beam tomography with the focal point traversing a planar orbit does not acquire sufficient data to give an accurate reconstruction. In this paper, the authors employ a data-acquisition method which obtains complete data for cone-beam SPECT by simultaneously rotating the gamma camera and translating the patient bed, so that cone-beam projections can be obtained with the focal point traversing a helix surrounding the patient. An implementation of Grangeat's algorithm for helical cone-beam projections is developed. The algorithm requires a rebinning step to convert cone-beam data to parallel-beam data which are then reconstructed using the 3D Radon inversion. A fast new rebinning scheme is developed which uses all of the detected data to reconstruct the image and properly normalizes any multiply scanned data. This algorithm is shown to produce less artifacts than the commonly used Feldkamp algorithm when applied to either a circular planar orbit or a helical orbit acquisition. The algorithm can easily be extended to any arbitrary orbit

  8. Functional complexity of the axonal growth cone: a proteomic analysis.

    Directory of Open Access Journals (Sweden)

    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  9. Experimental observation of Alfven wave cones

    International Nuclear Information System (INIS)

    Gekelman, W.; Leneman, D.; Maggs, J.; Vincena, S.

    1994-01-01

    The spatial evolution of the radial profile of the magnetic field of a shear Alfven wave launched by a disk exciter with radius on the order of the electron skin depth has been measured. The waves are launched using wire mesh disk exciters of 4 mm and 8 mm radius into a helium plasma of density about 1.0x10 12 cm -3 and magnetic field 1.1 kG. The electron skin depth δ=c/ω pe is about 5 mm. The current channel associated with the shear Alfven wave is observed to spread with distance away from the exciter. The spreading follows a cone-like pattern whose angle is given by tan θ=k A δ, where k A is the Alfven wave number. The dependence of the magnetic profiles on wave frequency and disk size are presented. The effects of dissipation by electron--neutral collisions and Landau damping are observed. The observations are in excellent agreement with theoretical predictions [Morales et al., Phys. Plasmas 1, 3765 (1994)

  10. Cone Beam Computed Tomographic imaging in orthodontics.

    Science.gov (United States)

    Scarfe, W C; Azevedo, B; Toghyani, S; Farman, A G

    2017-03-01

    Over the last 15 years, cone beam computed tomographic (CBCT) imaging has emerged as an important supplemental radiographic technique for orthodontic diagnosis and treatment planning, especially in situations which require an understanding of the complex anatomic relationships and surrounding structures of the maxillofacial skeleton. CBCT imaging provides unique features and advantages to enhance orthodontic practice over conventional extraoral radiographic imaging. While it is the responsibility of each practitioner to make a decision, in tandem with the patient/family, consensus-derived, evidence-based clinical guidelines are available to assist the clinician in the decision-making process. Specific recommendations provide selection guidance based on variables such as phase of treatment, clinically-assessed treatment difficulty, the presence of dental and/or skeletal modifying conditions, and pathology. CBCT imaging in orthodontics should always be considered wisely as children have conservatively, on average, a three to five times greater radiation risk compared with adults for the same exposure. The purpose of this paper is to provide an understanding of the operation of CBCT equipment as it relates to image quality and dose, highlight the benefits of the technique in orthodontic practice, and provide guidance on appropriate clinical use with respect to radiation dose and relative risk, particularly for the paediatric patient. © 2017 Australian Dental Association.

  11. Secondary ion shadow-cone enhanced desorption

    Energy Technology Data Exchange (ETDEWEB)

    Chechen Chang (Hawaii Univ., Honolulu (USA). Dept. of Chemistry)

    1990-02-01

    The incident angle dependence of the secondary particle emission process under keV ion bombardment has been investigated. The results from the full molecular dynamics calculations indicate that the flux anisotropy of the incident beam, resulting from the non-uniform impact parameters for the surface atom of a single crystal, affects the particle desorption in a systematic fashion. The enhanced desorption at certain angles of incidence corresponds to the intensive focusing of the incident beam to the near-surface atom and the extended dissipation of momentum by large-angle scattering. This observation has let us to develop a new theoretical model in which the enhanced desorption is described by the distance of closest encounter along the trajectory of the incident particle to the surface atom. The computer time for the simulation of the incident-angle-dependent emission process is significantly reduced. The results from the calculation based on this model are in good agreement both with the results from the full dynamics calculation and with the experimental results. The new model also allows a complementary evaluation of the microscopic dynamics involved in the shadow-cone enhanced desorption. (author).

  12. Singularities of plane complex curves and limits of Kähler metrics with cone singularities. I: Tangent Cones

    Directory of Open Access Journals (Sweden)

    Borbon Martin de

    2017-02-01

    Full Text Available The goal of this article is to provide a construction and classification, in the case of two complex dimensions, of the possible tangent cones at points of limit spaces of non-collapsed sequences of Kähler-Einstein metrics with cone singularities. The proofs and constructions are completely elementary, nevertheless they have an intrinsic beauty. In a few words; tangent cones correspond to spherical metrics with cone singularities in the projective line by means of the Kähler quotient construction with respect to the S1-action generated by the Reeb vector field, except in the irregular case ℂβ₁×ℂβ₂ with β₂/ β₁ ∉ Q.

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

    Science.gov (United States)

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

    2015-06-01

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

  14. Eruptive and Geomorphic Processes at the Lathrop Wells Scoria Cone

    International Nuclear Information System (INIS)

    G. Valentine; D.J. Krier; F.V. Perry; G. Heiken

    2006-01-01

    The ∼80 ka Lathrop Wells volcano (southern Nevada, U.S.A.) preserves evidence for a range of explosive processes and emplacement mechanisms of pyroclastic deposits and lava fields in a small-volume basaltic center. Early cone building by Strombolian bursts was accompanied by development of a fan-like lava field reaching ∼800 m distance from the cone, built upon a gently sloping surface. Lava flows carried rafts of cone deposits, which provide indirect evidence for cone facies in lieu of direct exposures in the active quarry. Subsequent activity was of a violent Strombolian nature, with many episodes of sustained eruption columns up to a few km in height. These deposited layers of scoria lapilli and ash in different directions depending upon wind direction at the time of a given episode, reaching up to ∼20 km from the vent, and also produced the bulk of the scoria cone. Lava effusion migrated from south to north around the eastern base of the cone as accumulation of lavas successively reversed the topography at the base of the cone. Late lavas were emplaced during violent Strombolian activity and continued for some time after explosive eruptions had waned. Volumes of the eruptive products are: fallout--0.07 km 3 , scoria cone--0.02 km 3 , and lavas--0.03 km 3 . Shallow-derived xenolith concentrations suggest an upper bound on average conduit diameter of ∼21 m in the uppermost 335 m beneath the volcano. The volcano was constructed over a period of at least seven months with cone building occurring only during part of that time, based upon analogy with historical eruptions. Post-eruptive geomorphic evolution varied for the three main surface types that were produced by volcanic activity: (1) scoria cone, (2) low relief surfaces (including lavas) with abundant pyroclastic material, and (3) lavas with little pyroclastic material. The role of these different initial textures must be accounted for in estimating relative ages of volcanic surfaces, and failure to

  15. Eruptive and Geomorphic Processes at the Lathrop Wells Scoria Cone

    Energy Technology Data Exchange (ETDEWEB)

    G. Valentine; D.J. Krier; F.V. Perry; G. Heiken

    2006-08-03

    The {approx}80 ka Lathrop Wells volcano (southern Nevada, U.S.A.) preserves evidence for a range of explosive processes and emplacement mechanisms of pyroclastic deposits and lava fields in a small-volume basaltic center. Early cone building by Strombolian bursts was accompanied by development of a fan-like lava field reaching {approx}800 m distance from the cone, built upon a gently sloping surface. Lava flows carried rafts of cone deposits, which provide indirect evidence for cone facies in lieu of direct exposures in the active quarry. Subsequent activity was of a violent Strombolian nature, with many episodes of sustained eruption columns up to a few km in height. These deposited layers of scoria lapilli and ash in different directions depending upon wind direction at the time of a given episode, reaching up to {approx}20 km from the vent, and also produced the bulk of the scoria cone. Lava effusion migrated from south to north around the eastern base of the cone as accumulation of lavas successively reversed the topography at the base of the cone. Late lavas were emplaced during violent Strombolian activity and continued for some time after explosive eruptions had waned. Volumes of the eruptive products are: fallout--0.07 km{sup 3}, scoria cone--0.02 km{sup 3}, and lavas--0.03 km{sup 3}. Shallow-derived xenolith concentrations suggest an upper bound on average conduit diameter of {approx}21 m in the uppermost 335 m beneath the volcano. The volcano was constructed over a period of at least seven months with cone building occurring only during part of that time, based upon analogy with historical eruptions. Post-eruptive geomorphic evolution varied for the three main surface types that were produced by volcanic activity: (1) scoria cone, (2) low relief surfaces (including lavas) with abundant pyroclastic material, and (3) lavas with little pyroclastic material. The role of these different initial textures must be accounted for in estimating relative ages of

  16. Studies concerning the photoreceptor pigments of stentor coeruleus and blepharisma japonicum

    International Nuclear Information System (INIS)

    Dax, T.G.

    2000-05-01

    In the presence of 1,8-bis-(dimethylamino)-naphthalene, solutions of 3-O-benzyl hypericin and 3,4-di-O-benzyl hypericin in aromatic solvents like benzene or toluene have shown to be photoreactive, whereas in the dark no reactions occurred. 3-O-benzyl hypericin was found to enter a photorearrangement reaction leading to a product species, whose structural details could be elicited by UV/VIS, NMR, and mass spectroscopy together with spectrophotometric titrations. Investigation results led to a 11-phenyl-11H-benz{4,10}anthra{2,1,9,8-nopqa}pleiadene skeleton forming the backbone of the photoproduct. This fundamental system is the more of interest since it highly resembles the parent compound of the blepharismins, the photoreceptor pigments of Blepharisma japonicum. In analogy to blepharismin C, which can be converted photochemically into oxyblepharismin C and further on into stentorin by treatment with acid, the photoproduct could be transformed into hypericin upon irradiation and additional acidic work up. As the photoproduct incorporates several equilibrium systems, computer aided calculations were executed to achieve an idea about the relative stability of the photoproduct's various isomeric forms. The described photoreaction represents a possible route for the total synthesis of blepharismins and oxyblepharismins. Furthermore, it could shed some light on the biogenesis of these photosensing pigments. Irradiation of 3,4-di-O-benzyl hypericin in benzene solution together with a large excess of 1,8-bis-(dimethylamino)-naphthalene produced a species exhibiting a tremendous absorption band in the near IR. By means of EPR spectroscopy it could be stated that this primary photoproduct was of radical nature. The product was examined by means of UV/VIS, NMR, IR and mass spectroscopy. (author)

  17. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    Science.gov (United States)

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  18. UV-B Perceived by the UVR8 Photoreceptor Inhibits Plant Thermomorphogenesis.

    Science.gov (United States)

    Hayes, Scott; Sharma, Ashutosh; Fraser, Donald P; Trevisan, Martine; Cragg-Barber, C Kester; Tavridou, Eleni; Fankhauser, Christian; Jenkins, Gareth I; Franklin, Keara A

    2017-01-09

    Small increases in ambient temperature can elicit striking effects on plant architecture, collectively termed thermomorphogenesis [1]. In Arabidopsis thaliana, these include marked stem elongation and leaf elevation, responses that have been predicted to enhance leaf cooling [2-5]. Thermomorphogenesis requires increased auxin biosynthesis, mediated by the bHLH transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) [6-8], and enhanced stability of the auxin co-receptor TIR1, involving HEAT SHOCK PROTEIN 90 (HSP90) [9]. High-temperature-mediated hypocotyl elongation additionally involves localized changes in auxin metabolism, mediated by the indole-3-acetic acid (IAA)-amido synthetase Gretchen Hagen 3 (GH3).17 [10]. Here we show that ultraviolet-B light (UV-B) perceived by the photoreceptor UV RESISTANCE LOCUS 8 (UVR8) [11] strongly attenuates thermomorphogenesis via multiple mechanisms inhibiting PIF4 activity. Suppression of thermomorphogenesis involves UVR8 and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1)-mediated repression of PIF4 transcript accumulation, reducing PIF4 abundance. UV-B also stabilizes the bHLH protein LONG HYPOCOTYL IN FAR RED (HFR1), which can bind to and inhibit PIF4 function. Collectively, our results demonstrate complex crosstalk between UV-B and high-temperature signaling. As plants grown in sunlight would most likely experience concomitant elevations in UV-B and ambient temperature, elucidating how these pathways are integrated is of key importance to the understanding of plant development in natural environments. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. GPU-based cone beam computed tomography.

    Science.gov (United States)

    Noël, Peter B; Walczak, Alan M; Xu, Jinhui; Corso, Jason J; Hoffmann, Kenneth R; Schafer, Sebastian

    2010-06-01

    The use of cone beam computed tomography (CBCT) is growing in the clinical arena due to its ability to provide 3D information during interventions, its high diagnostic quality (sub-millimeter resolution), and its short scanning times (60 s). In many situations, the short scanning time of CBCT is followed by a time-consuming 3D reconstruction. The standard reconstruction algorithm for CBCT data is the filtered backprojection, which for a volume of size 256(3) takes up to 25 min on a standard system. Recent developments in the area of Graphic Processing Units (GPUs) make it possible to have access to high-performance computing solutions at a low cost, allowing their use in many scientific problems. We have implemented an algorithm for 3D reconstruction of CBCT data using the Compute Unified Device Architecture (CUDA) provided by NVIDIA (NVIDIA Corporation, Santa Clara, California), which was executed on a NVIDIA GeForce GTX 280. Our implementation results in improved reconstruction times from minutes, and perhaps hours, to a matter of seconds, while also giving the clinician the ability to view 3D volumetric data at higher resolutions. We evaluated our implementation on ten clinical data sets and one phantom data set to observe if differences occur between CPU and GPU-based reconstructions. By using our approach, the computation time for 256(3) is reduced from 25 min on the CPU to 3.2 s on the GPU. The GPU reconstruction time for 512(3) volumes is 8.5 s. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  20. Theseus Nose and Pod Cones Being Unloaded

    Science.gov (United States)

    1996-01-01

    Crew members are seen here unloading the nose and pod cones of the Theseus prototype research aircraft at NASA's Dryden Flight Research Center, Edwards, California, in May of 1996. The Theseus aircraft, built and operated by Aurora Flight Sciences Corporation, Manassas, Virginia, was a unique aircraft flown at NASA's Dryden Flight Research Center, Edwards, California, under a cooperative agreement between NASA and Aurora. Dryden hosted the Theseus program, providing hangar space and range safety for flight testing. Aurora Flight Sciences was responsible for the actual flight testing, vehicle flight safety, and operation of the aircraft. The Theseus remotely piloted aircraft flew its maiden flight on May 24, 1996, at Dryden. During its sixth flight on November 12, 1996, Theseus experienced an in-flight structural failure that resulted in the loss of the aircraft. As of the beginning of the year 2000, Aurora had not rebuilt the aircraft. Theseus was built for NASA under an innovative, $4.9 million fixed-price contract by Aurora Flight Sciences Corporation and its partners, West Virginia University, Morgantown, West Virginia, and Fairmont State College, Fairmont, West Virginia. The twin-engine, unpiloted vehicle had a 140-foot wingspan, and was constructed largely of composite materials. Powered by two 80-horsepower, turbocharged piston engines that drove twin 9-foot-diameter propellers, Theseus was designed to fly autonomously at high altitudes, with takeoff and landing under the active control of a ground-based pilot in a ground control station 'cockpit.' With the potential ability to carry 700 pounds of science instruments to altitudes above 60,000 feet for durations of greater than 24 hours, Theseus was intended to support research in areas such as stratospheric ozone depletion and the atmospheric effects of future high-speed civil transport aircraft engines. Instruments carried aboard Theseus also would be able to validate satellite-based global environmental

  1. Cell Fate of Müller Cells During Photoreceptor Regeneration in an N-Methyl-N-nitrosourea-Induced Retinal Degeneration Model of Zebrafish.

    Science.gov (United States)

    Ogai, Kazuhiro; Hisano, Suguru; Sugitani, Kayo; Koriyama, Yoshiki; Kato, Satoru

    2016-01-01

    Zebrafish can regenerate several organs such as the tail fin, heart, central nervous system, and photoreceptors. Very recently, a study has demonstrated the photoreceptor regeneration in the alkylating agent N-methyl-N-nitrosourea (MNU)-induced retinal degeneration (RD) zebrafish model, in which whole photoreceptors are lost within a week after MNU treatment and then regenerated within a month. The research has also shown massive proliferation of Müller cells within a week. To address the question of whether proliferating Müller cells are the source of regenerating photoreceptors, which remains unknown in the MNU-induced zebrafish RD model, we employed a BrdU pulse-chase technique to label the proliferating cells within a week after MNU treatment. As a result of the BrdU pulse-chase technique, a number of BrdU(+) cells were observed in the outer nuclear layer as well as the inner nuclear layer. This implies that regenerating photoreceptors are derived from proliferating Müller cells in the zebrafish MNU-induced RD model.

  2. An Analysis Model for Water Cone Subsidence in Bottom Water Drive Reservoirs

    Science.gov (United States)

    Wang, Jianjun; Xu, Hui; Wu, Shucheng; Yang, Chao; Kong, lingxiao; Zeng, Baoquan; Xu, Haixia; Qu, Tailai

    2017-12-01

    Water coning in bottom water drive reservoirs, which will result in earlier water breakthrough, rapid increase in water cut and low recovery level, has drawn tremendous attention in petroleum engineering field. As one simple and effective method to inhibit bottom water coning, shut-in coning control is usually preferred in oilfield to control the water cone and furthermore to enhance economic performance. However, most of the water coning researchers just have been done on investigation of the coning behavior as it grows up, the reported studies for water cone subsidence are very scarce. The goal of this work is to present an analytical model for water cone subsidence to analyze the subsidence of water cone when the well shut in. Based on Dupuit critical oil production rate formula, an analytical model is developed to estimate the initial water cone shape at the point of critical drawdown. Then, with the initial water cone shape equation, we propose an analysis model for water cone subsidence in bottom water reservoir reservoirs. Model analysis and several sensitivity studies are conducted. This work presents accurate and fast analytical model to perform the water cone subsidence in bottom water drive reservoirs. To consider the recent interests in development of bottom drive reservoirs, our approach provides a promising technique for better understanding the subsidence of water cone.

  3. Parafoveal cone abnormalities and recovery on adaptive optics in posterior uveitis

    Directory of Open Access Journals (Sweden)

    Kristin Biggee

    2016-04-01

    Conclusions and importance: AO detects subclinical changes in the photoreceptor layer in posterior uveitis that can recover over time. AO may be useful in following outer retinal inflammatory conditions.

  4. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  5. Méthode analytique généralisée pour le calcul du coning. Nouvelle solution pour calculer le coning de gaz, d'eau et double coning dans les puits verticaux et horizontaux Generalized Analytical Method for Coning Calculation. New Solution to Calculation Both the Gas Coning, Water Coning and Dual Coning for Vertical and Horizontal Wells

    Directory of Open Access Journals (Sweden)

    Pietraru V.

    2006-11-01

    Full Text Available Une nouvelle méthode analytique d'évaluation du coning d'eau par bottom water drive et/ou de gaz par gas-cap drive dans les puits horizontaux et verticaux a été développée pour les réservoirs infinis [1]. Dans cet article, une généralisation de cette méthode est présentée pour les réservoirs confinés d'extension limitée dont le toit est horizontal. La généralisation proposée est basée sur la résolution des équations différentielles de la diffusivité avec prise en compte des effets de drainage par gravité et des conditions aux limites pour un réservoir confiné. La méthode est applicable aux réservoirs isotropes ou anisotropes. L'hypothèse de pression constante à la limite de l'aire de drainage dans l'eau et/ou dans le gaz a été adoptée. Les pertes de charge dans l'aquifère et dans le gas-cap sont donc négligées. Les principales contributions de cet article sont : - L'introduction de la notion de rayon de cône, différent du rayon de puits. La hauteur du cône et le débit critique dépendent du rayon de cône alors qu'ils sont indépendants du rayon du puits. - Une nouvelle corrélation pour le calcul du débit critique sous forme adimensionnelle en fonction de trois paramètres : le temps, la longueur du drain horizontal (nulle pour un puits vertical et le rayon de drainage. - Des corrélations pour le calcul du rapport des débits gaz/huile (GOR ou de la fraction en eau (fw, pendant les périodes critique et postcritique, qui tiennent compte de la pression capillaire et des perméabilités relatives. - Des corrélations pour le calcul des rapports de débits gaz/huile et eau/huile pendant les périodes pré, post et supercritique en double coning. - Des critères pour le calcul du temps de percée au puits en simple coning de gaz ou d'eau, ou en double coning de gaz et d'eau. A new analytical method for assessing water and/or gas coning in horizontal and vertical wells has been developed for infinite

  6. An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors.

    Science.gov (United States)

    Pan, Yuan; Laird, Joseph G; Yamaguchi, David M; Baker, Sheila A

    2015-06-01

    Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that trafficking HCN1 channels to specific compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identified a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward trafficking signal that could counter the function of the ER retention signal. We studied trafficking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward trafficking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. We identified an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane.

  7. A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells.

    Science.gov (United States)

    Maerker, Tina; van Wijk, Erwin; Overlack, Nora; Kersten, Ferry F J; McGee, Joann; Goldmann, Tobias; Sehn, Elisabeth; Roepman, Ronald; Walsh, Edward J; Kremer, Hannie; Wolfrum, Uwe

    2008-01-01

    The human Usher syndrome (USH) is the most frequent cause of combined deaf-blindness. USH is genetically heterogeneous with at least 12 chromosomal loci assigned to three clinical types, USH1-3. Although these USH types exhibit similar phenotypes in human, the corresponding gene products belong to very different protein classes and families. The scaffold protein harmonin (USH1C) was shown to integrate all identified USH1 and USH2 molecules into protein networks. Here, we analyzed a protein network organized in the absence of harmonin by the scaffold proteins SANS (USH1G) and whirlin (USH2D). Immunoelectron microscopic analyses disclosed the colocalization of all network components in the apical inner segment collar and the ciliary apparatus of mammalian photoreceptor cells. In this complex, whirlin and SANS directly interact. Furthermore, SANS provides a linkage to the microtubule transport machinery, whereas whirlin may anchor USH2A isoform b and VLGR1b (very large G-protein coupled receptor 1b) via binding to their cytodomains at specific membrane domains. The long ectodomains of both transmembrane proteins extend into the gap between the adjacent membranes of the connecting cilium and the apical inner segment. Analyses of Vlgr1/del7TM mice revealed the ectodomain of VLGR1b as a component of fibrous links present in this gap. Comparative analyses of mouse and Xenopus photoreceptors demonstrated that this USH protein network is also part of the periciliary ridge complex in Xenopus. Since this structural specialization in amphibian photoreceptor cells defines a specialized membrane domain for docking and fusion of transport vesicles, we suggest a prominent role of the USH proteins in cargo shipment.

  8. Spray cone angle and air core diameter of hollow cone swirl rocket injector

    Directory of Open Access Journals (Sweden)

    Ahmad Hussein Abdul Hamid

    2011-12-01

    Full Text Available ABSTRACT : Fuel injector for liquid rocket is a very critical component since that small difference in its design can dramatically affect the combustion efficiency. The primary function of the injector is to break the fuel up into very small droplets. The smaller droplets are necessary for fast quiet ignition and to establish a flame front close to the injector head, thus shorter combustion chamber is possible to be utilized. This paper presents an experimetal investigation of a mono-propellant hollow cone swirl injector. Several injectors with different configuration were investigated under cold flow test, where water is used as simulation fluid. This investigation reveals that higher injection pressure leads to higher spray cone angle. The effect of injection pressure on spray cone angle is more prominent for injector with least number of tangential ports. Furthermore, it was found that injector with the most number of tangential ports and with the smallest tangential port diameter produces the widest resulting spray. Experimental data also tells that the diameter of an air core that forms inside the swirl chamber is largest for the injector with smallest tangential port diameter and least number of tangential ports.ABSTRAK : Injektor bahan api bagi roket cecair merupakan satu komponen yang amat kritikal memandangkan perbezaan kecil dalam reka bentuknya akan secara langsung mempengaruhi kecekapan pembakaran. Fungsi utama injektor adalah untuk memecahkan bahan api kepada titisan yang amat kecil. Titisan kecil penting untuk pembakaran pantas secara senyap dan untuk mewujudkan satu nyalaan di hadapan, berhampiran dengan kepala injektor, maka kebuk pembakaran yang lebih pendek berkemungkinan dapat digunakan. Kertas kerja ini mebentangkan satu penyelidikan eksperimental sebuah injektor ekabahan dorong geronggang kon pusar. Beberapa injektor dengan konfigurasi berbeza telah dikaji di bawah ujian aliran sejuk, di mana air digunakan sebagai bendalir

  9. Predation and protection in the macroevolutionary history of conifer cones

    Science.gov (United States)

    Leslie, Andrew B.

    2011-01-01

    Conifers are an excellent group in which to explore how changing ecological interactions may have influenced the allocation of reproductive tissues in seed plants over long time scales, because of their extensive fossil record and their important role in terrestrial ecosystems since the Palaeozoic. Measurements of individual conifer pollen-producing and seed-producing cones from the Pennsylvanian to the Recent show that the relative amount of tissue invested in pollen cones has remained constant through time, while seed cones show a sharp increase in proportional tissue investment in the Jurassic that has continued to intensify to the present day. Since seed size in conifers has remained similar through time, this increase reflects greater investment in protective cone tissues such as robust, tightly packed scales. This shift in morphology and tissue allocation is broadly concurrent with the appearance of new vertebrate groups capable of browsing in tree canopies, as well as a diversification of insect-feeding strategies, suggesting that an important change in plant–animal interactions occurred over the Mesozoic that favoured an increase in seed cone protective tissues. PMID:21345864

  10. Large Scale Plasmonic nanoCones array For Spectroscopy Detection

    KAUST Repository

    Das, Gobind; Battista, Edmondo; Manzo, Gianluigi; Causa, Filippo; Netti, Paolo; Di Fabrizio, Enzo M.

    2015-01-01

    Advanced optical materials or interfaces are gaining attention for diagnostic applications. However, the achievement of large device interface as well as facile surface functionalization largely impairs their wide use. The present work is aimed to address different innovativ