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Sample records for 11-cis retinal chromophore

  1. Photoisomerization mechanism of the rhodopsin chromophore: picosecond photolysis of pigment containing 11-cis-locked eight-membered ring retinal.

    PubMed Central

    Mizukami, T; Kandori, H; Shichida, Y; Chen, A H; Derguini, F; Caldwell, C G; Biffe, C F; Nakanishi, K; Yoshizawa, T

    1993-01-01

    The primary photochemical event in rhodopsin is an 11-cis to 11-trans photoisomerization of its retinylidene chromophore to form the primary intermediate photorhodopsin. Earlier picosecond studies have shown that no intermediate is formed when the retinal 11-ene is fixed through a bridging five-membered ring, whereas a photorhodopsin-like intermediate is formed when it is fixed through a flexible seven-membered ring. Results from a rhodopsin analog formed from a retinal with locked 11-ene structure through the more flexible eight-membered ring (Ret8) are described. Incubation of bovine opsin with Ret8 formed two pigments absorbing at 425 nm (P425) and 500 nm (P500). P425, however, is an artifact because it formed from thermally denatured opsin or other proteins and Ret8. Excitation of P500 with a picosecond green pulse led to formation of two intermediates corresponding to photo- and bathorhodopsins. These results demonstrate that an appearance of early intermediates is dependent on the flexibility of the 11-ene and that the photoisomerization of P500 proceeds by stepwise changes of chromophore-protein interaction, which in turn leads to a relaxation of the highly twisted all-trans-retinylidene chromophore in photorhodopsin. PMID:8483923

  2. Investigation of the chromophore binding cavity in the 11-cis acceptable microbial rhodopsin MR

    NASA Astrophysics Data System (ADS)

    Mori, Arisa; Yagasaki, Jin; Homma, Michio; Reissig, Louisa; Sudo, Yuki

    2013-06-01

    Rhodopsins are photoactive molecules functioning as photo-energy or photo-signal converters with the chromophore retinal. Recently we characterized a unique microbial rhodopsin (middle rhodopsin, MR) which can also bind 11-cis retinal besides all-trans and 13-cis retinal at a particular ratio. In this study, we investigated the structural characteristics around the retinal binding cavity in MR. The results suggest that the space of the retinal binding site of MR is less restricted to the retinal chromophore and the presence of the 11-cis conformer is regulated by the residues located around the retinal. Furthermore, although the triple mutant of MR has identical residues with the well-studied microbial rhodopsin bacteriorhodopsin (BR) within 5 Å from the retinal, the absorption maximum and retinal composition of MR did not reach those of BR, indicating that some long-range effect(s) (>5 Å) is also important for the maintenance of the chemical properties of MR.

  3. Barrierless Photoisomerization of 11-cis Retinal Protonated Schiff Base in Solution.

    PubMed

    Bassolino, Giovanni; Sovdat, Tina; Soares Duarte, Alex; Lim, Jong Min; Schnedermann, Christoph; Liebel, Matz; Odell, Barbara; Claridge, Timothy D W; Fletcher, Stephen P; Kukura, Philipp

    2015-10-01

    A hallmark of the primary visual event is the barrierless, ultrafast, and efficient 11-cis to all-trans photoisomerization of the retinal protonated Schiff base (RPSB) chromophore. The remarkable reactivity of RPSB in the visual pigment rhodopsin has been attributed to potential energy surface modifications enabled by evolution-optimized chromophore-protein interactions. Here, we use a combined synthetic and ultrafast spectroscopic approach to show that barrierless photoisomerization is an intrinsic property of 11-cis RPSB, suggesting that the protein may merely adjust the ratio between fast reactive and slow unreactive decay channels. These results call for a re-evaluation of our understanding and theoretical description of RPSB photochemistry. PMID:26376448

  4. Effects of Infrared Laser Radiation on the In Vitro Isomerization of All-Trans Retinal to 11-Cis Retinal

    PubMed Central

    Liegner, J.; Taboada, J.; Tsin, A. T. C.

    2015-01-01

    The in vitro effect of infrared laser light on the isomerization of all-trans retinal dissolved in an ether/hexane and also an ethanol solvent was studied. Pulsed laser energy at 1064 nm was used to drive the molecular reconfiguration of all-trans retinal to 11-cis retinal. High pressure liquid chromatography (HPLC) was used to quantify the conversion. Overall isomerization was minimal (0.2 percent to 1.0 percent), yet, a significant difference in isomerization due to pulsed infrared laser energy over non-modulated monochromatic laser light was detected (up to 168 percent difference). Potentially, pulsed laser radiation tuned to the ethylenic stretch frequency of the C11=C12 bond of retinal may induce rotational changes to the chromophore. PMID:26321787

  5. 11-cis retinal torsion: A QTAIM and stress tensor analysis of the S1 excited state

    NASA Astrophysics Data System (ADS)

    Maza, Julio R.; Jenkins, Samantha; Kirk, Steven R.

    2016-05-01

    We investigate torsion about the C11-C12 bond mid-point for the S1 state of 11-cis retinal, using a QTAIM and stress tensor analysis. The QTAIM and stress tensor responses to a torsion ±α increase at a faster rate for the preferred direction of torsion though the CI seam. A QTAIM and stress tensor vector-based analysis provides an alternative way of characterising the asymmetry of the S1 potential energy surface. In the vicinity of the CI seam the ellipticity ε attained minimum values. The application of this analysis to molecular rotary motors is briefly discussed.

  6. 11-cis-retinal reduces constitutive opsin phosphorylation and improves quantum catch in retinoid-deficient mouse rod photoreceptors.

    PubMed

    Ablonczy, Zsolt; Crouch, Rosalie K; Goletz, Patrice W; Redmond, T Michael; Knapp, Daniel R; Ma, Jian-Xing; Rohrer, Barbel

    2002-10-25

    Rpe65(-/-) mice produce minimal amounts of 11-cis-retinal, the ligand necessary for the formation of photosensitive visual pigments. Therefore, the apoprotein opsin in these animals has not been exposed to its normal ligand. The Rpe65(-/-) mice contain less than 0.1% of wild type levels of rhodopsin. Mass spectrometric analysis of opsin from Rpe65(-/-) mice revealed unusually high levels of phosphorylation in dark-adapted mice but no other structural alterations. Single flash and flicker electroretinograms (ERGs) from 1-month-old animals showed trace rod function but no cone response. B-wave kinetics of the single-flash ERG are comparable with those of dark-adapted wild type mice containing a full compliment of rhodopsin. Application (intraperitoneal injection) of 11-cis-retinal to Rpe65(-/-) mice increased the rod ERG signal, increased levels of rhodopsin, and decreased opsin phosphorylation. Therefore, exogenous 11-cis-retinal improves photoreceptor function by regenerating rhodopsin and removes constitutive opsin phosphorylation. Our results indicate that opsin, which has not been exposed to 11-cis-retinal, does not generate the activity generally associated with the bleached apoprotein. PMID:12176991

  7. Protein Induced Torsion of the Retinal Chromophore and How it Affects the Photochemistry of Rhopdopsin

    SciTech Connect

    Weingart, Oliver; Buss, Volker

    2007-12-26

    The influence of protein induced chromophore deformations on reaction timescale and quantum yield is investigated using ab initio molecular dynamics in vacuo on four and five double bond models of the retinal chromophore. The opposite twist of the C11 = C12 and the C12-C13 bonds appears to be the prerequisite for the highly stereoselective and efficient cis-trans photodynamics of the retinal chromophore in the binding pocket of rhodopsin. The formation of the photoproduct is determined by the phase of the hydrogen out-of-plane mode of the 11-cis double bond.

  8. The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium.

    PubMed

    Hao, W; Fong, H K

    1999-03-01

    The recent identification of nonvisual opsins has revealed an expanding family of vertebrate opsin genes. The retinal pigment epithelium (RPE) and Müller cells contain a blue and UV light-absorbing opsin, the RPE retinal G protein-coupled receptor (RGR, or RGR opsin). The spectral properties of RGR purified from bovine RPE suggest that RGR is conjugated in vivo to a retinal chromophore through a covalent Schiff base bond. In this study, the isomeric structure of the endogenous chromophore of RGR was identified by the hydroxylamine derivatization method. The retinaloximes derived from RGR in the dark consisted predominantly of the all-trans isomer. Irradiation of RGR with 470-nm monochromatic or near-UV light resulted in stereospecific isomerization of the bound all-trans-retinal to an 11-cis configuration. The stereospecificity of photoisomerization of the all-trans-retinal chromophore of RGR was lost by denaturation of the protein in SDS. Under the in vitro conditions, the photosensitivity of RGR is at least 34% that of bovine rhodopsin. These results provide evidence that RGR is bound in vivo primarily to all-trans-retinal and is capable of operating as a stereospecific photoisomerase that generates 11-cis-retinal in the pigment epithelium. PMID:10037690

  9. S1 and S2 Excited States of Gas-Phase Schiff-Base Retinal Chromophores

    NASA Astrophysics Data System (ADS)

    Nielsen, I. B.; Lammich, L.; Andersen, L. H.

    2006-01-01

    Photoabsorption studies of 11-cis and all-trans Schiff-base retinal chromophore cations in the gas phase have been performed at the electrostatic ion storage ring in Aarhus. A broad absorption band due to the optically allowed excitation to the first electronically excited singlet state (S1) is observed at around 600 nm. A second “dark” excited state (S2) just below 400 nm is reported for the first time. It is located ˜1.2eV above S1 for both chromophores. The S2 state was not visible in a solution measurement where only one highly blueshifted absorption band corresponding to the first excited state was visible. Knowledge of the position of the excited states in retinal is essential for the understanding of the fast photoisomerization in, for example, visual pigments.

  10. Isotope Labeling Study of Retinal Chromophore Fragmentation.

    PubMed

    Musbat, Lihi; Nihamkin, Maria; Ytzhak, Shany; Hirshfeld, Amiram; Friedman, Noga; Dilger, Jonathan M; Sheves, Mordechai; Toker, Yoni

    2016-04-28

    Previous studies have shown that the gas-phase fragmentation of the retinal chromophore after S0-S1 photoexcitation results in a prominent fragment of mass 248 which cannot be explained by the cleavage of any single bond along the polyene chain. It was therefore theorized that the fragmentation mechanism involves a series of isomerizations and cyclization processes, and two mechanisms for these processes were suggested. Here we used isotope labeling MS-MS to provide conclusive support for the fragmentation mechanism suggested by Coughlan et al. (J. Phys. Chem. Lett. 2014, 5, 3195). PMID:27046667

  11. Effect of 11-Cis 13-Demethylretinal on Phototransduction in Bleach-Adapted Rod and Cone Photoreceptors

    PubMed Central

    Corson, D.Wesley; Kefalov, Vladimir J.; Cornwall, M. Carter; Crouch, Rosalie K.

    2000-01-01

    We used 11-cis 13-demethylretinal to examine the physiological consequences of retinal's noncovalent interaction with opsin in intact rod and cone photoreceptors during visual pigment regeneration. 11-Cis 13-demethylretinal is an analog of 11-cis retinal in which the 13 position methyl group has been removed. Biochemical experiments have shown that it is capable of binding in the chromophore pocket of opsin, forming a Schiff-base linkage with the protein to produce a pigment, but at a much slower rate than the native 11-cis retinal (Nelson, R., J. Kim deReil, and A. Kropf. 1970. Proc. Nat. Acad. Sci. USA. 66:531–538). Experimentally, this slow rate of pigment formation should allow separate physiological examination of the effects of the initial binding of retinal in the pocket and the subsequent formation of the protonated Schiff-base linkage. Currents from solitary rods and cones from the tiger salamander were recorded in darkness before and after bleaching and then after exposure to 11-cis 13-demethylretinal. In bleach-adapted rods, 11-cis 13-demethylretinal caused transient activation of phototransduction, as evidenced by a decrease of the dark current and sensitivity, acceleration of the dim flash responses, and activation of cGMP phosphodiesterase and guanylyl cyclase. The steady state of phototransduction activity was still higher than that of the bleach-adapted rod. In contrast, exposure of bleach-adapted cones to 11-cis 13-demethylretinal resulted in an immediate deactivation of transduction as measured by the same parameters. These results extend the validity of a model for the effects of the noncovalent binding of a retinoid in the chromophore pockets of rod and cone opsins to analogs capable of forming a Schiff-base and imply that the noncovalent binding by itself may play a role for the dark adaptation of photoreceptors. PMID:10919871

  12. Nuclear Wavepacket Propogation Model for the Retinal Chromophore in Rhodopsin

    NASA Astrophysics Data System (ADS)

    Corn, Brittany; Malinovskaya, Svetlana

    2009-05-01

    Rhodopsin, consisting of a retinal chromophore and a protein opsin, is responsible for the first steps in the vision process through a cis to trans photoisomerization, which is completed within 200 fs[1]. Efforts to control the ultrafast dynamics of this molecule have been carried out experimentally[2] as well as through quantum mechanical modeling of nuclear wave packet propagation[3]. We propose a two state model in which the ground electronic Potential Energy Surface (PES) is made up of two adjacent harmonic potentials, representing the cis and trans retinal saddle points, as well as an excited PES, characterized by the Morse potential, which meets the ground PES at a conical intersection. We explore the achievement of a high quantum yield of the trans retinal configuration by varying parameters of the external field and choosing the most adequate shape. Another investigation is presented in which we compare the charge distribution of cis and trans retinal in order to reveal a charge transfer mechanism behind the isomerization of rhodopsin. The results of the Lowdin and Natural Population Analyses demonstrate a significant transfer of charge in and around the isomerization region. [1] RW Schoenlein, LA Peteanu, RA Mathies, CV Shank, Science 254, 412 (1991) [2] VI Prokhorenko, AM Nagy, SA Waschuk, LS Brown, RR Birge, RJD Miller, Science 313, 1257 (2006) [3] S Hahn, G Stock, Chem Phys 259, 297-312 (2000)

  13. Retinal analog restoration of photophobic responses in a blind Chlamydomonas reinhardtii mutant. Evidence for an archaebacterial like chromophore in a eukaryotic rhodopsin.

    PubMed Central

    Lawson, M A; Zacks, D N; Derguini, F; Nakanishi, K; Spudich, J L

    1991-01-01

    The strain CC-2359 of the unicellular eukaryotic alga Chlamydomonas reinhardtii originally described as a low pigmentation mutant is found to be devoid of photophobic stop responses to photostimuli over a wide range of light intensities. Photophobic responses of the mutant are restored by exogenous addition of all-trans retinal. We have combined computer-based cell-tracking and motion analysis with retinal isomer and retinal analog reconstitution of CC-2359 to investigate properties of the photophobic response receptor. Most rapid and most complete reconstitution is obtained with all-trans retinal compared to 13-cis, 11-cis, and 9-cis retinal. An analog locked by a carbon bridge in a 6-s-trans conformation reconstitutes whereas the corresponding 6-s-cis locked analog does not. Retinal analogs prevented from isomerization around the 13-14 double bond by a five-membered ring in the polyene chain (locked in either the 13-trans or 13-cis configuration) do not restore the response, but enter the chromophore binding pocket as evidenced by their inhibition of all-trans retinal regeneration of the response. Results of competition experiments between all-trans and each of the 13-locked analogs fit a model in which each chromophore exhibits reversible binding to the photoreceptor apoprotein. A competitive inhibition scheme closely fits the data and permits calculation of apparent dissociation constants for the in vivo reconstitution process of 2.5 x 10(-11) M, 5.2 x 10(-10) M, and 5.4 x 10(-9) M, for all-trans, 13-trans-locked and 13-cis-locked analogs, respectively. The chromophore requirement for the trans configuration and 6-s-trans conformation, and the lack of signaling function from analogs locked at the 13 position, are characteristic of archaebacterial rhodopsins, rather than the previously studied eukaryotic rhodopsins (i.e., visual pigments). PMID:1777569

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

    PubMed Central

    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.—Babino, D., Perkins, B. D., Kindermann, A., Oberhauser, V., von Lintig, J. The role of 11-cis-retinyl esters in vertebrate cone vision. PMID:25326538

  15. Probing the Photodynamics of Rhodopsins with Reduced Retinal Chromophores.

    PubMed

    Manathunga, Madushanka; Yang, Xuchun; Luk, Hoi Ling; Gozem, Samer; Frutos, Luis Manuel; Valentini, Alessio; Ferrè, Nicolas; Olivucci, Massimo

    2016-02-01

    While the light-induced population dynamics of different photoresponsive proteins has been investigated spectroscopically, systematic computational studies have not yet been possible due to the phenomenally high cost of suitable high level quantum chemical methods and the need of propagating hundreds, if not thousands, of nonadiabatic trajectories. Here we explore the possibility of studying the photodynamics of rhodopsins by constructing and investigating quantum mechanics/molecular mechanics (QM/MM) models featuring reduced retinal chromophores. In order to do so we use the sensory rhodopsin found in the cyanobacterium Anabaena PCC7120 (ASR) as a benchmark system. We find that the basic mechanistic features associated with the excited state dynamics of ASR QM/MM models are reproduced using models incorporating a minimal (i.e., three double-bond) chromophore. Furthermore, we show that ensembles of nonadiabatic ASR trajectories computed using the same abridged models replicate, at both the CASPT2 and CASSCF levels of theory, the trends in spectroscopy and lifetimes estimated using unabridged models and observed experimentally at room temperature. We conclude that a further expansion of these studies may lead to low-cost QM/MM rhodopsin models that may be used as effective tools in high-throughput in silico mutant screening. PMID:26640959

  16. Excited-state structure and isomerization dynamics of the retinal chromophore in rhodopsin from resonance Raman intensities.

    PubMed Central

    Loppnow, G R; Mathies, R A

    1988-01-01

    Resonance Raman excitation profiles have been measured for the bovine visual pigment rhodopsin using excitation wavelengths ranging from 457.9 to 647.1 nm. A complete Franck-Condon analysis of the absorption spectrum and resonance Raman excitation profiles has been performed using an excited-state, time-dependent wavepacket propagation technique. This has enabled us to determine the change in geometry upon electronic excitation of rhodopsin's 11-cis-retinal protonated Schiff base chromophore along 25 normal coordinates. Intense low-frequency Raman lines are observed at 98, 135, 249, 336, and 461 cm-1 whose intensities provide quantitative, mode-specific information about the excited-state torsional deformations that lead to isomerization. The dominant contribution to the width of the absorption band in rhodopsin results from Franck-Condon progressions in the 1,549 cm-1 ethylenic normal mode. The lack of vibronic structure in the absorption spectrum is shown to be caused by extensive progressions in low-frequency torsional modes and a large homogeneous linewidth (170 cm-1 half-width) together with thermal population of low-frequency modes and inhomogeneous site distribution effects. The resonance Raman cross-sections of rhodopsin are unusually weak because the excited-state wavepacket moves rapidly (approximately 35 fs) and permanently away from the Franck-Condon geometry along skeletal stretching and torsional coordinates. PMID:3416032

  17. Crystal Structure of the 11-cis Isomer of Pharaonis Halorhodopsin: Structural Constraints on Interconversions among Different Isomeric States.

    PubMed

    Chan, Siu Kit; Kawaguchi, Haruki; Kubo, Hiroki; Murakami, Midori; Ihara, Kunio; Maki, Kosuke; Kouyama, Tsutomu

    2016-07-26

    Like other microbial rhodopsins, the light driven chloride pump halorhodopsin from Natronomonas pharaonis (pHR) contains a mixture of all-trans/15-anti and 13-cis/15-syn isomers in the dark adapted state. A recent crystallographic study of the reaction states of pHR has shown that reaction states with 13-cis/15-syn retinal occur in the anion pumping cycle that is initiated by excitation of the all-trans isomer. In this study, we investigated interconversions among different isomeric states of pHR in the absence of chloride ions. The illumination of chloride free pHR with red light caused a large blue shift in the absorption maximum of the retinal visible band. During this "red adaptation", the content of the 11-cis isomer increased significantly, while the molar ratio of the 13-cis isomer to the all-trans isomer remained unchanged. The results suggest that the thermally activated interconversion between the 13-cis and the all-trans isomers is very rapid. Diffraction data from red adapted crystals showed that accommodation of the retinal chromophore with the 11-cis/15-syn configuration was achieved without a large change in the retinal binding pocket. The measurement of absorption kinetics under illumination showed that the 11-cis isomer, with a λmax at 565 nm, was generated upon excitation of a red-shifted species (λmax = 625 nm) that was present as a minor component in the dark adapted state. It is possible that this red-shifted species mimics an O-like reaction state with 13-cis/15-syn retinal, which was hypothesized to occur at a late stage of the anion pumping cycle. PMID:27352034

  18. FATP1 Inhibits 11-cis Retinol Formation via Interaction with the Visual Cycle Retinoid Isomerase RPE65 and Lecithin:Retinol Acyltransferase*

    PubMed Central

    Guignard, Thomas J. P.; Jin, Minghao; Pequignot, Marie O.; Li, Songhua; Chassigneux, Yolaine; Chekroud, Karim; Guillou, Laurent; Richard, Eric; Hamel, Christian P.; Brabet, Philippe

    2010-01-01

    The isomerization of all-trans retinol (vitamin A) to 11-cis retinol in the retinal pigment epithelium (RPE) is a key step in the visual process for the regeneration of the visual pigment chromophore, 11-cis retinal. LRAT and RPE65 are recognized as the minimal isomerase catalytic components. However, regulators of this rate-limiting step are not fully identified and could account for the phenotypic variability associated with inherited retinal degeneration (RD) caused by mutations in the RPE65 gene. To identify new RPE65 partners, we screened a porcine RPE mRNA library using a yeast two-hybrid assay with full-length human RPE65. One identified clone (here named FATP1c), containing the cytosolic C-terminal sequence from the fatty acid transport protein 1 (FATP1 or SLC27A1, solute carrier family 27 member 1), was demonstrated to interact dose-dependently with the native RPE65 and with LRAT. Furthermore, these interacting proteins colocalize in the RPE. Cellular reconstitution of human interacting proteins shows that FATP1 markedly inhibits 11-cis retinol production by acting on the production of all-trans retinyl esters and the isomerase activity of RPE65. The identification of this new visual cycle inhibitory component in RPE may contribute to further understanding of retinal pathogenesis. PMID:20356843

  19. Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice.

    PubMed

    Sahu, Bhubanananda; Sun, Wenyu; Perusek, Lindsay; Parmar, Vipulkumar; Le, Yun-Zheng; Griswold, Michael D; Palczewski, Krzysztof; Maeda, Akiko

    2015-11-01

    Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5(-/-)Rdh11(-/-) mice as compared with Rdh5(-/-) mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5(-/-) and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision. PMID:26391396

  20. Dynamic Electron Correlation Effects on the Ground State Potential Energy Surface of a Retinal Chromophore Model.

    PubMed

    Gozem, Samer; Huntress, Mark; Schapiro, Igor; Lindh, Roland; Granovsky, Alexander A; Angeli, Celestino; Olivucci, Massimo

    2012-11-13

    The ground state potential energy surface of the retinal chromophore of visual pigments (e.g., bovine rhodopsin) features a low-lying conical intersection surrounded by regions with variable charge-transfer and diradical electronic structures. This implies that dynamic electron correlation may have a large effect on the shape of the force fields driving its reactivity. To investigate this effect, we focus on mapping the potential energy for three paths located along the ground state CASSCF potential energy surface of the penta-2,4-dieniminium cation taken as a minimal model of the retinal chromophore. The first path spans the bond length alternation coordinate and intercepts a conical intersection point. The other two are minimum energy paths along two distinct but kinetically competitive thermal isomerization coordinates. We show that the effect of introducing the missing dynamic electron correlation variationally (with MRCISD) and perturbatively (with the CASPT2, NEVPT2, and XMCQDPT2 methods) leads, invariably, to a stabilization of the regions with charge transfer character and to a significant reshaping of the reference CASSCF potential energy surface and suggesting a change in the dominating isomerization mechanism. The possible impact of such a correction on the photoisomerization of the retinal chromophore is discussed. PMID:26605574

  1. Resonance Raman studies of the HOOP modes in octopus bathorhodopsin with deuterium-labeled retinal chromophores

    SciTech Connect

    Deng, H.; Manor, D.; Weng, G.; Rath, P.; Callender, R.H. ); Koutalos, Y.; Ebrey, T. ); Gebhard, R.; Lugtenburg, J. ); Tsuda, M. )

    1991-05-07

    Resonance Raman spectra of the hydrogen out-of-plane (HOOP) vibrational modes in the retinal chromophore of octopus bathorhodopsin with deuterium label(s) along the polyene chain have been obtained. In clear contrast with bovine bathorhodopsin's HOOP modes, there are only two major HOOP bands at 887 and 940 cm{sup {minus}1} for octopus bathorhodopsin. On the basis of their isotopic shifts upon deuterium labeling, the authors have assigned the band at 887 cm{sup {minus}1} to C{sub 10}H and C{sub 14}H HOOP modes, and the band at 940 cm{sup {minus}1} to C{sub 11}H{double bond}C{sub 12}H A{sub u}-like HOOP mode. They found also that the C{sub 10}H and C{sub 14}H HOOP wags are also similar to those in the model-compound studies. However, they have found that the interaction between the C{sub 7}H and C{sub 8}H HOOP internal coordinates of the chromophore in octopus bathorhodopsin is different from that of the chromophore in solution. The twisted nature of the chromophore, semiquantitatively discussed here, likely affects the {lambda}{sub max} of the chromophore and its enthalpy. The nature of the HOOP modes of octopus bathorhodopsin differs substantially from those found in bovine bathorhodopsin.

  2. Mechanism of Rhodopsin Activation as Examined with Ring-constrained Retinal Analogs and the Crystal Structure of the Ground State Protein*

    PubMed Central

    Jang, Geeng-Fu; Kuksa, Vladimir; Filipek, Stawomir; Bartl||, Franz; Ritter, Eglof; Gelb, Michael H.; Hofmann, Klaus Peter; Palczewski, Krzysztof

    2006-01-01

    The guanine nucleotide-binding protein (G-protein)-coupled receptor superfamily (GPCR) is comprised of a large group of membrane proteins involved in a wide range of physiological signaling processes. The functional switch from a quiescent to an active conformation is at the heart of GPCR action. The GPCR rhodopsin has been studied extensively because of its key role in scotopic vision. The ground state chromophore, 11-cis-retinal, holds the transmembrane region of the protein in the inactive conformation. Light induces cis-trans isomerization and rhodopsin activation. Here we show that rhodopsin regenerated with a ring-constrained 11-cis-retinal analog undergoes photoisomerization; however, it remains marginally active because isomerization occurs without the chromophore-induced conformational change of the opsin moiety. Modeling the locked chromophore analogs in the active site of rhodopsin suggests that the β-ionone ring rotates but is largely confined within the binding site of the natural 11-cis-retinal chromophore. This constraint is a result of the geometry of the stable 11-cis-locked configuration of the chromophore analogs. These results suggest that the native chromophore cis-trans isomerization is merely a mechanism for repositioning of the β-ionone ring which ultimately leads to helix movements and determines receptor activation. PMID:11316815

  3. Molecular bases for the selection of the chromophore of animal rhodopsins.

    PubMed

    Luk, Hoi Ling; Melaccio, Federico; Rinaldi, Silvia; Gozem, Samer; Olivucci, Massimo

    2015-12-15

    The functions of microbial and animal rhodopsins are triggered by the isomerization of their all-trans and 11-cis retinal chromophores, respectively. To lay the molecular basis driving the evolutionary transition from the all-trans to the 11-cis chromophore, multiconfigurational quantum chemistry is used to compare the isomerization mechanisms of the sensory rhodopsin from the cyanobacterium Anabaena PCC 7120 (ASR) and of the bovine rhodopsin (Rh). It is found that, despite their evolutionary distance, these eubacterial and vertebrate rhodopsins start to isomerize via distinct implementations of the same bicycle-pedal mechanism originally proposed by Warshel [Warshel A (1976) Nature 260:678-683]. However, by following the electronic structure changes of ASR (featuring the all-trans chromophore) during the isomerization, we find that ASR enters a region of degeneracy between the first and second excited states not found in Rh (featuring the 11-cis chromophore). We show that such degeneracy is modulated by the preorganized structure of the chromophore and by the position of the reactive double bond. It is argued that the optimization of the electronic properties of the chromophore, which affects the photoisomerization efficiency and the thermal isomerization barrier, provided a key factor for the emergence of the striking amino acid sequence divergence observed between the microbial and animal rhodopsins. PMID:26607446

  4. Molecular bases for the selection of the chromophore of animal rhodopsins

    PubMed Central

    Luk, Hoi Ling; Melaccio, Federico; Rinaldi, Silvia; Gozem, Samer; Olivucci, Massimo

    2015-01-01

    The functions of microbial and animal rhodopsins are triggered by the isomerization of their all-trans and 11-cis retinal chromophores, respectively. To lay the molecular basis driving the evolutionary transition from the all-trans to the 11-cis chromophore, multiconfigurational quantum chemistry is used to compare the isomerization mechanisms of the sensory rhodopsin from the cyanobacterium Anabaena PCC 7120 (ASR) and of the bovine rhodopsin (Rh). It is found that, despite their evolutionary distance, these eubacterial and vertebrate rhodopsins start to isomerize via distinct implementations of the same bicycle-pedal mechanism originally proposed by Warshel [Warshel A (1976) Nature 260:678–683]. However, by following the electronic structure changes of ASR (featuring the all-trans chromophore) during the isomerization, we find that ASR enters a region of degeneracy between the first and second excited states not found in Rh (featuring the 11-cis chromophore). We show that such degeneracy is modulated by the preorganized structure of the chromophore and by the position of the reactive double bond. It is argued that the optimization of the electronic properties of the chromophore, which affects the photoisomerization efficiency and the thermal isomerization barrier, provided a key factor for the emergence of the striking amino acid sequence divergence observed between the microbial and animal rhodopsins. PMID:26607446

  5. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    PubMed Central

    Perusek, Lindsay; Maeda, Tadao

    2013-01-01

    The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients. PMID:23857173

  6. Pharmacological Chaperone-mediated in Vivo Folding and Stabilization of the P23H-opsin Mutant Associated with Autosomal Dominant Retinitis Pigmentosa*

    PubMed Central

    Imanishi, Yoshikazu; Zhu, Li; Filipek, Sławomir; Palczewski, Krzysztof; Kaushal, Shalesh

    2006-01-01

    Protein conformational disorders, which include certain types of retinitis pigmentosa, are a set of inherited human diseases in which mutant proteins are misfolded and often aggregated. Many opsin mutants associated with retinitis pigmentosa, the most common being P23H, are misfolded and retained within the cell. Here, we describe a pharmacological chaperone, 11-cis-7-ring retinal, that quantitatively induces the in vivo folding of P23H-opsin. The rescued protein forms pigment, acquires mature glycosylation, and is transported to the cell surface. Additionally, we determined the temperature stability of the rescued protein as well as the reactivity of the retinal-opsin Schiff base to hydroxylamine. Our study unveils novel properties of P23H-opsin and its interaction with the chromophore. These properties suggest that 11-cis-7-ring retinal may be a useful therapeutic agent for the rescue of P23H-opsin and the prevention of retinal degeneration. PMID:12566452

  7. Nonlinear Optical Properties of Bacteriorhodopsin and Retinal Chromophores and Their Applications for Optical Information Storage and Processing.

    NASA Astrophysics Data System (ADS)

    Chen, Zhongping

    Retinal, a conjugated polyene, plays a crucial role in biology. Both the visual pigments and the energy transducing protein, bacteriorhodopsin (BR) have a form of retinal as their chromophores. Because visual excitation and energy transduction in these systems is initiated by the promotion of retinal to an excited electronic state, information about the excited-state structure of retinal and the effect of chromophore/protein interactions on this structure are essential to understanding the functions of these systems. In this thesis, surface second harmonic (SH) generation is used to measure the light-induced dipole moment changes of a series of retinal derivatives that were designed and synthesized to model specific components of chromophore/protein interactions. In addition, we report an in situ probe of the dipole moment change of the retinal chromophore bound in BR by SH generation from oriented purple membranes. The dipole moment changes of various forms of BR, including light-adapted, dark-adapted, blue, and acid purple membrane, were measured and compared. These results, combined with the results from model compounds, elucidate the effects of the chromophore/protein interactions on light-induced charge redistribution and give insight on the fundamental nature of light excitation and energy storage in SR and rhodopsin. Furthermore, the dependence of the molecular hyperpolarizability of the conjugated molecules on donor/acceptor strength, protonation, conjugate length, planarity, and nonconjugate charges is investigated. Our study shows for the first time that nonconjugated charges have a very large effect on the nonlinear optical properties of conjugated molecules. BR has interesting photochromic characteristics, very large optical nonlinearities, and a unique optoelectrical property where the polarity of the photovoltage depends on both its photochromic state and the excitation wavelength. These unique characteristics coupled with its high stability make BR

  8. Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice

    PubMed Central

    Berkowitz, Bruce A.; Kern, Timothy S.; Bissig, David; Patel, Priya; Bhatia, Ankit; Kefalov, Vladimir J.; Roberts, Robin

    2015-01-01

    Purpose Diabetes appears to induce a visual cycle defect because rod dysfunction is correctable with systemic treatment of the visual cycle chromophore 11-cis-retinaldehyde. However, later studies have found no evidence for visual cycle impairment. Here, we further examined whether photoreceptor dysfunction is corrected with 11-cis-retinaldehyde. Because antioxidants correct photoreceptor dysfunction in diabetes, the hypothesis that exogenous visual chromophores have antioxidant activity in the retina of diabetic mice in vivo was tested. Methods Rod function in 2-month-old diabetic mice was evaluated using transretinal electrophysiology in excised retinas and apparent diffusion coefficient (ADC) MRI to measure light-evoked expansion of subretinal space (SRS) in vivo. Optokinetic tracking was used to evaluate cone-based visual performance. Retinal production of superoxide free radicals, generated mostly in rod cells, was biochemically measured with lucigenin. Diabetic mice were systemically treated with a single injection of either 11-cis-retinaldehyde, 9-cis-retinaldehyde (a chromophore surrogate), or all-trans-retinaldehyde (the photoisomerization product of 11-cis-retinaldehyde). Results Consistent with previous reports, diabetes significantly reduced (1) dark-adapted rod photo responses (transretinal recording) by ∼18%, (2) rod-dominated light-stimulated SRS expansion (ADC MRI) by ∼21%, and (3) cone-dominated contrast sensitivity (using optokinetic tracking [OKT]) by ∼30%. Both 11-cis-retinaldehyde and 9-cis-retinaldehyde largely corrected these metrics of photoreceptor dysfunction. Higher-than-normal retinal superoxide production in diabetes by ∼55% was also significantly corrected following treatment with 11-cis-retinaldehyde, 9-cis-retinaldehyde, or all-trans-retinaldehyde. Conclusions Collectively, data suggest that retinaldehydes improve photoreceptor dysfunction in diabetic mice, independent of the visual cycle, via an antioxidant mechanism. PMID

  9. Delayed Dark Adaptation in 11-cis-Retinol Dehydrogenase-deficient Mice

    PubMed Central

    Kim, Tom S.; Maeda, Akiko; Maeda, Tadao; Heinlein, Cynthia; Kedishvili, Natalia; Palczewski, Krzysztof; Nelson, Peter S.

    2005-01-01

    The oxidation of 11-cis-retinol to 11-cis-retinal in the retinal pigment epithelium (RPE) represents the final step in a metabolic cycle that culminates in visual pigment regeneration. Retinol dehydrogenase 5 (RDH5) is responsible for a majority of the 11-cis-RDH activity in the RPE, but the formation of 11-cis-retinal in rdh5−/− mice suggests another enzyme(s) is present. We have previously shown that RDH11 is also highly expressed in RPE cells and has dual specificity for both cis- and trans-retinoid substrates. To investigate the role of RDH11 in the retinoid cycle, we generated rdh11−/− and rdh5−/− rdh11−/− mice and examined their electrophysiological responses to various intensities of illumination and during dark adaptation. Retinoid profiles of dark-adapted rdh11−/− mice did not show significant differences compared with wild-type mice, whereas an accumulation of cis-esters was detected in rdh5−/− and rdh5−/− rdh11−/− mice. Following light stimulation, 73% more cis-retinyl esters were stored in rdh5−/− rdh11−/− mice compared with rdh5−/− mice. Single-flash ERGs of rdh11−/− showed normal responses under dark- and light-adapted conditions, but exhibited delayed dark adaptation following high bleaching levels. Double knockout mice also had normal ERG responses in dark- and light-adapted conditions, but had a further delay in dark adaptation relative to either rdh11−/− or rdh5−/− mice. Taken together, these results suggest that RDH11 has a measurable role in regenerating the visual pigment by complementing RDH5 as an 11-cis-RDH in RPE cells, and indicate that an additional unidentified enzyme(s) oxidizes 11-cis-retinol or that an alternative pathway contributes to the retinoid cycle. PMID:15634683

  10. Low-temperature solid-state /sup 13/C NMR studies of the retinal chromophore in rhodopsin

    SciTech Connect

    Smith, S.O.; Palings, I.; Copie, V.; Raleigh, D.P.; Courtin, J.; Pardoen, J.A.; Lugtenburg, J.; Mathies, R.A.; Griffin, R.G.

    1987-03-24

    Magic angle sample spinning (MASS) /sup 13/C NMR spectra have been obtained of bovine rhodopsin regenerated with retinal prosthetic groups isotopically enriched with /sup 13/C at C-5 and C-14. In order to observe the /sup 13/C retinal chromophore resonances, it was necessary to employ low temperatures (-15 ..-->.. -35/sup 0/C) to restrict rotational diffusion of the protein. The isotropic chemical shift and principal values of the chemical shift tensor of the /sup 13/C-5 label indicate that the retinal chromophore is in the twisted 6-s-cis conformation in rhodopsin, in contrast to the planar 6-s-trans confirmation found in bacteriorhodopsin. The /sup 13/C-14 isotropic shift and shift tensor principal values show that the Schiff base C=N bond is anti. Furthermore, the /sup 13/C-14 chemical shift (121.2 ppm) is within the range of values (120-123 ppm) exhibited by protonated (C=N anti) Schiff base model compounds, indicating that the C=N linkage is protonated. The results are discussed with regard to the mechanism of wavelength regulation in rhodopsin.

  11. Primary structural response in tryptophan residues of Anabaena sensory rhodopsin to photochromic reactions of the retinal chromophore

    NASA Astrophysics Data System (ADS)

    Inada, Seisuke; Mizuno, Misao; Kato, Yoshitaka; Kawanabe, Akira; Kandori, Hideki; Wei, Zhengrong; Takeuchi, Satoshi; Tahara, Tahei; Mizutani, Yasuhisa

    2013-06-01

    Anabaena sensory rhodopsin (ASR) is a microbial rhodopsin found in eubacteria and functions as a photosensor. The photoreaction of ASR is photochromic between all-trans, 15-anti (ASRAT), and 13-cis, 15-syn (ASR13C) isomers. To understand primary protein dynamics in the photoreaction starting in ASRAT and ASR13C, picosecond time-resolved ultraviolet resonance Raman spectra were obtained. In the intermediate state appearing in the picosecond temporal region, spectral changes of Trp bands were observed. For both ASRAT and ASR13C, the intensities of the Trp bands were bleached within the instrumental response time and recovered with a time constant of 30 ps. This suggests that the rates of structural changes in the Trp residue in the vicinity of the chromophore do not depend on the direction of the isomerization of retinal. A comparison between spectra of the wild-type and Trp mutants indicates that the structures of Trp76 and Trp46 change upon the primary photoreaction of retinal.

  12. Localization of the retinal protonated Schiff base counterion in rhodopsin.

    PubMed Central

    Han, M.; DeDecker, B. S.; Smith, S. O.

    1993-01-01

    Semiempirical molecular orbital calculations are combined with 13C NMR chemical shifts to localize the counterion in the retinal binding site of vertebrate rhodopsin. Charge densities along the polyene chain are calculated for an 11-cis-retinylidene protonated Schiff base (11-cis-RPSB) chromophore with 1) a chloride counterion at various distances from the Schiff base nitrogen, 2) one or two chloride counterions at different positions along the retinal chain from C10 to C15 and at the Schiff base nitrogen, and 3) a carboxylate counterion out of the retinal plane near C12. Increasing the distance of the negative counterion from the Schiff base results in an enhancement of alternating negative and positive partial charge on the even- and odd-numbered carbons, respectively, when compared to the 11-cis-RPSB chloride model compound. In contrast, the observed 13C NMR data of rhodopsin exhibit downfield chemical shifts from C8 to C13 relative to the 11-cis-RPSB.Cl corresponding to a net increase of partial positive or decrease of partial negative charge at these positions (Smith, S. O., I. Palings, M. E. Miley, J. Courtin, H. de Groot, J. Lugtenburg, R. A. Mathies, and R. G. Griffin. 1990. Biochemistry. 29:8158-8164). The anomalous changes in charge density reflected in the rhodopsin NMR chemical shifts can be qualitatively modeled by placing a single negative charge above C12. The calculated fit improves when a carboxylate counterion is used to model the retinal binding site. Inclusion of water in the model does not alter the fit to the NMR data, although it is consistent with observations based on other methods. These data constrain the location and the orientation of the Glu113 side chain, which is known to be the counterion in rhodopsin, and argue for a strong interaction centered at C12 of the retinylidene chain. PMID:8105993

  13. Photoelectrochromism in the Retinal Protonated Schiff Base Chromophore: Photoisomerization Speed and Selectivity under a Homogeneous Electric Field at Different Operational Regimes.

    PubMed

    El-Tahawy, Mohsen M T; Nenov, Artur; Garavelli, Marco

    2016-09-13

    The spectral tunability, photoisomerization efficiency and selectivity, of the native all-trans retinal protonated Shiff base (PSB) chromophore driven by a homogeneous electric field is systematically investigated. By analyzing the absorption wavelength dependence, charge distribution, and PES profiles along selected torsional angles, as well as the electronic structure, energetics, and topography of the CI seam in the presence of strong positive and negative electric fields, we recognize the existence of qualitatively/fundamentally different photophysics and photochemistry with respect to the unperturbed (i.e., absence of an electric field) chromophore. We rationalize the findings within the scope of molecular orbital theory and deliver a unified picture of the photophysics of the retinal PSB chromophore over a wide, even beyond the usually observed, spectral regime, ranging from the near-infrared to the ultraviolet absorption energies. This work has a 3-fold impact: a) it accounts for, and extends, previous theoretical studies on the subject; b) it delivers a rationale for the ES lifetimes observed in retinal proteins, both archeal and visual rhodopsins, as well as in solvent; and c) the transferability of the discovered trends on PSB mimics is demonstrated. PMID:27494352

  14. Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation.

    PubMed

    Kimata, Naoki; Pope, Andreyah; Eilers, Markus; Opefi, Chikwado A; Ziliox, Martine; Hirshfeld, Amiram; Zaitseva, Ekaterina; Vogel, Reiner; Sheves, Mordechai; Reeves, Philip J; Smith, Steven O

    2016-01-01

    The 11-cis retinal chromophore is tightly packed within the interior of the visual receptor rhodopsin and isomerizes to the all-trans configuration following absorption of light. The mechanism by which this isomerization event drives the outward rotation of transmembrane helix H6, a hallmark of activated G protein-coupled receptors, is not well established. To address this question, we use solid-state NMR and FTIR spectroscopy to define the orientation and interactions of the retinal chromophore in the active metarhodopsin II intermediate. Here we show that isomerization of the 11-cis retinal chromophore generates strong steric interactions between its β-ionone ring and transmembrane helices H5 and H6, while deprotonation of its protonated Schiff's base triggers the rearrangement of the hydrogen-bonding network involving residues on H6 and within the second extracellular loop. We integrate these observations with previous structural and functional studies to propose a two-stage mechanism for rhodopsin activation. PMID:27585742

  15. Photoisomerization Dynamics of dMe-OMe-NAIP, a Model for the Retinal Chromophore

    NASA Astrophysics Data System (ADS)

    Dunkelberger, Adam D.; Kieda, Ryan D.; Shin, Jaeyoon; Paccani, Ricardo Rossi; Fusi, Stefania; Olivucci, Massimo; Crim, F. Fleming

    2012-06-01

    The N-alkylated indanylidene pyrroline Schiff bases (NAIP) mimic the speed and efficiency of photoisomerization of retinal, whose photoisomerization is a key step in the molecular mechanism of vision. We present here a study of the ultrafast isomerization and subsequent relaxation of dMe-OMe-NAIP, a newly synthesized compound in the NAIP class with less steric congestion near the reactive double bond. We show that the excited-state dynamics of dMe-OMe-NAIP are slower than in previously studied NAIP compounds. This simpler compound also lacks the pronounced coherent vibrational motion observed in retinal and other NAIP compounds. We attribute these differences to pre-twisting about the double bond in the ground state of the previously studied compounds that is absent in dMe-OMe-NAIP. The speed of the isomerization and structure of the electronically excited potential energy surface in NAIP compounds make them attractive targets for studies of vibrationally mediated photochemistry. Previous studies from our group have shown that vibrational excitation before promotion to reactive electronic states can influence the course of reactions in isolated molecules. We seek to extend these experiments to molecules in more complicated environments, specifically the solution phase. To that end, we also present preliminary results of experiments probing the timescale of vibrational energy transfer in dMe-OMe-NAIP and other photoreactive Schiff bases.

  16. Primary amines protect against retinal degeneration in mouse models of retinopathies

    PubMed Central

    Maeda, Akiko; Golczak, Marcin; Chen, Yu; Okano, Kiichiro; Kohno, Hideo; Shiose, Satomi; Ishikawa, Kaede; Harte, William; Palczewska, Grazyna; Maeda, Tadao; Palczewski, Krzysztof

    2011-01-01

    Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore, 11-cis-retinal, and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the photoisomered product, all-trans-retinal, can cause severe retinal pathology. Here we lowered peak concentrations of free all-trans-retinal with primary amine-containing FDA-approved drugs that did not inhibit chromophore regeneration in mouse models of retinal degeneration. Schiff base adducts between all-trans-retinal and these amines were identified by mass spectrometry. Adducts were observed in mouse eyes only when an experimental drug protected the retina from degeneration in both short-term and long-term treatment experiments. This study demonstrates a molecular basis of all-trans-retinal-induced retinal pathology and identifies an assemblage of FDA-approved compounds with protective effects against this pathology in a mouse model that displays features of Stargardt’s and age-related retinal degeneration. PMID:22198730

  17. Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration.

    PubMed

    Zhang, Jianye; Dong, Zhiqian; Mundla, Sreenivasa Reddy; Hu, X Eric; Seibel, William; Papoian, Ruben; Palczewski, Krzysztof; Golczak, Marcin

    2015-01-01

    All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation. PMID:25538117

  18. Expansion of First-in-Class Drug Candidates That Sequester Toxic All-Trans-Retinal and Prevent Light-Induced Retinal Degeneration

    PubMed Central

    Zhang, Jianye; Dong, Zhiqian; Mundla, Sreenivasa Reddy; Hu, X. Eric; Seibel, William; Papoian, Ruben

    2015-01-01

    All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation. PMID:25538117

  19. Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations*♦

    PubMed Central

    Sakami, Sanae; Maeda, Tadao; Bereta, Grzegorz; Okano, Kiichiro; Golczak, Marcin; Sumaroka, Alexander; Roman, Alejandro J.; Cideciyan, Artur V.; Jacobson, Samuel G.; Palczewski, Krzysztof

    2011-01-01

    Rhodopsin, the visual pigment mediating vision under dim light, is composed of the apoprotein opsin and the chromophore ligand 11-cis-retinal. A P23H mutation in the opsin gene is one of the most prevalent causes of the human blinding disease, autosomal dominant retinitis pigmentosa. Although P23H cultured cell and transgenic animal models have been developed, there remains controversy over whether they fully mimic the human phenotype; and the exact mechanism by which this mutation leads to photoreceptor cell degeneration remains unknown. By generating P23H opsin knock-in mice, we found that the P23H protein was inadequately glycosylated with levels 1–10% that of wild type opsin. Moreover, the P23H protein failed to accumulate in rod photoreceptor cell endoplasmic reticulum but instead disrupted rod photoreceptor disks. Genetically engineered P23H mice lacking the chromophore showed accelerated photoreceptor cell degeneration. These results indicate that most synthesized P23H protein is degraded, and its retinal cytotoxicity is enhanced by lack of the 11-cis-retinal chromophore during rod outer segment development. PMID:21224384

  20. Retinal chromophore structure and Schiff base interactions in red-shifted channelrhodopsin-1 from Chlamydomonas augustae.

    PubMed

    Ogren, John I; Mamaev, Sergey; Russano, Daniel; Li, Hai; Spudich, John L; Rothschild, Kenneth J

    2014-06-24

    Channelrhodopsins (ChRs), which form a distinct branch of the microbial rhodopsin family, control phototaxis in green algae. Because ChRs can be expressed and function in neuronal membranes as light-gated cation channels, they have rapidly become an important optogenetic tool in neurobiology. While channelrhodopsin-2 from the unicellular alga Chlamydomonas reinhardtii (CrChR2) is the most commonly used and extensively studied optogenetic ChR, little is known about the properties of the diverse group of other ChRs. In this study, near-infrared confocal resonance Raman spectroscopy along with hydrogen-deuterium exchange and site-directed mutagenesis were used to study the structure of red-shifted ChR1 from Chlamydomonas augustae (CaChR1). These measurements reveal that (i) CaChR1 has an all-trans-retinal structure similar to those of the light-driven proton pump bacteriorhodopsin (BR) and sensory rhodopsin II but different from that of the mixed retinal composition of CrChR2, (ii) lowering the pH from 7 to 2 or substituting neutral residues for Glu169 or Asp299 does not significantly shift the ethylenic stretch frequency more than 1-2 cm(-1) in contrast to BR in which a downshift of 7-9 cm(-1) occurs reflecting neutralization of the Asp85 counterion, and (iii) the CaChR1 protonated Schiff base (SB) has stronger hydrogen bonding than BR. A model is proposed to explain these results whereby at pH 7 the predominant counterion to the SB is Asp299 (the homologue to Asp212 in BR) while Glu169 (the homologue to Asp85 in BR) exists in a neutral state. We observe an unusual constancy of the resonance Raman spectra over the broad range from pH 9 to 2 and discuss its implications. These results are in accord with recent visible absorption and current measurements of CaChR1 [Sineshchekov, O. A., et al. (2013) Intramolecular proton transfer in channelrhodopsins. Biophys. J. 104, 807-817; Li, H., et al. (2014) Role of a helix B lysine residue in the photoactive site in

  1. Quantum Monte Carlo Treatment of the Charge Transfer and Diradical Electronic Character in a Retinal Chromophore Minimal Model

    PubMed Central

    2015-01-01

    The penta-2,4-dieniminium cation (PSB3) displays similar ground state and first excited state potential energy features as those of the retinal protonated Schiff base (RPSB) chromophore in rhodopsin. Recently, PSB3 has been used to benchmark several electronic structure methods, including highly correlated multireference wave function approaches, highlighting the necessity to accurately describe the electronic correlation in order to obtain reliable properties even along the ground state (thermal) isomerization paths. In this work, we apply two quantum Monte Carlo approaches, the variational Monte Carlo and the lattice regularized diffusion Monte Carlo, to study the energetics and electronic properties of PSB3 along representative minimum energy paths and scans related to its thermal cis–trans isomerization. Quantum Monte Carlo is used in combination with the Jastrow antisymmetrized geminal power ansatz, which guarantees an accurate and balanced description of the static electronic correlation thanks to the multiconfigurational nature of the antisymmetrized geminal power term, and of the dynamical correlation, due to the presence of the Jastrow factor explicitly depending on electron–electron distances. Along the two ground state isomerization minimum energy paths of PSB3, CASSCF calculations yield wave functions having either charge transfer or diradical character in proximity of the two transition state configurations. Here, we observe that at the quantum Monte Carlo level of theory, only the transition state with charge transfer character can be located. The conical intersection, which becomes highly sloped, is observed only if the path connecting the two original CASSCF transition states is extended beyond the diradical one, namely by increasing the bond-length-alternation (BLA). These findings are in good agreement with the results obtained by MRCISD+Q calculations, and they demonstrate the importance of having an accurate description of the static and

  2. Quantum Monte Carlo Treatment of the Charge Transfer and Diradical Electronic Character in a Retinal Chromophore Minimal Model.

    PubMed

    Zen, Andrea; Coccia, Emanuele; Gozem, Samer; Olivucci, Massimo; Guidoni, Leonardo

    2015-03-10

    The penta-2,4-dieniminium cation (PSB3) displays similar ground state and first excited state potential energy features as those of the retinal protonated Schiff base (RPSB) chromophore in rhodopsin. Recently, PSB3 has been used to benchmark several electronic structure methods, including highly correlated multireference wave function approaches, highlighting the necessity to accurately describe the electronic correlation in order to obtain reliable properties even along the ground state (thermal) isomerization paths. In this work, we apply two quantum Monte Carlo approaches, the variational Monte Carlo and the lattice regularized diffusion Monte Carlo, to study the energetics and electronic properties of PSB3 along representative minimum energy paths and scans related to its thermal cis–trans isomerization. Quantum Monte Carlo is used in combination with the Jastrow antisymmetrized geminal power ansatz, which guarantees an accurate and balanced description of the static electronic correlation thanks to the multiconfigurational nature of the antisymmetrized geminal power term, and of the dynamical correlation, due to the presence of the Jastrow factor explicitly depending on electron–electron distances. Along the two ground state isomerization minimum energy paths of PSB3, CASSCF calculations yield wave functions having either charge transfer or diradical character in proximity of the two transition state configurations. Here, we observe that at the quantum Monte Carlo level of theory, only the transition state with charge transfer character can be located. The conical intersection, which becomes highly sloped, is observed only if the path connecting the two original CASSCF transition states is extended beyond the diradical one, namely by increasing the bond-length-alternation (BLA). These findings are in good agreement with the results obtained by MRCISD+Q calculations, and they demonstrate the importance of having an accurate description of the static and

  3. Structure and dynamics of retinal in rhodopsin elucidated by deuterium solid state NMR

    NASA Astrophysics Data System (ADS)

    Salgado, Gilmar Fernandes De Jesus

    Rhodopsin is a seven transmembrane helix GPCR found which mediates dim light vision, in which the binding pocket is occupied by the ligand 11- cis-retinal. A site-directed 2H-labeling approach utilizing solid-state 2H NMR spectroscopy was used to investigate the structure and dynamics of retinal within its binding pocket in the dark state of rhodopsin, and as well the MetaI and MetaII. 11-cis-[5-C 2H3]-, 11-cis-[9-C 2H3]-, and 11-cis-[13-C2H 3]-retinal were used to regenerate bleached rhodopsin. Recombinant membranes comprising purified rhodopsin and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were prepared (1:50 molar ratio). Solid-state 2H NMR spectra were obtained for the aligned rhodopsin/POPC recombinant membranes at temperatures below the order-disorder phase transition temperature of POPC. The solid-state NMR studies of aligned samples, give the orientations of the 2H nuclear coupling tensor relative to the membrane frame, which involve both the conformation and orientation of the bound retinal chromophore. Theoretical simulations of the experimental 2H NMR spectra employed a new lineshape treatment for a semi-random distribution due to static uniaxial disorder. The analysis gives the orientation of the 2H-labeled C-C2H3 methyl bond axes relative to the membrane plane as well as the extent of three-dimensional alignment disorder (mosaic spread). These results clearly demonstrate the applicability of site-directed 2H NMR methods for investigating conformational changes and dynamics of ligands bound to rhodopsin and other GPCRs in relation to their characteristic mechanisms of action.

  4. Photon Echoes from Retinal Proteins

    NASA Astrophysics Data System (ADS)

    Johnson, Philip James Maddigan

    This thesis focuses on the ultrafast isomerization reaction of retinal in both rhodopsin and bacteriorhodopsin, examples of sensory and energy transduction proteins that exploit the same photoactive chromophore for two very different functions. In bacteriorhodopsin, retinal isomerizes from an all-trans to 13-cis conformation as the primary event in light- driven proton pumping. In the visual pigment rhodopsin, the retinal chromophore isomerizes from an 11-cis to all-trans geometry as the primary step leading to our sense of vision. This diversity of function for nominally identical systems raises the question as to just how optimized are these proteins to arrive at such drastically different functions? Previous work has employed transient absorption spectroscopy to probe retinal protein photochemistry, but many of the relevant electronic and nuclear dynamics of isomerization are masked by inhomogeneous broadening effects and strong spectral overlap between reactant and photoproduct states. This work exploits the unique properties of two-dimensional photon echo spectroscopy to deconvolve inhomogeneous broadening and spectral overlap effects and fully reveal the dynamics that direct retinal isomerization in proteins. In bacteriorhodopsin, vibrational coupling to the reaction coordinate results in a surface crossing event prior to the conventional conical intersection associated with isomerization to the J intermediate. In rhodopsin, however, a similarly early vibrationally-mediated barrier crossing event is observed, resulting in spectral signals consistent with the known photoproduct state appearing an order of magnitude faster than determined from conventional transient absorption measurements. The competing overlapping spectral signals that obscured the initial dynamics when probed with transient absorption spectroscopy are now clearly resolved with two-dimensional photon echo spectroscopy. These experiments illustrate the critical role of the protein in directing

  5. Isomerization of 11-cis-retinol to all-trans-retinol in bovine rod outer segments.

    PubMed

    Shimizu, T; Ishiguro, S; Tamai, M

    1998-05-01

    It is known that exogenous 11-cis-retinol inhibits the recovery of photosensitivity of bleached rod outer segments (ROS) and 11-cis-retinol exists in the interphotorecepter matrix. We examined the conversion of 11-cis-retinol with bovine ROS. ROS was incubated with 11-cis-retinol under dim red light. Retinoids were extracted from the reaction mixture with hexane and analyzed by HPLC coupled with a fluorescence spectrophotometer. Isomerization of 11-cis-retinol to all-trans-retinol was observed in the presence of ROS. This isomerization was not suppressed by heat treatment and did not have stereospecificity. In addition, we incubated purified rhodopsin and phospholipids extracted from ROS with 11-cis-retinol. Rhodopsin was found to isomerize 11-cis-retinol to all-trans-retinol as well as ROS, but phospholipids did not. In contrast, the phospholipids inhibited the isomerization of 11-cis-retinol to all-trans-retinol by the purified rhodopsin. Commercially available phospholipids, especially phosphatidylserine, also inhibited the isomerization. Our results suggest that rhodopsin has activity for the isomerization of 11-cis-retinol to all-trans-retinol and may play an important role in the detoxification of 11-cis-retinol in the ROS. PMID:9562631

  6. Energetics of the all-trans{yields}13-cis isomerization of the retinal chromophore of bacteriorhodopsin: Electronic structure calculations for a simple model system

    SciTech Connect

    Woywod, Clemens; Vallet, Valerie; Li, Jingrui; Goerling, Andreas

    2008-12-08

    Understanding the molecular mechanism for the photoinduced transmembrane proton pump in the bacteriorhodopsin system is of fundamental importance. This study attempts to investigate the energetics of the initial step of the proton transport cycle, the photoisomerization of the retinal chromophore. The exact reaction pathway and the question of how many excited electronic states are involved in the internal conversion process are still unresolved. The problem is approached by constructing a reaction coordinate suggested by crystallographic studies for a simplified chromophore model system. The CASSCF and CASPT2 electronic structure methods are employed to calculate the energies of the four lowest lying singlet states as a function of the reaction coordinate. The effect of negatively charged protein residues on the reaction is simulated by inclusion of a negative point charge in the model. The results indicate that trans{yields}cis isomerization around the C{sub {beta}} = C{sub {gamma}} bond may be accompanied by twisting around the C{sub {alpha}}-C{sub {beta}} bond in order to drive the proton pump. The presence of a counterion does not seem to reduce the barrier for isomerization or the S{sub 0}-S{sub 1} energy difference but clearly stabilizes the cis--product. At first sight the results appear to support the idea of a participation of no other electronic states beyond S{sub 0} and first singly {pi}{pi}* excited state in the photoreaction. However, the relevance of this prediction is rather limited because of the small size of the model system. Other states of retinal, corresponding in particular to the partly doubly {pi}{pi}* excited S{sub 2} state of the model, are likely to have a vertical excitation energy similar to the first singly {pi}{pi}* excited state or even below.

  7. Assessing the Accuracy of Various Ab Initio Methods for Geometries and Excitation Energies of Retinal Chromophore Minimal Model by Comparison with CASPT3 Results.

    PubMed

    Grabarek, Dawid; Walczak, Elżbieta; Andruniów, Tadeusz

    2016-05-10

    The effect of the quality of the ground-state geometry on excitation energies in the retinal chromophore minimal model (PSB3) was systematically investigated using various single- (within Møller-Plesset and coupled-cluster frameworks) and multiconfigurational [within complete active space self-consistent field (CASSCF) and CASSCF-based perturbative approaches: second-order CASPT2 and third-order CASPT3] methods. Among investigated methods, only CASPT3 provides geometry in nearly perfect agreement with the CCSD(T)-based equilibrium structure. The second goal of the present study was to assess the performance of the CASPT2 methodology, which is popular in computational spectroscopy of retinals, in describing the excitation energies of low-lying excited states of PSB3 relative to CASPT3 results. The resulting CASPT2 excitation energy error is up to 0.16 eV for the S0 → S1 transition but only up to 0.06 eV for the S0 → S2 transition. Furthermore, CASPT3 excitation energies practically do not depend on modification of the zeroth-order Hamiltonian (so-called IPEA shift parameter), which does dramatically and nonsystematically affect CASPT2 excitation energies. PMID:27049438

  8. Study of the orientation of retinal in bovine rhodopsin: the use of a photoactivatable retinal analog

    SciTech Connect

    Nakayama, T.

    1987-05-01

    Rhodopsin is the major transmembrane protein in the photoreceptor cells of vertebrate and invertebrate retina. Bovine rhodopsin consists of a polypeptide chain of 348 amino acids of known sequence in which the chromophore, 11-cis-retinal, is linked to Lys-296 as a Schiff base. To investigate the orientation of retinal in the protein and to study the interactions between retinal and the protein, the authors have developed a crosslinking approach using a /sup 3/H-labeled photoactivatable analog of retinal. Bleached rhodopsin in rod outer segments was reconstituted with the analog to give a pigment with lambda/sub max/ at 460nm. Reduction of the Schiff base with borane dimenthylamine, followed by degradation with CNBr and sequencing of the radioactive fragment showed that the analog is attached to Lys-296, as in the native rhodopsin. Further, the reconstitute protein after photolysis was phosphorylated by rhodopsin kinase. Photolysis of the reconstituted pigment at -15/sup 0/C resulted in crosslinking of the analog to the opsin to the extent of 30% as analyzed by SDS electrophoresis. The site(s) of crosslinking in the protein are under investigation.

  9. Thermal Stability of Rhodopsin and Progression of Retinitis Pigmentosa

    PubMed Central

    Liu, Monica Yun; Liu, Jian; Mehrotra, Devi; Liu, Yuting; Guo, Ying; Baldera-Aguayo, Pedro A.; Mooney, Victoria L.; Nour, Adel M.; Yan, Elsa C. Y.

    2013-01-01

    Over 100 point mutations in the rhodopsin gene have been associated with retinitis pigmentosa (RP), a family of inherited visual disorders. Among these, we focused on characterizing the S186W mutation. We compared the thermal properties of the S186W mutant with another RP-causing mutant, D190N, and with WT rhodopsin. To assess thermal stability, we measured the rate of two thermal reactions contributing to the thermal decay of rhodopsin as follows: thermal isomerization of 11-cis-retinal and hydrolysis of the protonated Schiff base linkage between the 11-cis-retinal chromophore and opsin protein. We used UV-visible spectroscopy and HPLC to examine the kinetics of these reactions at 37 and 55 °C for WT and mutant rhodopsin purified from HEK293 cells. Compared with WT rhodopsin and the D190N mutant, the S186W mutation dramatically increases the rates of both thermal isomerization and dark state hydrolysis of the Schiff base by 1–2 orders of magnitude. The results suggest that the S186W mutant thermally destabilizes rhodopsin by disrupting a hydrogen bond network at the receptor's active site. The decrease in the thermal stability of dark state rhodopsin is likely to be associated with higher levels of dark noise that undermine the sensitivity of rhodopsin, potentially accounting for night blindness in the early stages of RP. Further studies of the thermal stability of additional pathogenic rhodopsin mutations in conjunction with clinical studies are expected to provide insight into the molecular mechanism of RP and test the correlation between rhodopsin's thermal stability and RP progression in patients. PMID:23625926

  10. Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice*S⃞

    PubMed Central

    Maeda, Akiko; Maeda, Tadao; Golczak, Marcin; Chou, Steven; Desai, Amar; Hoppel, Charles L.; Matsuyama, Shigemi; Palczewski, Krzysztof

    2009-01-01

    Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration. PMID:19304658

  11. Retinal isomer composition in some bacteriorhodopsin mutants under light and dark adaptation conditions

    SciTech Connect

    Song, L.; Yang, D.; El-Sayed, M.A.; Lanyi, J.K.

    1995-06-15

    The isomeric composition of retinal was measured in a number of bacteriorhodopsin (bR) mutants (D85N, D212N, R82A, Y185F, and D115N) under various conditions, using a rapid retinal extraction technique followed by HPLC analysis. Besides the 13-cis and the all-trans retinal isomers observed in wild type (wt) bR under physiological conditions, the 11-cis and 9-cis retinal isomers were observed in variable but minor amounts in the bR mutants. In addition, the values of the equilibrium constant at two temperatures and the enthalpy change for the all-trans to 13-cis isomerization process in the dark-adapted state of D212N, D85N, deionized blue bR, and wt bR were determined. We find that perturbation of the retinal cavity (pocket) by residue replacement changes the relative thermal stability of the different retinal isomers, allowing for thermal-and/or photoisomerization of the retinal chromophore along C{sub 9}-C{sub 10} and C{sub 11}-C{sub 12} bonds to moderately compete with the isomerization around the C{sub 13}-C{sub 14} bond. The bR mutants expressed in Halobacterium salinarium studied in the present work showed normal 13-cis to all-trans light adaptation, in contrast with abnormal all-trans to 13-cis light adaptation observed for D212E, D212A, and D212N expressed in Escherichia coli, suggesting an influence of the purple membrane lattice and/or the lipids on the stability of the different retinal isomers within the protein. 38 refs., 2 tabs.

  12. Molecular mechanism of spontaneous pigment activation in retinal cones.

    PubMed

    Sampath, Alapakkam P; Baylor, Denis A

    2002-07-01

    Spontaneous current and voltage fluctuations (dark noise) in the photoreceptor cells of the retina limit the ability of the visual system to detect dim light. We recorded the dark current noise of individual salamander L cones. Previous work showed that the dark noise in these cells arises from thermal activation of the visual pigment. From the temperature dependence of the rate of occurrence of elementary noise events, we found an Arrhenius activation energy E(a) of 25 +/- 7 kcal/mol (mean +/- SD). This E(a) is similar to that reported for the thermal isomerization of 11-cis retinal in solution, suggesting that the cone pigment noise results from isomerization of the retinal chromophore. E(a) for the cone noise is similar to that previously reported for the "photon-like" noise of rods, but the preexponential factor is five orders of magnitude higher. To test the hypothesis that thermal isomerization can only occur in molecules whose Schiff base linkage is unprotonated, we changed the pH of the solution bathing the cone outer segment. This had little effect on the rate of occurrence of elementary noise events. The rate was also unchanged when the cone was exposed to Ringer solution made up from heavy water, whose solvent isotope effect should reduce the probability, that the Schiff base nitrogen is naked. PMID:12080111

  13. The molecular basis for UV vision in birds: spectral characteristics, cDNA sequence and retinal localization of the UV-sensitive visual pigment of the budgerigar (Melopsittacus undulatus).

    PubMed Central

    Wilkie, S E; Vissers, P M; Das, D; Degrip, W J; Bowmaker, J K; Hunt, D M

    1998-01-01

    Microspectrophotometric (msp) studies have shown that the colour-vision system of many bird species is based on four pigments with absorption peaks in the red, green, blue and UV regions of the spectrum. The existence of a fourth pigment (UV) is the major difference between the trichromacy of humans and the tetrachromacy of such birds, and recent studies have shown that it may play a determining role in such diverse aspects of behaviour as mate selection and detection of food. Avian visual pigments are composed of an opsin protein covalently bound via a Schiff-base linkage to the chromophore 11-cis-retinal. Here we report the cDNA sequence of a UV opsin isolated from an avian species, Melopsittacus undulatus (budgerigar or small parakeet). This sequence has been expressed using the recombinant baculovirus system; the pigment generated from the expressed protein on addition of 11-cis-retinal yielded an absorption spectrum typical of a UV photopigment, with lambdamax 365+/-3 nm. This is the first UV opsin from an avian species to be sequenced and expressed in a heterologous system. In situ hybridization of this sequence to budgerigar retinas selectively labelled a sub-set of UV cones, representing approx. 9% of the total cone population, that are distributed in a semi-regular pattern across the entire retina. PMID:9461554

  14. Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin

    PubMed Central

    Fu, Yingbin; Zhong, Haining; Wang, Min-Hua H.; Luo, Dong-Gen; Liao, Hsi-Wen; Maeda, Hidetaka; Hattar, Samer; Frishman, Laura J.; Yau, King-Wai

    2005-01-01

    In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate non-image-forming visual functions such as pupillary light reflex (PLR) and circadian photoentrainment. This photosensitivity requires melanopsin, an invertebrate opsin-like protein expressed by the ipRGCs. The precise role of melanopsin remains uncertain. One suggestion has been that melanopsin may be a photoisomerase, serving to regenerate an unidentified pigment in ipRGCs. This possibility was echoed by a recent report that melanopsin is expressed also in the mouse retinal pigment epithelium (RPE), a key center for regeneration of rod and cone pigments. To address this question, we studied mice lacking RPE65, a protein essential for the regeneration of rod and cone pigments. Rpe65-/- ipRGCs were ≈20- to 40-fold less photosensitive than normal at both single-cell and behavioral (PLR) levels but were rescued by exogenous 9-cis-retinal (an 11-cis-retinal analog), indicating the requirement of a vitamin A-based chromophore for ipRGC photosensitivity. In contrast, 9-cis-retinal was unable to restore intrinsic photosensitivity to melanopsin-ablated ipRGCs, arguing against melanopsin functioning merely in photopigment regeneration. Interestingly, exogenous all-trans-retinal was also able to rescue the low sensitivity of rpe65-/- ipRGCs, suggesting that melanopsin could be a bistable pigment. Finally, we detected no melanopsin in the RPE and no changes in rod and cone sensitivities due to melanopsin ablation. Together, these results strongly suggest that melanopsin is the photopigment in the ipRGCs. PMID:16014418

  15. Nonadiabatic ab initio dynamics of a model protonated Schiff base of 9-cis retinal.

    PubMed

    Chung, Wilfredo Credo; Nanbu, Shinkoh; Ishida, Toshimasa

    2010-08-19

    The dynamics of the photoisomerization of a model protonated Schiff base of 9-cis retinal in isorhodopsin is investigated using nonadiabatic molecular dynamics simulation combined with ab initio quantum chemical calculations on-the-fly. The quantum chemical part is treated at the complete-active space self-consistent field level for six electrons in six active pi orbitals with the 6-31G basis set (CASSCF(6,6)/6-31G). The probabilities of nonadiabatic transitions between the S(1) ((1)pipi*) and S(0) states are estimated in light of the Zhu-Nakamura theory. The photoinduced cis-trans isomerization of 9-cis retinal proceeds slower than that of its 11-cis analogue and at a lower quantum yield, confirming experimental observations. An energetic barrier in the excited state impedes the elongation and twist of the C(9)=C(10) stretch and torsion coordinates, respectively, resulting in the trapping of trajectories before transition. Consequently, the isomerization takes longer time and the transition more often occurs at smaller twist angle of =C(8)-C(9)=C(10)-C(11)=, which leads to regeneration of the 9-cis reactant. Thus, neither the smaller twist observed in the X-ray crystal nor the slower movement of nuclei in the transition region would be the main reason for the longer reaction time and lower yield. A well-known space-saving asynchronous bicycle pedal or crankshaft photoisomerization mechanism is found to be operational in 9-cis retinal. The simulation in vacuo suggests that the excited-state barrier and the photoisomerization itself are intrinsic properties of the visual chromophore and not triggered mainly by the protein environment that surrounds the chromophore. PMID:20666503

  16. The Origin of Bond Selectivity and Excited-State Reactivity in Retinal Analogues.

    PubMed

    Schapiro, Igor

    2016-05-19

    The effect of different conformations and substitutions on the photoisomerization of a retinal protonated Schiff base model is investigated by nonadiabatic molecular dynamics simulations. Three groups of retinal analogues are studied: (i) conformational isomers, (ii) methyl-substituted retinals, and (iii) C11-C12 bond locked retinals. In total 259 trajectories are calculated in the gas phase starting from different initial conditions. The effect on bond selectivity, the directionality of the isomerization, excited-state lifetime, and product distribution is derived from the ensemble of trajectories. Among the group of four isomers (9-, 11-, 13-cis, and all-trans) the 11-cis analogue is the most selective in terms of isomerizing double bond, while the other three produce a mixture of isomers. However, there is no preference for isomerization directionality and the product formation for the 11-cis isomer. In the group of analogues with different methylation patterns, it is found that a methyl group at position C10 can introduce unidirectionality. This methyl group also speeds the photoisomerization. In case of the analogue that is demethylated at the positions C10 and C13, all trajectories isomerize successfully from cis to trans conformation. The three C11-C12 bond locked retinals are found to have very different properties, which depend on the number of methylene units bridging this bond. The five-membered ring imposes a too-large restriction; hence, all trajectories remain on the excited state in the simulation time of 300 fs. The seven-membered ring is more flexible with preference for isomerization of the C9-C10 bond. Interestingly, the eight-membered ring leads to the fastest isomerization time and full directionality of C11-C12 bond isomerization. The trends observed in these simulations can help to understand whether the effects are intrinsic to the chromophore or are induced by the protein environment, by comparing to the trends from experiment. Furthermore

  17. Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity

    PubMed Central

    Bavik, Claes; Henry, Susan Hayes; Zhang, Yan; Mitts, Kyoko; McGinn, Tim; Budzynski, Ewa; Pashko, Andriy; Lieu, Kuo Lee; Zhong, Sheng; Blumberg, Bruce; Kuksa, Vladimir; Orme, Mark; Scott, Ian; Fawzi, Ahmad; Kubota, Ryo

    2015-01-01

    Increased exposure to blue or visible light, fluctuations in oxygen tension, and the excessive accumulation of toxic retinoid byproducts places a tremendous amount of stress on the retina. Reduction of visual chromophore biosynthesis may be an effective method to reduce the impact of these stressors and preserve retinal integrity. A class of non-retinoid, small molecule compounds that target key proteins of the visual cycle have been developed. The first candidate in this class of compounds, referred to as visual cycle modulators, is emixustat hydrochloride (emixustat). Here, we describe the effects of emixustat, an inhibitor of the visual cycle isomerase (RPE65), on visual cycle function and preservation of retinal integrity in animal models. Emixustat potently inhibited isomerase activity in vitro (IC50 = 4.4 nM) and was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg). Measure of drug effect on the retina by electroretinography revealed a dose-dependent slowing of rod photoreceptor recovery (ED50 = 0.21 mg/kg) that was consistent with the pattern of visual chromophore reduction. In albino mice, emixustat was shown to be effective in preventing photoreceptor cell death caused by intense light exposure. Pre-treatment with a single dose of emixustat (0.3 mg/kg) provided a ~50% protective effect against light-induced photoreceptor cell loss, while higher doses (1–3 mg/kg) were nearly 100% effective. In Abca4-/- mice, an animal model of excessive lipofuscin and retinoid toxin (A2E) accumulation, chronic (3 month) emixustat treatment markedly reduced lipofuscin autofluorescence and reduced A2E levels by ~60% (ED50 = 0.47 mg/kg). Finally, in the retinopathy of prematurity rodent model, treatment with emixustat during the period of ischemia and reperfusion injury produced a ~30% reduction in retinal neovascularization (ED50 = 0.46mg/kg). These data demonstrate the ability of

  18. Rapid thermal tuning of chromophore structure in membrane protein.

    PubMed

    Wang, Jianping; El-Sayed, Mostafa A

    2009-04-01

    We show that the configuration and the optical property of the retinal chromophore in bacteriorhodopsin (bR) can be tuned dynamically from the all-trans configuration to the 13-cis by using a nanosecond laser-induced temperature-jump. The rapid bleach in the visible absorption optical density of retinal has an apparent formation time of ca. 170 ns, whereas the relaxation process finishes within tens of ms. The dynamical transition of retinal from the all-trans to 13-cis species is believed to occur as a result of rapid protein conformational change especially in the vicinity of retinal binding site. Our study reveals the intrinsic dynamical aspect of the retinal chromophore with respect to the protein structure. PMID:19275202

  19. Retinitis Pigmentosa

    MedlinePlus

    ... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... available? Are there any related diseases? What is retinitis pigmentosa? Retinitis pigmentosa (RP) refers to a group of ...

  20. Photosensitivity of 10-substituted visual pigment analogues: detection of a specific secondary opsin-retinal interaction.

    PubMed

    Liu, R S; Crescitelli, F; Denny, M; Matsumoto, H; Asato, A E

    1986-11-01

    The photosensitivities of the bovine rhodopsin and gecko pigment 521 analogues regenerated from C-10-substituted analogues of 11-cis- and 9-cis-retinals were determined by two different methods. A similar reactivity trend was noted for both pigment systems as revealed in the photosensitivity of the gecko pigments and relative quantum yields of the bovine analogues. The 10-fluoro-11-cis photopigments had a photosensitivity less than, but approaching, that of the native (11-cis) visual pigment while the 10-fluoro-9-cis photopigments had a much lower photosensitivity than the parent 9-cis regenerated pigment. The results are interpreted in terms of recently described models of rhodopsin architecture and of the primary molecular reaction of visual pigments to light. The unusually low photoreactivity of the 10-fluoro-9-cis pigment molecule is viewed as the result of a regiospecific hydrogen-bonding interaction of the electronegative fluorine atom to the opsin. PMID:2948555

  1. Bruise chromophore concentrations over time

    NASA Astrophysics Data System (ADS)

    Duckworth, Mark G.; Caspall, Jayme J.; Mappus, Rudolph L., IV; Kong, Linghua; Yi, Dingrong; Sprigle, Stephen H.

    2008-03-01

    During investigations of potential child and elder abuse, clinicians and forensic practitioners are often asked to offer opinions about the age of a bruise. A commonality between existing methods of bruise aging is analysis of bruise color or estimation of chromophore concentration. Relative chromophore concentration is an underlying factor that determines bruise color. We investigate a method of chromophore concentration estimation that can be employed in a handheld imaging spectrometer with a small number of wavelengths. The method, based on absorbance properties defined by Beer-Lambert's law, allows estimation of differential chromophore concentration between bruised and normal skin. Absorption coefficient data for each chromophore are required to make the estimation. Two different sources of this data are used in the analysis- generated using Independent Component Analysis and taken from published values. Differential concentration values over time, generated using both sources, show correlation to published models of bruise color change over time and total chromophore concentration over time.

  2. Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure

    PubMed Central

    Boyer, Nicholas P.; Higbee, Daniel; Currin, Mark B.; Blakeley, Lorie R.; Chen, Chunhe; Ablonczy, Zsolt; Crouch, Rosalie K.; Koutalos, Yiannis

    2012-01-01

    The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4−/− than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane. PMID:22570475

  3. Chromophores with auxochrome-like function

    NASA Technical Reports Server (NTRS)

    Kauffmann, H.

    1985-01-01

    Chromophores exist which can exert an auxochromic effect in addition to their chromophoric one. Styryl and cyan radicals are considered. Numerous chromophores were checked and those with auxochromic functions are described and tabulated.

  4. Explaining the mobility of retinal in activated rhodopsin and opsin.

    PubMed

    Mertz, Blake; Feng, Jun; Corcoran, Conor; Neeley, Brandon

    2015-11-01

    Rhodopsin, the mammalian dim light photoreceptor, is the canonical model for G protein-coupled receptors. Activation of rhodopsin occurs when the covalently bound inverse agonist, retinal, absorbs a photon and undergoes an 11-cis to all-trans isomerization. Two critical components of the visual cycle occur with the (1) hydrolytic release of all-trans retinaldehyde and subsequent (2) uptake of 11-cis retinaldehyde to reform the Schiff base linkage in the apoprotein opsin. Two pores on the surface of opsin are connected via the retinal channel, as discovered upon solution of the X-ray crystal structure (Park et al., Nature, 2008), and could serve as potential entryways for uptake and release. Using molecular dynamics simulations, we examined the behavior of rhodopsin in the Meta-II conformation (active) under Meta-I conditions (inactive), and discovered that the retinal binding pocket is flexible enough to allow a 180° rotation along the long axis of the retinal polyene chain. This result reconciles a discrepancy between the known polyene chain orientation from crystallographic and spectroscopic studies and opens the door for further investigation into the intermolecular interactions between the retinal ligand and the apoprotein opsin. Subsequent docking studies of both isomers of retinal into the opsin channel were then conducted to identify the mechanism for uptake and release. Our results suggest that retinal undergoes unidirectional uptake through Pore A and release through Pore B, and that aromatic sidechain interactions play a key role in stabilizing retinal within the opsin channel. These findings are significant in developing our understanding of the retinoid cycle and how ligand-receptor interactions in rhodopsin relate to G protein-coupled receptor activation. PMID:26248892

  5. Assessment of Approximate Coupled-Cluster and Algebraic-Diagrammatic-Construction Methods for Ground- and Excited-State Reaction Paths and the Conical-Intersection Seam of a Retinal-Chromophore Model.

    PubMed

    Tuna, Deniz; Lefrancois, Daniel; Wolański, Łukasz; Gozem, Samer; Schapiro, Igor; Andruniów, Tadeusz; Dreuw, Andreas; Olivucci, Massimo

    2015-12-01

    As a minimal model of the chromophore of rhodopsin proteins, the penta-2,4-dieniminium cation (PSB3) poses a challenging test system for the assessment of electronic-structure methods for the exploration of ground- and excited-state potential-energy surfaces, the topography of conical intersections, and the dimensionality (topology) of the branching space. Herein, we report on the performance of the approximate linear-response coupled-cluster method of second order (CC2) and the algebraic-diagrammatic-construction scheme of the polarization propagator of second and third orders (ADC(2) and ADC(3)). For the ADC(2) method, we considered both the strict and extended variants (ADC(2)-s and ADC(2)-x). For both CC2 and ADC methods, we also tested the spin-component-scaled (SCS) and spin-opposite-scaled (SOS) variants. We have explored several ground- and excited-state reaction paths, a circular path centered around the S1/S0 surface crossing, and a 2D scan of the potential-energy surfaces along the branching space. We find that the CC2 and ADC methods yield a different dimensionality of the intersection space. While the ADC methods yield a linear intersection topology, we find a conical intersection topology for the CC2 method. We present computational evidence showing that the linear-response CC2 method yields a surface crossing between the reference state and the first response state featuring characteristics that are expected for a true conical intersection. Finally, we test the performance of these methods for the approximate geometry optimization of the S1/S0 minimum-energy conical intersection and compare the geometries with available data from multireference methods. The present study provides new insight into the performance of linear-response CC2 and polarization-propagator ADC methods for molecular electronic spectroscopy and applications in computational photochemistry. PMID:26642989

  6. Human cellular retinaldehyde-binding protein has secondary thermal 9-cis-retinal isomerase activity.

    PubMed

    Bolze, Christin S; Helbling, Rachel E; Owen, Robin L; Pearson, Arwen R; Pompidor, Guillaume; Dworkowski, Florian; Fuchs, Martin R; Furrer, Julien; Golczak, Marcin; Palczewski, Krzysztof; Cascella, Michele; Stocker, Achim

    2014-01-01

    Cellular retinaldehyde-binding protein (CRALBP) chaperones 11-cis-retinal to convert opsin receptor molecules into photosensitive retinoid pigments of the eye. We report a thermal secondary isomerase activity of CRALBP when bound to 9-cis-retinal. UV/vis and (1)H NMR spectroscopy were used to characterize the product as 9,13-dicis-retinal. The X-ray structure of the CRALBP mutant R234W:9-cis-retinal complex at 1.9 Å resolution revealed a niche in the binding pocket for 9-cis-aldehyde different from that reported for 11-cis-retinal. Combined computational, kinetic, and structural data lead us to propose an isomerization mechanism catalyzed by a network of buried waters. Our findings highlight a specific role of water molecules in both CRALBP-assisted specificity toward 9-cis-retinal and its thermal isomerase activity yielding 9,13-dicis-retinal. Kinetic data from two point mutants of CRALBP support an essential role of Glu202 as the initial proton donor in this isomerization reaction. PMID:24328211

  7. Cytomegalovirus retinitis

    MedlinePlus

    ... to prevent its return. Alternative Names Cytomegalovirus retinitis Images Eye CMV retinitis CMV (cytomegalovirus) References Crumpacker CS. ... 5. Read More Antibody HIV/AIDS Immune response Retinal detachment Systemic WBC count Update Date 12/10/ ...

  8. Human infrared vision is triggered by two-photon chromophore isomerization

    PubMed Central

    Palczewska, Grazyna; Vinberg, Frans; Stremplewski, Patrycjusz; Bircher, Martin P.; Salom, David; Komar, Katarzyna; Zhang, Jianye; Cascella, Michele; Wojtkowski, Maciej; Kefalov, Vladimir J.; Palczewski, Krzysztof

    2014-01-01

    Vision relies on photoactivation of visual pigments in rod and cone photoreceptor cells of the retina. The human eye structure and the absorption spectra of pigments limit our visual perception of light. Our visual perception is most responsive to stimulating light in the 400- to 720-nm (visible) range. First, we demonstrate by psychophysical experiments that humans can perceive infrared laser emission as visible light. Moreover, we show that mammalian photoreceptors can be directly activated by near infrared light with a sensitivity that paradoxically increases at wavelengths above 900 nm, and display quadratic dependence on laser power, indicating a nonlinear optical process. Biochemical experiments with rhodopsin, cone visual pigments, and a chromophore model compound 11-cis-retinyl-propylamine Schiff base demonstrate the direct isomerization of visual chromophore by a two-photon chromophore isomerization. Indeed, quantum mechanics modeling indicates the feasibility of this mechanism. Together, these findings clearly show that human visual perception of near infrared light occurs by two-photon isomerization of visual pigments. PMID:25453064

  9. Chromophores in lignin-free cellulosic materials belong to three compound classes. Chromophores in cellulosics, XII

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The CRI (chromophore release and identification) method isolates well-defined chromophoric substances from different cellulosic matrices, such as highly bleached pulps, cotton linters, bacterial cellulose, viscose or lyocell fibers, and cellulose acetates. The chromophores are present only in extrem...

  10. Search for Singlet Fission Chromophores

    SciTech Connect

    Havlas, Z.; Akdag, A.; Smith, M. B.; Dron, P.; Johnson, J. C.; Nozik, A. J.; Michl, J.

    2012-01-01

    Singlet fission, in which a singlet excited chromophore shares its energy with a ground-state neighbor and both end up in their triplet states, is of potential interest for solar cells. Only a handful of compounds, mostly alternant hydrocarbons, are known to perform efficiently. In view of the large number of conditions that a successful candidate for a practical cell has to meet, it appears desirable to extend the present list of high performers to additional classes of compounds. We have (i) identified design rules for new singlet fission chromophores and for their coupling to covalent dimers, (ii) synthesized them, and (iii) evaluated their performance as neat solids or covalent dimers.

  11. Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Carr, Ronald E.

    1979-01-01

    The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

  12. Synthesis of polycarbonates containing nonlinear optical chromophores

    SciTech Connect

    Moore, C.G.; Brittain, W.J.

    1995-12-31

    A new nonlinear (NLO) chromophore has been prepared. The chromophore is similar in structure to DANS (N,N-dimethylamino-4-nitrostilbene), but includes bisphenol moities. The bisphenol structure makes this system an excellent candidate for cyclic polycarbonate chemistry. The ring-opening polymerization of cyclic precursors containing NLO chromophore provides a novel processing pathway to NLO polymers.

  13. Theoretical prediction of nuclear magnetic shieldings and indirect spin-spin coupling constants in 1,1-, cis-, and trans-1,2-difluoroethylenes

    SciTech Connect

    Nozirov, Farhod E-mail: farhod.nozirov@gmail.com; Stachów, Michał; Kupka, Teobald E-mail: farhod.nozirov@gmail.com

    2014-04-14

    A theoretical prediction of nuclear magnetic shieldings and indirect spin-spin coupling constants in 1,1-, cis- and trans-1,2-difluoroethylenes is reported. The results obtained using density functional theory (DFT) combined with large basis sets and gauge-independent atomic orbital calculations were critically compared with experiment and conventional, higher level correlated electronic structure methods. Accurate structural, vibrational, and NMR parameters of difluoroethylenes were obtained using several density functionals combined with dedicated basis sets. B3LYP/6-311++G(3df,2pd) optimized structures of difluoroethylenes closely reproduced experimental geometries and earlier reported benchmark coupled cluster results, while BLYP/6-311++G(3df,2pd) produced accurate harmonic vibrational frequencies. The most accurate vibrations were obtained using B3LYP/6-311++G(3df,2pd) with correction for anharmonicity. Becke half and half (BHandH) density functional predicted more accurate {sup 19}F isotropic shieldings and van Voorhis and Scuseria's τ-dependent gradient-corrected correlation functional yielded better carbon shieldings than B3LYP. A surprisingly good performance of Hartree-Fock (HF) method in predicting nuclear shieldings in these molecules was observed. Inclusion of zero-point vibrational correction markedly improved agreement with experiment for nuclear shieldings calculated by HF, MP2, CCSD, and CCSD(T) methods but worsened the DFT results. The threefold improvement in accuracy when predicting {sup 2}J(FF) in 1,1-difluoroethylene for BHandH density functional compared to B3LYP was observed (the deviations from experiment were −46 vs. −115 Hz)

  14. Molecular pharmacodynamics of emixustat in protection against retinal degeneration.

    PubMed

    Zhang, Jianye; Kiser, Philip D; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P; Palczewski, Krzysztof

    2015-07-01

    Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. PMID:26075817

  15. Molecular pharmacodynamics of emixustat in protection against retinal degeneration

    PubMed Central

    Zhang, Jianye; Kiser, Philip D.; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P.; Palczewski, Krzysztof

    2015-01-01

    Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. PMID:26075817

  16. Retinal degeneration in animal models with a defective visual cycle.

    PubMed

    Maeda, Akiko; Palczewski, Krzysztof

    2013-01-01

    Continuous generation of visual chromophore through the visual (retinoid) cycle is essential to maintain eyesight and retinal heath. Impairments in this cycle and related pathways adversely affect vision. In this review, we summarize the chemical reactions of vitamin A metabolites involved in the retinoid cycle and describe animal models of associated human diseases. Development of potential therapies for retinal disorders in these animal models is also introduced. PMID:25210527

  17. Retinal degeneration in animal models with a defective visual cycle

    PubMed Central

    Maeda, Akiko; Palczewski, Krzysztof

    2014-01-01

    Continuous generation of visual chromophore through the visual (retinoid) cycle is essential to maintain eyesight and retinal heath. Impairments in this cycle and related pathways adversely affect vision. In this review, we summarize the chemical reactions of vitamin A metabolites involved in the retinoid cycle and describe animal models of associated human diseases. Development of potential therapies for retinal disorders in these animal models is also introduced. PMID:25210527

  18. Chromophore/protein and chromophore/anion interactions in halorhodopsin.

    PubMed Central

    Lanyi, J K; Zimányi, L; Nakanishi, K; Derguini, F; Okabe, M; Honig, B

    1988-01-01

    Halorhodopsin (HR), the light-driven chloride transport pigment of Halobacterium halobium, was bleached and reconstituted with retinal analogues with the pi electron system interrupted at different locations (dihydroretinals). The absorption maxima of the artificial pigments formed with the dihydroretinals are found to be very similar to those of the corresponding pigments formed by reconstitution of bacteriorhodopsin (BR) and sensory rhodopsin (SR). This strongly suggests that the distribution of charges around the retinal is similar in all three bacterial rhodopsins. Comparison of the primary, and proposed secondary, structures for HR and BR reveal conserved asparagine (asp) and arginine (arg) residues, which are likely candidates for the ionizable amino acids that interact with the retinal. In a second set of experiments absorption shifts due to the binding of anions to Sites I and II in HR, reconstituted with different retinal analogues, were used to estimate the locations of these binding sites relative to the retinal. Site I is localized near the Schiff base, and Site II near the ionone ring. On the basis of these results a structural model for HR is proposed, which accounts for the spectroscopic properties of HR in terms of the three buried arg residues and two of the buried asp residues in the protein. PMID:3345330

  19. Chromophore-enhanced bacterial photothermolysis

    NASA Astrophysics Data System (ADS)

    Huckleby, Jana K.; Morton, Rebecca J.; Bartels, Kenneth E.

    1999-06-01

    The use of chromophore dyes to enhance the bactericidal effect of laser energy was studied as a means to optimize laser treatment for the decontamination of wound. Using an in vitro study, various concentrations of indocyanine green (ICG), carbon black, and fluorescein were mixed with a suspension of bacteria and plated on tryptic soy agar. Plates were exposed to a laser beam of 10-15 watts for times ranging from 0 to 180 seconds, incubated overnight, and colony counts were performed. Bacteria not mixed with chromophore were used as controls. Six bacterial strains encompassing a range of bacterial types were used: Staphylococcus aureau, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus spore suspensions, and Clostridium perfringens. Laser treatment alone had no effect on any of the bacteria. Significant killing of gram-positive bacteria, including spores of Bacillus cereus, was observed only with the use of ICG and diode laser energy. No effect was observed using any of the chromophores on the gram-negative bacteria. The results of this study indicate that successful killing of gram-positive bacteria can be achieved using ICG combined with appropriate laser energy and wavelength. Efforts to enhance the susceptibility of gram-negative bacteria to photothermolysis by laser energy were unsuccessful.

  20. Chromophores in cellulosics, VI. First isolation and identification of residual chromophores from aged cotton linters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present work, aged cotton linters have been analyzed for their chromophore content according to the CRI (“chromophore release & identification”) method. Despite the very low contents in the ppb range, nine chromophores have been unambiguously identified, which makes this account the first one...

  1. Biliprotein maturation: the chromophore attachment

    PubMed Central

    Scheer, H; Zhao, K-H

    2008-01-01

    Biliproteins are a widespread group of brilliantly coloured photoreceptors characterized by linear tetrapyrrolic chromophores, bilins, which are covalently bound to the apoproteins via relatively stable thioether bonds. Covalent binding stabilizes the chromoproteins and is mandatory for phycobilisome assembly; and, it is also important in biliprotein applications such as fluorescence labelling. Covalent binding has, on the other hand, also considerably hindered biliprotein research because autocatalytic chromophore additions are rare, and information on enzymatic addition by lyases was limited to a single example, an EF-type lyase attaching phycocyanobilin to cysteine-α84 of C-phycocyanin. The discovery of new activities for the latter lyases, and of new types of lyases, have reinvigorated research activities in the subject. So far, work has mainly concentrated on cyanobacterial phycobiliproteins. Methodological advances in the process, however, as well as the finding of often large numbers of homologues, opens new possibilities for research on the subsequent assembly/disassembly of the phycobilisome in cyanobacteria and red algae, on the assembly and organization of the cryptophyte light-harvesting system, on applications in basic research such as protein folding, and on the use of phycobiliproteins for labelling. PMID:18284595

  2. Retinal Prosthesis

    PubMed Central

    Weiland, James D.; Humayun, Mark S.

    2015-01-01

    Retinal prosthesis have been translated from the laboratory to the clinical over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration and patients use this improved vision in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This paper reviews the recent clinical trials, highlights technology breakthroughs that will contribute to next generation of retinal prostheses. PMID:24710817

  3. Foveomacular retinitis.

    PubMed Central

    Kuming, B S

    1986-01-01

    A group of patients is described who developed the clinical features of foveomacular retinitis. No causative factors were isolated, and all patients strongly denied any type of sun gazing. It is possible that there is a group of patients who have the features of foveomacular retinitis but have not had any direct exposure to the sun. These patients would then constitute a primary type of foveomacular retinitis, as opposed to a secondary type which has a known cause and is synonymous with solar retinopathy. Images PMID:3790482

  4. Retinal Disorders

    MedlinePlus

    ... be serious enough to cause blindness. Examples are Macular degeneration - a disease that destroys your sharp, central vision Diabetic eye disease Retinal detachment - a medical emergency, when the retina is ... children. Macular pucker - scar tissue on the macula Macular hole - ...

  5. Retinal Detachment

    MedlinePlus

    ... immediately. Treatment How is retinal detachment treated? Small holes and tears are treated with laser surgery or ... laser surgery tiny burns are made around the hole to “weld” the retina back into place. Cryopexy ...

  6. Mode damping rates in a protein chromophore

    NASA Astrophysics Data System (ADS)

    Leitner, David M.

    2012-03-01

    A variety of optical studies reveal coherent low-frequency oscillations during photochemical reactions in proteins. We recently argued [New J. Phys. 12, Art. No. 085004 (2010)] that the vibrational eigenstates of an isolated chromophore may be localized, which can give rise to long-lived low-frequency vibrational modes when the chromophore is embedded in a protein. Here we show that, even if vibrational eigenstates are not localized, bottlenecks to vibrational energy flow that are absent in much larger molecules give rise to slow damping of low-frequency modes in many protein chromophores. Examples including rhodopsin, photoactive yellow protein and green fluorescent protein are discussed.

  7. Retinal pathways influence temporal niche

    PubMed Central

    Doyle, Susan E.; Yoshikawa, Tomoko; Hillson, Holly; Menaker, Michael

    2008-01-01

    In mammals, light input from the retina entrains central circadian oscillators located in the suprachiasmatic nuclei (SCN). The phase of circadian activity rhythms with respect to the external light:dark cycle is reversed in diurnal and nocturnal species, although the phase of SCN rhythms relative to the light cycle remains unchanged. Neural mechanisms downstream from the SCN are therefore believed to determine diurnality or nocturnality. Here, we report a switch from nocturnal to diurnal entrainment of circadian activity rhythms in double-knockout mice lacking the inner-retinal photopigment melanopsin (OPN4) and RPE65, a key protein used in retinal chromophore recycling. These mice retained only a small amount of rod function. The change in entrainment phase of Rpe65−/−;Opn4−/− mice was accompanied by a reversal of the rhythm of clock gene expression in the SCN and a reversal in acute masking effects of both light and darkness on activity, suggesting that the nocturnal to diurnal switch is due to a change in the neural response to light upstream from the SCN. A switch from nocturnal to diurnal activity rhythms was also found in wild-type mice transferred from standard intensity light:dark cycles to light:dark cycles in which the intensity of the light phase was reduced to scotopic levels. These results reveal a novel mechanism by which changes in retinal input can mediate acute temporal-niche switching. PMID:18695249

  8. Vibrational spectroscopy of bacteriorhodopsin mutants: Evidence for the interaction of proline-186 with the retinylidene chromophore

    SciTech Connect

    Rothschild, K.J.; He, Y.W.; Mogi, T.; Marti, T.; Stern, L.J.; Khorana, H.G. )

    1990-06-26

    Fourier-transform infrared difference spectroscopy has been used to study the role of the three membrane-embedded proline residues, Pro-50, Pro-91, and Pro-186, in the structure and function of bacteriorhodopsin. All three prolines were replaced by alanine and glycine; in addition, Pro-186 was changed to valine. Difference spectra were recorded for the bR----K and bR----M photoreactions of each of these mutants and compared to those of wild-type bacteriorhodopsin. Only substitutions of Pro-186 caused significant perturbations in the frequency of the C = C and C - C stretching modes of the retinylidene chromophore. In addition, these substitutions reduced bands in the amide I and II region associated with secondary structural changes and altered signals assigned to the adjacent Tyr-185. Pro-186----Val caused the largest alterations, producing a second species similar to bR548 and nearly blocking chromophore isomerization at 78 K but not at 250 K. These results are consistent with a model of the retinal binding site in which Pro-186 and Tyr-185 are located in direct proximity to the chromophore and may be involved in linking chromophore isomerization to protein structural changes. Evidence is also found that Pro-50 may be structurally active during the bR----K transition and that substitution of this residue by glycine preserves the normal protein structural changes during the photocycle.

  9. Beyond spectral tuning: human cone visual pigments adopt different transient conformations for chromophore regeneration.

    PubMed

    Srinivasan, Sundaramoorthy; Cordomí, Arnau; Ramon, Eva; Garriga, Pere

    2016-03-01

    Human red and green visual pigments are seven transmembrane receptors of cone photoreceptor cells of the retina that mediate color vision. These pigments share a very high degree of homology and have been assumed to feature analogous structural and functional properties. We report on a different regeneration mechanism among red and green cone opsins with retinal analogs using UV-Vis/fluorescence spectroscopic analyses, molecular modeling and site-directed mutagenesis. We find that photoactivated green cone opsin adopts a transient conformation which regenerates via an unprotonated Schiff base linkage with its natural chromophore, whereas red cone opsin forms a typical protonated Schiff base. The chromophore regeneration kinetics is consistent with a secondary retinal uptake by the cone pigments. Overall, our findings reveal, for the first time, structural differences in the photoactivated conformation between red and green cone pigments that may be linked to their molecular evolution, and support the proposal of secondary retinal binding to visual pigments, in addition to binding to the canonical primary site, which may serve as a regulatory mechanism of dark adaptation in the phototransduction process. PMID:26387074

  10. Fluorescence imaging using synthetic GFP chromophores.

    PubMed

    Walker, Christopher L; Lukyanov, Konstantin A; Yampolsky, Ilia V; Mishin, Alexander S; Bommarius, Andreas S; Duraj-Thatte, Anna M; Azizi, Bahareh; Tolbert, Laren M; Solntsev, Kyril M

    2015-08-01

    Green fluorescent protein and related proteins carry chromophores formed within the protein from their own amino acids. Corresponding synthetic compounds are non-fluorescent in solution due to photoinduced isomerization of the benzylideneimidiazolidinone core. Restriction of this internal rotation by binding to host molecules leads to pronounced, up to three orders of magnitude, increase of fluorescence intensity. This property allows using GFP chromophore analogs as fluorogenic dyes to detect metal ions, proteins, nucleic acids, and other hosts. For example, RNA aptamer named Spinach, which binds to and activates fluorescence of some GFP chromophores, was proved to be a unique label for live-cell imaging of specific RNAs, endogenous metabolites and target proteins. Chemically locked GFP chromophores are brightly fluorescent and represent potentially useful dyes due to their small size and high water solubility. PMID:26117808

  11. Retinal detachment

    MedlinePlus

    ... of the first symptoms of new flashes of light and floaters. ... diabetes. See your eye care specialist once a year. You may need more frequent visits if you have risk factors for retinal detachment. Be alert to symptoms of new flashes of light and floaters.

  12. First hyperpolarizability of bacteriorhodopsin, retinal and related molecules revisited

    NASA Astrophysics Data System (ADS)

    Ghosh, Sampa; Ranjini, Arumugam Sri; Pandey, Ravindra; Das, Puspendu Kumar

    2009-06-01

    The previously reported β values of BR and retinal based chromophores were very high but subsequent measurements found them to be much less. We have found that the β values of these compounds do not vary so much with experimental conditions as with the method of analysis. Hyper-Rayleigh scattering measurements at 1543 and 1907 nm produce more realistic β values close to the intrinsic (static) hyperpolarizability, β0 which for BR is still very high (275 × 10 -30 esu). The optical nonlinearity of BR arises entirely due to the protonated retinal Schiff Base (PRSB) which in its isolated form has the same intrinsic hyperpolarizability as that of the protein.

  13. Retinal Detachment Vision Simulator

    MedlinePlus

    ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment Vision Simulator Mar. 01, 2016 How does a detached or torn retina affect your vision? If a retinal tear is occurring, you may ...

  14. Biophotons Contribute to Retinal Dark Noise.

    PubMed

    Li, Zehua; Dai, Jiapei

    2016-06-01

    The discovery of dark noise in retinal photoreceptors resulted in a long-lasting controversy over its origin and the underlying mechanisms. Here, we used a novel ultra-weak biophoton imaging system (UBIS) to detect biophotonic activity (emission) under dark conditions in rat and bullfrog (Rana catesbeiana) retinas in vitro. We found a significant temperature-dependent increase in biophotonic activity that was completely blocked either by removing intracellular and extracellular Ca(2+) together or inhibiting phosphodiesterase 6. These findings suggest that the photon-like component of discrete dark noise may not be caused by a direct contribution of the thermal activation of rhodopsin, but rather by an indirect thermal induction of biophotonic activity, which then activates the retinal chromophore of rhodopsin. Therefore, this study suggests a possible solution regarding the thermal activation energy barrier for discrete dark noise, which has been debated for almost half a century. PMID:27059222

  15. Rapid Retinal Release from a Cone Visual Pigment Following Photoactivation*

    PubMed Central

    Chen, Min-Hsuan; Kuemmel, Colleen; Birge, Robert R.; Knox, Barry E.

    2012-01-01

    As part of the visual cycle, the retinal chromophore in both rod and cone visual pigments undergoes reversible Schiff base hydrolysis and dissociation following photobleaching. We characterized light-activated retinal release from a short-wavelength sensitive cone pigment (VCOP) in 0.1% dodecyl maltoside using fluorescence spectroscopy. The half-time (t1/2) of retinal release from VCOP was 7.1 s, 250-fold faster than rhodopsin. VCOP exhibited pH-dependent release kinetics, with the t1/2 decreasing from 23 s to 4 s with pH 4.1 to 8, respectively. However, the Arrhenius activation energy (Ea) for VCOP derived from kinetic measurements between 4° and 20°C was 17.4 kcal/mol, similar to 18.5 kcal/mol for rhodopsin. There was a small kinetic isotope (D2O) effect in VCOP, but less than that observed in rhodopsin. Mutation of the primary Schiff base counterion (VCOPD108A) produced a pigment with an unprotonated chromophore (⌊max = 360 nm) and dramatically slowed (t1/2 ~ 6.8 min) light-dependent retinal release. Using homology modeling, a VCOP mutant with two substitutions (S85D/ D108A) was designed to move the counterion one alpha helical turn into the transmembrane region from the native position. This double mutant had a UV-visible absorption spectrum consistent with a protonated Schiff base (⌊max = 420 nm). Moreover, VCOPS85D/D108A mutant had retinal release kinetics (t1/2 = 7 s) and Ea (18 kcal/mol) similar to the native pigment exhibiting no pH-dependence. By contrast, the single mutant VCOPS85D had a ~3-fold decrease in retinal release rate compared to the native pigment. Photoactivated VCOPD108A had kinetics comparable to a rhodopsin counterion mutant, RhoE113Q, both requiring hydroxylamine to fully release retinal. These results demonstrate that the primary counterion of cone visual pigments is necessary for efficient Schiff base hydrolysis. We discuss how the large differences in retinal release rates between rod and cone visual pigments arise, not from

  16. Fluorescence and excited state dynamics of the deprotonated Schiff base retinal in proteorhodopsin.

    PubMed

    Bühl, Elena; Braun, Markus; Lakatos, Andrea; Glaubitz, Clemens; Wachtveitl, Josef

    2015-09-01

    The UV light absorbing species of proteorhodopsin with deprotonated Schiff base retinal was investigated using steady-state fluorescence and femtosecond pump-probe spectroscopy. Compared to the all-trans retinal with protonated Schiff base, the deprotonated chromophore absorbs at 365 nm and exhibits a blue-shifted fluorescence spectrum. The unusually long-lived excited state decays bi-exponentially with time constants of 8 ps and 130 ps to form a deprotonated 13-cis retinal as the primary photo-product. PMID:26083266

  17. Molecular Selectivity of Brown Carbon Chromophores

    SciTech Connect

    Laskin, Julia; Laskin, Alexander; Nizkorodov, Sergey; Roach, Patrick J.; Eckert, Peter A.; Gilles, Mary K.; Wang, Bingbing; Lee, Hyun Ji; Hu, Qichi

    2014-10-21

    Complementary methods of high-resolution mass spectrometry and micro-spectroscopy were utilized for molecular analysis of secondary organic aerosol (SOA) generated from ozonolysis of two structural monoterpene isomers: D-limonene (LSOA) and a-pinene (PSOA). Laboratory simulated aging of LSOA and PSOA, through conversion of carbonyls into imines mediated by NH3 vapors in humid air, resulted in selective browning of the LSOA sample, while the PSOA sample remained white. Comparative analysis of the reaction products in the aged LSOA and PSOA samples provided insights into chemistry relevant to formation of brown carbon chromophores. A significant fraction of carbonyl-imine conversion products with identical molecular formulas were detected in both samples. This reflects the high level of similarity in the molecular composition of these two closely related SOA materials. Several highly conjugated products were detected exclusively in the brown LSOA sample and were identified as potential chromophores responsible for the observed color change. The majority of the unique products in the aged LSOA sample with the highest number of double bonds contain two nitrogen atoms. We conclude that chromophores characteristic of the carbonyl- imine chemistry in LSOA are highly conjugated oligomers of secondary imines (Schiff bases) present at relatively low concentrations. Formation of this type of conjugated compounds in PSOA is hindered by the structural rigidity of the a-pinene oxidation products. Our results suggest that the overall light-absorbing properties of SOA may be determined by trace amounts of strong brown carbon chromophores.

  18. Vibronic interactions in multi-chromophores

    NASA Astrophysics Data System (ADS)

    Slipchenko, Lyudmila

    2015-03-01

    Understanding and control of excitation energy transfer and electron-phonon interactions is quintessential for advances in solar energy utilization. Recently, we developed a vibronic model that is capable of predicting vibronic spectra in complex multi-chromophore systems. Parameters to the model are obtained from electronic structure calculations on monomer units of a multi-chromophore. This model can account for multiple vibrational modes, asymmetric wave functions, and inter-chromophore vibrations. Using this model, we explored vibronic spectra in a series of flexible bichromophores with available high-resolution experimental spectra. One of the goals of this work was to understand the effects of asymmetry in monomer units on vibronic interactions in bichromophores. Detailed investigation of diphenylmethane, partially deuterated diphenylmethane, and diphenylethane resulted in intriguing observation that asymmetry leads to a partial localization of one of the exciton states but leaves the other one delocalized. Extension of the developed methodology to modeling spectroscopy and dynamics in synthetic and biological multi-chromophore systems such as photosynthetic proteins will be also discussed.

  19. Tuning the Protein-Induced Absorption Shifts of Retinal in Engineered Rhodopsin Mimics.

    PubMed

    Suomivuori, Carl-Mikael; Lang, Lucas; Sundholm, Dage; Gamiz-Hernandez, Ana P; Kaila, Ville R I

    2016-06-01

    Rational design of light-capturing properties requires understanding the molecular and electronic structure of chromophores in their native chemical or biological environment. We employ here large-scale quantum chemical calculations to study the light-capturing properties of retinal in recently designed human cellular retinol binding protein II (hCRBPII) variants (Wang et al. Science, 2012, 338, 1340-1343). Our calculations show that these proteins absorb across a large part of the visible spectrum by combined polarization and electrostatic effects. These effects stabilize the ground or excited state energy levels of the retinal by perturbing the Schiff-base or β-ionone moieties of the chromophore, which in turn modulates the amount of charge transfer within the molecule. Based on the predicted tuning principles, we design putative in silico mutations that further shift the absorption properties of retinal in hCRBPII towards the ultraviolet and infrared regions of the spectrum. PMID:27120137

  20. Breaking the Covalent Bond—A Pigment Property that Contributes to Desensitization in Cones

    PubMed Central

    Kefalov, Vladimir J.; Estevez, Maureen E.; Kono, Massahiro; Goletz, Patrice W.; Crouch, Rosalie K.; Cornwall, M. Carter; Yau, King-Wai

    2010-01-01

    Summary Retinal rod and cone pigments consist of an apoprotein, opsin, covalently linked to a chromophore, 11-cis retinal. Here we demonstrate that the formation of the covalent bond between opsin and 11-cis retinal is reversible in darkness in amphibian red cones, but essentially irreversible in red rods. This dissociation, apparently a general property of cone pigments, results in a surprisingly large amount of free opsin—about 10% of total opsin—in dark-adapted red cones. We attribute this significant level of free opsin to the low concentration of intracellular free 11-cis retinal, estimated to be only a tiny fraction (~0.1 %) of the pigment content in red cones. With its constitutive transducin-stimulating activity, the free cone opsin produces an ~2-fold desensitization in red cones, equivalent to that produced by a steady light causing 500 photoisomerizations s−1. Cone pigment dissociation therefore contributes to the sensitivity difference between rods and cones. PMID:15953417

  1. Branch retinal vein occlusion.

    PubMed

    Hamid, Sadaf; Mirza, Sajid Ali; Shokh, Ishrat

    2008-01-01

    Retinal vein occlusions (RVO) are the second commonest sight threatening vascular disorder. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are the two basic types of vein occlusion. Branch retinal vein occlusion is three times more common than central retinal vein occlusion and- second only to diabetic retinopathy as the most common retinal vascular cause of visual loss. The origin of branch retinal vein occlusion undoubtedly includes both systemic factors such as hypertension and local anatomic factors such as arteriovenous crossings. Branch retinal vein occlusion causes a painless decrease in vision, resulting in misty or distorted vision. Current treatment options don't address the underlying aetiology of branch retinal vein occlusion. Instead they focus on treating sequelae of the occluded venous branch, such as macular oedema, vitreous haemorrhage and traction retinal detachment from neovascularization. Evidences suggest that the pathogenesis of various types of retinal vein occlusion, like many other ocular vascular occlusive disorders, is a multifactorial process and there is no single magic bullet that causes retinal vein occlusion. A comprehensive management of patients with retinal vascular occlusions is necessary to correct associated diseases or predisposing abnormalities that could lead to local recurrences or systemic event. Along with a review of the literature, a practical approach for the management of retinal vascular occlusions is required, which requires collaboration between the ophthalmologist and other physicians: general practitioner, cardiologist, internist etc. as appropriate according to each case. PMID:19385476

  2. Molecular selectivity of brown carbon chromophores.

    PubMed

    Laskin, Julia; Laskin, Alexander; Nizkorodov, Sergey A; Roach, Patrick; Eckert, Peter; Gilles, Mary K; Wang, Bingbing; Lee, Hyun Ji Julie; Hu, Qichi

    2014-10-21

    Complementary methods of high-resolution mass spectrometry and microspectroscopy were utilized for molecular analysis of secondary organic aerosol (SOA) generated from ozonolysis of two structural monoterpene isomers: D-limonene SOA (LSOA) and α-pinene SOA (PSOA). The LSOA compounds readily formed adducts with Na(+) under electrospray ionization conditions, with only a small fraction of compounds detected in the protonated form. In contrast, a significant fraction of PSOA compounds appeared in the protonated form because of their increased molecular rigidity. Laboratory simulated aging of LSOA and PSOA, through conversion of carbonyls into imines mediated by NH3 vapors in humid air, resulted in selective browning of the LSOA sample, while the PSOA sample remained white. Comparative analysis of the reaction products in the aged LSOA and PSOA samples provided insights into chemistry relevant to formation of brown carbon chromophores. A significant fraction of carbonyl-imine conversion products with identical molecular formulas was detected in both samples. This reflects the high level of similarity in the molecular composition of these two closely related SOA materials. Several highly conjugated products were detected exclusively in the brown LSOA sample and were identified as potential chromophores responsible for the observed color change. The majority of the unique products in the aged LSOA sample with the highest number of double bonds contain two nitrogen atoms. We conclude that chromophores characteristic of the carbonyl-imine chemistry in LSOA are highly conjugated oligomers of secondary imines (Schiff bases) present at relatively low concentrations. Formation of this type of conjugated compounds in PSOA is hindered by the structural rigidity of the α-pinene oxidation products. Our results suggest that the overall light-absorbing properties of SOA may be determined by trace amounts of strong brown carbon chromophores. PMID:25233355

  3. Molecular physiology of rhodopsin: Computer simulation

    NASA Astrophysics Data System (ADS)

    Fel'Dman, T. B.; Kholmurodov, Kh. T.; Ostrovsky, M. A.

    2008-03-01

    Computer simulation is used for comparative investigation of the molecular dynamics of rhodopsin containing the chromophore group (11- cis-retinal) and free opsin. Molecular dynamics is traced within a time interval of 3000 ps; 3 × 106 discrete conformational states of rhodopsin and opsin are obtained and analyzed. It is demonstrated that the presence of the chromophore group in the chromophore center of opsin influences considerably the nearest protein environment of 11- cis-retinal both in the region of the β-ionone ring and in the region of the protonated Schiff base bond. Based on simulation results, a possible intramolecular mechanism of keeping rhodopsin as a G-protein-coupled receptor in the inactive state, i.e., the chromophore function as an efficient ligand antagonist, is discussed.

  4. Crystallographic structure of xanthorhodopsin, the light-driven proton pump with a dual chromophore

    PubMed Central

    Luecke, Hartmut; Schobert, Brigitte; Stagno, Jason; Imasheva, Eleonora S.; Wang, Jennifer M.; Balashov, Sergei P.; Lanyi, Janos K.

    2008-01-01

    Homologous to bacteriorhodopsin and even more to proteorhodopsin, xanthorhodopsin is a light-driven proton pump that, in addition to retinal, contains a noncovalently bound carotenoid with a function of a light-harvesting antenna. We determined the structure of this eubacterial membrane protein–carotenoid complex by X-ray diffraction, to 1.9-Å resolution. Although it contains 7 transmembrane helices like bacteriorhodopsin and archaerhodopsin, the structure of xanthorhodopsin is considerably different from the 2 archaeal proteins. The crystallographic model for this rhodopsin introduces structural motifs for proton transfer during the reaction cycle, particularly for proton release, that are dramatically different from those in other retinal-based transmembrane pumps. Further, it contains a histidine–aspartate complex for regulating the pKa of the primary proton acceptor not present in archaeal pumps but apparently conserved in eubacterial pumps. In addition to aiding elucidation of a more general proton transfer mechanism for light-driven energy transducers, the structure defines also the geometry of the carotenoid and the retinal. The close approach of the 2 polyenes at their ring ends explains why the efficiency of the excited-state energy transfer is as high as ≈45%, and the 46° angle between them suggests that the chromophore location is a compromise between optimal capture of light of all polarization angles and excited-state energy transfer. PMID:18922772

  5. Jovian chromophore characteristics from multispectral HST images

    NASA Astrophysics Data System (ADS)

    Strycker, Paul D.; Chanover, Nancy J.; Simon-Miller, Amy A.; Banfield, Don; Gierasch, Peter J.

    2011-10-01

    The chromophores responsible for coloring the jovian atmosphere are embedded within Jupiter's vertical aerosol structure. Sunlight propagates through this vertical distribution of aerosol particles, whose colors are defined by ϖ0( λ), and we remotely observe the culmination of the radiative transfer as I/ F( λ). In this study, we employed a radiative transfer code to retrieve ϖ0( λ) for particles in Jupiter's tropospheric haze at seven wavelengths in the near-UV and visible regimes. The data consisted of images of the 2008 passage of Oval BA to the south of the Great Red Spot obtained by the Wide Field Planetary Camera 2 on-board the Hubble Space Telescope. We present derived particle colors for locations that were selected from 14 weather regions, which spanned a large range of observed colors. All ϖ0( λ) curves were absorbing in the blue, and ϖ0( λ) increased monotonically to approximately unity as wavelength increased. We found accurate fits to all ϖ0( λ) curves using an empirically derived functional form: ϖ0( λ) = 1 - A exp(- Bλ). The best-fit parameters for the mean ϖ0( λ) curve were A = 25.4 and B = 0.0149 for λ in units of nm. We performed a principal component analysis (PCA) on our ϖ0( λ) results and found that one or two independent chromophores were sufficient to produce the variations in ϖ0( λ). A PCA of I/ F( λ) for the same jovian locations resulted in principal components (PCs) with roughly the same variances as the ϖ0( λ) PCA, but they did not result in a one-to-one mapping of PC amplitudes between the ϖ0( λ) PCA and I/ F( λ) PCA. We suggest that statistical analyses performed on I/ F( λ) image cubes have limited applicability to the characterization of chromophores in the jovian atmosphere due to the sensitivity of I/ F( λ) to horizontal variations in the vertical aerosol distribution.

  6. Genetic pediatric retinal diseases

    PubMed Central

    Say, Emil Anthony T.

    2014-01-01

    Hereditary pediatric retinal diseases are a diverse group of disorders with pathologies affecting different cellular structures or retinal development. Many can mimic typical pediatric retinal disease such as retinopathy of prematurity, vitreous hemorrhage, retinal detachment and cystoid macular edema. Multisystem involvement is frequently seen in hereditary pediatric retinal disease. A thorough history coupled with a good physical examination can oftentimes lead the ophthalmologist or pediatrician to the correct genetic test and correct diagnosis. In some instances, evaluation of parents or siblings may be required to determine familial involvement when the history is inconclusive or insufficient and clinical suspicion is high.

  7. Conformational Selection and Equilibrium Governs the Ability of Retinals to Bind Opsin*

    PubMed Central

    Schafer, Christopher T.; Farrens, David L.

    2015-01-01

    Despite extensive study, how retinal enters and exits the visual G protein-coupled receptor rhodopsin remains unclear. One clue may lie in two openings between transmembrane helix 1 (TM1) and TM7 and between TM5 and TM6 in the active receptor structure. Recently, retinal has been proposed to enter the inactive apoprotein opsin (ops) through these holes when the receptor transiently adopts the active opsin conformation (ops*). Here, we directly test this “transient activation” hypothesis using a fluorescence-based approach to measure rates of retinal binding to samples containing differing relative fractions of ops and ops*. In contrast to what the transient activation hypothesis model would predict, we found that binding for the inverse agonist, 11-cis-retinal (11CR), slowed when the sample contained more ops* (produced using M257Y, a constitutively activating mutation). Interestingly, the increased presence of ops* allowed for binding of the agonist, all-trans-retinal (ATR), whereas WT opsin showed no binding. Shifting the conformational equilibrium toward even more ops* using a G protein peptide mimic (either free in solution or fused to the receptor) accelerated the rate of ATR binding and slowed 11CR binding. An arrestin peptide mimic showed little effect on 11CR binding; however, it stabilized opsin·ATR complexes. The TM5/TM6 hole is apparently not involved in this conformational selection. Increasing its size by mutagenesis did not enable ATR binding but instead slowed 11CR binding, suggesting that it may play a role in trapping 11CR. In summary, our results indicate that conformational selection dictates stable retinal binding, which we propose involves ATR and 11CR binding to different states, the latter a previously unidentified, open-but-inactive conformation. PMID:25451936

  8. Cleavage of β-Carotene to Retinal

    NASA Astrophysics Data System (ADS)

    Wyss, Adrian; von Lintig, Johannes

    Elucidating the physiological roles played by vitamins has always been a major goal of nutritionists and biochemists. In humans, vitamin A deficiency disorder (VADD) in milder forms leads to night blindness, whilst more severe progression can lead to corneal malformations, e.g. xerophthalmia (See Volume 5, Chapters 8 and 9). This deficiency also affects the immune system, leads to infertility and causes malformations during embryogenesis. The molecular basis for these diverse effects lies in the dual role of vitamin A (retinol, 1) derivatives. In all visual systems, retinal (2), or a closely related compound such as 3-hydroxyretinal (3), is the chromophore of the visual pigments (e.g. rhodopsin) [1,2]. In vertebrates, the derivative retinoic acid (RA, 4) is a major signalling molecule that controls a wide range of processes. Retinoic acid is the ligand of the nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) [3-6] (see Chapter 15).

  9. Phospholipid meets all-trans-retinal: the making of RPE bisretinoids

    PubMed Central

    Sparrow, Janet R.; Wu, Yalin; Kim, Chul Y.; Zhou, Jilin

    2010-01-01

    The lipid phase of the photoreceptor outer segment membrane is essential to the photon capturing and signaling functions of rhodopsin. Rearrangement of phospholipids in the bilayer accompanies the formation of the active intermediates of rhodopsin following photon absorption. Furthermore, evidence for the formation of a condensation product between the photolyzed chromophore all-trans-retinal and phosphatidylethanolamine indicates that phospholipid may also participate in the movement of the retinoid in the membrane. The downside of these interactions is the formation of bisretinoid-phosphatidylethanolamine compounds that accumulate in retinal pigment epithelial cells with age and that are particularly abundant in some retinal disorders. The propensity of these compounds to negatively impact on the cells has been linked to the pathogenesis of some retinal disorders including juvenile onset recessive Stargardt disease and age-related macular degeneration. PMID:19666736

  10. Probing a Polar Cluster in the Retinal Binding Pocket of Bacteriorhodopsin by a Chemical Design Approach

    PubMed Central

    Simón-Vázquez, Rosana; Domínguez, Marta; Lórenz-Fonfría, Víctor A.; Álvarez, Susana; Bourdelande, José-Luís; de Lera, Ángel R.; Padrós, Esteve; Perálvarez-Marín, Alex

    2012-01-01

    Bacteriorhodopsin has a polar cluster of amino acids surrounding the retinal molecule, which is responsible for light harvesting to fuel proton pumping. From our previous studies, we have shown that threonine 90 is the pivotal amino acid in this polar cluster, both functionally and structurally. In an attempt to perform a phenotype rescue, we have chemically designed a retinal analogue molecule to compensate the drastic effects of the T90A mutation in bacteriorhodopsin. This analogue substitutes the methyl group at position C13 of the retinal hydrocarbon chain by and ethyl group (20-methyl retinal). We have analyzed the effect of reconstituting the wild-type and the T90A mutant apoproteins with all-trans-retinal and its 20-methyl derivative (hereafter, 13-ethyl retinal). Biophysical characterization indicates that recovering the steric interaction between the residue 90 and retinal, eases the accommodation of the chromophore, however it is not enough for a complete phenotype rescue. The characterization of these chemically engineered chromoproteins provides further insight into the role of the hydrogen bond network and the steric interactions involving the retinal binding pocket in bacteriorhodopsin and other microbial sensory rhodopsins. PMID:22879987

  11. Jovian Chromophore Characteristics from Multispectral HST Images

    NASA Technical Reports Server (NTRS)

    Strycker, Paul D.; Chanover, Nancy J.; Simon-Miller, Amy A.; Banfield, Don; Gierasch, Peter J.

    2011-01-01

    The chromophores responsible for coloring the jovian atmosphere are embedded within Jupiter's vertical aerosol structure. Sunlight propagates through this vertical distribution of aerosol particles, whose colors are defined by omega-bar (sub 0)(lambda), and we remotely observe the culmination of the radiative transfer as I/F(lambda). In this study, we employed a radiative transfer code to retrieve omega-bar (sub 0)(lambda) for particles in Jupiter's tropospheric haze at seven wavelengths in the near-UV and visible regimes. The data consisted of images of the 2008 passage of Oval BA to the south of the Great Red Spot obtained by the Wide Field Planetary Camera 2 on-board the Hubble Space Telescope. We present derived particle colors for locations that were selected from 14 weather regions, which spanned a large range of observed colors. All omega-bar (sub 0)(lambda) curves were absorbing in the blue, and omega-bar (sub 0)(lambda) increased monotonically to approximately unity as wavelength increased. We found accurate fits to all omega-bar (sub 0)(lambda) curves using an empirically derived functional form: omega-bar (sub 0)(lambda) = 1 A exp(-B lambda). The best-fit parameters for the mean omega-bar (sub 0)(lambda) curve were A = 25.4 and B = 0.0149 for lambda in units of nm. We performed a principal component analysis (PCA) on our omega-bar (sub 0)(lambda) results and found that one or two independent chromophores were sufficient to produce the variations in omega-bar (sub 0)(lambda). A PCA of I/F(lambda) for the same jovian locations resulted in principal components (PCs) with roughly the same variances as the omega-bar (sub 0)(lambda) PCA, but they did not result in a one-to-one mapping of PC amplitudes between the omega-bar (sub 0)(lambda) PCA and I/F(lambda) PCA. We suggest that statistical analyses performed on I/ F(lambda) image cubes have limited applicability to the characterization of chromophores in the jovian atmosphere due to the sensitivity of 1/ F

  12. Photoinduced electric currents in carotenoid-deficient Chlamydomonas mutants reconstituted with retinal and its analogs.

    PubMed Central

    Sineshchekov, O A; Govorunova, E G; Dér, A; Keszthelyi, L; Nultsch, W

    1994-01-01

    Reconstitution of the photoelectric responses involved in photosensory transduction in "blind" cells of Chlamydomonas reinhardtii carotenoid-deficient mutants was studied by means of a recently developed population method. Both the photoreceptor current and the regenerative response can be restored by addition of all-trans-retinal, 9-demethyl-retinal, or dimethyl-octatrienal, while the retinal analogs prevented from 13-cis/trans isomerization, 13-demethyl-retinal and citral, are not effective. Fluence dependence, spectral sensitivity, and effect of hydroxylamine treatment on retinal-induced photoelectric responses are similar to those found earlier in green strains of Chlamydomonas, although an alternative mechanism of antenna directivity in white cells of reconstituted "blind" mutants (likely based on the focusing effect of the transparent cell bodies) leads to the reversed sign of phototaxis in mutant cells under the same conditions. The results obtained indicate that both photoreceptor current and regenerative response are initiated by the same or similar rhodopsins with arhaebacterial-like chromophore(s) and prove directly the earlier suggested identity of the photoreceptor pigment(s) involved in photomotile and photoelectric responses in flagellated algae. PMID:8075341

  13. Tuning the electronic absorption of protein-embedded all-trans-retinal.

    PubMed

    Wang, Wenjing; Nossoni, Zahra; Berbasova, Tetyana; Watson, Camille T; Yapici, Ipek; Lee, Kin Sing Stephen; Vasileiou, Chrysoula; Geiger, James H; Borhan, Babak

    2012-12-01

    Protein-chromophore interactions are a central component of a wide variety of critical biological processes such as color vision and photosynthesis. To understand the fundamental elements that contribute to spectral tuning of a chromophore inside the protein cavity, we redesigned human cellular retinol binding protein II (hCRBPII) to fully encapsulate all-trans-retinal and form a covalent bond as a protonated Schiff base. This system, using rational mutagenesis designed to alter the electrostatic environment within the binding pocket of the host protein, enabled regulation of the absorption maximum of the pigment in the range of 425 to 644 nanometers. With only nine point mutations, the hCRBPII mutants induced a systematic shift in the absorption profile of all-trans-retinal of more than 200 nanometers across the visible spectrum. PMID:23224553

  14. Tuning the Electronic Absorption of Protein-Embedded All-trans-Retinal

    SciTech Connect

    Wang, Wenjing; Nossoni, Zahra; Berbasova, Tetyana; Watson, Camille T.; Yapici, Ipek; Lee, Kin Sing Stephen; Vasileiou, Chrysoula; Geiger, James H.; Borhan, Babak

    2014-10-02

    Protein-chromophore interactions are a central component of a wide variety of critical biological processes such as color vision and photosynthesis. To understand the fundamental elements that contribute to spectral tuning of a chromophore inside the protein cavity, we redesigned human cellular retinol binding protein II (hCRBPII) to fully encapsulate all-trans-retinal and form a covalent bond as a protonated Schiff base. The system, using rational mutagenesis designed to alter the electrostatic environment within the binding pocket of the host protein, enabled regulation of the absorption maximum of the pigment in the range of 425 to 644 nanometers. Moreover, with only nine point mutations, the hCRBPII mutants induced a systematic shift in the absorption profile of all-trans-retinal of more than 200 nanometers across the visible spectrum.

  15. Genetics Home Reference: retinitis pigmentosa

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions retinitis pigmentosa retinitis pigmentosa Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Retinitis pigmentosa is a group of related eye disorders that ...

  16. Deactivation mechanism of the green fluorescent chromophore.

    PubMed

    Gepshtein, Rinat; Huppert, Dan; Agmon, Noam

    2006-03-01

    We report time-resolved fluorescence data for the anion of p-hydroxybenzylidene dimethylimidazolinone (p-HBDI), a model chromophore of the green fluorescence protein, in viscous glycerol-water mixtures over a range of temperatures, T. The markedly nonexponential decay of the excited electronic state is interpreted with the aid of an inhomogeneous model possessing a Gaussian coordinate-dependent sink term. A nonlinear least-squares fitting routine enables us to achieve quantitative fits by adjusting a single activation parameter, which is found to depend linearly on 1/T. We derive an analytic expression for the absolute quantum yield, which is compared with the integrated steady-state fluorescence spectra. The microscopic origins of the model are discussed in terms of two-dimensional dynamics, coupling the phenyl-ring rotation to a swinging mode that brings this flexible molecule to the proximity of a conical intersection on its multidimensional potential energy surface. PMID:16509746

  17. Retinal Attachment Instability Is Diversified among Mammalian Melanopsins.

    PubMed

    Tsukamoto, Hisao; Kubo, Yoshihiro; Farrens, David L; Koyanagi, Mitsumasa; Terakita, Akihisa; Furutani, Yuji

    2015-11-01

    Melanopsins play a key role in non-visual photoreception in mammals. Their close phylogenetic relationship to the photopigments in invertebrate visual cells suggests they have evolved to acquire molecular characteristics that are more suited for their non-visual functions. Here we set out to identify such characteristics by comparing the molecular properties of mammalian melanopsin to those of invertebrate melanopsin and visual pigment. Our data show that the Schiff base linking the chromophore retinal to the protein is more susceptive to spontaneous cleavage in mammalian melanopsins. We also find this stability is highly diversified between mammalian species, being particularly unstable for human melanopsin. Through mutagenesis analyses, we find that this diversified stability is mainly due to parallel amino acid substitutions in extracellular regions. We propose that the different stability of the retinal attachment in melanopsins may contribute to functional tuning of non-visual photoreception in mammals. PMID:26416885

  18. Lake and Sea Populations of Mysis relicta (Crustacea, Mysida) with Different Visual-Pigment Absorbance Spectra Use the Same A1 Chromophore

    PubMed Central

    Belikov, Nikolai; Yakovleva, Marina; Feldman, Tatiana; Demina, Olga; Khodonov, Andrei; Lindström, Magnus; Donner, Kristian; Ostrovsky, Mikhail

    2014-01-01

    Glacial-relict species of the genus Mysis (opossum shrimps) inhabiting both fresh-water lakes and brackish sea waters in northern Europe show a consistent lake/sea dichotomy in eye spectral sensitivity. The absorbance peak (λmax) recorded by microspectrophotometry in isolated rhabdoms is invariably 20–30 nm red-shifted in “lake” compared with “sea” populations. The dichotomy holds across species, major opsin lineages and light environments. Chromophore exchange from A1 to A2 (retinal → 3,4-didehydroretinal) is a well-known mechanism for red-shifting visual pigments depending on environmental conditions or stages of life history, present not only in fishes and amphibians, but in some crustaceans as well. We tested the hypothesis that the lake/sea dichotomy in Mysis is due to the use of different chromophores, focussing on two populations of M. relicta from, respectively, a Finnish lake and the Baltic Sea. They are genetically very similar, having been separated for less than 10 kyr, and their rhabdoms show a typical lake/sea difference in λmax (554 nm vs. 529 nm). Gene sequencing has revealed no differences translating into amino acid substitutions in the transmembrane parts of their opsins. We determined the chromophore identity (A1 or A2) in the eyes of these two populations by HPLC, using as standards pure chromophores A1 and A2 as well as extracts from bovine (A1) and goldfish (A2) retinas. We found that the visual-pigment chromophore in both populations is A1 exclusively. Thus the spectral difference between these two populations of M. relicta is not due to the use of different chromophores. We argue that this conclusion is likely to hold for all populations of M. relicta as well as its European sibling species. PMID:24516590

  19. The retinal ciliopathies.

    PubMed

    Adams, N A; Awadein, Ahmed; Toma, Hassanain S

    2007-09-01

    While the functions of many of the proteins located in or associated with the photoreceptor cilia are poorly understood, disruption of the function of these proteins may result in a wide variety of phenotypes ranging from isolated retinal degeneration to more pleiotropic phenotypes. Systemic findings include neurosensory hearing loss, developmental delay, situs-inversus, infertility, disorders of limb and digit development, obesity, kidney disease, liver disease, and respiratory disease. The concept of "retinal ciliopathies" brings to attention the importance of further molecular analysis of this organelle as well as provides a potential common target for therapies for these disorders. The retinal ciliopathies include retinitis pigmentosa, macular degeneration, cone-dystrophy, cone-rod dystrophy, Leber congenital amaurosis, as well as retinal degenerations associated with Usher syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, Laurence-Moon syndrome, McKusick-Kaufman syndrome, and Biemond syndrome. Mutations for these disorders have been found in retinitis pigmentosa-1 (RP1), retinitis pigmentosa GTPase regulator (RPGR), retinitis pigmentosa GTPase regulator interacting protein (RPGR-IP), as well as the Usher, Bardet-Biedl, and nephronophthisis genes. Other systemic disorders associated with retinal degenerations that may also involve ciliary abnormalities include: Alstrom, Edwards-Sethi, Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes. Understanding these conditions as ciliopathies may help the ophthalmologist to recognize associations between seemingly unrelated diseases and have a high degree of suspicion that a systemic finding may be present. PMID:17896309

  20. Impacts of retinal polyene (de)methylation on the photoisomerization mechanism and photon energy storage of rhodopsin.

    PubMed

    Walczak, Elżbieta; Andruniów, Tadeusz

    2015-07-14

    Ab initio multiconfigurational quantum chemical methodology combined with molecular mechanics (CASPT2//CASSCF/AMBER) was applied to probe impacts of retinal protonated Schiff base (RPSB) polyene methylation and/or demethylation on the mechanism of photochemical isomerization in bovine rhodopsin. We have examined structural and spectroscopic properties of wild-type rhodopsin (with 11-cis-9,13-dimethyl-RPSB) and artificial rhodopsins, hosting four 11-cis-RPSB derivatives, 13-demethyl-, 9-demethyl-, 10-methyl-13-demethyl-, and 10-methyl-RPSB, evolving along the photoisomerization coordinate. It is found that the addition of 10-methyl or/and deletion of 9-/13-methyl groups do not appear to interfere structurally with the photoisomerization pathway in the S1 excited state. Remarkably, the two-mode space-saving mechanism initiated by bond order inversion and followed by asynchronous bicycle-pedal distortion in the RPSB backbone drives the photoreaction in all rhodopsin analogues studied here. However, methylation and/or demethylation is responsible for perturbation of excess energy deposited in the conical intersection structures. The analysis of photon energy stored by bathorhodopsin in synthetic pigments reveals that it is affected by steric crowding of methyl substituents in the RPSB backbone. PMID:26074351

  1. Investigation into chromophore excited-state coupling in allophycocyanin

    NASA Astrophysics Data System (ADS)

    Zheng, Xiguang; Zhao, Fuli; Wang, He Z.; Gao, Zhaolan; Yu, Zhenxin; Zhu, Jinchang; Xia, Andong; Jiang, Lijin

    1994-08-01

    Both theoretical and experimental studies are presented on chromophore excited-state coupling in linker-free allophycocyanin (APC), one of the antenna phycobiliproteins in algal photosynthesis. A three-site-coupling model has been introduced to describe the exciton interaction mechanism amoung the excited (beta) chromophore in APC, and the exciton energy splitting is estimated. Picosecond polarized fluorescence experiments both on monomeric and trimeric APC isolated from alga Spirulina platensis have been performed. The experimental results show that APC monomer and trimer exhibit remarkedly different spectropic characteristics, and satisfy the suggestion of strong excited- state coupling among chromophores in APC.

  2. Raman Spectroscopy Reveals Direct Chromophore Interactions in the Leu/Gln105 Spectral Tuning Switch of Proteorhodopsins

    PubMed Central

    Kralj, Joel M.; Spudich, Elena N.; Spudich, John L.; Rothschild, Kenneth J.

    2013-01-01

    Proteorhodopsins are an extensive family of photoactive membrane proteins found in proteobacteria distributed throughout the world’s oceans which are often classified as green- or blue-absorbing (GPR and BPR, respectively) on the basis of their visible absorption maxima. GPR and BPR have significantly different properties including photocycle lifetimes and wavelength dependence on pH. Previous studies revealed that these different properties are correlated with a single residue, Leu105 in GPR and Gln105 in BPR, although the molecular basis for the different properties of GPR and BPR has not yet been elucidated. We have studied the unexcited states of GPR and BPR using resonance Raman spectroscopy which enhances almost exclusively chromophore vibrations. We find that both spectra are remarkably similar, indicating that the retinylidene structure of GPR and BPR are almost identical. However, the frequency of a band assigned to the retinal C13-methyl-rock vibration is shifted from 1006 cm−1 in GPR to 1012 cm−1 in BPR. A similar shift is observed in the GPR mutant L105Q indicating Leu and Gln residues interact differently with the retinal C13-methyl group. The environment of the Schiff base of GPR and BPR differ as indicated by differences in the H/D induced down-shift of the Schiff base vibration. Residues located in transmembrane helices (D–G) do not contribute to the observed differences in the protein–chromophore interaction between BPR and GPR based on the Raman spectra of chimeras. These results support a model whereby the substitution of the hydrophilic Gln105 in BPR with the smaller hydrophobic Leu105 in GPR directly alters the environment of both the retinal C13 group and the Schiff base. PMID:18717545

  3. [Phototransduction mediated by melanopsin in intrinsically photosensitive retinal ganglion cells].

    PubMed

    Domínguez-Solís, Carlos Augusto; Pérez-León, Jorge Alberto

    2015-01-01

    Melanopsin is the most recent photopigment described. As all the other opsins, it attaches in the retina as chromophore. Its amino acid sequence resembles more invertebrate opsins than those of vertebrates. The signal transduction pathway of opsins in vertebrates is based on the coupling to the G protein transducin, triggering a signaling cascade that results in the hyperpolarization of the plasma membrane. On the contrary, the photoreceptors of invertebrates activate the Gq protein pathway, which leads to depolarizing responses. Phototransduction mediated by melanopsin leads to the depolarization of those cells where it is expressed, the intrinsically photosensitive retinal ganglion cells; the cellular messengers and the ion channel type(s) responsible for the cells´ response is still unclear. Studies to elucidate the signaling cascade of melanopsin in heterologous expression systems, in retina and isolated/cultured intrinsically photosensitive retinal ganglion cells, have provided evidence for the involvement of protein Gq and phospholipase C together with the likely participation of an ion channel member of the transient receptor potential-canonical family, a transduction pathway similar to invertebrate photopigments, particularly Drosophila melanogaster. The intrinsically photosensitive retinal ganglion cells are the sole source of retinal inferences to the suprachiasmatic nucleus; thus, clarifying completely the melanopsin signaling pathway will impact the chronobiology field, including the clinical aspects. PMID:26581535

  4. VANISHING RETINAL DETACHMENT

    PubMed Central

    2015-01-01

    Purpose: The purpose of this report is to describe a case of rhegmatogenous retinal detachment in the setting of chronic kidney disease that exhibited complete retinal reattachment after serial hemodialysis. Methods: Retrospective case report. Results: A 58-year-old woman with acute vision loss was found to have a macula-involving rhegmatogenous retinal detachment. Due to chronic kidney disease, she continued with routinely scheduled hemodialysis for 1 week until surgical clearance was obtained. Preoperative examination revealed complete reattachment of the retina with a persistent retinal tear. Barrier laser was applied to the tear and the retina remained attached until the most recent follow-up 8 months later. The workup of alternate etiologies was unrevealing. Conclusion: This case describes a temporal association between hemodialysis and resolution of subretinal fluid due to rhegmatogenous retinal detachment. A potential causal linkage is suggested based on shifting fluid dynamics associated with hemodialysis. A shift in treatment paradigm is not advised. PMID:26352323

  5. The second chromophore in Drosophila photolyase/cryptochrome family photoreceptors.

    PubMed

    Selby, Christopher P; Sancar, Aziz

    2012-01-10

    The photolyase/cryptochrome family of proteins are FAD-containing flavoproteins which carry out blue-light-dependent functions including DNA repair, plant growth and development, and regulation of the circadian clock. In addition to FAD, many members of the family contain a second chromophore which functions as a photo-antenna, harvesting light and transferring the excitation energy to FAD and thus increasing the efficiency of the system. The second chromophore is methenyltetrahydrofolate (MTHF) in most photolyases characterized to date and FAD, FMN, or 5-deazariboflavin in others. To date, no second chromophore has been identified in cryptochromes. Drosophila contains three members of the cryptochrome/photolyase family: cyclobutane pyrimidine dimer (CPD) photolyase, (6-4) photoproduct photolyase, and cryptochrome. We developed an expression system capable of incorporating all known second chromophores into the cognate cryptochrome/photolyase family members. Using this system, we demonstrate that Drosophila CPD photolyase and (6-4) photolyase employ 5-deazariboflavin as their second chromophore, but Drosophila cryptochrome, which is evolutionarily closer to (6-4) photolyase than the CPD photolyase, lacks a second chromophore. PMID:22175817

  6. Communication: Analytical optimal pulse shapes obtained with the aid of genetic algorithms: Controlling the photoisomerization yield of retinal

    NASA Astrophysics Data System (ADS)

    Guerrero, R. D.; Arango, C. A.; Reyes, A.

    2016-07-01

    We recently proposed a Quantum Optimal Control (QOC) method constrained to build pulses from analytical pulse shapes [R. D. Guerrero et al., J. Chem. Phys. 143(12), 124108 (2015)]. This approach was applied to control the dissociation channel yields of the diatomic molecule KH, considering three potential energy curves and one degree of freedom. In this work, we utilized this methodology to study the strong field control of the cis-trans photoisomerization of 11-cis retinal. This more complex system was modeled with a Hamiltonian comprising two potential energy surfaces and two degrees of freedom. The resulting optimal pulse, made of 6 linearly chirped pulses, was capable of controlling the population of the trans isomer on the ground electronic surface for nearly 200 fs. The simplicity of the pulse generated with our QOC approach offers two clear advantages: a direct analysis of the sequence of events occurring during the driven dynamics, and its reproducibility in the laboratory with current laser technologies.

  7. Differential Diagnosis of Retinal Vasculitis

    PubMed Central

    Abu El-Asrar, Ahmed M.; Herbort, Carl P.; Tabbara, Khalid F.

    2009-01-01

    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings. PMID:20404987

  8. Retinal vascular regeneration.

    PubMed

    Otani, Atsushi; Friedlander, Martin

    2005-01-01

    We discuss the potential use of stem cells for therapeutic angiogenesis in the treatment of retinal diseases. We demonstrate that the clinical utility of these EPC may be not limited in the treatment of ischemic retinal diseases but may also have application for the treatment of retinal degenerative disorders and for a form of cell-based gene therapy. One of the greatest potential benefits of bone marrow derived EPC therapy is the possible use of autologous grafts. Nonetheless, potential toxicities and unregulated cell growth will need to be carefully evaluated before this approach is brought to the clinics. PMID:15804843

  9. Pyridalthiadiazole-based narrow band gap chromophores.

    PubMed

    Henson, Zachary B; Welch, Gregory C; van der Poll, Thomas; Bazan, Guillermo C

    2012-02-29

    π-Conjugated materials containing pyridal[2,1,3]thiadiazole (PT) units have recently achieved record power conversion efficiencies of 6.7% in solution-processed, molecular bulk-heterojunction (BHJ) organic photovoltaics. Recognizing the importance of this new class of molecular systems and with the aim of establishing a more concrete path forward to predict improvements in desirable solid-state properties, we set out to systematically alter the molecular framework and evaluate structure-property relationships. Thus, the synthesis and properties of 13 structurally related D(1)-PT-D(2)-PT-D(1) compounds, where D represents a relatively electron-rich aromatic segment compared to PT, are provided. Physical properties were examined using a combination of absorption spectroscopy, cyclic voltammetry, thermal gravimetric analysis, differential scanning calorimetry, and solubility analysis. Changes to end-capping D(1) units allowed for fine control over electronic energy levels both in solution and in the bulk. Substitution of different alkyl chains on D(2) gives rise to controllable melting and crystallization temperatures and tailored solubility. Alterations to the core donor D(2) lead to readily identifiable changes in all properties studied. Finally, the regiochemistry of the pyridal N-atom in the PT heterocycle was investigated. The tailoring of structures via subtle structural modifications in the presented molecular series highlights the simplicity of accessing this chromophore architecture. Examination of the resulting materials properties relevant for device fabrication sets forth which can be readily predicted by consideration of molecular structure and which lack a systematic understanding. Guidelines can be proposed for the design of new molecular frameworks with the possibility of outperforming the current state of the art OPV performance. PMID:22283693

  10. Retinal vein occlusion

    MedlinePlus

    ... Berrocal MH, Rodriguez FJ, et al. Pan-American Collaborative Retina Study Group (PACORES). Comparison of two doses ... retinal vein occlusion: results from the Pan-American Collaborative Retina Study Group at 6 months of follow- ...

  11. [Acute retinal necrosis].

    PubMed

    Lucke, K; Reinking, U; el-Hifnawi, E; Dennin, R H; Laqua, H

    1988-12-01

    The authors report on three patients with acute retinal necrosis who were treated with the virostatic agent Acyclovir and who underwent vitreoretinal surgery with silicone oil filling for total retinal detachment. In two eyes the retina was reattached, but useful vision was only preserved in one patient. Titers from blood and the vitreous, as well as microscopic findings in retinal biopsies, support the view that the necrosis is caused by a herpes simplex virus infection. After therapy with Acyclovir was instituted no further progression on the necrosis was observed. However, the development of retinal detachment could not be prevented. Early diagnosis and antiviral therapy are essential to improve the otherwise poor prognosis in this rare syndrome. PMID:3221657

  12. Retinal detachment in pseudophakia.

    PubMed

    Galin, M A; Poole, T A; Obstbaum, S A

    1979-07-01

    In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively. PMID:464014

  13. Key enzymes of the retinoid (visual) cycle in vertebrate retina

    PubMed Central

    Kiser, Philip D.; Golczak, Marcin; Maeda, Akiko; Palczewski, Krzysztof

    2011-01-01

    A major goal in vision research over the past few decades has been to understand the molecular details of retinoid processing within the retinoid (visual) cycle. This includes the consequences of side reactions that result from delayed all-trans-retinal clearance and condensation with phospholipids that characterize a variety of serious retinal diseases. Knowledge of the basic retinoid biochemistry involved in these diseases is essential for development of effective therapeutics. Photoisomerization of the 11-cis-retinal chromophore of rhodopsin triggers a complex set of metabolic transformations collectively termed phototransduction that ultimately lead to light perception. Continuity of vision depends on continuous conversion of all-trans-retinal back to the 11-cis-retinal isomer. This process takes place in a series of reactions known as the retinoid cycle, which occur in photoreceptor and RPE cells. All-trans-retinal, the initial substrate of this cycle, is a chemically reactive aldehyde that can form toxic conjugates with proteins and lipids. Therefore, much experimental effort has been devoted to elucidate molecular mechanisms of the retinoid cycle and all-trans-retinal-mediated retinal degeneration, resulting in delineation of many key steps involved in regenerating 11-cis-retinal. Three particularly important reactions are catalyzed by enzymes broadly classified as acyltransferases, short-chain dehydrogenases/reductases and carotenoid/retinoid isomerases/oxygenases. PMID:21447403

  14. Giant retinal tears.

    PubMed

    Shunmugam, Manoharan; Ang, Ghee Soon; Lois, Noemi

    2014-01-01

    A giant retinal tear (GRT) is a full-thickness neurosensory retinal break that extends circumferentially around the retina for three or more clock hours in the presence of a posteriorly detached vitreous. Its incidence in large population-based studies has been estimated as 1.5% of rhegmatogenous retinal detachments, with a significant male preponderance, and bilaterality in 12.8%. Most GRTs are idiopathic, with trauma, hereditary vitreoretinopathies and high myopia each being causative in decreasing frequency. The vast majority of GRTs are currently managed with a pars plana vitrectomy; the use of adjunctive circumferential scleral buckling is debated, but no studies have shown a clear anatomical or visual advantage with its use. Similarly, silicone oil tamponade does not influence long-term outcomes when compared with gas. Primary and final retinal reattachment rates are achieved in 88% and 95% of patients, respectively. Even when the retina remains attached, however, visual recovery may be limited. Furthermore, fellow eyes of patients with a GRT are at higher risk of developing retinal tears and retinal detachment. Prophylactic treatment under these circumstances may be considered but there is no firm evidence of its efficacy at the present time. PMID:24138895

  15. Inherent Instability of the Retinitis Pigmentosa P23H Mutant Opsin*

    PubMed Central

    Chen, Yuanyuan; Jastrzebska, Beata; Cao, Pengxiu; Zhang, Jianye; Wang, Benlian; Sun, Wenyu; Yuan, Yiyuan; Feng, Zhaoyang; Palczewski, Krzysztof

    2014-01-01

    The P23H opsin mutation is the most common cause of autosomal dominant retinitis pigmentosa. Even though the pathobiology of the resulting retinal degeneration has been characterized in several animal models, its complex molecular mechanism is not well understood. Here, we expressed P23H bovine rod opsin in the nervous system of Caenorhabditis elegans. Expression was low due to enhanced protein degradation. The mutant opsin was glycosylated, but the polysaccharide size differed from that of the normal protein. Although P23H opsin aggregated in the nervous system of C. elegans, the pharmacological chaperone 9-cis-retinal stabilized it during biogenesis, producing a variant of rhodopsin called P23H isorhodopsin. In vitro, P23H isorhodopsin folded correctly, formed the appropriate disulfide bond, could be photoactivated but with reduced sensitivity, and underwent Meta II decay at a rate similar to wild type isorhodopsin. In worm neurons, P23H isorhodopsin initiated phototransduction by coupling with the endogenous Gi/o signaling cascade that induced loss of locomotion. Using pharmacological interventions affecting protein synthesis and degradation, we showed that the chromophore could be incorporated either during or after mutant protein translation. However, regeneration of P23H isorhodopsin with chromophore was significantly slower than that of wild type isorhodopsin. This effect, combined with the inherent instability of P23H rhodopsin, could lead to the structural cellular changes and photoreceptor death found in autosomal dominant retinitis pigmentosa. These results also suggest that slow regeneration of P23H rhodopsin could prevent endogenous chromophore-mediated stabilization of rhodopsin in the retina. PMID:24515108

  16. Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin

    PubMed Central

    Chiang, Wei-Chieh; Joseph, Victory; Matthes, Michael T.; Lewin, Alfred S.; Gorbatyuk, Marina S.; Ahern, Kelly; LaVail, Matthew M.

    2016-01-01

    RHO (Rod opsin) encodes a G-protein coupled receptor that is expressed exclusively by rod photoreceptors of the retina and forms the essential photopigment, rhodopsin, when coupled with 11-cis-retinal. Many rod opsin disease mutations cause rod opsin protein misfolding and trigger endoplasmic reticulum (ER) stress, leading to activation of the Unfolded Protein Response (UPR) signal transduction network. Chop is a transcriptional activator that is induced by ER stress and promotes cell death in response to chronic ER stress. Here, we examined the role of Chop in transgenic mice expressing human P23H rhodopsin (hP23H Rho Tg) that undergo retinal degeneration. With the exception of one time point, we found no significant induction of Chop in these animals and no significant change in retinal degeneration by histology and electrophysiology when hP23H Rho Tg animals were bred into a Chop−/− background. Our results indicate that Chop does not play a significant causal role during retinal degeneration in these animals. We suggest that other modules of the ER stress-induced UPR signaling network may be involved photoreceptor disease induced by P23H rhodopsin. PMID:26427410

  17. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    PubMed

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-01-01

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. PMID:27511757

  18. Optical rotation of the second harmonic radiation from retinal in bacteriorhodopsin monomers in Langmuir-Blodgett film: evidence for nonplanar retinal structure.

    PubMed Central

    Volkov, V; Svirko, Y P; Kamalov, V F; Song, L; El-Sayed, M A

    1997-01-01

    We observed optical rotation of the plane of polarization of the second harmonic (SH) radiation at 532 nm (in resonance with the retinal absorption) generated in reflection geometry in Langmuir-Blodgett film of bacteriorhodopsin (bR). The analysis of the experimental data showed that this effect arises from the nonvanishing contribution of the antisymmetrical part of the hyperpolarizability tensor. This requires that the dipole moment of the resonant electronic transition, the change of the dipole moment upon electronic excitation, and the long axis of the retinal not be coplanar. Such conditions are satisfied only if the retinal has a nonplanar geometry, a conclusion that could lend support to the heterogeneity model of the origin of the biphasic band shape of the linear CD spectrum of the retinal in bR. On the basis of our theoretical analysis, we were able to estimate the angle between the induced dipole moment and the plan that contains the long axis of the chromophore and the transition dipole moment of the retinal absorption. Images FIGURE 2 PMID:9414228

  19. Study of smartphone suitability for mapping of skin chromophores.

    PubMed

    Kuzmina, Ilona; Lacis, Matiss; Spigulis, Janis; Berzina, Anna; Valeine, Lauma

    2015-09-01

    RGB (red-green-blue) technique for mapping skin chromophores by smartphones is proposed and studied. Three smartphones of different manufacturers were tested on skin phantoms and in vivo on benign skin lesions using a specially designed light source for illumination. Hemoglobin and melanin indices obtained by these smartphones showed differences in both tests. In vitro tests showed an increment of hemoglobin and melanin indices with the concentration of chromophores in phantoms. In vivo tests indicated higher hemoglobin index in hemangiomas than in nevi and healthy skin, and nevi showed higher melanin index compared to the healthy skin. Smartphones that allow switching off the automatic camera settings provided useful data, while those with “embedded” automatic settings appear to be useless for distant skin chromophore mapping. PMID:26405818

  20. Study of smartphone suitability for mapping of skin chromophores

    NASA Astrophysics Data System (ADS)

    Kuzmina, Ilona; Lacis, Matiss; Spigulis, Janis; Berzina, Anna; Valeine, Lauma

    2015-09-01

    RGB (red-green-blue) technique for mapping skin chromophores by smartphones is proposed and studied. Three smartphones of different manufacturers were tested on skin phantoms and in vivo on benign skin lesions using a specially designed light source for illumination. Hemoglobin and melanin indices obtained by these smartphones showed differences in both tests. In vitro tests showed an increment of hemoglobin and melanin indices with the concentration of chromophores in phantoms. In vivo tests indicated higher hemoglobin index in hemangiomas than in nevi and healthy skin, and nevi showed higher melanin index compared to the healthy skin. Smartphones that allow switching off the automatic camera settings provided useful data, while those with "embedded" automatic settings appear to be useless for distant skin chromophore mapping.

  1. Modern fluorescent proteins: from chromophore formation to novel intracellular applications

    PubMed Central

    Stepanenko, Olesya V.; Stepanenko, Olga V.; Shcherbakova, Daria M.; Kuznetsova, Irina M.; Turoverov, Konstantin K.; Verkhusha, Vladislav V.

    2015-01-01

    The diverse biochemical and photophysical properties of fluorescent proteins (FPs) have enabled the generation of a growing palette of colors, providing unique opportunities for their use in a variety of modern biology applications. Modulation of these FP characteristics is achieved through diversity in both the structure of the chromophore as well as the contacts between the chromophore and the surrounding protein barrel. Here we review our current knowledge of blue, green, and red chromophore formation in permanently emitting FPs, photoactivatable FPs, and fluorescent timers. Progress in understanding the interplay between FP structure and function has allowed the engineering of FPs with many desirable features, and enabled recent advances in microscopy techniques such as super-resolution imaging of single molecules, imaging of protein dynamics, photochromic FRET, deep-tissue imaging, and multicolor two-photon microscopy in live animals. PMID:22054544

  2. Photovoltaic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Loudin, James; Mathieson, Keith; Kamins, Ted; Wang, Lele; Galambos, Ludwig; Huie, Philip; Sher, Alexander; Harris, James; Palanker, Daniel

    2011-03-01

    Electronic retinal prostheses seek to restore sight to patients suffering from retinal degenerative disorders. Implanted electrode arrays apply patterned electrical stimulation to surviving retinal neurons, producing visual sensations. All current designs employ inductively coupled coils to transmit power and/or data to the implant. We present here the design and initial testing of a photovoltaic retinal prosthesis fabricated with a pixel density of up to 177 pixels/mm2. Photodiodes within each pixel of the subretinal array directly convert light to stimulation current, avoiding the use of bulky coil implants, decoding electronics, and wiring, and thereby reducing surgical complexity. A goggles-mounted camera captures the visual scene and transmits the data stream to a pocket processor. The resulting images are projected into the eyes by video goggles using pulsed, near infrared (~900 nm) light. Prostheses with three pixel densities (15, 55, and 177 pix/mm2) are being fabricated, and tests indicate a charge injection limit of 1.62 mC/cm2 at 25Hz. In vitro tests of the photovoltaic retinal stimulation using a 512-element microelectrode array have recorded stimulated spikes from the ganglion cells, with latencies in the 1-100ms range, and with peak irradiance stimulation thresholds varying from 0.1 to 1 mW/mm2. With 1ms pulses at 25Hz the average irradiance is more than 100 times below the IR retinal safety limit. Elicited retinal response disappeared upon the addition of synaptic blockers, indicating that the inner retina is stimulated rather than the ganglion cells directly, and raising hopes that the prosthesis will preserve some of the retina's natural signal processing.

  3. Differential Light-induced Responses in Sectorial Inherited Retinal Degeneration*

    PubMed Central

    Ramon, Eva; Cordomí, Arnau; Aguilà, Mònica; Srinivasan, Sundaramoorthy; Dong, Xiaoyun; Moore, Anthony T.; Webster, Andrew R.; Cheetham, Michael E.; Garriga, Pere

    2014-01-01

    Retinitis pigmentosa (RP) is a group of genetically and clinically heterogeneous inherited degenerative retinopathies caused by abnormalities of photoreceptors or retinal pigment epithelium in the retina leading to progressive sight loss. Rhodopsin is the prototypical G-protein-coupled receptor located in the vertebrate retina and is responsible for dim light vision. Here, novel M39R and N55K variants were identified as causing an intriguing sector phenotype of RP in affected patients, with selective degeneration in the inferior retina. To gain insights into the molecular aspects associated with this sector RP phenotype, whose molecular mechanism remains elusive, the mutations were constructed by site-directed mutagenesis, expressed in heterologous systems, and studied by biochemical, spectroscopic, and functional assays. M39R and N55K opsins had variable degrees of chromophore regeneration when compared with WT opsin but showed no gross structural misfolding or altered trafficking. M39R showed a faster rate for transducin activation than WT rhodopsin with a faster metarhodopsinII decay, whereas N55K presented a reduced activation rate and an altered photobleaching pattern. N55K also showed an altered retinal release from the opsin binding pocket upon light exposure, affecting its optimal functional response. Our data suggest that these sector RP mutations cause different protein phenotypes that may be related to their different clinical progression. Overall, these findings illuminate the molecular mechanisms of sector RP associated with rhodopsin mutations. PMID:25359768

  4. Quantitative Photoacoustic Image Reconstruction using Fluence Dependent Chromophores

    PubMed Central

    Cox, B.T.; Laufer, J.G.; Beard, P.C.

    2010-01-01

    In biomedical photoacoustic imaging the images are proportional to the absorbed optical energy density, and not the optical absorption, which makes it difficult to obtain a quantitatively accurate image showing the concentration of a particular absorbing chromophore from photoacoustic measurements alone. Here it is shown that the spatially varying concentration of a chromophore whose absorption becomes zero above a threshold light fluence can be estimated from photoacoustic images obtained at increasing illumination strengths. This technique provides an alternative to model-based multiwavelength approaches to quantitative photoacoustic imaging, and a new approach to photoacoustic molecular and functional imaging. PMID:21258458

  5. Synthesis of Polymers Containing Covalently Bonded NLO Chromophores

    NASA Technical Reports Server (NTRS)

    Denga, Xiao-Hua; Sanghadasa, Mohan; Walton, Connie; Penn, Benjamin B.; Amai, Robert L. S.; Clark, Ronald D.

    1998-01-01

    Polymers containing covalently bonded nonlinear optical (NLO) chromophores are expected to possess special properties such as greater stability, better mechanical processing, and easier film formation than their non-polymeric equivalent. For the present work, polymethylmethacrylate (PMMA) was selected as the basic polymer unit on which to incorporate different NLO chromophores. The NLO components were variations of DIVA {[2-methoxyphenyl methylidene]-propanedinitrile} which we prepared from vanillin derivatives and malononitrile. These were esterified with methacrylic acid and polymerized either directly or with methyl methacrylate to form homopolymers or copolymers respectively. Characterization of the polymers and NLO property studies are underway.

  6. Probabilistic retinal vessel segmentation

    NASA Astrophysics Data System (ADS)

    Wu, Chang-Hua; Agam, Gady

    2007-03-01

    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  7. Retinal lesions in septicemia.

    PubMed

    Neudorfer, M; Barnea, Y; Geyer, O; Siegman-Igra, Y

    1993-12-15

    We explored the association between septicemia and specific retinal lesions in a prospective controlled study. Hemorrhages, cotton-wool spots, or Roth's spots were found in 24 of 101 septicemic patients (24%), compared to four of 99 age- and gender-matched control patients (4%) (P = .0002). There was no significant association between types of organisms or focus of infection and the presence of specific lesions. Histologic examination of affected eyes disclosed cytoid bodies in the nerve fiber layer without inflammation. A definite association between septicemia and retinal lesions was found and indicates the need for routine ophthalmoscopy in septicemic patients. PMID:8250076

  8. Pathway to Retinal Oximetry

    PubMed Central

    Beach, James

    2014-01-01

    Events and discoveries in oxygen monitoring over the past two centuries are presented as the background from which oximetry of the human retina evolved. Achievements and the people behind them are discussed, showing parallels between the work in tissue measurements and later in the eye. Developments in the two-wavelength technique for oxygen saturation measurements in retinal vessels are shown to exploit the forms of imaging technology available over time. The last section provides a short summary of the recent research in retinal diseases using vessel oximetry. PMID:25237591

  9. Unraveling the chromophoric disorder of poly(3-hexylthiophene)

    PubMed Central

    Thiessen, Alexander; Vogelsang, Jan; Adachi, Takuji; Steiner, Florian; Vanden Bout, David; Lupton, John M.

    2013-01-01

    The spectral breadth of conjugated polymers gives these materials a clear advantage over other molecular compounds for organic photovoltaic applications and is a key factor in recent efficiencies topping 10%. However, why do excitonic transitions, which are inherently narrow, lead to absorption over such a broad range of wavelengths in the first place? Using single-molecule spectroscopy, we address this fundamental question in a model material, poly(3-hexylthiophene). Narrow zero-phonon lines from single chromophores are found to scatter over 200 nm, an unprecedented inhomogeneous broadening that maps the ensemble. The giant red shift between solution and bulk films arises from energy transfer to the lowest-energy chromophores in collapsed polymer chains that adopt a highly ordered morphology. We propose that the extreme energetic disorder of chromophores is structural in origin. This structural disorder on the single-chromophore level may actually enable the high degree of polymer chain ordering found in bulk films: both structural order and disorder are crucial to materials physics in devices. PMID:24003119

  10. Chromophore Deprotonation State Alters the Optical Properties of Blue Chromoprotein.

    PubMed

    Chiang, Cheng-Yi; Lee, Cheng-Chung; Lo, Shin-Yi; Wang, Andrew H-J; Tsai, Huai-Jen

    2015-01-01

    Chromoproteins (CPs) have unique colors and can be used in biological applications. In this work, a novel blue CP with a maximum absorption peak (λmax) at 608 nm was identified from the carpet anemone Stichodactyla gigantea (sgBP). In vivo expression of sgBP in zebrafish would change the appearance of the fishes to have a blue color, indicating the potential biomarker function. To enhance the color properties, the crystal structure of sgBP at 2.25 Å resolution was determined to allow structure-based protein engineering. Among the mutations conducted in the Gln-Tyr-Gly chromophore and chromophore environment, a S157C mutation shifted the λmax to 604 nm with an extinction coefficient (ε) of 58,029 M-1·cm-1 and darkened the blue color expression. The S157C mutation in the sgBP chromophore environment could affect the color expression by altering the deprotonation state of the phenolic group in the chromophore. Our results provide a structural basis for the blue color enhancement of the biomarker development. PMID:26218063

  11. Cis-trans photoisomerization of fluorescent-protein chromophores.

    PubMed

    Voliani, Valerio; Bizzarri, Ranieri; Nifosì, Riccardo; Abbruzzetti, Stefania; Grandi, Elena; Viappiani, Cristiano; Beltram, Fabio

    2008-08-28

    Photochromic variants of fluorescent proteins are opening the way to a number of opportunities for high-sensitivity regioselective studies in the cellular environment and may even lead to applications in information and communication technology. Yet, the detailed photophysical processes at the basis of photoswitching have not been fully clarified. In this paper, we used synthetic FP chromophores to clarify the photophysical processes associated with the photochromic behavior. In particular, we investigated the spectral modification of synthetic chromophore analogues of wild-type green fluorescent protein (GFP), Y66F GFP (BFPF), and Y66W GFP (CFP) upon irradiation in solutions of different polarities. We found that the cis-trans photoisomerization mechanism can be induced in all the chromophores. The structural assignments were carried out both by NMR measurements and DFT calculations. Remarkably, we determined for the first time the spectra of neutral trans isomers in different solvents. Finally, we calculated the photoconversion quantum yields by absorption measurements under continuous illumination at different times and by a nanosecond laser-flash photolysis method. Our results indicate that cis-trans photoisomerization is a general mechanism of FP chromophores whose efficiency is modulated by the detailed mutant-specific protein environment. PMID:18671358

  12. Chromophore Deprotonation State Alters the Optical Properties of Blue Chromoprotein

    PubMed Central

    Chiang, Cheng-Yi; Lee, Cheng-Chung; Lo, Shin-Yi; Wang, Andrew H.-J.; Tsai, Huai-Jen

    2015-01-01

    Chromoproteins (CPs) have unique colors and can be used in biological applications. In this work, a novel blue CP with a maximum absorption peak (λmax) at 608 nm was identified from the carpet anemone Stichodactyla gigantea (sgBP). In vivo expression of sgBP in zebrafish would change the appearance of the fishes to have a blue color, indicating the potential biomarker function. To enhance the color properties, the crystal structure of sgBP at 2.25 Å resolution was determined to allow structure-based protein engineering. Among the mutations conducted in the Gln-Tyr-Gly chromophore and chromophore environment, a S157C mutation shifted the λmax to 604 nm with an extinction coefficient (ε) of 58,029 M-1·cm-1 and darkened the blue color expression. The S157C mutation in the sgBP chromophore environment could affect the color expression by altering the deprotonation state of the phenolic group in the chromophore. Our results provide a structural basis for the blue color enhancement of the biomarker development. PMID:26218063

  13. Total synthesis and structure revision of the (-)-maduropeptin chromophore.

    PubMed

    Komano, Kazuo; Shimamura, Satoshi; Norizuki, Yutaro; Zhao, Donglin; Kabuto, Chizuko; Sato, Itaru; Hirama, Masahiro

    2009-09-01

    The proposed structure of the maduropeptin chromophore, the biologically active component of the highly potent chromoprotein antitumor antibiotics, was stereoselectively synthesized but did not satisfy the spectra of the natural product. We demonstrated that the correct structure is diastereomeric, which possesses an antipodal sugar moiety. PMID:19655742

  14. Redox chromophore compounds and electrodes of metal containing substituted bipyridines

    DOEpatents

    Elliott, Cecil M.; Redepenning, Jody G.

    1986-01-01

    Chromophoric compounds, each having a wide range of distinct color changes in response to changes in the oxidation states thereof, are provided in the form of polymerizable monomers, and polymers thereof, of certain metal containing, and electron group substituted, 2,2'-bipyridine compounds.

  15. Ultraviolet light absorbers having two different chromophors in the same molecule

    DOEpatents

    Vogl, Otto; Li, Shanjun

    1988-05-17

    Ultraviolet light absorbing compounds having two different chromophors in the same molecule, particularly the benzotriazole chromophor and either the dihydroxybenzophenone or dihydroxyacetophenone chromophor; specifically, the two compounds 3,5-[di(2H-benzotriazole-2-yl)]-2,4-dihydroxyacetophenone and 3,5-[di(2H-benzotriazole-2-yl)]2,4-dihydroxybenzophenone.

  16. Chromosphores in cellulosics, XI: isoloation and identification of residual chromophores from bacterial cellulose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present work, bacterial cellulose (BC) was analyzed for its chromophore content with the chromophore release and identification (CRI) method. In aged BC, seven chromophores were unambiguously identified, despite their very low (ppb) presence. The compounds contain 2-hydroxy-[1,4]benzoquinone,...

  17. Two-Photon Absorption of Metal-Assisted Chromophores.

    PubMed

    Li, Xin; Rinkevicius, Zilvinas; Ågren, Hans

    2014-12-01

    Aiming to understand the effect of a metal surface on nonlinear optical properties and the combined effects of surface and solvent environments on such properties, we present a multiscale response theory study, integrated with dynamics of the two-photon absorption of 4-nitro-4'-amino-trans-stilbene physisorbed on noble metal surfaces, considering two such surfaces, Ag(111) and Au(111), and two solvents, cyclohexane and water, as cases for demonstration. A few conclusions of general character could be drawn: While the geometrical change of the chromophore induced by the environment was found to notably alter (diminish) the two-photon absorption cross section in the polar medium, the effects of the metal surface and solvent on the electronic structure of the chromophore surpasses the geometrical effects and leads to a considerably enhanced two-photon absorption cross section in the polar solvent. This enhancement of two-photon absorption arises essentially from the metal charge image induced enlargement of the difference between the dipole moment of the excited state and the ground state. The orientation-dependence of the two-photon absorption is found to connect with the lateral rotation of the chromophore, where the two-photon absorption reaches its maximum when the polarization of the incident light coincides with the long-axis of the chromophore. Our results demonstrate a distinct enhancement of the two-photon absorption by a metal surface and a polar medium and envisage the employment of metal-chromophore composite materials for future development of nonlinear optical materials with desirable properties. PMID:26583246

  18. Vitamin A activates rhodopsin and sensitizes it to ultraviolet light

    PubMed Central

    Miyazono, Sadaharu; Isayama, Tomoki; Delori, François C.; Makino, Clint L.

    2013-01-01

    The visual pigment, rhodopsin, consists of opsin protein with 11-cis retinal chromophore, covalently bound. Light activates rhodopsin by isomerizing the chromophore to the all-trans conformation. The activated rhodopsin sets in motion a biochemical cascade that evokes an electrical response by the photoreceptor. All-trans retinal is eventually released from the opsin and reduced to vitamin A. Rod and cone photoreceptors contain vast amounts of rhodopsin, so after exposure to bright light, the concentration of vitamin A can reach relatively high levels within their outer segments. Since a retinal analog, β-ionone, is capable of activating some types of visual pigments, we tested whether vitamin A might produce a similar effect. In single-cell recordings from isolated dark-adapted salamander green-sensitive rods, exogenously applied vitamin A decreased circulating current and flash sensitivity and accelerated flash response kinetics. These changes resembled those produced by exposure of rods to steady light. Microspectrophotometric measurements showed that vitamin A accumulated in the outer segments and binding of vitamin A to rhodopsin was confirmed in in vitro assays. In addition, vitamin A improved the sensitivity of photoreceptors to ultraviolet (UV) light. Apparently, the energy of a UV photon absorbed by vitamin A transferred by a radiationless process to the 11-cis retinal chromophore of rhodopsin, which subsequently isomerized. Therefore, our results suggest that vitamin A binds to rhodopsin at an allosteric binding site distinct from the chromophore binding pocket for 11-cis retinal to activate the rhodopsin, and that it serves as a sensitizing chromophore for UV light. PMID:22192505

  19. The Biochemical Basis of Vitamin A3 Production in Arthropod Vision.

    PubMed

    Babino, Darwin; Golczak, Marcin; Kiser, Philip D; Wyss, Adrian; Palczewski, Krzysztof; von Lintig, Johannes

    2016-04-15

    Metazoan photochemistry involves cis-trans isomerization of a retinylidene chromophore bound to G protein coupled receptors. Successful production of chromophores is critical for photoreceptor function and survival. For chromophore production, animals have to choose from more than 600 naturally occurring carotenoids and process them by oxidative cleavage and geometric isomerization of double bonds. Vertebrates employ three carotenoid cleavage oxygenases to tailor the carotenoid precursor in the synthesis of 11-cis-retinal (vitamin A1). Lepidoptera (butterfly and moth) possess only one such enzyme, NinaB, which faces the challenge to catalyze these reactions in unison to produce 11-cis-3-hydroxy-retinal (vitamin A3). We here showed that key to this multitasking is a bipartite substrate recognition site that conveys regio- and stereoselectivity for double bond processing. One side performed the specific C11, C12 cis-isomerization and preferentially binds 3-OH-β-ionone rings sites. The other side maintained a trans configuration in the resulting product and preferentially binds noncanonical ionone ring sites. Concurrent binding of carotenoids containing two cyclohexyl rings to both domains is required for specific oxidative cleavage at position C15, C15' of the substrate. The unique reaction sequence follows a dioxygenase mechanism with a carbocation/radical intermediate. This ingenious quality control system guarantees 11-cis-3-hydroxy-retinal production, the essential retinoid for insect (vitamin A3) vision. PMID:26811964

  20. A semiempirical study of the optimized ground and excited state potential energy surfaces of retinal and its protonated Schiff base

    NASA Technical Reports Server (NTRS)

    Parusel, A. B.; Pohorille, A.

    2001-01-01

    The electronic ground and first excited states of retinal and its Schiff base are optimized for the first time using the semiempirical AM1 Hamiltonian. The barrier for rotation about the C(11)-C(12) double bond is characterized by variation of both the twist angle delta(C(10)-C(11)-C(12)-C(13)) and the bond length d(C(11)-C(12)). The potential energy surface is obtained by varying these two parameters. The calculated ground state rotational barrier is equal to 15.6 kcal/mol for retinal and 20.5 kcal/mol for its Schiff base. The all-trans conformation is more stable by 3.7 kcal/mol than the 11-cis geometry. For the first excited state, S(1,) the 90 degrees twisted geometry represents a saddle point for retinal with the rotational barrier of 14.6 kcal/mol. In contrast, this conformation is an energy minimum for the Schiff base. It can be easily reached at room temperature from the planar minima since it is separated from them by a barrier of only 0.6 kcal/mol. The 90 degrees minimum conformation is more stable than the all-trans by 8.6 kcal/mol. We are thus able to present a reaction path on the S(1) surface of the retinal Schiff base with an almost barrier-less geometrical relaxation into a twisted minimum geometry, as observed experimentally. The character of the ground and first excited singlet states underscores the need for the inclusion of double excitations in the calculations.

  1. Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

    SciTech Connect

    Tomasello, Gaia; Altoe, Piero; Stenta, Marco; Olaso-Gonzalez, Gloria; Garavelli, Marco; Orlandi, Giorgio

    2007-12-26

    Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the {beta}-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutral GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, {beta}-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data.

  2. Retinal Detachment: Torn or Detached Retina Diagnosis

    MedlinePlus

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

  3. Retinal Detachment: Torn or Detached Retina Symptoms

    MedlinePlus

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

  4. Photothermal Confocal Spectromicroscopy of Multiple Cellular Chromophores and Fluorophores

    PubMed Central

    Nedosekin, D.A.; Galanzha, E.I.; Ayyadevara, Srinivas; Shmookler Reis, Robert J.; Zharov, V.P.

    2012-01-01

    Confocal fluorescence microscopy is a powerful biological tool providing high-resolution, three-dimensional (3D) imaging of fluorescent molecules. Many cellular components are weakly fluorescent, however, and thus their imaging requires additional labeling. As an alternative, label-free imaging can be performed by photothermal (PT) microscopy (PTM), based on nonradiative relaxation of absorbed energy into heat. Previously, little progress has been made in PT spectral identification of cellular chromophores at the 3D microscopic scale. Here, we introduce PTM integrating confocal thermal-lens scanning schematic, time-resolved detection, PT spectral identification, and nonlinear nanobubble-induced signal amplification with a tunable pulsed nanosecond laser. The capabilities of this confocal PTM were demonstrated for high-resolution 3D imaging and spectral identification of up to four chromophores and fluorophores in live cells and Caenorhabditis elegans. Examples include cytochrome c, green fluorescent protein, Mito-Tracker Red, Alexa-488, and natural drug-enhanced or genetically engineered melanin as a PT contrast agent. PTM was able to guide spectral burning of strong absorption background, which masked weakly absorbing chromophores (e.g., cytochromes in the melanin background). PTM provided label-free monitoring of stress-related changes to cytochrome c distribution, in C. elegans at the single-cell level. In nonlinear mode ultrasharp PT spectra from cyt c and the lateral resolution of 120 nm during calibration with 10-nm gold film were observed, suggesting a potential of PTM to break through the spectral and diffraction limits, respectively. Confocal PT spectromicroscopy could provide a valuable alternative or supplement to fluorescence microscopy for imaging of nonfluorescent chromophores and certain fluorophores. PMID:22325291

  5. Small Animal Retinal Imaging

    NASA Astrophysics Data System (ADS)

    Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.

    Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.

  6. Inherited Retinal Degenerative Disease Registry

    ClinicalTrials.gov

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  7. LDRD final report : chromophore-functionalized aligned carbon nanotube arrays.

    SciTech Connect

    Vance, Andrew L.; Yang, Chu-Yeu Peter; Krafcik, Karen Lee

    2011-09-01

    The goal of this project was to expand upon previously demonstrated single carbon nanotube devices by preparing a more practical, multi-single-walled carbon nanotube (SWNT) device. As a late-start, proof-of-concept project, the work focused on the fabrication and testing of chromophore-functionalized aligned SWNT field effect transistors (SWNT-FET). Such devices have not yet been demonstrated. The advantages of fabricating aligned SWNT devices include increased device cross-section to improve sensitivity to light, elimination of increased electrical resistance at nanotube junctions in random mat devices, and the ability to model device responses. The project did not achieve the goal of fabricating and testing chromophore-modified SWNT arrays, but a new SWNT growth capability was established that will benefit future projects. Although the ultimate goal of fabricating and testing chromophore-modified SWNT arrays was not achieved, the work did lead to a new carbon nanotube growth capability at Sandia/CA. The synthesis of dense arrays of horizontally aligned SWNTs is a developing area of research with significant potential for new discoveries. In particular, the ability to prepare arrays of carbon nanotubes of specific electronic types (metallic or semiconducting) could yield new classes of nanoscale devices.

  8. Supramolecular Packing Controls H2 Photocatalysis in Chromophore Amphiphile Hydrogels

    PubMed Central

    2015-01-01

    Light harvesting supramolecular assemblies are potentially useful structures as components of solar-to-fuel conversion materials. The development of these functional constructs requires an understanding of optimal packing modes for chromophores. We investigated here assembly in water and the photocatalytic function of perylene monoimide chromophore amphiphiles with different alkyl linker lengths separating their hydrophobic core and the hydrophilic carboxylate headgroup. We found that these chromophore amphiphiles (CAs) self-assemble into charged nanostructures of increasing aspect ratio as the linker length is increased. The addition of salt to screen the charged nanostructures induced the formation of hydrogels and led to internal crystallization within some of the nanostructures. For linker lengths up to seven methylenes, the CAs were found to pack into 2D crystalline unit cells within ribbon-shaped nanostructures, whereas the nine methylene CAs assembled into long nanofibers without crystalline molecular packing. At the same time, the different molecular packing arrangements after charge screening led to different absorbance spectra, despite the identical electronic properties of all PMI amphiphiles. While the crystalline CAs formed electronically coupled H-aggregates, only CAs with intermediate linker lengths showed evidence of high intermolecular orbital overlap. Photocatalytic hydrogen production using a nickel-based catalyst was observed in all hydrogels, with the highest turnovers observed for CA gels having intermediate linker lengths. We conclude that the improved photocatalytic performance of the hydrogels formed by supramolecular assemblies of the intermediate linker CA molecules likely arises from improved exciton splitting efficiencies due to their higher orbital overlap. PMID:26593389

  9. Method Of Signal Amplification In Multi-Chromophore Luminescence Sensors

    DOEpatents

    Levitsky, Igor A.; Krivoshlykov, Sergei G.

    2004-02-03

    A fluorescence-based method for highly sensitive and selective detection of analyte molecules is proposed. The method employs the energy transfer between two or more fluorescent chromophores in a carefully selected polymer matrix. In one preferred embodiment, signal amplification has been achieved in the fluorescent sensing of dimethyl methylphosphonate (DMMP) using two dyes, 3-aminofluoranthene (AM) and Nile Red (NR), in a hydrogen bond acidic polymer matrix. The selected polymer matrix quenches the fluorescence of both dyes and shifts dye emission and absorption spectra relative to more inert matrices. Upon DMMP sorption, the AM fluorescence shifts to the red at the same time the NR absorption shifts to the blue, resulting in better band overlap and increased energy transfer between chromophores. In another preferred embodiment, the sensitive material is incorporated into an optical fiber system enabling efficient excitation of the dye and collecting the fluorescent signal form the sensitive material on the remote end of the system. The proposed method can be applied to multichromophore luminescence sensor systems incorporating N-chromophores leading to N-fold signal amplification and improved selectivity. The method can be used in all applications where highly sensitive detection of basic gases, such as dimethyl methylphosphonate (DMMP), Sarin, Soman and other chemical warfare agents having basic properties, is required, including environmental monitoring, chemical industry and medicine.

  10. Different nonlinear optical performances of polymers containing benzimidazole chromophores

    NASA Astrophysics Data System (ADS)

    Carella, Antonio; Casalboni, Mauro; Centore, Roberto; Fusco, Sandra; Noce, Canio; Quatela, Alessia; Peluso, Andrea; Sirigu, Augusto

    2007-11-01

    Two NLO azo-benzimidazolic chromophores, bis-ethanol, 2,2‧-[[4-[[4-(1-ethyl-6-nitro-1H-benzimidazol-2-yl)phenyl]azo]phenyl]imino] (BZI1) and bis-ethanol, 2,2‧-[[4-[[4-[(1E)-2-(1-ethyl-6-nitro-1H-benzimidazol-2-yl)ethenyl]phenyl]azo]phenyl]imino] (BZI2), properly functionalised for polycondensation reactions, have been used for the synthesis of new NLO polyurethanes and polyesters. The polymers have high thermal stability and Tg ranging between 146 and 173 °C. Thin films of polymers have been prepared and oriented by electrical poling. The resonance free NLO activity has been measured at a fundamental wavelength of 1368 nm by second harmonic generation (SHG) and a maximum d33 of 2.3 pm/V has been observed. Polymers containing the less active chromophore (BZI1, μβ = 950 × 10-48 esu) show higher d33 value than the analogous polymers containing BZI2 chromophore (μβ = 1400 × 10-48). A theoretical analysis suggests that this unexpected behaviour can be only partially attributed to thermodynamic effects, dynamical effects should also play a role.

  11. Characterization of luminescent chromophore obtained from silica spheres

    NASA Astrophysics Data System (ADS)

    Kang, Kwang-Sun

    2015-02-01

    Blue light emitting chromophores have been separated from silica spheres by soaking them into acetone for 120 days. The luminescent chromophores were not obtained from other solvents, including ether, methanol, ethanol, 2-propanol, chloroform and tetrahydrofuran. According to the Fourier transform infrared spectrum, the luminescent material is composed of C-OH, -CH2, -CH3, C=O, and Si-O-Si. UV-visible absorption peak of the chromophore is at 5.17 eV (240 nm). Field emission scanning electron microscope images show small cracks on the surface of aged spheres. The luminescence peak was at 2.81 eV (441 nm) for excitation energy between 3.88 and 3.35 eV and slightly shifted toward lower energy for excitation energy lower than 3.35 eV. The deconvoluted luminescent spectrum shows two emission bands at 3.08 and 2.74 eV, which are well-matched the oxygen deficient center model. Compared to the absorption peak (5.17 eV) and the emission peak (2.81 eV), large Stokes shift (2.36 eV) is observed.

  12. Supramolecular clippers for controlling photophysical processes through preorganized chromophores.

    PubMed

    Kumar, Mohit; Ushie, Onumashi Afi; George, Subi J

    2014-04-22

    A novel supramolecular clipping design for influencing the photophysical properties of functional molecular assemblies, by the preorganization (clipping) of chromophores, is described. Several chromophores end functionalized with molecular recognition units were designed. These molecular recognition units serve as handles to appropriately position these systems upon noncovalent interactions with multivalent guest molecules (supramolecular clippers). Towards this goal, we have synthesized 1,5-dialkoxynaphthalene (DAN) and naphthalenediimide (NDI) functionalized with dipicolylethylenediamine (DPA) motifs. These molecules could preorganize upon noncovalent clipping with adenosine di- or triphosphates, which resulted in preassociated excimers and mixed (cofacial) charge-transfer (CT) assemblies. Chiral guest binding could also induce supramolecular chirality, not only into the individual chromophoric assembly but also into the heteromeric CT organization, as seen from the strong circular dichroism (CD) signal of the CT transition. The unique ability of this design to influence the intermolecular interactions by changing the binding strength of the clippers furthermore makes it very attractive for controlling the bimolecular photophysical processes. PMID:24623564

  13. Supramolecular Packing Controls H₂ Photocatalysis in Chromophore Amphiphile Hydrogels.

    PubMed

    Weingarten, Adam S; Kazantsev, Roman V; Palmer, Liam C; Fairfield, Daniel J; Koltonow, Andrew R; Stupp, Samuel I

    2015-12-01

    Light harvesting supramolecular assemblies are potentially useful structures as components of solar-to-fuel conversion materials. The development of these functional constructs requires an understanding of optimal packing modes for chromophores. We investigated here assembly in water and the photocatalytic function of perylene monoimide chromophore amphiphiles with different alkyl linker lengths separating their hydrophobic core and the hydrophilic carboxylate headgroup. We found that these chromophore amphiphiles (CAs) self-assemble into charged nanostructures of increasing aspect ratio as the linker length is increased. The addition of salt to screen the charged nanostructures induced the formation of hydrogels and led to internal crystallization within some of the nanostructures. For linker lengths up to seven methylenes, the CAs were found to pack into 2D crystalline unit cells within ribbon-shaped nanostructures, whereas the nine methylene CAs assembled into long nanofibers without crystalline molecular packing. At the same time, the different molecular packing arrangements after charge screening led to different absorbance spectra, despite the identical electronic properties of all PMI amphiphiles. While the crystalline CAs formed electronically coupled H-aggregates, only CAs with intermediate linker lengths showed evidence of high intermolecular orbital overlap. Photocatalytic hydrogen production using a nickel-based catalyst was observed in all hydrogels, with the highest turnovers observed for CA gels having intermediate linker lengths. We conclude that the improved photocatalytic performance of the hydrogels formed by supramolecular assemblies of the intermediate linker CA molecules likely arises from improved exciton splitting efficiencies due to their higher orbital overlap. PMID:26593389

  14. [News in Retinal Imaging].

    PubMed

    Werkmeister, R; Schmidl, D; Garhöfer, G; Schmetterer, L

    2015-09-01

    New developments in retinal imaging have revolutionised ophthalmology in recent years. In particular, optical coherence tomography (OCT) provides highly resolved and well reproducible images and has rung in a new era in ophthalmological imaging. The technology was introduced in the early 1990 s, and has rapidly developed. There have been improvements in resolution, sensitivity and processing speed. There have also been developments in functional processing. OCT angiography is the first application in routine clinical work. PMID:26372783

  15. Glutamatergic Retinal Waves

    PubMed Central

    Kerschensteiner, Daniel

    2016-01-01

    Spontaneous activity patterns propagate through many parts of the developing nervous system and shape the wiring of emerging circuits. Prior to vision, waves of activity originating in the retina propagate through the lateral geniculate nucleus (LGN) of the thalamus to primary visual cortex (V1). Retinal waves have been shown to instruct the wiring of ganglion cell axons in LGN and of thalamocortical axons in V1 via correlation-based plasticity rules. Across species, retinal waves mature in three stereotypic stages (I–III), in which distinct circuit mechanisms give rise to unique activity patterns that serve specific functions in visual system refinement. Here, I review insights into the patterns, mechanisms, and functions of stage III retinal waves, which rely on glutamatergic signaling. As glutamatergic waves spread across the retina, neighboring ganglion cells with opposite light responses (ON vs. OFF) are activated sequentially. Recent studies identified lateral excitatory networks in the inner retina that generate and propagate glutamatergic waves, and vertical inhibitory networks that desynchronize the activity of ON and OFF cells in the wavefront. Stage III wave activity patterns may help segregate axons of ON and OFF ganglion cells in the LGN, and could contribute to the emergence of orientation selectivity in V1. PMID:27242446

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

    PubMed Central

    Arcinue, Cheryl A.; Bartsch, Dirk-Uwe; El-Emam, Sharif Y.; Ma, Feiyan; Doede, Aubrey; Sharpsten, Lucie; Gomez, Maria Laura; Freeman, William R.

    2015-01-01

    Purpose 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. Methods 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. Results 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. Conclusion 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. PMID:26244973

  17. [Application of retinal oximeter in ophthalmology].

    PubMed

    Li, Jing; Ma, Jianmin; Wang, Ningli

    2015-11-01

    Retinal oximeter is a new machine which has been used in the diagnose, treatment and research of several ophthalmic diseases for recent years. It allows ophthalmologists to gain retinal oxygen saturation directly. Therefore, retinal oximeter might be useful for ophthalmologists to understand ophthalmic diseases more deeper and clarify the impact of ischemia on retinal function. It has been reported in the literatures that retinal oximeter has potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, central retinal vein and artery occlusion, retinitis pigmentosa, glaucomatous optic neuropathy, et al. In this thesis, the application of retinal oximeter in ophthalmology is reviewed. PMID:26850588

  18. Structure-function studies on bacteriorhodopsin. IX. Substitutions of tryptophan residues affect protein-retinal interactions in bacteriorhodopsin

    SciTech Connect

    Mogi, T.; Marti, T.; Khorana, H.G. )

    1989-08-25

    Bacteriorhodopsin contains 8 tryptophan residues distributed across the membrane-embedded helices. To study their possible functions, we have replaced them one at a time by phenylalanine; in addition, Trp-137 and -138 have been replaced by cysteine. The mutants were prepared by cassette mutagenesis of the synthetic bacterio-opsin gene, expression and purification of the mutant apoproteins, renaturation, and chromophore regeneration. The replacement of Trp-10, Trp-12 (helix A), Trp-80 (helix C), and Trp-138 (helix E) by phenylalanine and of Trp-137 and Trp-138 by cysteine did not significantly alter the absorption spectra or affect their proton pumping. However, substitution of the remaining tryptophans by phenylalanine had the following effects. (1) Substitution of Trp-86 (helix C) and Trp-137 gave chromophores blue-shifted by 20 nm and resulted in reduced proton pumping to about 30%. (2) As also reported previously, substitution of Trp-182 and Trp-189 (helix F) caused large blue shifts (70 and 40 nm, respectively) in the chromophore and affected proton pumping. (3) The substitution of Trp-86 and Trp-182 by phenylalanine conferred acid instability on these mutants. The spectral shifts indicate that Trp-86, Trp-182, Trp-189, and possibly Trp-137 interact with retinal. It is proposed that these tryptophans, probably along with Tyr-57 (helix B) and Tyr-185 (helix F), form a retinal binding pocket. We discuss the role of tryptophan residues that are conserved in bacteriorhodopsin, halorhodopsin, and the related family of opsin proteins.

  19. Cardiac Optogenetics: Enhancement by All-trans-Retinal

    PubMed Central

    Yu, Jinzhu; Chen, Kay; Lucero, Rachel V.; Ambrosi, Christina M.; Entcheva, Emilia

    2015-01-01

    All-trans-Retinal (ATR) is a photosensitizer, serving as the chromophore for depolarizing and hyperpolarizing light-sensitive ion channels and pumps (opsins), recently employed as fast optical actuators. In mammalian optogenetic applications (in brain and heart), endogenous ATR availability is not considered a limiting factor, yet it is unclear how ATR modulation may affect the response to optical stimulation. We hypothesized that exogenous ATR may improve light responsiveness of cardiac cells modified by Channelrhodopsin2 (ChR2), hence lowering the optical pacing energy. In virally-transduced (Ad-ChR2(H134R)-eYFP) light-sensitive cardiac syncytium in vitro, ATR supplements ≤2 μM improved cardiomyocyte viability and augmented ChR2 membrane expression several-fold, while >4 μM was toxic. Employing integrated optical actuation (470 nm) and optical mapping, we found that 1–2 μM ATR dramatically reduced optical pacing energy (over 30 times) to several μW/mm2, lowest values reported to date, but also caused action potential prolongation, minor changes in calcium transients and no change in conduction. Theoretical analysis helped explain ATR-caused reduction of optical excitation threshold in cardiomyocytes. We conclude that cardiomyocytes operate at non-saturating retinal levels, and carefully-dosed exogenous ATR can enhance the performance of ChR2 in cardiac cells and yield energy benefits over orders of magnitude for optogenetic stimulation. PMID:26568132

  20. Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy.

    PubMed

    Gray, Ellyn J; Gardner, Thomas W

    2015-12-01

    Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of "retinal failure." Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes. PMID:26458378

  1. LDRD final report : energy conversion using chromophore-functionalized carbon nanotubes.

    SciTech Connect

    Vance, Andrew L.; Zifer, Thomas; Zhou, Xinjian; Leonard, Francois Leonard; Wong, Bryan Matthew; Kane, Alexander; Katzenmeyer, Aaron Michael; Krafcik, Karen Lee

    2010-09-01

    With the goal of studying the conversion of optical energy to electrical energy at the nanoscale, we developed and tested devices based on single-walled carbon nanotubes functionalized with azobenzene chromophores, where the chromophores serve as photoabsorbers and the nanotube as the electronic read-out. By synthesizing chromophores with specific absorption windows in the visible spectrum and anchoring them to the nanotube surface, we demonstrated the controlled detection of visible light of low intensity in narrow ranges of wavelengths. Our measurements suggested that upon photoabsorption, the chromophores isomerize to give a large change in dipole moment, changing the electrostatic environment of the nanotube. All-electron ab initio calculations were used to study the chromophore-nanotube hybrids, and show that the chromophores bind strongly to the nanotubes without disturbing the electronic structure of either species. Calculated values of the dipole moments supported the notion of dipole changes as the optical detection mechanism.

  2. Perceptual Fading without Retinal Adaptation

    ERIC Educational Resources Information Center

    Hsieh, Po-Jang; Colas, Jaron T.

    2012-01-01

    A retinally stabilized object readily undergoes perceptual fading and disappears from consciousness. This startling phenomenon is commonly believed to arise from local bottom-up sensory adaptation to edge information that occurs early in the visual pathway, such as in the lateral geniculate nucleus of the thalamus or retinal ganglion cells. Here…

  3. High resolution optoelectronic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Loudin, Jim; Dinyari, Rostam; Huie, Phil; Butterwick, Alex; Peumans, Peter; Palanker, Daniel

    2009-02-01

    Electronic retinal prostheses seek to restore sight in patients with retinal degeneration by delivering pulsed electric currents to retinal neurons via an array of microelectrodes. Most implants use inductive or optical transmission of information and power to an intraocular receiver, with decoded signals subsequently distributed to retinal electrodes through an intraocular cable. Surgical complexity could be minimized by an "integrated" prosthesis, in which both power and data are delivered directly to the stimulating array without any discrete components or cables. We present here an integrated retinal prosthesis system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a video goggle projection system operating at near-infrared wavelengths (~ 900 nm). Photodiodes convert light into pulsed electric current, with charge injection maximized by specially optimized series photodiode circuits. Prostheses of three different pixel densities (16 pix/mm2, 64 pix/mm2, and 256 pix/mm2) have been designed, simulated, and prototyped. Retinal tissue response to subretinal implants made of various materials has been investigated in RCS rats. The resulting prosthesis can provide sufficient charge injection for high resolution retinal stimulation without the need for implantation of any bulky discrete elements such as coils or tethers. In addition, since every pixel functions independently, pixel arrays may be placed separately in the subretinal space, providing visual stimulation to a larger field of view.

  4. Retinal Imaging and Image Analysis

    PubMed Central

    Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan

    2011-01-01

    Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:21743764

  5. Quantitative analysis of retinal OCT.

    PubMed

    Sonka, Milan; Abràmoff, Michael D

    2016-10-01

    Clinical acceptance of 3-D OCT retinal imaging brought rapid development of quantitative 3-D analysis of retinal layers, vasculature, retinal lesions as well as facilitated new research in retinal diseases. One of the cornerstones of many such analyses is segmentation and thickness quantification of retinal layers and the choroid, with an inherently 3-D simultaneous multi-layer LOGISMOS (Layered Optimal Graph Image Segmentation for Multiple Objects and Surfaces) segmentation approach being extremely well suited for the task. Once retinal layers are segmented, regional thickness, brightness, or texture-based indices of individual layers can be easily determined and thus contribute to our understanding of retinal or optic nerve head (ONH) disease processes and can be employed for determination of disease status, treatment responses, visual function, etc. Out of many applications, examples provided in this paper focus on image-guided therapy and outcome prediction in age-related macular degeneration and on assessing visual function from retinal layer structure in glaucoma. PMID:27503080

  6. [Intrinsically Photosensitive Retinal Ganglion Cells].

    PubMed

    Skorkovská, K; Skorkovská, Š

    2015-06-01

    Recently discovered intrinsically photosensitive melanopsin-containing retinal ganglion cells contribute to circadian photoentrainment and pupillary constriction; recent works have also brought new evidence for their accessory role in the visual system in humans. Pupil light reaction driven by individual photoreceptors can be isolated by means of the so called chromatic pupillography. The use of chromatic stimuli to elicit different pupillary responses may become an objective clinical pupil test in the detection of retinal diseases and in assessing new therapeutic approaches particularly in hereditary retinal degenerations like retinitis pigmentosa. In advanced stages of disease, the pupil light reaction is even more sensitive than standard electroretinography for detecting residual levels of photoreceptor activity. This review summarizes current knowledge on intrinsically photosensitive retinal cells and highlights its possible implications for clinical practice. PMID:26201360

  7. Retinal connectivity and primate vision

    PubMed Central

    Lee, Barry B.; Martin, Paul R.; Grünert, Ulrike

    2012-01-01

    The general principles of retinal organization are now well known. It may seem surprising that retinal organization in the primate, which has a complex visual behavioral repertoire, appears relatively simple. In this review, we primarily consider retinal structure and function in primate species. Photoreceptor distribution and connectivity are considered as are connectivity in the outer and inner retina. One key issue is the specificity of retinal connections; we suggest that the retina shows connectional specificity but this is seldom complete, and we consider here the functional consequences of imprecise wiring. Finally, we consider how retinal systems can be linked to psychophysical descriptions of different channels, chromatic and luminance, which are proposed to exist in the primate visual system. PMID:20826226

  8. Retinal connectivity and primate vision.

    PubMed

    Lee, Barry B; Martin, Paul R; Grünert, Ulrike

    2010-11-01

    The general principles of retinal organization are now well known. It may seem surprising that retinal organization in the primate, which has a complex visual behavioral repertoire, appears relatively simple. In this review, we primarily consider retinal structure and function in primate species. Photoreceptor distribution and connectivity are considered as are connectivity in the outer and inner retina. One key issue is the specificity of retinal connections; we suggest that the retina shows connectional specificity but this is seldom complete, and we consider here the functional consequences of imprecise wiring. Finally, we consider how retinal systems can be linked to psychophysical descriptions of different channels, chromatic and luminance, which are proposed to exist in the primate visual system. PMID:20826226

  9. Iso-halorhodopsin: a stable, 9-cis retinal containing photoproduct of halorhodopsin.

    PubMed Central

    Zimányi, L; Lanyi, J K

    1987-01-01

    Dark-adapted halorhodopsin is a mixture of 13-cis and all-trans retinal chromophoric species. It is known that illumination with blue light increases the all-trans content, and this is reversed partially by brief red illumination. We now find that extended red-light illumination produces a third spectroscopic form. Analysis of composite absorption spectra recorded during various illumination regimes yielded the spectrum for the new species, whose absorption is shifted approximately 100 nm to the blue. The isomeric composition of retinal extracted from the illuminated pigment indicates that this form contains 9-cis retinal. This species, which we name iso-halorhodopsin, is stable in the dark at room temperature for at least a day, but can be quantitatively reconverted into a mixture of all-trans and 13-cis halorhodopsin by blue-light illumination. A kinetic scheme for the isomeric interconversions was drawn up, where iso-halorhodopsin is produced from either all-trans halorhodopsin only, or both 13-cis and all-trans forms. This kind of scheme is supported by the finding that red illumination of halo-opsin reconstituted with 13-trans-locked retinal will generate iso-halorhodopsin. A similar experiment with 13-cis-locked retinal could not be done because reconstitution with this retinal analogue was not possible. The photoreaction that leads to iso-halorhodopsin can be readily demonstrated in detergent-solubilized halorhodopsin or in halorhodopsin in liposomes made from phosphatidylcholine plus phosphatidyl-ethanolamine, but only to much reduced extent in cell envelope vesicles and in halorhodopsin incorporated into liposomes made from halobacterial polar lipids. PMID:3427194

  10. [Multifocal Vitelliform Retinal Lesion].

    PubMed

    Streicher, T; Špirková, J; Ilavská, M

    2015-06-01

    The authors present retrospective follow up of patient with bilateral multifocal vitelliform retinal lesion during the 18 years period. At this time, spontaneous improvement of objective picture on retina and subjective visual troubles was observed. It is probable, that this case is a part of the same symptom complex as a variant of Best´s hereditary disease. This conclusion was based on initial stadium of phenotypical expressivity and additional evaluations. The course and outcomes of visual functions were different. The hereditary transmission was not confirmed. PMID:26201364

  11. trans- cis Isomerism and acylimine formation in DsRed chromophore models: Intrinsic rotation barriers

    NASA Astrophysics Data System (ADS)

    Olsen, Seth; Smith, Sean C.

    2006-07-01

    The chromophore of the red fluorescent protein DsRed contains an acylimine substituent to a GFP-like chromophore structure. The acylimine is formed from the trans peptide linkage between residues F65 and Q66 in immature DsRed, but has a cis configuration in the mature protein. The relationship between acylimine formation and trans- cis isomerization is unresolved. We have calculated bond rotation profiles for models of mature and immature DsRed chromophores using B3LYP DFT. The isomerization barrier is substantially reduced in acylimine-substituted models, providing prima facie evidence that acylimine formation precedes trans- cis isomerization in DsRed chromophores.

  12. Mechanism of chromophore assisted laser inactivation employing fluorescent proteins.

    PubMed

    McLean, Mark A; Rajfur, Zenon; Chen, Zaozao; Humphrey, David; Yang, Bing; Sligar, Stephen G; Jacobson, Ken

    2009-03-01

    Chromophore assisted laser inactivation (CALI) is a technique that uses irradiation of chromophores proximate to a target protein to inactivate function. Previously, enhanced green fluorescent protein (EGFP) mediated CALI has been used to inactivate EGFP-fusion proteins in a spatio-temporally defined manner within cells, but the mechanism of inactivation is unknown. To help elucidate the mechanism of protein inactivation mediated by fluorescent protein CALI ([FP]-CALI), the activities of purified glutathione-S-transferase-FP (GST-EXFP) fusions were measured after laser irradiation in vitro. Singlet oxygen and free radical quenchers as well as the removal of oxygen inhibited CALI, indicating the involvement of a reactive oxygen species (ROS). At higher concentrations of protein, turbidity after CALI increased significantly indicating cross-linking of proximate fusion proteins suggesting that damage of residues on the surface of the protein, distant from the active site, results in inactivation. Control experiments removed sample heating as a possible cause of these effects. Different FP mutants fused to GST vary in their CALI efficiency in the order enhanced green fluorescent protein (EGFP) > enhanced yellow fluorescent protein (EYFP) > enhanced cyan fluorescent protein (ECFP), while a GST construct that binds fluorescein-based arsenical hairpin binder (FlAsH) results in significantly higher CALI efficiency than any of the fluorescent proteins (XFPs) tested. It is likely that the hierarchy of XFP effectiveness reflects the balance between ROS that are trapped within the XFP structure and cause fluorophore and chromophore bleaching and those that escape to effect CALI of proximate proteins. PMID:19199572

  13. H- and J-aggregation of fluorene-based chromophores.

    PubMed

    Deng, Yonghong; Yuan, Wen; Jia, Zhe; Liu, Gao

    2014-12-11

    Understanding of H- and J-aggregation behaviors in fluorene-based polymers is significant both for determining the origin of various red-shifted emissions occurring in blue-emitting polyfluorenes and for developing polyfluorene-based device performance. In this contribution, we demonstrate a new theory of the H- and J-aggregation of polyfluorenes and oligofluorenes, and understand the influence of chromosphere aggregation on their photoluminescent properties. H- and J-aggregates are induced by a continuous increasing concentration of the oligofluorene or polyfluorene solution. A relaxed molecular configuration is simulated to illustrate the spatial arrangement of the bonding of fluorenes. It is indicated that the relaxed state adopts a 21 helical backbone conformation with a torsion angle of 18° between two connected repeat units. This configuration makes the formation of H- and J-aggregates through the strong π-π interaction between the backbone rings. A critical aggregation concentration is observed to form H- and J-aggregates for both polyfluorenes and oligofluorenes. These aggregates show large spectral shifts and distinct shape changes in photoluminescent excitation (PLE) and emission (PL) spectroscopy. Compared with "isolated" chromophores, H-aggregates induce absorption spectral blue-shift and fluorescence spectral red-shift but largely reduce fluorescence efficiency. "Isolated" chromophores not only refer to "isolated molecules" but also include those associated molecules if their conjugated backbones are not compact enough to exhibit perturbed absorption and emission. J-aggregates induce absorption spectral red-shift and fluorescence spectral red-shift but largely enhance fluorescence efficiency. The PLE and PL spectra also show that J-aggregates dominate in concentrated solutions. Different from the excimers, the H- and J-aggregate formation changes the ground-state absorption of fluorene-based chromophores. H- and J-aggregates show changeable

  14. Photoinduced charge separation by polymer-bound chromophores

    SciTech Connect

    Rodgers, M.A.J.

    1991-09-01

    This project has examined the photodynamic behavior of water-soluble polymers that have covalently linked hydrophobic chromophores spaced along the chains. These polymeric systems have been examined for photoinduced charge separation with electron-accepting ions having different total charge. Focus has been on the excited singlet (S{sub 1}) state formed by laser flash absorption. The effects of pH and ionic strength -- factors that govern the conformational nature of the polymer in solution -- have been studied. A second major effort has been to study photoinduced redox processes involving excited states of water-soluble variants of anthracene and acridine. 27 refs., 16 figs., 2 tabs.

  15. Multiphoton excitation of organic chromophores in microbubble resonators

    NASA Astrophysics Data System (ADS)

    Cohoon, Gregory A.; Kieu, Khanh; Norwood, Robert A.

    2014-03-01

    We report the observation of multiphoton excitation of organic chromophores in microbubble whispering gallery mode resonators. High-Q microbubble resonators are a formed by heating a pressurized fused silica capillary to form a hollow bubble which can be filled with liquid. In this case, the microbubble is filled with a solution of Rhodamine 6G dye. The resonator and dye are excited by evanescently coupling CW light from a 980nm laser diode using a tapered optical fiber. The two-photon fluorescence of the dye can be seen with pump powers as low as 1 mW.

  16. Altered etioplast development in phytochrome chromophore-deficient mutants.

    PubMed

    Terry, M J; Ryberg, M; Raitt, C E; Page, A M

    2001-12-01

    Inhibition of chromophore synthesis in the phytochrome-deficient aurea (au) and yellow-green-2 (yg-2) mutants of tomato (Solanum lycopersicum L.) results in a severe reduction of protochlorophyllide (Pchlide) accumulation in dark-grown hypocotyls. Experiments with apophytochrome-deficient mutants indicate that the inhibition of Pchlide accumulation results from two separate effects: one dependent on the activity of phytochromes A and B1 and one phytochrome-independent effect that is attributed to a feedback inhibition of the tetrapyrrole biosynthesis pathway. Cotyledons only show phytochrome-independent inhibition of Pchlide synthesis. Analysis of NADPH:protochlorophyllide oxidoreductase levels by western blotting showed that the reduction in Pchlide in au and yg-2 is accompanied by a correlative, but less substantial, decrease in NADPH:protochlorophyllide oxidoreductase. Consistent with this result, in vivo fluorescence spectra demonstrate that both mutants are primarily deficient in non-phototransformable Pchlide. Analysis of etioplast structure indicates that plastid development in au and yg-2 is retarded in hypocotyls and partially impaired in cotyledons, again correlating with the reduction in Pchlide. Since Pchlide synthesis is also reduced in chromophore-deficient mutants of pea (Pisum sativum L.) and Arabidopsis thaliana (L.) Heynh. (Landsberg erecta) these results may be significant for explaining aspects of the phenotype of this mutant class that are independent of the loss of phytochrome. PMID:11800397

  17. New TFO conjugates containing a carminomycinone-derived chromophore.

    PubMed

    Capobianco, M L; De Champdoré, M; Francini, L; Lena, S; Garbesi, A; Arcamone, F

    2001-01-01

    Conjugates obtained by linking the anthracycline intercalating chromophore to triple helix forming oligonucleotides (TFOs) have been used in a physicochemical study of the stability of triple helices with DNA sequences of pharmacological relevance. The intercalating moiety is represented by carminomycinone derivatives obtained upon O-demethylation and hydrolysis of the glycosidic linkage of daunomycin followed by the introduction of an alkylating residue at two different positions. Results of experiments with a polypurinic region present in the multidrug resistance (MDR) gene indicate that the stability of the triple helix is significantly enhanced by replacement of C's with (5-Me)C's in the TFO sequences tested. The stability is not changed when a 3'-TpT is present in place of a 3'-CpG at the presumed intercalation site of the anthraquinone chromophore. The same carminomycinone derivatives were used for the preparation of conjugates able to form triple helices with the polypurine tract (PPT) present in the human integrated genome of HIV-1 infected cells. Three different TFOs (T(4)(Me)CT(4)(Me)CC, C2; T(4)(Me)CT(4)(Me)CC(Me)CC(Me)CCT, C6; and T(4)(Me)CT(4)G(6), G6) were designed and linked to the anthraquinone moiety. These conjugates showed a significantly enhanced ability to bind the PPT region of HIV with respect to the nonconjugated TFOs. PMID:11459456

  18. Skin image illumination modeling and chromophore identification for melanoma diagnosis

    NASA Astrophysics Data System (ADS)

    Liu, Zhao; Zerubia, Josiane

    2015-05-01

    The presence of illumination variation in dermatological images has a negative impact on the automatic detection and analysis of cutaneous lesions. This paper proposes a new illumination modeling and chromophore identification method to correct lighting variation in skin lesion images, as well as to extract melanin and hemoglobin concentrations of human skin, based on an adaptive bilateral decomposition and a weighted polynomial curve fitting, with the knowledge of a multi-layered skin model. Different from state-of-the-art approaches based on the Lambert law, the proposed method, considering both specular reflection and diffuse reflection of the skin, enables us to address highlight and strong shading effects usually existing in skin color images captured in an uncontrolled environment. The derived melanin and hemoglobin indices, directly relating to the pathological tissue conditions, tend to be less influenced by external imaging factors and are more efficient in describing pigmentation distributions. Experiments show that the proposed method gave better visual results and superior lesion segmentation, when compared to two other illumination correction algorithms, both designed specifically for dermatological images. For computer-aided diagnosis of melanoma, sensitivity achieves 85.52% when using our chromophore descriptors, which is 8~20% higher than those derived from other color descriptors. This demonstrates the benefit of the proposed method for automatic skin disease analysis.

  19. PIMASERTIB AND SEROUS RETINAL DETACHMENTS

    PubMed Central

    AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem

    2016-01-01

    Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523

  20. The role of chromophore coupling in singlet fission.

    PubMed

    Johnson, Justin C; Nozik, Arthur J; Michl, Josef

    2013-06-18

    Certain organic materials can generate more than one electron-hole pair per absorbed photon, a property that could revolutionize the prospects for solar energy. This process, called singlet fission, is one possible "exciton multiplication" scheme that could be useful in a variety of photovoltaic device designs from dye-sensitized solar cells to solar cell bilayers to bulk heterojunctions. For such applications to be possible, however, singlet fission must occur with near perfect efficiency in compounds that also have other requisite properties such as strong visible light absorption and photostability. Many recent investigations of singlet fission have focused on crystalline polyacenes, which have been known for some time to undergo singlet fission. While these materials have promise, limitations in stability, cost, and performance may hinder practical application of polyacene solar cells, while their complex photophysics may limit our fundamental understanding of singlet fission in crystalline polyacenes. In this Account, we describe rationally designed singlet fission chromophores whose excited state dynamics should be fairly simple and whose coupling can be well controlled through the formation of covalent dimers, aggregates, or polycrystalline films. In principle, investigations of these chromophores should provide the clearest connection to theoretical concepts explaining how an excited state evolves from a singlet (S1) into two triplets (TT). Realizing the promise of efficient singlet fission rests with two tasks: (i) producing an ideal molecular energy level structure and (ii) inducing the correct type and strength of chromophore coupling. In this Account, we offer theoretical guidance for achieving (i) and consider more extensively recent results aimed at (ii). For (i), theoretical guidance suggests that, in addition to alternant hydrocarbons like tetracene and pentacene, biradicals (i.e., molecules with two independent radical centers) may also be used as

  1. Di-retinoid-pyridinium-ethanolamine (A2E) Accumulation and the Maintenance of the Visual Cycle Are Independent of Atg7-mediated Autophagy in the Retinal Pigmented Epithelium.

    PubMed

    Perusek, Lindsay; Sahu, Bhubanananda; Parmar, Tanu; Maeno, Hiroshi; Arai, Eisuke; Le, Yun-Zheng; Subauste, Carlos S; Chen, Yu; Palczewski, Krzysztof; Maeda, Akiko

    2015-11-27

    Autophagy is an evolutionarily conserved catabolic mechanism that relieves cellular stress by removing/recycling damaged organelles and debris through the action of lysosomes. Compromised autophagy has been implicated in many neurodegenerative diseases, including retinal degeneration. Here we examined retinal phenotypes resulting from RPE-specific deletion of the autophagy regulatory gene Atg7 by generating Atg7(flox/flox);VMD2-rtTA-cre+ mice to determine whether autophagy is essential for RPE functions including retinoid recycling. Atg7-deficient RPE displayed abnormal morphology with increased RPE thickness, cellular debris and vacuole formation indicating that autophagy is important in maintaining RPE homeostasis. In contrast, 11-cis-retinal content, ERGs and retinal histology were normal in mice with Atg7-deficient RPE in both fasted and fed states. Because A2E accumulation in the RPE is associated with pathogenesis of both Stargardt disease and age-related macular degeneration (AMD) in humans, deletion of Abca4 was introduced into Atg7(flox/flox);VMD2-rtTA-cre+ mice to investigate the role of autophagy during A2E accumulation. Comparable A2E concentrations were detected in the eyes of 6-month-old mice with and without Atg7 from both Abca4(-/-) and Abca4(+/+) backgrounds. To identify other autophagy-related molecules involved in A2E accumulation, we performed gene expression array analysis on A2E-treated human RPE cells and found up-regulation of four autophagy related genes; DRAM1, NPC1, CASP3, and EIF2AK3/PERK. These observations indicate that Atg7-mediated autophagy is dispensable for retinoid recycling and A2E deposition; however, autophagy plays a role in coping with stress caused by A2E accumulation. PMID:26468292

  2. A PYP chromophore acts as a 'photoacid' in an isolated hydrogen bonded complex.

    PubMed

    Andersen, Lars H; Bochenkova, Anastasia V; Houmøller, Jørgen; Kiefer, Hjalte V; Lattouf, Elie; Stockett, Mark H

    2016-04-21

    The light-induced response of a neutral Photoactive Yellow Protein chromophore in a hydrogen-bonded complex with a proton acceptor has been studied by dual-detection action absorption spectroscopy and density functional theory. We show that the chromophore is a 'photoacid' and that ultrafast excited-state proton transfer might be operative in an isolated complex. PMID:27009407

  3. Synthesis and photochemistry of pH-sensitive GFP chromophore analogues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nobel GFP chromophore analogues containing 2-thienyl-, 5-methyl-2-furyl-, 2-pyrryl, and 6-methyl-2-pyridyl-groups were synthesized, and their fluorescence spectra were recorded across pH range of 1 to 7. The GFP chromophores prevent photoisomerizaiton in acidic media and increase their fluorescent a...

  4. Homologs of vertebrate Opn3 potentially serve as a light sensor in nonphotoreceptive tissue.

    PubMed

    Koyanagi, Mitsumasa; Takada, Eiichiro; Nagata, Takashi; Tsukamoto, Hisao; Terakita, Akihisa

    2013-03-26

    Most opsins selectively bind 11-cis retinal as a chromophore to form a photosensitive pigment, which underlies various physiological functions, such as vision and circadian photoentrainment. Recently, opsin 3 (Opn3), originally called encephalopsin or panopsin, and its homologs were identified in various tissues including brain, eye, and liver in both vertebrates and invertebrates, including human. Because Opn3s are mainly expressed in tissues that are not considered to contain sufficient amounts of 11-cis retinal to form pigments, the photopigment formation ability of Opn3 has been of interest. Here, we report the successful expression of Opn3 homologs, pufferfish teleost multiple tissue opsin (PufTMT) and mosquito Opn3 (MosOpn3) and show that these proteins formed functional photopigments with 11-cis and 9-cis retinals. The PufTMT- and MosOpn3-based pigments have absorption maxima in the blue-to-green region and exhibit a bistable nature. These Opn3 homolog-based pigments activate Gi-type and Go-type G proteins light dependently, indicating that they potentially serve as light-sensitive Gi/Go-coupled receptors. We also demonstrated that mammalian cultured cells transfected with the MosOpn3 or PufTMT became light sensitive without the addition of 11-cis retinal and the photosensitivity retained after the continuous light exposure, showing a reusable pigment formation with retinal endogenously contained in culture medium. Interestingly, we found that the MosOpn3 also acts as a light sensor when constituted with 13-cis retinal, a ubiquitously present retinal isomer. Our findings suggest that homologs of vertebrate Opn3 might function as photoreceptors in various tissues; furthermore, these Opn3s, particularly the mosquito homolog, could provide a promising optogenetic tool for regulating cAMP-related G protein-coupled receptor signalings. PMID:23479626

  5. Flexible retinal electrode array

    DOEpatents

    Okandan, Murat; Wessendorf, Kurt O.; Christenson, Todd R.

    2006-10-24

    An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

  6. Building retinal connectomes.

    PubMed

    Marc, Robert E; Jones, Bryan W; Lauritzen, J Scott; Watt, Carl B; Anderson, James R

    2012-08-01

    Understanding vertebrate vision depends on knowing, in part, the complete network graph of at least one representative retina. Acquiring such graphs is the business of synaptic connectomics, emerging as a practical technology due to improvements in electron imaging platform control, management software for large-scale datasets, and availability of data storage. The optimal strategy for building complete connectomes uses transmission electron imaging with 2 nm or better resolution, molecular tags for cell identification, open-access data volumes for navigation, and annotation with open-source tools to build 3D cell libraries, complete network diagrams and connectivity databases. The first forays into retinal connectomics have shown that even nominally well-studied cells have much richer connection graphs than expected. PMID:22498714

  7. Femtosecond infrared spectroscopy of channelrhodopsin-1 chromophore isomerization

    PubMed Central

    Stensitzki, T.; Yang, Y.; Muders, V.; Schlesinger, R.; Heberle, J.; Heyne, K.

    2016-01-01

    Vibrational dynamics of the retinal all-trans to 13-cis photoisomerization in channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) was investigated by femtosecond visible pump mid-IR probe spectroscopy. After photoexcitation, the transient infrared absorption of C-C stretching modes was detected. The formation of the 13-cis photoproduct marker band at 1193 cm−1 was observed within the time resolution of 0.3 ps. We estimated the photoisomerization yield to (60 ± 6) %. We found additional time constants of (0.55 ± 0.05) ps and (6 ± 1) ps, assigned to cooling, and cooling processes with a back-reaction pathway. An additional bleaching band demonstrates the ground-state heterogeneity of retinal. PMID:27191011

  8. Femtosecond infrared spectroscopy of channelrhodopsin-1 chromophore isomerization.

    PubMed

    Stensitzki, T; Yang, Y; Muders, V; Schlesinger, R; Heberle, J; Heyne, K

    2016-07-01

    Vibrational dynamics of the retinal all-trans to 13-cis photoisomerization in channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) was investigated by femtosecond visible pump mid-IR probe spectroscopy. After photoexcitation, the transient infrared absorption of C-C stretching modes was detected. The formation of the 13-cis photoproduct marker band at 1193 cm(-1) was observed within the time resolution of 0.3 ps. We estimated the photoisomerization yield to (60 ± 6) %. We found additional time constants of (0.55 ± 0.05) ps and (6 ± 1) ps, assigned to cooling, and cooling processes with a back-reaction pathway. An additional bleaching band demonstrates the ground-state heterogeneity of retinal. PMID:27191011

  9. Nutrition and retinal degenerations.

    PubMed

    Berson, E L

    2000-01-01

    Considerable progress has been made in the understanding and management of degenerative diseases of the retina involving photoreceptors. Nutritional approaches to treatment have proved successful in the case of the common forms of retinitis pigmentosa (supplementation with vitamin A), Bassen-Kornzweig disease (supplementation with vitamins A, E, and K), gyrate atrophy (low-protein, low-arginine diet and/or supplementation with vitamin B6), and Refsum disease (low-phytol, low-phytanic acid diet). The night blindness associated with Sorsby fundus dystrophy can be reversed over the short term with vitamin A. A significant trend for decreased risk for advanced or exudative ARMD has been reported among those whose diets contain a higher content of carotenoids, such as spinach and collard greens. A randomized trial is in progress to determine whether beta-carotene, vitamin C, and vitamin E as well as trace minerals, particularly zinc, will modify the course of ARMD. The difficulties that patients with retinal degenerations face as a result of their diminishing vision, sometimes over decades, cannot be underestimated. Nutritional therapy has proved effective in modifying the course of a number of these conditions; the therapeutic benefit of nutritional modification in diseases that have a genetic basis is of particular interest. Further research is warranted to determine the mechanisms by which these treatments provide their benefit as well as to identify other conditions that may yield to nutritional intervention. Risk-factor analyses of well-defined populations followed over time with food-frequency questionnaires in conjunction with careful assessments of visual function may reveal other dietary constituents that can modify the course of degenerative diseases of the retina. PMID:11064860

  10. Advances in understanding the molecular basis of the first steps in color vision.

    PubMed

    Hofmann, Lukas; Palczewski, Krzysztof

    2015-11-01

    Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis-trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation. PMID:26187035

  11. Advances in understanding the molecular basis of the first steps in color vision

    PubMed Central

    Hofmann, Lukas; Palczewski, Krzysztof

    2015-01-01

    Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation. PMID:26187035

  12. Molecular genetics of retinitis pigmentosa.

    PubMed Central

    Farber, D. B.; Heckenlively, J. R.; Sparkes, R. S.; Bateman, J. B.

    1991-01-01

    Retinitis pigmentosa is a model for the study of genetic diseases. Its genetic heterogeneity is reflected in the different forms of inheritance (autosomal dominant, autosomal recessive, or X-linked) and, in a few families, in the presence of mutations in the visual pigment rhodopsin. Clinical and molecular genetic studies of these disorders are discussed. Animal models of retinal degeneration have been investigated for many years with the hope of gaining insight into the cause of photoreceptor cell death. Recently, the genes responsible for two of these animal disorders, the rds and rd mouse genes, have been isolated and characterized. The retinal degeneration of the rd mouse is presented in detail. The possible involvement of human analogues of these mouse genes in human retinal diseases is being investigated. Images PMID:1771877

  13. Chromophoric signatures of microbial by-products in the dark ocean

    NASA Astrophysics Data System (ADS)

    Catalá, Teresa S.; Reche, Isabel; Ramón, Cintia L.; López-Sanz, Àngel; Álvarez, Marta; Calvo, Eva; Álvarez-Salgado, Xosé A.

    2016-07-01

    Detailed examination of the absorption spectra from dark ocean samples allowed us to identify and deconvolve two distinct chromophores centered at 302 nm (UV) and 415 nm (visible) from the exponential decay curve characteristic of humic substances. The UV chromophore was ubiquitous in intermediate and deep waters, and it has been proposed as the secondary absorption peak of nitrate. The visible chromophore was prominent at the central and intermediate water masses of the North Pacific, and it has been proposed as cytochrome c. Subtraction of the modeled absorption spectra of the two chromophores from the measured absorption spectrum of the samples leads to a spectral slope overestimation by 13.3 ± 6.0% for S275-295 and 14.8 ± 10.6% for S350-400. To only consider the chromophoric fraction of DOM, the absorption spectra of nitrate should be subtracted in samples with a [NO3-]:a302 ratio > 70 µM m.

  14. Photophysics of GFP-related chromophores imposed by a scaffold design.

    PubMed

    Dolgopolova, E A; Moore, T M; Fellows, W B; Smith, M D; Shustova, N B

    2016-06-14

    In this paper, a rigid scaffold imposes the photophysics of chromophores with a benzylidene imidazolidinone core by mimicking the β-barrel structure of the green fluorescent protein (GFP) and its analogs. The designed artificial frameworks maintain fluorescence responses and, therefore, conformational rigidity of typically non-emissive GFP-related chromophores. To replicate a small weight percent of the chromophore inside the natural GFP, two synthetic approaches were utilized: coordinative immobilization and non-coordinative inclusion. Despite low chromophore loading in the rigid matrix, both approaches resulted in formation of photoluminescent hybrid materials. Furthermore, the rigid scaffold dictates chromophore fluorescence by replicating its behavior in solution or the solid state. The presented results open an avenue for utilization of rigid scaffolds in the engineering of materials with tunable photoluminescence profiles for a variety of practical applications. PMID:26927627

  15. Second-order nonlinear optical susceptibilities in nonelectrically poled guest-host polymers with tricyanofuran chromophores

    NASA Astrophysics Data System (ADS)

    Ito, Kazuma; Sato, Yasuaki; Takasu, Ryosuke; Mase, Nobuyuki; Kawata, Yoshimasa; Tasaka, Shigeru; Sugita, Atsushi

    2014-01-01

    In this manuscript, we describe the current manuscript describes the second-order nonlinear optical susceptibility of guest-host polymers possessing chromophores with strongly electron-accepting tricyanofuran (TCF). Chromophores substituted with different numbers of hydroxyl groups were prepared. Our experimental results demonstrated that the guest-host polymers exhibited nonlinear optical susceptibilities simply upon annealing at temperatures higher than the glass transition point of the host polymers even in the absence of applied external DC electric fields. Nonelectrical poling behaviors were only available for the materials possessing hydroxyl-group-functionalized chromophores. The results indicate that chemisorption of the hydroxyl groups on the substrate led to the orientation order of the guest chromophores. The orientation order of the chromophores was reproduced well by the model of poled polymers in previous studies.

  16. Primary Role of the Chromophore Bond Length Alternation in Reversible Photoconversion of Red Fluorescence Proteins

    PubMed Central

    Drobizhev, Mikhail; Hughes, Thomas E.; Stepanenko, Yuriy; Wnuk, Pawel; O'Donnell, Kieran; Scott, J. Nathan; Callis, Patrik R.; Mikhaylov, Alexander; Dokken, Leslie; Rebane, Aleksander

    2012-01-01

    Rapid photobleaching of fluorescent proteins can limit their use in imaging applications. The underlying kinetics is multi-exponential and strongly depends on the local chromophore environment. The first, reversible, step may be attributed to a rotation around one of the two exocyclic C-C bonds bridging phenol and imidazolinone groups in the chromophore. However it is not clear how the protein environment controls this motion - either by steric hindrances or by modulating the electronic structure of the chromophore through electrostatic interactions. Here we study the first step of the photobleaching kinetics in 13 red fluorescent proteins (RFPs) with different chromophore environment and show that the associated rate strongly correlates with the bond length alternation (BLA) of the two bridge bonds. The sign of the BLA appears to determine which rotation is activated. Our results present experimental evidence for the dominance of electronic effects in the conformational dynamics of the RFP chromophore. PMID:23008753

  17. Microsystems Technology for Retinal Implants

    NASA Astrophysics Data System (ADS)

    Weiland, James

    2005-03-01

    The retinal prosthesis is targeted to treat age-related macular degeneration, retinitis pigmentosa, and other outer retinal degenerations. Simulations of artificial vision have predicted that 600-1000 individual pixels will be needed if a retinal prosthesis is to restore function such as reading large print and face recognition. An implantable device with this many electrode contacts will require microsystems technology as part of its design. An implantable retinal prosthesis will consist of several subsystems including an electrode array and hermetic packaging. Microsystems and microtechnology approaches are being investigated as possible solutions for these design problems. Flexible polydimethylsiloxane (PDMS) substrate electrode arrays and silicon micromachined electrode arrays are under development. Inactive PDMS electrodes have been implanted in 3 dogs to assess mechanical biocompatibility. 3 dogs were followed for 6 months. The implanted was securely fastened to the retina with a single retinal tack. No post-operative complications were evident. The array remained within 100 microns of the retinal surface. Histological evaluation showed a well preserved retina underneath the electrode array. A silicon device with electrodes suspended on micromachined springs has been implanted in 4 dogs (2 acute implants, 2 chronic implants). The device, though large, could be inserted into the eye and positioned on the retina. Histological analysis of the retina from the spring electrode implants showed that spring mounted posts penetrated the retina, thus the device will be redesigned to reduce the strength of the springs. These initial implants will provide information for the designers to make the next generation silicon device. We conclude that microsystems technology has the potential to make possible a retinal prosthesis with 1000 individual contacts in close proximity to the retina.

  18. Quantum dynamics of electronic excitations in biomolecular chromophores: role of the protein environment and solvent.

    PubMed

    Gilmore, Joel; McKenzie, Ross H

    2008-03-20

    A biomolecular chromophore can be viewed as a quantum system with a small number of degrees of freedom interacting with an environment (the surrounding protein and solvent) which has many degrees of freedom, the majority of which can be described classically. The system-environment interaction can be described by a spectral density for a spin-boson model. The quantum dynamics of electronic excitations in the chromophore are completely determined by this spectral density, which is of great interest for describing quantum decoherence and quantum measurements. Specifically, the spectral density determines the time scale for the "collapse" of the wave function of the chromophore due to continuous measurement of its quantum state by the environment. Although of fundamental interest, there very few physical systems for which the spectral density has been determined experimentally and characterized. In contrast, here, we give the parameters for the spectral densities for a wide range of chromophores, proteins, and solvents. Expressions for the spectral density are derived for continuum dielectric models of the chromophore environment. There are contributions to the spectral density from each component of the environment: the protein, the water bound to the protein, and the bulk solvent. Each component affects the quantum dynamics of the chromophore on distinctly different time scales. Our results provide a natural description of the different time scales observed in ultrafast laser spectroscopy, including three pulse photon echo decay and dynamic Stokes shift measurements. We show that even if the chromophore is well separated from the solvent by the surrounding protein, ultrafast solvation can be still be dominated by the solvent. Consequently, we suggest that the subpicosecond solvation observed in some biomolecular chromophores should not necessarily be assigned to ultrafast protein dynamics. The magnitude of the chromophore-environment coupling is sufficiently strong

  19. Retinal oxygen extraction in humans

    NASA Astrophysics Data System (ADS)

    Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

    2015-10-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.

  20. General pathophysiology in retinal degeneration.

    PubMed

    Wert, Katherine J; Lin, Jonathan H; Tsang, Stephen H

    2014-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  1. General Pathophysiology in Retinal Degeneration

    PubMed Central

    Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.

    2015-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  2. The mechanics of retinal detachment

    NASA Astrophysics Data System (ADS)

    Chou, Tom; Siegel, Michael

    2013-03-01

    We present a model of the mechanical and fluid forces associated with exudative retinal detachments where the retinal photoreceptor cells separate typically from the underlying retinal pigment epithelium (RPE). By computing the total fluid volume flow arising from transretinal, vascular, and retinal pigment epithelium (RPE) pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an irreversible, extended retinal delamination. We also investigate localized, blister-like retinal detachments by balancing mechanical tension in the retina with both the retina-RPE adhesion energy and the hydraulic pressure jump across the retina. For detachments induced by traction forces, we find a critical radius beyond which the blister is unstable to growth. Growth of a detached blister can also be driven by inflamed tissue within which e.g., the hydraulic conductivities of the retina or choroid increase, the RPE pumps fail, or the adhesion properties change. We determine the parameter regimes in which the blister either becomes unstable to growth, remains stable and finite-sized, or shrinks, allowing possible healing. This work supported by the Army Research Office through grant 58386MA

  3. Cytomegalovirus retinitis mimicking intraocular lymphoma.

    PubMed

    Gooi, Patrick; Farmer, James; Hurley, Bernard; Brodbaker, Elliott

    2008-12-01

    We present a case of an unusual retinal infiltrate requiring retinal biopsy for definitive diagnosis. A 62-year-old man with treated lymphoma presented with decreased vision in the right eye associated with a white retinal lesion, which extended inferonasally from an edematous disc. Intraocular lymphoma was considered as a diagnosis; thus, the patient was managed with vitrectomy and retinal biopsy. Cytological analysis of the vitreous aspirate could not rule out a lymphoproliferative disorder. The microbial analysis was negative. Histology of the lesion showed extensive necrosis and large cells with prominent nucleoli. To rule out lymphoma, a battery of immunostains was performed and all were negative. However the limited amount of tissue was exhausted in the process. Subsequently, a hematoxylin and eosin (H/E) slide was destained, on which a CMV immunostain was performed. This revealed positivity in the nuclei and intranuclear inclusions within the large atypical cells. A diagnosis of CMV retinitis was made. Retinal biopsy may provide a definitive diagnosis and direct patient care toward intravenous gancyclovir in the case of CMV or toward radiation and chemotherapy for intraocular lymphoma. When faced with a limited amount of tissue, destaining regular H/E slides is a possible avenue to performing additional immunohistochemical studies. PMID:19668455

  4. Retinal oxygen extraction in humans.

    PubMed

    Werkmeister, René M; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A; Leitgeb, Rainer A; Schmetterer, Leopold

    2015-01-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332

  5. Retinal oxygen extraction in humans

    PubMed Central

    Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

    2015-01-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332

  6. Influence of Architecture, Concentration, and Thermal History on the Poling of Nonlinear Optical Chromophores in Block Copolymer Domains

    SciTech Connect

    Leolukman, Melvina; Paoprasert, Peerasak; Wang, Yao; Makhija, Varun; McGee, David J.; Gopalan, Padma

    2008-10-02

    Factors affecting the electric-field-induced poling of nonlinear optical chromophores in block copolymer domains were investigated by encapsulating the chromophores in a linear-diblock copolymer [poly(styrene-b-4-vinylpyridine)] and linear-dendritic (poly(methyl methacrylate)-dendron) block copolymer via hydrogen bonding. Temperature-dependent Fourier transform infrared spectroscopy and morphology evaluation by X-ray scattering and transmission electron microscopy were used with in situ second harmonic generation to correlate domain architectures, processing conditions such as thermal history, and chromophore concentrations with poling efficiency. Poling of chromophores encapsulated in the minority domain (spheres or cylinders) of a linear-diblock copolymer was inhibited by the increasing chromophore concentration within the domain and the chemical nature of the majority domain. Chromophore encapsulation in the majority domain produced the most favorable conditions for poling as measured by in situ second harmonic generation. Thermal annealing of the linear-diblock copolymer/chromophore composites resulted in chromophore aggregation with a corresponding decrease in nonlinear optical activity. The linear-dendron/chromophore system presented the most effective architecture for spatially dispersing chromophores. These findings suggest that while well-ordered phase-separated systems such as block copolymers enhance chromophore isolation over homopolymer systems, a more effective approach is to explore polymer chains end functionalized with chromophores.

  7. Imaging chromophores with undetectable fluorescence by stimulated emission microscopy.

    PubMed

    Min, Wei; Lu, Sijia; Chong, Shasha; Roy, Rahul; Holtom, Gary R; Xie, X Sunney

    2009-10-22

    Fluorescence, that is, spontaneous emission, is generally more sensitive than absorption measurement, and is widely used in optical imaging. However, many chromophores, such as haemoglobin and cytochromes, absorb but have undetectable fluorescence because the spontaneous emission is dominated by their fast non-radiative decay. Yet the detection of their absorption is difficult under a microscope. Here we use stimulated emission, which competes effectively with the nonradiative decay, to make the chromophores detectable, and report a new contrast mechanism for optical microscopy. In a pump-probe experiment, on photoexcitation by a pump pulse, the sample is stimulated down to the ground state by a time-delayed probe pulse, the intensity of which is concurrently increased. We extract the miniscule intensity increase with shot-noise-limited sensitivity by using a lock-in amplifier and intensity modulation of the pump beam at a high megahertz frequency. The signal is generated only at the laser foci owing to the nonlinear dependence on the input intensities, providing intrinsic three-dimensional optical sectioning capability. In contrast, conventional one-beam absorption measurement exhibits low sensitivity, lack of three-dimensional sectioning capability, and complication by linear scattering of heterogeneous samples. We demonstrate a variety of applications of stimulated emission microscopy, such as visualizing chromoproteins, non-fluorescent variants of the green fluorescent protein, monitoring lacZ gene expression with a chromogenic reporter, mapping transdermal drug distributions without histological sectioning, and label-free microvascular imaging based on endogenous contrast of haemoglobin. For all these applications, sensitivity is orders of magnitude higher than for spontaneous emission or absorption contrast, permitting nonfluorescent reporters for molecular imaging. PMID:19847261

  8. Cyp27c1 Red-Shifts the Spectral Sensitivity of Photoreceptors by Converting Vitamin A1 into A2.

    PubMed

    Enright, Jennifer M; Toomey, Matthew B; Sato, Shin-ya; Temple, Shelby E; Allen, James R; Fujiwara, Rina; Kramlinger, Valerie M; Nagy, Leslie D; Johnson, Kevin M; Xiao, Yi; How, Martin J; Johnson, Stephen L; Roberts, Nicholas W; Kefalov, Vladimir J; Guengerich, F Peter; Corbo, Joseph C

    2015-12-01

    Some vertebrate species have evolved means of extending their visual sensitivity beyond the range of human vision. One mechanism of enhancing sensitivity to long-wavelength light is to replace the 11-cis retinal chromophore in photopigments with 11-cis 3,4-didehydroretinal. Despite over a century of research on this topic, the enzymatic basis of this perceptual switch remains unknown. Here, we show that a cytochrome P450 family member, Cyp27c1, mediates this switch by converting vitamin A1 (the precursor of 11-cis retinal) into vitamin A2 (the precursor of 11-cis 3,4-didehydroretinal). Knockout of cyp27c1 in zebrafish abrogates production of vitamin A2, eliminating the animal's ability to red-shift its photoreceptor spectral sensitivity and reducing its ability to see and respond to near-infrared light. Thus, the expression of a single enzyme mediates dynamic spectral tuning of the entire visual system by controlling the balance of vitamin A1 and A2 in the eye. PMID:26549260

  9. Recovery of Red Fluorescent Protein Chromophore Maturation Deficiency through Rational Design

    PubMed Central

    Moore, Matthew M.; Oteng-Pabi, Samuel K.; Pandelieva, Antonia T.; Mayo, Stephen L.; Chica, Roberto A.

    2012-01-01

    Red fluorescent proteins (RFPs) derived from organisms in the class Anthozoa have found widespread application as imaging tools in biological research. For most imaging experiments, RFPs that mature quickly to the red chromophore and produce little or no green chromophore are most useful. In this study, we used rational design to convert a yellow fluorescent mPlum mutant to a red-emitting RFP without reverting any of the mutations causing the maturation deficiency and without altering the red chromophore’s covalent structure. We also created an optimized mPlum mutant (mPlum-E16P) that matures almost exclusively to the red chromophore. Analysis of the structure/function relationships in these proteins revealed two structural characteristics that are important for efficient red chromophore maturation in DsRed-derived RFPs. The first is the presence of a lysine residue at position 70 that is able to interact directly with the chromophore. The second is an absence of non-bonding interactions limiting the conformational flexibility at the peptide backbone that is oxidized during red chromophore formation. Satisfying or improving these structural features in other maturation-deficient RFPs may result in RFPs with faster and more complete maturation to the red chromophore. PMID:23285050

  10. Chromophore composition of the phycobiliprotein Cr-PC577 from the cryptophyte Hemiselmis pacifica.

    PubMed

    Overkamp, Kristina E; Langklotz, Sina; Aras, Marco; Helling, Stefan; Marcus, Katrin; Bandow, Julia E; Hoef-Emden, Kerstin; Frankenberg-Dinkel, Nicole

    2014-12-01

    The cryptophyte phycocyanin Cr-PC577 from Hemiselmis pacifica is a close relative of Cr-PC612 found in Hemiselmis virescens and Hemiselmis tepida. The two biliproteins differ in that Cr-PC577 lacks the major peak at around 612 nm in the absorption spectrum. Cr-PC577 was thus purified and characterized with respect to its bilin chromophore composition. Like other cryptophyte phycobiliproteins, Cr-PC577 is an (αβ)(α'β) heterodimer with phycocyanobilin (PCB) bound to the α-subunits. While one chromophore of the β-subunit is also PCB, mass spectrometry identified an additional chromophore with a mass of 585 Da at position β-Cys-158. This mass can be attributed to either a dihydrobiliverdin (DHBV), mesobiliverdin (MBV), or bilin584 chromophore. The doubly linked bilin at position β-Cys-50 and β-Cys-61 could not be identified unequivocally but shares spectral features with DHBV. We found that Cr-PC577 possesses a novel chromophore composition with at least two different chromophores bound to the β-subunit. Overall, our data contribute to a better understanding of cryptophyte phycobiliproteins and furthermore raise the question on the biosynthetic pathway of cryptophyte chromophores. PMID:25134685

  11. Communication: Analytical optimal pulse shapes obtained with the aid of genetic algorithms: Controlling the photoisomerization yield of retinal.

    PubMed

    Guerrero, R D; Arango, C A; Reyes, A

    2016-07-21

    We recently proposed a Quantum Optimal Control (QOC) method constrained to build pulses from analytical pulse shapes [R. D. Guerrero et al., J. Chem. Phys. 143(12), 124108 (2015)]. This approach was applied to control the dissociation channel yields of the diatomic molecule KH, considering three potential energy curves and one degree of freedom. In this work, we utilized this methodology to study the strong field control of the cis-trans photoisomerization of 11-cis retinal. This more complex system was modeled with a Hamiltonian comprising two potential energy surfaces and two degrees of freedom. The resulting optimal pulse, made of 6 linearly chirped pulses, was capable of controlling the population of the trans isomer on the ground electronic surface for nearly 200 fs. The simplicity of the pulse generated with our QOC approach offers two clear advantages: a direct analysis of the sequence of events occurring during the driven dynamics, and its reproducibility in the laboratory with current laser technologies. PMID:27448862

  12. A Large and Phylogenetically Diverse Class of Type 1 Opsins Lacking a Canonical Retinal Binding Site.

    PubMed

    Becker, Erin A; Yao, Andrew I; Seitzer, Phillip M; Kind, Tobias; Wang, Ting; Eigenheer, Rich; Shao, Katie S Y; Yarov-Yarovoy, Vladimir; Facciotti, Marc T

    2016-01-01

    Opsins are photosensitive proteins catalyzing light-dependent processes across the tree of life. For both microbial (type 1) and metazoan (type 2) opsins, photosensing depends upon covalent interaction between a retinal chromophore and a conserved lysine residue. Despite recent discoveries of potential opsin homologs lacking this residue, phylogenetic dispersal and functional significance of these abnormal sequences have not yet been investigated. We report discovery of a large group of putatively non-retinal binding opsins, present in a number of fungal and microbial genomes and comprising nearly 30% of opsins in the Halobacteriacea, a model clade for opsin photobiology. We report phylogenetic analyses, structural modeling, genomic context analysis and biochemistry, to describe the evolutionary relationship of these recently described proteins with other opsins, show that they are expressed and do not bind retinal in a canonical manner. Given these data, we propose a hypothesis that these abnormal opsin homologs may represent a novel family of sensory opsins which may be involved in taxis response to one or more non-light stimuli. If true, this finding would challenge our current understanding of microbial opsins as a light-specific sensory family, and provides a potential analogy with the highly diverse signaling capabilities of the eukaryotic G-protein coupled receptors (GPCRs), of which metazoan type 2 opsins are a light-specific sub-clade. PMID:27327432

  13. A Large and Phylogenetically Diverse Class of Type 1 Opsins Lacking a Canonical Retinal Binding Site

    PubMed Central

    Becker, Erin A.; Yao, Andrew I.; Seitzer, Phillip M.; Kind, Tobias; Wang, Ting; Eigenheer, Rich; Shao, Katie S. Y.; Yarov-Yarovoy, Vladimir; Facciotti, Marc T.

    2016-01-01

    Opsins are photosensitive proteins catalyzing light-dependent processes across the tree of life. For both microbial (type 1) and metazoan (type 2) opsins, photosensing depends upon covalent interaction between a retinal chromophore and a conserved lysine residue. Despite recent discoveries of potential opsin homologs lacking this residue, phylogenetic dispersal and functional significance of these abnormal sequences have not yet been investigated. We report discovery of a large group of putatively non-retinal binding opsins, present in a number of fungal and microbial genomes and comprising nearly 30% of opsins in the Halobacteriacea, a model clade for opsin photobiology. We report phylogenetic analyses, structural modeling, genomic context analysis and biochemistry, to describe the evolutionary relationship of these recently described proteins with other opsins, show that they are expressed and do not bind retinal in a canonical manner. Given these data, we propose a hypothesis that these abnormal opsin homologs may represent a novel family of sensory opsins which may be involved in taxis response to one or more non-light stimuli. If true, this finding would challenge our current understanding of microbial opsins as a light-specific sensory family, and provides a potential analogy with the highly diverse signaling capabilities of the eukaryotic G-protein coupled receptors (GPCRs), of which metazoan type 2 opsins are a light-specific sub-clade. PMID:27327432

  14. Retinal AO OCT

    NASA Astrophysics Data System (ADS)

    Zawadzki, Robert J.; Miller, Donald T.

    The last two decades have witnessed extraordinary advances in optical technology to image noninvasively and at high resolution the posterior segment of the eye. Two of the most impactful technological advancements over this period have arguably been optical coherence tomography (OCT) and adaptive optics (AO). The strengths of these technologies complement each other and when combined have been shown to provide unprecedented, micron-scale resolution (<3 μm) in all three dimensions and sensitivity to image the cellular retina in the living eye. This powerful extension of OCT, that is AO-OCT, is the focus of this chapter. It presents key aspects of designing and implementing AO-OCT systems. Particular attention is devoted to the relevant optical properties of the eye that ultimately define these systems, AO componentry and operation tailored for ophthalmic use, and of course use of the latest technologies and methods in OCT for ocular imaging. It surveys the wide range of AO-OCT designs that have been developed for retinal imaging, with AO integrated into every major OCT design configuration. Finally, it reviews the scientific and clinical studies reported to date that show the exciting potential of AO-OCT to image the microscopic retina and fundus in ways not previously possible with other noninvasive methods and a look to future developments in this rapidly growing field.

  15. Temperature controlled retinal photocoagulation

    NASA Astrophysics Data System (ADS)

    Schlott, Kerstin; Koinzer, Stefan; Baade, Alexander; Birngruber, Reginald; Roider, Johann; Brinkmann, Ralf

    2013-06-01

    Retinal photocoagulation lacks objective dosage in clinical use, thus the commonly applied lesions are too deep and strong, associated with pain reception and the risk of visual field defects and induction of choroidal neovascularisations. Optoacoustics allows real-time non-invasive temperature measurement in the fundus during photocoagulation by applying short probe laser pulses additionally to the treatment radiation, which excite the emission of ultrasonic waves. Due to the temperature dependence of the Grüneisen parameter, the amplitudes of the ultrasonic waves can be used to derive the temperature of the absorbing tissue. By measuring the temperatures in real-time and automatically controlling the irradiation by feedback to the treatment laser, the strength of the lesions can be defined. Different characteristic functions for the time and temperature dependent lesion sizes were used as rating curves for the treatment laser, stopping the irradiation automatically after a desired lesion size is achieved. The automatically produced lesion sizes are widely independent of the adjusted treatment laser power and individual absorption. This study was performed on anaesthetized rabbits and is a step towards a clinical trial with automatically controlled photocoagulation.

  16. Color Doppler imaging of retinal diseases.

    PubMed

    Dimitrova, Galina; Kato, Satoshi

    2010-01-01

    Color Doppler imaging (CDI) is a widely used method for evaluating ocular circulation that has been used in a number of studies on retinal diseases. CDI assesses blood velocity parameters by using ultrasound waves. In ophthalmology, these assessments are mainly performed on the retrobulbar blood vessels: the ophthalmic, the central retinal, and the short posterior ciliary arteries. In this review, we discuss CDI use for the assessment of retinal diseases classified into the following: vascular diseases, degenerations, dystrophies, and detachment. The retinal vascular diseases that have been investigated by CDI include diabetic retinopathy, retinal vein occlusions, retinal artery occlusions, ocular ischemic conditions, and retinopathy of prematurity. Degenerations and dystrophies included in this review are age-related macular degeneration, myopia, and retinitis pigmentosa. CDI has been used for the differential diagnosis of retinal detachment, as well as the evaluation of retrobulbar circulation in this condition. CDI is valuable for research and is a potentially useful diagnostic tool in the clinical setting. PMID:20385332

  17. Synthesis and self-assembly of DNA-chromophore hybrid amphiphiles.

    PubMed

    Albert, Shine K; Golla, Murali; Thelu, Hari Veera Prasad; Krishnan, Nithiyanandan; Deepak, Perapaka; Varghese, Reji

    2016-08-01

    DNA based spherical nanostructures are one of the promising nanostructures for several biomedical and biotechnological applications due to their excellent biocompatibility and DNA-directed surface addressability. Herein, we report the synthesis and amphiphilicity-driven self-assembly of two classes of DNA (hydrophilic)-chromophore (hydrophobic) hybrid amphiphiles into spherical nanostructures. A solid-phase "click" chemistry based modular approach is demonstrated for the synthesis of DNA-chromophore amphiphiles. Various spectroscopic and microscopic analyses reveal the self-assembly of the amphiphiles into vesicular and micellar assemblies with the corona made of hydrophilic DNA and the hydrophobic chromophoric unit as the core of the spherical nanostructures. PMID:27241196

  18. Enhanced microscopic nonlinear optical properties of novel Y-type chromophores with dual electron donor groups

    NASA Astrophysics Data System (ADS)

    Tang, Xiang; Pan, Lin; Jia, Kun; Tang, Xianzhong

    2016-03-01

    In this Letter, novel Y-type chromophores with dual electron donor groups, containing either styryl or azobenzene based π-conjugated bridge structures, were synthesized and their chemical structures, molecular configuration, microscopic optical properties as well as thermal properties were systematically characterized. The experimental results indicated that eight times increasing of second-order molecular hyperpolarizability as well as 50-100 nm blue shift of maximum absorption band for azobenzene based chromophore were observed by introducing Y-type dual electron donor groups, which was derived from the highly efficient 'total charge transfer' in this kind of chromophore as confirmed by the density functional theory calculation.

  19. Automated retinal robotic laser system.

    PubMed

    Barrett, S F; Wright, C H; Jerath, M R; Lewis, R S; Dillard, B C; Rylander, H G; Welch, A J

    1995-01-01

    Researchers at the University of Texas and the USAF Academy have worked toward the development of a retinal robotic laser system. The overall goal of this ongoing project is to precisely place and control the depth of laser lesions for the treatment of various retinal diseases such as diabetic retinopathy and retinal tears. Separate low speed prototype subsystems have been developed to control lesion depth using lesion reflectance feedback parameters and lesion placement using retinal vessels as tracking landmarks. Both subsystems have been successfully demonstrated in vivo on pigmented rabbits using an argon continuous wave laser. Recent efforts have concentrated on combining the two subsystems into a single prototype capable of simultaneously controlling both lesion depth and placement. We have designated this combined system CALOSOS for Computer Aided Laser Optics System for Ophthalmic Surgery. Following the dual-use concept, this system is being adapted for clinical use as a retinal treatment system as well as a research tool for military laser-tissue interaction studies. PMID:7654990

  20. Neuroglobin Protection in Retinal Ischemia

    PubMed Central

    Chan, Anita S.Y.; Saraswathy, Sindhu; Rehak, Matus; Ueki, Mari

    2012-01-01

    Purpose. Neuroglobin (Ngb) is a vertebrate globin that is predominantly expressed in the retina and brain. To explore the role of Ngb in retinal neuroprotection during ischemia reperfusion (IR), the authors examined the effect of Ngb overexpression in the retina in vivo by using Ngb-transgenic (Ngb-Tg) mice. Methods. Retinal IR was induced in Ngb overexpressing Ngb-Tg mice and wild type (WT) mice by cannulating the anterior chamber and transiently elevating the IOP for 60 minutes. After Day 7 of reperfusion, the authors evaluated Ngb mRNA and protein expression in nonischemic control as well as ischemic mice and its effect on retinal histology, mitochondrial oxidative stress, and apoptosis, using morphometry and immunohistochemistry, quantitative PCR analysis and Western blot techniques. Results. Ngb-Tg mice without ischemia overexpress Ngb mRNA 11.3-fold (SE ± 0.457, P < 0.05) higher than WT control mice, and this overexpression of Ngb protein was localized to the mitochondria of the ganglion cells, outer and inner plexiform layers, and photoreceptor inner segments. This overexpression of Ngb is associated with decreased mitochondrial DNA damage in Ngb-Tg mice with IR in comparison with WT. Ngb-Tg mice with IR also revealed significant preservation of retinal thickness, significantly less activated caspase 3 protein expression, and apoptosis in comparison with WT mice. Conclusions. Neuroglobin overexpression plays a neuroprotective role against retinal ischemia reperfusion injury due to decreasing of mitochondrial oxidative stress-mediated apoptosis. PMID:22167093

  1. [Unusual retinal abnormality: retinal hemorrhages related to scurvy].

    PubMed

    Errera, M-H; Dupas, B; Man, H; Gualino, V; Gaudric, A; Massin, P

    2011-03-01

    A diet restricted to rice and boiled fruit and vegetables leads to vitamin C deficiency. We describe the third case, to our knowledge, of retinal hemorrhages related to scurvy. Reduced bilateral visual acuity in a 50-year-old patient was associated with macrocytic anemia, denutrition, and cutaneous ecchymoses. Oral vitamin C treatment provided subjective clinical improvement and regression of the retinal hemorrhages on fundus examination, with no side effects. Vitamin C plays an important role in collagen stability in vascular and bone walls. PMID:21392843

  2. Transcorneal Electrical Stimulation Therapy for Retinal Disease

    ClinicalTrials.gov

    2012-05-03

    Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema

  3. Clinical Trials in Retinal Dystrophies

    PubMed Central

    Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean

    2016-01-01

    Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field – the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. PMID:26957839

  4. Retinal spot size with wavelength

    NASA Astrophysics Data System (ADS)

    Rockwell, Benjamin A.; Hammer, Daniel X.; Kennedy, Paul K.; Amnotte, Rodney E.; Eilert, Brent; Druessel, Jeffrey J.; Payne, Dale J.; Phillips, Shana L.; Stolarski, David J.; Noojin, Gary D.; Thomas, Robert J.; Cain, Clarence P.

    1997-06-01

    We have made an indirect in-vivo determination of spot size focusing in the rhesus monkey model. Measurement of the laser induced breakdown threshold both in-vitro and in-vivo allow correlation and assignment of a spot size after focusing through the living eye. We discuss and analyze the results and show how trends in minimum visible lesion data should be assessed in light of chromatic aberration. National laser safety standards are based on minimal visual lesion (MVL) threshold studies in different animal models. The energy required for a retinal lesion depends upon may parameters including wavelength and retinal spot size. We attempt to explain trends in reported MVL threshold studies using a model of the eye which allows calculation of changes in retinal spot size due to chromatic aberration.

  5. Diabetes and Retinal Vascular Dysfunction

    PubMed Central

    Shin, Eui Seok; Sorenson, Christine M.; Sheibani, Nader

    2014-01-01

    Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR). We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR. PMID:25667739

  6. Exploring the retinal connectome

    PubMed Central

    Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross

    2011-01-01

    Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive

  7. Retinal Image Quality During Accommodation

    PubMed Central

    López-Gil, N.; Martin, J.; Liu, T.; Bradley, A.; Díaz-Muñoz, D.; Thibos, L.

    2013-01-01

    Purpose We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Methods Subjects viewed a monochromatic (552nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Results Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Conclusions Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye’s higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced

  8. Retinal Optical Coherence Tomography Imaging

    NASA Astrophysics Data System (ADS)

    Drexler, Wolfgang; Fujimoto, James G.

    The eye is essentially transparent, transmitting light with only minimal optical attenuation and scattering providing easy optical access to the anterior segment as well as the retina. For this reason, ophthalmic and especially retinal imaging has been not only the first but also most successful clinical application for optical coherence tomography (OCT). This chapter focuses on the development of OCT technology for retinal imaging. OCT has significantly improved the potential for early diagnosis, understanding of retinal disease pathogenesis, as well as monitoring disease progression and response to therapy. Development of ultrabroad bandwidth light sources and high-speed detection techniques has enabled significant improvements in ophthalmic OCT imaging performance, demonstrating the potential of three-dimensional, ultrahigh-resolution OCT (UHR OCT) to perform noninvasive optical biopsy of the living human retina, i.e., the in vivo visualization of microstructural, intraretinal morphology in situ approaching the resolution of conventional histopathology. Significant improvements in axial resolution and speed not only enable three-dimensional rendering of retinal volumes but also high-definition, two-dimensional tomograms, topographic thickness maps of all major intraretinal layers, as well as volumetric quantification of pathologic intraretinal changes. These advances in OCT technology have also been successfully applied in several animal models of retinal pathologies. The development of light sources emitting at alternative wavelengths, e.g., around #1,060 nm, not only enabled three-dimensional OCT imaging with enhanced choroidal visualization but also improved OCT performance in cataract patients due to reduced scattering losses in this wavelength region. Adaptive optics using deformable mirror technology, with unique high stroke to correct higher-order ocular aberrations, with specially designed optics to compensate chromatic aberration of the human eye, in

  9. New Wrinkles in Retinal Densitometry

    PubMed Central

    Masella, Benjamin D.; Hunter, Jennifer J.; Williams, David R.

    2014-01-01

    Purpose. Retinal densitometry provides objective information about retinal function. But, a number of factors, including retinal reflectance changes that are not directly related to photopigment depletion, complicate its interpretation. We explore these factors and suggest a method to minimize their impact. Methods. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to measure changes in photoreceptor reflectance in monkeys before and after photopigment bleaching with 514-nm light. Reflectance measurements at 514 nm and 794 nm were recorded simultaneously. Several methods of normalization to extract the apparent optical density of the photopigment were compared. Results. We identified stimulus-related fluctuations in 794-nm reflectance that are not associated with photopigment absorptance and occur in both rods and cones. These changes had a magnitude approaching those associated directly with pigment depletion, precluding the use of infrared reflectance for normalization. We used a spatial normalization method instead, which avoided the fluctuations in the near infrared, as well as a confocal AOSLO designed to minimize light from layers other than the receptors. However, these methods produced a surprisingly low estimate of the apparent rhodopsin density (animal 1: 0.073 ± 0.006, animal 2: 0.032 ± 0.003). Conclusions. These results confirm earlier observations that changes in photopigment absorption are not the only source of retinal reflectance change during dark adaptation. It appears that the stray light that has historically reduced the apparent density of cone photopigment in retinal densitometry arises predominantly from layers near the photoreceptors themselves. Despite these complications, this method provides a valuable, objective measure of retinal function. PMID:25316726

  10. CHROMOPHORIC DISSOLVED ORGANIC MATTER (CDOM) SOURCE CHARACTERIZATION IN THE LOUISIANA BIGHT

    EPA Science Inventory

    Chromophoric dissolved organic matter (CDOM) in the Mississippi plume region may have several distinct sources: riverine (terrestrial soils), wetland (terrestrial plants), biological production (phytoplankton, zooplankton, microbial), and sediments. Complex mixing, photodegradati...

  11. CHROMOPHORIC DISSOLVED ORGANIC MATTER (CDOM) DERIVED FROM DECOMPOSITION OF VARIOUS VASCULAR PLANT AND ALGAL SOURCES

    EPA Science Inventory

    Chromophoric dissolved organic (CDOM) in aquatic environments is derived from the microbial decomposition of terrestrial and microbial organic matter. Here we present results of studies of the spectral properties and photoreactivity of the CDOM derived from several organic matter...

  12. THE ROLE OF NITROGEN IN CHROMOPHORIC AND FLUORESCENT DISSOLVED ORGANIC MATTER FORMATION

    EPA Science Inventory

    Microbial and photochemical processes affect chromophoric dissolved organic matter (CDOM) dynamics in the ocean. Some evidence suggests that dissolved nitrogen plays a role in CDOM formation, although this has received little systematic attention in marine ecosystems. Coastal sea...

  13. Self-Restricted Green Fluorescent Protein Chromophore Analogues: Dramatic Emission Enhancement and Remarkable Solvatofluorochromism.

    PubMed

    Deng, Hongping; Yu, Chunyang; Gong, Lidong; Zhu, Xinyuan

    2016-08-01

    The confinement effect of the β-barrel defines the emission profiles of the chromophores of the green fluorescent protein (GFP) family. Here, we describe the design strategy and mimicking of confinement effects via the chromophore itself, termed the self-restricted effect. By systematically tailoring the GFP core, a family of 2,5-dialkoxy-substituted GFP chromophore analogues is found to be highly emissive and show remarkable solvatofluorochromism in fluid solvents. Fluorescence quantum yield (QY) and lifetime measurements, in combination with theoretical calculations, illustrate the mechanism relying on inhibition of torsional rotation around the exocyclic CC bond. Meanwhile, theoretical calculations further reveal that the electrostatic interaction between the solvent and the imidazolinone oxygen can contribute to suppress the radiationless decay channel around the exocyclic C═C double bond. Our findings put forward a universal approach toward unlocked highly emissive GFPc analogues, potentially promoting the understanding of the photophysics and biochemical application of GFP chromophore analogues. PMID:27404318

  14. Preparation and optical characteristics of layered perovskite-type lead-bromide-incorporated azobenzene chromophores

    NASA Astrophysics Data System (ADS)

    Sasai, Ryo; Shinomura, Hisashi

    2013-02-01

    Lead bromide-based layered perovskite powders with azobenzene derivatives were prepared by a homogeneous precipitation method. From the diffuse reflectance (DR) and photoluminescence (PL) spectra of the hybrid powder materials, the present hybrids exhibited sharp absorption and PL peaks originating from excitons produced in the PbBr42- layer. When the present hybrid powder was irradiated with UV light at 350 nm, the absorption band from the trans-azobenzene chromophore, observed around 350 nm, decreased, while the absorption band from the cis-azobenzene chromophore, observed around 450 nm, increased. These results indicate that azobenzene chromophores in the present hybrid materials exhibit reversible photoisomerization. Moreover, it was found that the PL intensity from the exciton also varied due to photoisomerization of the azobenzene chromophores in the present hybrid. Thus, for the first time we succeeded in preparing the azobenzene derivative lead-bromide-based layered perovskite with photochromism before and after UV light irradiation.

  15. Photobleaching Kinetics of Chromophoric Dissolved Organic Matter Derived from Mangrove Leaf Litter and Floating Sargassum Colonies

    EPA Science Inventory

    We examined the photoreactivity of chromophoric dissolved organic matter (CDOM) derived from Rhizophora mangle (red mangrove) leaf litter and floating Sargassum colonies as these marine plants can be important contributors to coastal and open ocean CDOM pools, respectively. Mangr...

  16. Beta-Barrel Scaffold of Fluorescent Proteins: Folding, Stability and Role in Chromophore Formation

    PubMed Central

    Stepanenko, Olesya V.; Stepanenko, Olga V.; Kuznetsova, Irina M.; Verkhusha, Vladislav V.; Turoverov, Konstantin K.

    2013-01-01

    This review focuses on the current view of the interaction between the β-barrel scaffold of fluorescent proteins and their unique chromophore located in the internal helix. The chromophore originates from the polypeptide chain and its properties are influenced by the surrounding protein matrix of the β-barrel. On the other hand, it appears that a chromophore tightens the β-barrel scaffold and plays a crucial role in its stability. Furthermore, the presence of a mature chromophore causes hysteresis of protein unfolding and refolding. We survey studies measuring protein unfolding and refolding using traditional methods as well as new approaches, such as mechanical unfolding and reassembly of truncated fluorescent proteins. We also analyze models of fluorescent protein unfolding and refolding obtained through different approaches, and compare the results of protein folding in vitro to co-translational folding of a newly synthesized polypeptide chain. PMID:23351712

  17. X-ray Radiation Induces Deprotonation of the Bilin Chromophore in Crystalline D. Radiodurans Phytochrome

    SciTech Connect

    Li, Feifei; Burgie, E. Sethe; Yu, Tao; Heroux, Annie; Schatz, George C.; Vierstra, Richard D.; Orville, Allen M.

    2015-02-04

    We report that in the red light-absorbing (Pr) state, the bilin chromophore of the Deinococcus radiodurans proteobacterial phytochrome (DrBphP) is hypersensitive to X-ray photons used in typical synchrotron X-ray protein crystallography experiments. This causes the otherwise fully protonated chromophore to deprotonate without additional major structural changes. Furthermore, these results have major implications for our understanding of the structural and chemical characteristics of the resting and intermediate states of phytochromes and other photoreceptor proteins.

  18. ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual

  19. Comparison of biological chromophores: photophysical properties of cyanophenylalanine derivatives.

    PubMed

    Martin, Joshua P; Fetto, Natalie R; Tucker, Matthew J

    2016-07-27

    Within this work, the family of cyanophenylalanine spectroscopic reporters is extended by showing the ortho and meta derivatives have intrinsic photophysical properties that are useful for studies of protein structure and dynamics. The molar absorptivities of 2-cyanophenylalanine and 3-cyanophenylalanine are shown to be comparable to that of 4-cyanophenylalanine with similar spectral features in their absorbance and emission profiles, demonstrating that these probes can be utilized interchangeably. The fluorescence quantum yields are also on the same scale as commonly used fluorophores in peptides and proteins, tyrosine and tryptophan. These new cyano-fluorophores can be paired with either 4-cyanophenylalanine or tryptophan to capture distances in peptide structure through Förster resonance energy transfer. Additionally, the spectroscopic properties of these chromophores can report the local solvent environment via changes in fluorescence emission intensity as a result of hydrogen bonding and/or hydration. A decrease in the quantum yield is also observed in basic environments due to photoinduced electron transfer from a deprotonated amine in the free PheCN species and at the N-terminus of a short peptide, providing an avenue to detect pH in biological systems. Our results show the potential of these probes, 2-cyanophenylalanine and 3-cyanophenylalanine, to be incorporated into a single peptide chain, either individually or in tandem with 4-cyanophenylalanine, tryptophan, or tyrosine, in order to obtain information about peptide structure and dynamics. PMID:27412819

  20. Molecular mobility in self-assembled dendritic chromophore glasses.

    PubMed

    Knorr, Daniel B; Zhou, Xing-Hua; Shi, Zhengwei; Luo, Jingdong; Jang, Sei-Hum; Jen, Alex K-Y; Overney, René M

    2009-10-29

    Increasing complexity in bottom-up molecular designs of amorphous structures with multiple relaxation modes demands an integrated and cognitive design approach, where chemical synthesis is guided by both analytical tools and theoretical simulations. In particular, this is apparent for novel organic second-order nonlinear optical materials of self-assembling molecular glasses involving dendritic arene stabilization moieties (phenyl, naphthyl, and anthryl) with electro-optical activities above 300 pm/V. In this study, nanoscale thermo-mechanical analyses yield direct insight into the molecular enthalpic and entropic relaxation modes. Arene-perfluoroarene interactions for coarse self-assembly are found to impose three phase relaxation regimes, with intermediate regimes of 8-15 degrees C in width and apparent activation energies between 40 and 60 kcal/mol to be the most effective for poling. Energetic analyses based on intrinsic friction microscopy (IFA) identify increasing temporal stability with increasing arene size for the low-temperature regime. Electric field poling efficiency is found to be inversely proportional to entropic cooperative contributions that can make up 80% of the overall apparent relaxation energy for the high-temperature regime. The origin for the activation energies below the incipient glass transition temperature, based on complementary molecular dynamic simulations, is tied primarily to noncovalent interactions between chromophore (dipole), dendritic (quadrupole) moieties, and combinations thereof. PMID:19780549

  1. Chromophore detection by fluorescence spectroscopy in tissue-like phantoms

    NASA Astrophysics Data System (ADS)

    Cerussi, Albert E.; Fantini, Sergio; Maier, John S.; Mantulin, William W.; Gratton, Enrico

    1997-08-01

    In the near-infrared spectral region (700 - 900 nm) light penetrates a few centimeters into tissues and hemoglobin dominates the absorption. Consequently, in vivo near-infrared tissue absorption spectroscopy becomes difficult for endogenous compounds of biological interest other than hemoglobin. Exogenous chromophore detection by fluorescence spectroscopy has the potential to provide enhanced sensitivity and specificity for in vivo optical tissue spectroscopy, facilitating the study of many important metabolites in tissues other than hemoglobin. We have performed measurements of the dc fluorescence intensity generated by a fluorophore (rhodamine B) homogeneously dissolved inside a highly scattering tissue-simulating phantom (aqueous suspension of titanium-dioxide particles). The phantom was prepared with optical coefficients (absorption and reduced scattering) similar to those of tissue in the near-infrared; these coefficients were measured with a frequency-domain spectrometer. Measurable dc fluorescence intensity signals from 1 nM rhodamine concentrations inside the phantom are reported. Furthermore, we were able to resolve changes in rhodamine concentration on the order of 1% using the dc fluorescence intensity. This dc fluorescence sensitivity is characterized experimentally at two concentrations (55 and 360 nM) and over a range of source-detector separations. Other aspects of the sensitivity are discussed over a large range of concentrations using a fluorescence photon migration model.

  2. Enhancement of hydrophobic chromophore fluorescence by adsorption to nanospheres

    NASA Astrophysics Data System (ADS)

    Blair, Elizabeth; Carr, Aaron; Krishnan, Rajagopal; Nordlund, Thomas M.

    2003-11-01

    Optical properties of hydrophobic molecules are usually studied in solvents of low dielectric constant. However, biologically or medically important molecules often exist in a mixed hydrophobic/ aqueous environment, e.g., in emulsions or membranes. In order to study optical processes occurring in oily sunscreen agents, octyl salicylate and octyl methoxycinnamate, in a model aqueous/hydrophobic environment, we dispersed the agents in suspensions of polystyrene nanospheres, ranging in diameter from 30 to 1500 nm. The spheres had sulfate functional groups and a low negative charge on the surface. Adsorption of salicylate resulted in a fluorescence intensity enhancement of 6 +/- 0.5 compared to a solution in methanol. The enhancement was independent of sphere diameter. Cinnamate had a much lower enhancement, about 1.5. The enhancement correlates with fluorescence yield vs. dielectric constant in organic solvents: the adsorbed chromophore acts as if it were surrounded by a material of dielectric constant less than 2, in spite of the presence of neighboring water molecules.

  3. Contaminant-mediated photobleaching of wetland chromophoric dissolved organic matter.

    PubMed

    Langlois, Maureen C; Weavers, Linda K; Chin, Yu-Ping

    2014-09-20

    Photolytic transformation of organic contaminants in wetlands can be mediated by chromophoric dissolved organic matter (CDOM), which in turn can lose its reactivity from photobleaching. We collected water from a small agricultural wetland (Ohio), Kawai Nui Marsh (Hawaii), the Everglades (Florida), and Okefenokee Swamp (Georgia) to assess the effect of photobleaching on the photofate of two herbicides, acetochlor and isoproturon. Analyte-spiked water samples were irradiated using a solar simulator and monitored for changes in CDOM light absorbance and dissolved oxygen. Photobleaching did not significantly impact the indirect photolysis rates of either herbicide over 24 hours of irradiation. Surprisingly, the opposite effect was observed with isoproturon, which accelerated DOM photobleaching. This phenomenon was more pronounced in higher-CDOM waters, and we believe that the redox pathway between triplet-state CDOM and isoproturon may be responsible for our observations. By contrast, acetochlor indirect photolysis was dependent on reaction with the hydroxyl radical and did not accelerate photobleaching of wetland water as much as isoproturon. Finally, herbicide indirect photolysis rate constants did not correlate strongly to any one chemical or optical property of the sampled waters. PMID:24828085

  4. EDXRF quantitative analysis of chromophore chemical elements in corundum samples.

    PubMed

    Bonizzoni, L; Galli, A; Spinolo, G; Palanza, V

    2009-12-01

    Corundum is a crystalline form of aluminum oxide (Al(2)O(3)) and is one of the rock-forming minerals. When aluminum oxide is pure, the mineral is colorless, but the presence of trace amounts of other elements such as iron, titanium, and chromium in the crystal lattice gives the typical colors (including blue, red, violet, pink, green, yellow, orange, gray, white, colorless, and black) of gemstone varieties. The starting point for our work is the quantitative evaluation of the concentration of chromophore chemical elements with a precision as good as possible to match the data obtained by different techniques as such as optical absorption photoluminescence. The aim is to give an interpretation of the absorption bands present in the NIR and visible ranges which do not involve intervalence charge transfer transitions (Fe(2+) --> Fe(3+) and Fe(2+) --> Ti(4+)), commonly considered responsible of the important features of the blue sapphire absorption spectra. So, we developed a method to evaluate as accurately as possible the autoabsorption effects and the secondary excitation effects which frequently are sources of relevant errors in the quantitative EDXRF analysis. PMID:19821113

  5. Synergistic "ping-pong" energy transfer for efficient light activation in a chromophore-catalyst dyad.

    PubMed

    Quaranta, Annamaria; Charalambidis, Georgios; Herrero, Christian; Margiola, Sofia; Leibl, Winfried; Coutsolelos, Athanassios; Aukauloo, Ally

    2015-10-01

    The synthesis of a porphyrin-Ru(II) polypyridine complex where the porphyrin acts as a photoactive unit and the Ru(II) polypyridine as a catalytic precursor is described. Comparatively, the free base porphyrin was found to outperform the ruthenium based chromophore in the yield of light induced electron transfer. Mechanistic insights indicate the occurrence of a ping-pong energy transfer from the (1)LC excited state of the porphyrin chromophore to the (3)MCLT state of the catalyst and back to the (3)LC excited state of the porphyrin unit. The latter, triplet-triplet energy transfer back to the chromophore, efficiently competes with fast radiationless deactivation of the excited state at the catalyst site. The energy thus recovered by the chromophore allows improved yield of formation of the oxidized form of the chromophore and concomitantly of the oxidation of the catalytic unit by intramolecular charge transfer. The presented results are among the rare examples where a porphyrin chromophore is successfully used to drive an oxidative activation process where reductive processes prevail in the literature. PMID:26327298

  6. In vitro assembly of phytochrome B apoprotein with synthetic analogs of the phytochrome chromophore

    PubMed Central

    Hanzawa, Hiroko; Inomata, Katsuhiko; Kinoshita, Hideki; Kakiuchi, Takashi; Jayasundera, Krishanthi Padmarani; Sawamoto, Daisuke; Ohta, Atsuko; Uchida, Kenko; Wada, Keishiro; Furuya, Masaki

    2001-01-01

    Phytochrome B (PhyB), one of the major photosensory chromoproteins in plants, mediates a variety of light-responsive developmental processes in a photoreversible manner. To analyze the structural requirements of the chromophore for the spectral properties of PhyB, we have designed and chemically synthesized 20 analogs of the linear tetrapyrrole (bilin) chromophore and reconstituted them with PhyB apoprotein (PHYB). The A-ring acts mainly as the anchor for ligation to PHYB, because the modification of the side chains at the C2 and C3 positions did not significantly influence the formation or difference spectra of adducts. In contrast, the side chains of the B- and C-rings are crucial to position the chromophore properly in the chromophore pocket of PHYB and for photoreversible spectral changes. The side-chain structure of the D-ring is required for the photoreversible spectral change of the adducts. When methyl and ethyl groups at the C17 and C18 positions are replaced with an n-propyl, n-pentyl, or n-octyl group, respectively, the photoreversible spectral change of the adducts depends on the length of the side chains. From these studies, we conclude that each pyrrole ring of the linear tetrapyrrole chromophore plays a different role in chromophore assembly and the photochromic properties of PhyB. PMID:11248126

  7. Suppression and retinal correspondence in intermittent exotropia.

    PubMed Central

    Cooper, J; Record, C D

    1986-01-01

    Suppression scotomas and retinal projection (retinal correspondence) were measured in six intermittent exotropes during deviation. Measurements used red-green anaglyph stimuli presented on a black background which could be varied from 3.4 minutes of arc to 3 degrees 24'. Results showed non-suppression of all points between the fovea and the diplopia point. Harmonious anomalous retinal correspondence was usually observed. Two subjects had spontaneous changes from anomalous retinal correspondence to normal retinal correspondence without a concurrent change in ocular position. Conventional testing resulted in more variable results in regard to retinal correspondence and suppression, suggesting that non-suppression and anomalous retinal correspondence occur when black backgrounds are used for testing. PMID:3756124

  8. Retinitis Pigmentosa and Education Issues

    ERIC Educational Resources Information Center

    Brown, Thomas J.

    2005-01-01

    Retinitis Pigmentosa includes a number of inherited diseases which usually result in blindness. The disease is progressive in nature and begins with the deterioration of cells in the eye responsible for peripheral vision. As the condition worsens there is a gradual loss of peripheral vision and night blindness. Proper educational planning requires…

  9. Photochemical chromophore isomerization in histidine kinase rhodopsin HKR1.

    PubMed

    Luck, Meike; Bruun, Sara; Keidel, Anke; Hegemann, Peter; Hildebrandt, Peter

    2015-04-28

    Histidine kinase rhodopsin 1 is a photoreceptor in green algae functioning as a UV-light sensor. It switches between a UV-absorbing state (Rh-UV) and a blue-absorbing state (Rh-Bl) with a protonated retinal Schiff base (RSB) cofactor in a mixture of 13-trans,15-anti and 13-cis,15-syn isomers. The present spectroscopic study now shows that cofactor-protein assembly stabilizes the protonated 13-trans,15-anti RSB isomer. Formation of the active photoswitch requires the photoinduced conversion to Rh-UV. The transitions between the Rh-Bl isomers and the deprotonated 13-cis,15-anti and 13-trans,15-syn isomers of Rh-UV proceed via multiple photoisomerizations of one or simultaneously two double bonds. PMID:25836735

  10. A conserved aromatic residue regulating photosensitivity in short-wavelength sensitive cone visual pigments.

    PubMed

    Kuemmel, Colleen M; Sandberg, Megan N; Birge, Robert R; Knox, Barry E

    2013-07-30

    Visual pigments have a conserved phenylalanine in transmembrane helix 5 located near the β-ionone ring of the retinal chromophore. Site-directed mutants of this residue (F207) in a short-wavelength sensitive visual pigment (VCOP) were studied using UV-visible spectroscopy to investigate its role in photosensitivity and formation of the light-activated state. The side chain is important for pigment formation: VCOP(F207A), VCOP(F207L), VCOP(F207M), and VCOP(F207W) substitutions all bound 11-cis-retinal and formed a stable visual pigment, while VCOP(F207V), VCOP(F207S), VCOP(F207T), and VCOP(F207Y) substitutions do not. The extinction coefficients of all pigments are close, ranging between 35800 and 45600 M⁻¹ cm⁻¹. Remarkably, the mutants exhibit an up to 5-fold reduction in photosensitivity and also abnormal photobleaching behavior. One mutant, VCOP(F207A), forms an isomeric composition of the retinal chromophore after illumination comparable to that of wild-type VCOP yet does not release the all-trans-retinal chromophore. These findings suggest that the conserved F207 residue is important for a normal photoactivation pathway, formation of the active conformation and the exit of all-trans-retinal from the chromophore-binding pocket. PMID:23808485

  11. Spectral tuning by opsin coexpression in retinal regions that view different parts of the visual field.

    PubMed

    Dalton, Brian E; Loew, Ellis R; Cronin, Thomas W; Carleton, Karen L

    2014-12-22

    Vision frequently mediates critical behaviours, and photoreceptors must respond to the light available to accomplish these tasks. Most photoreceptors are thought to contain a single visual pigment, an opsin protein bound to a chromophore, which together determine spectral sensitivity. Mechanisms of spectral tuning include altering the opsin, changing the chromophore and incorporating pre-receptor filtering. A few exceptions to the use of a single visual pigment have been documented in which a single mature photoreceptor coexpresses opsins that form spectrally distinct visual pigments, and in these exceptions the functional significance of coexpression is unclear. Here we document for the first time photoreceptors coexpressing spectrally distinct opsin genes in a manner that tunes sensitivity to the light environment. Photoreceptors of the cichlid fish, Metriaclima zebra, mix different pairs of opsins in retinal regions that view distinct backgrounds. The mixing of visual pigments increases absorbance of the corresponding background, potentially aiding the detection of dark objects. Thus, opsin coexpression may be a novel mechanism of spectral tuning that could be useful for detecting prey, predators and mates. However, our calculations show that coexpression of some opsins can hinder colour discrimination, creating a trade-off between visual functions. PMID:25377457

  12. Spectral tuning by opsin coexpression in retinal regions that view different parts of the visual field

    PubMed Central

    Dalton, Brian E.; Loew, Ellis R.; Cronin, Thomas W.; Carleton, Karen L.

    2014-01-01

    Vision frequently mediates critical behaviours, and photoreceptors must respond to the light available to accomplish these tasks. Most photoreceptors are thought to contain a single visual pigment, an opsin protein bound to a chromophore, which together determine spectral sensitivity. Mechanisms of spectral tuning include altering the opsin, changing the chromophore and incorporating pre-receptor filtering. A few exceptions to the use of a single visual pigment have been documented in which a single mature photoreceptor coexpresses opsins that form spectrally distinct visual pigments, and in these exceptions the functional significance of coexpression is unclear. Here we document for the first time photoreceptors coexpressing spectrally distinct opsin genes in a manner that tunes sensitivity to the light environment. Photoreceptors of the cichlid fish, Metriaclima zebra, mix different pairs of opsins in retinal regions that view distinct backgrounds. The mixing of visual pigments increases absorbance of the corresponding background, potentially aiding the detection of dark objects. Thus, opsin coexpression may be a novel mechanism of spectral tuning that could be useful for detecting prey, predators and mates. However, our calculations show that coexpression of some opsins can hinder colour discrimination, creating a trade-off between visual functions. PMID:25377457

  13. Captodatively stabilized biradicaloids as chromophores for singlet fission.

    PubMed

    Wen, Jin; Havlas, Zdenĕk; Michl, Josef

    2015-01-14

    Singlet fission offers an opportunity to improve solar cell efficiency, but its practical use is hindered by the limited number of known efficient materials. We look for chromophores that satisfy the desirable but rarely encountered adiabatic energy conditions, E(T2) - E(S0) > E(S1) - E(S0) ≈ 2[E(T1) - E(S0)], and are small enough to permit highly accurate calculations. We provide a rationale for the use of captodative biradicaloids, i.e., biradicals stabilized by direct interaction between their radical centers, which carry both an acceptor and a donor group. A computation of vertical excitation energies of 14 structures of this type by time-dependent density functional theory (TD-DFT) yielded 11 promising candidates. The vertical excitation energies from S0 and T1 were recalculated by complete-active-space second-order perturbation theory (CASPT2), and five of the compounds met the above energy criteria. Their adiabatic excitation energies from the S0 into the S1, S2, T1, and T2 excited states were subsequently calculated, and three of them look promising. For 2,3-diamino-1,4-benzoquinone, adiabatic E(T1) and E(S1) energies were close to optimal (1.12 and 2.23 eV above the S0 ground state, respectively), and for its more practical N-peralkylated derivative they were even lower (0.63 and 1.06 eV above S0, respectively). PCM/CASPT2 results suggested that the relative energies can be further tuned by varying the polarity of the environment. PMID:25478747

  14. Retinal vasculature classification using novel multifractal features

    NASA Astrophysics Data System (ADS)

    Ding, Y.; Ward, W. O. C.; Duan, Jinming; Auer, D. P.; Gowland, Penny; Bai, L.

    2015-11-01

    Retinal blood vessels have been implicated in a large number of diseases including diabetic retinopathy and cardiovascular diseases, which cause damages to retinal blood vessels. The availability of retinal vessel imaging provides an excellent opportunity for monitoring and diagnosis of retinal diseases, and automatic analysis of retinal vessels will help with the processes. However, state of the art vascular analysis methods such as counting the number of branches or measuring the curvature and diameter of individual vessels are unsuitable for the microvasculature. There has been published research using fractal analysis to calculate fractal dimensions of retinal blood vessels, but so far there has been no systematic research extracting discriminant features from retinal vessels for classifications. This paper introduces new methods for feature extraction from multifractal spectra of retinal vessels for classification. Two publicly available retinal vascular image databases are used for the experiments, and the proposed methods have produced accuracies of 85.5% and 77% for classification of healthy and diabetic retinal vasculatures. Experiments show that classification with multiple fractal features produces better rates compared with methods using a single fractal dimension value. In addition to this, experiments also show that classification accuracy can be affected by the accuracy of vessel segmentation algorithms.

  15. Synthesis and electrocatalytic water oxidation by electrode-bound helical peptide chromophore-catalyst assemblies.

    PubMed

    Ryan, Derek M; Coggins, Michael K; Concepcion, Javier J; Ashford, Dennis L; Fang, Zhen; Alibabaei, Leila; Ma, Da; Meyer, Thomas J; Waters, Marcey L

    2014-08-01

    Artificial photosynthesis based on dye-sensitized photoelectrosynthesis cells requires the assembly of a chromophore and catalyst in close proximity on the surface of a transparent, high band gap oxide semiconductor for integrated light absorption and catalysis. While there are a number of approaches to assemble mixtures of chromophores and catalysts on a surface for use in artificial photosynthesis based on dye-sensitized photoelectrosynthesis cells, the synthesis of discrete surface-bound chromophore-catalyst conjugates is a challenging task with few examples to date. Herein, a versatile synthetic approach and electrochemical characterization of a series of oligoproline-based light-harvesting chromophore-water-oxidation catalyst assemblies is described. This approach combines solid-phase peptide synthesis for systematic variation of the backbone, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) as an orthogonal approach to install the chromophore, and assembly of the water-oxidation catalyst in the final step. Importantly, the catalyst was found to be incompatible with the conditions both for amide bond formation and for the CuAAC reaction. The modular nature of the synthesis with late-stage assembly of the catalyst allows for systematic variation in the spatial arrangement of light-harvesting chromophore and water-oxidation catalyst and the role of intrastrand distance on chromophore-catalyst assembly properties. Controlled potential electrolysis experiments verified that the surface-bound assemblies function as water-oxidation electrocatalysts, and electrochemical kinetics data demonstrate that the assemblies exhibit greater than 10-fold rate enhancements compared to the homogeneous catalyst alone. PMID:25046035

  16. Unveiling the mechanism of photoinduced isomerization of the photoactive yellow protein (PYP) chromophore

    SciTech Connect

    Gromov, Evgeniy V.

    2014-12-14

    A detailed theoretical analysis, based on extensive ab initio second-order approximate coupled cluster calculations, has been performed for the S{sub 1} potential energy surface (PES) of four photoactive yellow protein (PYP) chromophore derivatives that are hydrogen bonded with two water molecules and differ merely in the carbonyl substituent. The main focus is put on contrasting the isomerization properties of these four species in the S{sub 1} excited state, related to torsion around the chromophore's single and double carbon-carbon bonds. The analysis provides evidence of the different isomerization behavior of these four chromophore complexes, which relates to the difference in their carbonyl substituents. While a stable double-bond torsion pathway exists on the S{sub 1} PES of the chromophores bearing the –O–CH{sub 3} and –NH{sub 2} substituents, this is not the case for the –S–CH{sub 3} and –CH{sub 3} substituted species. The presence of the –S–CH{sub 3} group leads to a strong instability of the chromophore with respect to the single-bond twist, whereas in the case of the –CH{sub 3} substituent a crossing of the S{sub 1} and S{sub 2} PESs occurs, which perturbs the pathway. Based on this analysis, the key factors that support the double-bond torsion have been identified. These are (i) the hydrogen bonds at the phenolic oxygen of the chromophore, (ii) the weak electron-acceptor character of the carbonyl group, and (iii) the ethylene-like pattern of the torsion in the beginning of the process. Our results suggest that the interplay between these factors determines the chromophore's isomerization in the solvent environment and in the native PYP environment.

  17. Photochromism of halorhodopsin. cis/trans isomerization of the retinal around the 13-14 double bond.

    PubMed

    Lanyi, J K

    1986-10-25

    The isomeric composition of retinal in membrane-bound and in purified but detergent-free, dark-adapted halorhodopsin was found to be about 70% 13-cis and 30% all-trans. Any illumination increased the all-trans content relative to the dark-adapted state, but blue illumination shifted the isomeric composition more toward all-trans while red illumination of blue-adapted samples shifted it more toward 13-cis. In the presence of chloride this photoisomerization caused the kind of photochromic behavior reported earlier in Smith, S. O., Marvin, M. J., Bogomolni, R. A., and Mathies, R. A. (1984) J. Biol. Chem. 259, 12326-12329, i.e. blue light caused the absorption maximum to move toward longer wavelengths and red light reversed the shift. Only the all-trans chromophore exhibited the complete photocycle described earlier in detergent-solubilized halorhodopsin, and this was the form that could be associated with light-driven chloride transport activity in cell envelope vesicles. In the absence of chloride the spectroscopic changes caused by illumination were much smaller. Reconstitution of bleached preparations with 13-cis- and all-trans-retinal, in the presence and absence of chloride, confirmed that the difference between the absorption maxima of the two isomeric forms of the chromophore is affected by chloride: 13-cis-halorhodopsin absorbs at about 567-568 nm with and without chloride, and the all-trans pigment absorbs near 568 nm in the absence of chloride, but at 578 nm in its presence. The simplest explanation of this finding is that most of the red-shift which accompanies the 13-cis----all-trans transition originates from electrostatic interaction of the retinal with chloride bound in its vicinity. PMID:3771521

  18. Role of retinal metabolism in methanol-induced retinal toxicity

    SciTech Connect

    Garner, C.D. |; Lee, E.W.; Terzo, T.S.; Louis-Ferdinand, R.T.

    1995-08-01

    Methanol is a toxicant that causes systemic and ocular toxicity after acute exposure. The folate-reduced (FR) rat is an excellent animal model that mimics characteristic human methanol toxic responses. The present study examines the role of the methanol metabolites formaldehyde and formate in the initiation of methanol-induced retinal toxicity. After a single oral dose of 3.0 g/kg methanol, blood methanol concentrations were not significantly different in FR rats compared with folate-sufficient (FS) (control) rats. However, FR rats treated with 3.0 g/kg methanol displayed elevated blood (14.6 mM) and vitreous humor (19.5 mM) formate levels and abnormal electroretinograms (loss of b-wave) 48 h postdose. FR rats pretreated with disulfiram (DSF) prior to 3.0 g/kg methanol treatment failed to display these symptoms. Formaldehyde was not detected in blood or vitreous humor with or without DSF treatment, suggesting that formate is the toxic metabolite in methanol-induced retinal toxicity. Additionally, creating a blood formate profile (14.2 mM at 48 h) similar to that observed in methanol-treated rats by iv infusion of pH-buffered formate does not alter the electroretinogram as is observed with methanol treatment. These data suggest that intraretinal metabolism of methanol is necessary for the formate-mediated initiation of methanol-induced retinal toxicity. 31 refs., 5 figs., 2 tabs.

  19. Excited States and Photochemistry of Chromophores in the Photoactive Proteins Explored by the Combined Quantum Mechanical and Molecular Mechanical Calculations.

    PubMed

    Liu, Lihong; Cui, Ganglong; Fang, Wei-Hai

    2015-01-01

    A photoactive protein usually contains a unique chromophore that is responsible for the initial photoresponse and functions of the photoactive protein are determined by the interaction between the chromophore and its protein surroundings. The combined quantum mechanical and molecular mechanical (QM/MM) approach is demonstrated to be a very useful tool for exploring structures and functions of a photoactive protein with the chromophore and its protein surroundings treated by the QM and MM methods, respectively. In this review, we summarize the basic formulas of the QM/MM approach and emphasize its applications to excited states and photoreactions of chromophores in rhodopsin protein, photoactive yellow protein, and green fluorescent protein. PMID:26415847

  20. Role of retinal vascular endothelial cells in development of CMV retinitis.

    PubMed Central

    Rao, N A; Zhang, J; Ishimoto, S

    1998-01-01

    PURPOSE: Although cytomegalovirus (CMV) retinitis is known to occur in association with retinal microangiopathy in individuals with marked immunodeficiency, glial cells are believed to be the initial target cells in the development of retinitis. Moreover, it has been hypothesized that CMV gains access to the retinal glia because of altered vascular permeability. In an attempt to address the hypothesis, we studied 30 autopsy eyes of AIDS patients with systemic CMV infection, with or without clinically apparent CMV retinitis. METHODS: The autopsy eyes were processed in three ways. First, dual immunohistochemical studies were done by using anti-CMV antibodies for immediate early, early, and late antigens. The retinal cell types infected with the virus were then determined by using anti-GFAP, anti-VonWillebrand's factor, neuronal specific enolase, and leukocyte marker CD68. Second, selected eyes were processed for in situ hybridization with DNA probe specific to CMV. Third, an eye with clinically apparent CMV retinitis was submitted for electron microscopic examination. RESULTS: At the site of retinal necrosis in those eyes with a clinical diagnosis of CMV retinitis, the immunohistochemical, in situ hybridization, and ultrastructural examinations revealed that CMV was present primarily in the Müller cells and in perivascular glial cells. Adjacent to these infected cells, focal areas of positive staining for CMV antigen were seen in the glial cells, neuronal cells, and retinal pigment epithelial cells. At these sites most of the retinal capillaries were devoid of endothelial cells. Few vessels located at the advancing margin of retinal necrosis showed the presence of viral proteins in the endothelial cells. CONCLUSIONS: The present results indicate that retinal vascular endothelial cells could be the initial target in the development of viral retinitis, with subsequent spread of the infection to perivascular glia, Müller cells, and other retinal cells, including the

  1. Current perspectives of herpesviral retinitis and choroiditis.

    PubMed

    Madhavan, H N; Priya, K; Biswas, J

    2004-10-01

    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens. PMID:16295367

  2. Retinal abnormalities in β-thalassemia major.

    PubMed

    Bhoiwala, Devang L; Dunaief, Joshua L

    2016-01-01

    Patients with beta (β)-thalassemia (β-TM: β-thalassemia major, β-TI: β-thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelial degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-thalassemia major are transfusion dependent and require iron chelation therapy to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by iron chelation therapy. Some who were never treated with iron chelation therapy exhibited retinopathy, and others receiving iron chelation therapy had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-thalassemia major viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. PMID:26325202

  3. Gene Therapy for Retinal Diseases

    PubMed Central

    Samiy, Nasrollah

    2014-01-01

    Gene therapy has a growing research potential particularly in the field of ophthalmic and retinal diseases owing to three main characteristics of the eye; accessibility in terms of injections and surgical interventions, its immune-privileged status facilitating the accommodation to the antigenicity of a viral vector, and tight blood-ocular barriers which save other organs from unwanted contamination. Gene therapy has tremendous potential for different ocular diseases. In fact, the perspective of gene therapy in the field of eye research does not confine to exclusive monogenic ophthalmic problems and it has the potential to include gene based pharmacotherapies for non-monogenic problems such as age related macular disease and diabetic retinopathy. The present article has focused on how gene transfer into the eye has been developed and used to treat retinal disorders with no available therapy at present. PMID:25709778

  4. Retinitis pigmentosa in southern Africa.

    PubMed

    Greenberg, J; Bartmann, L; Ramesar, R; Beighton, P

    1993-11-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders which are a common cause of genetic blindness. The relative frequencies of the different forms of RP in South Africa, as determined from the register at the DNA banking centre for RP at the Department of Human Genetics, University of Cape Town, are presented and discussed. Of the 125 families analysed, 29 (23%) showed autosomal dominant, 33 (27%) autosomal recessive and 3 (3%) X-linked inheritance. In 10 families the pedigree data were insufficient to allow accurate genetic subtyping and a further 50 patients were sporadic without a family history of RP or other syndromic features which would allow categorization. PMID:8313621

  5. Retinal vein occlusion: current treatment.

    PubMed

    Lattanzio, Rosangela; Torres Gimeno, Ana; Battaglia Parodi, Maurizio; Bandello, Francesco

    2011-01-01

    Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management. PMID:20938213

  6. Operational challenges of retinal prostheses.

    PubMed

    Schmid, Erich W; Fink, Wolfgang; Wilke, Robert

    2014-12-01

    Two computational models for research on retinal implants are presented. In the first model, the electric field produced by a multi-electrode array in a uniform retina is calculated. It is shown how cross talk of activated electrodes and the resulting bunching of field lines in monopole and dipole activation prevent high resolution imaging with retinal implants. Furthermore, it is demonstrated how sequential stimulation and multipolar stimulation may overcome this limitation. In the second model a target volume, i.e., a probe cylinder approximating a bipolar cell, in the retina is chosen, and the passive Heaviside cable equation is solved inside this target volume to calculate the depolarization of the cell membrane. The depolarization as a function of time indicates that shorter signals stimulate better as long as the current does not change sign during stimulation of the retina, i.e., mono-phasic stimulation. Both computational models are equally applicable to epiretinal, subretinal, and suprachoroidal vision implants. PMID:25443535

  7. Processing of organic electro-optic materials: solution-phase assisted reorientation of chromophores

    NASA Astrophysics Data System (ADS)

    Olbricht, Benjamin C.; Eng, David L. K.; Kozacik, Stephen T.; Ross, Dylan; Prather, Dennis W.

    2013-03-01

    Organic EO materials, sometimes called EO polymers, offer a variety of very promising properties that have improved at remarkable rates over the last decade, and will continue to improve. However, these materials rely on a "poling" process to afford EO activity, which is commonly cited as the bottleneck for the widespread implementation of organic EO material-containing devices. The Solution Phase-Assisted Reorientation of Chromophores (SPARC) is a process that utilizes the mobility of chromophores in the solution phase to afford acentric molecular order during deposition. The electric field can be generated by a corona discharge in a carefully-controlled gas environment. The absence of a poling director during conventional spin deposition forms centric pairs of chromophores which may compromise the efficacy of thermal poling. Direct spectroscopic evidence of linear dichroism in modern organic EO materials has estimated the poling-induced order of the chromophores to be 10-15% of its theoretical maximum, offering the potential for a manyfold enhancement in EO activity if poling is improved. SPARC is designed to overcome these limitations and also to allow the poling of polymeric hosts with temporal thermal (alignment) stabilities greater than the decomposition temperature of the guest chromophore. In this report evidence supporting the theory motivating the SPARC process and the resulting EO activities will be presented. Additionally, the results of trials towards a device demonstration of the SPARC process will be discussed.

  8. Frequency-agile hyper-Rayleigh scattering studies of electro-optic chromophores

    NASA Astrophysics Data System (ADS)

    Firestone, Kimberly A.; Lao, David B.; Casmier, Daniel M.; Clot, Olivier; Dalton, Larry R.; Reid, Philip J.

    2005-08-01

    Hyper-Rayleigh scattering (HRS) is used to measure the first-hyperpolarizability (β) of electro-optic (EO) chromophores. One of the inherent concerns in any HRS measurement is the extent to which resonant enhancement contributes to the observed intensity thereby leading to inaccuracies when evaluating chromophore potential for application in electro-optical devices. One way to address this concern is to employ increasingly longer excitation wavelengths far from resonance. However, in charge-transfer-based non-linear optical chromophores, enhanced β generally correlates with a red-shift of the charge transfer absorption band so that even at the longest excitation wavelengths generally employed in HRS studies, resonant enhancement remains an issue. We have adopted an alternative approach in which the wavelength dispersion of the HRS intensity is determined by performing measurements at a variety of excitation wavelengths. This approach allows one to ascertain the role of resonance enhancement thereby allowing for more accurate correlation of improved β with molecular architecture. We report the results of our HRS studies for nine chromophores employing excitation wavelengths ranging from 780 to 1907 nm. Our HRS results demonstrate good agreement with the predictions of density functional theory. This synthesis of experimental and theoretical techniques has resulted in more effective designs for the next generations of electro-optical chromophores.

  9. The native forms of the phycobilin chromophores of algal biliproteins. A clarification.

    PubMed Central

    O'Carra, P; Murphy, R F; Killilea, S D

    1980-01-01

    Pigments released from phycoerythrins and phycocyanins by treatment with hot methanol are currently regarded as equivalent to the native chromophores phycoerythrobilin and phycocyanobilin. However, evidence presented here confirms the original view of O'Carra & O'hEocha [(1966 Phytochemistry 5, 993-997] that these methanol-released pigments are artefacts differing in their chromophoric conjugated systems from the native protein-bound prosthetic groups. By contrast, the native spectral properties are retained in pigments released by careful acid treatment of the biliproteins and these acid-released phycobilins, rather than the methanol-released pigments, are therefore regarded as the protein-free forms of the native chromophores. The conclusion reached by Chapman, Cole & Siegelman [(1968) J. Am. Chem. Soc. 89, 3643-3645], that all the algal biliproteins contain only phycoerythrobilin and phycocyanobilin, is shown to be incorrect. The identification of a urobilinoid chromophore, phycourobilin, accompanying phycoerythrobilin in B- and R- phycoerythrins is confirmed and supported by more extensive evidence. The cryptomonad phycocyanins are shown to contain a phycobilin chromophore accompanying phycocyanobilin. This further phycobilin has the spectral properties of the class of bilins known as violins and the provisional name "cryptoviolin" is proposed pending elucidation of its structure. PMID:7396851

  10. Revealing Brown Carbon Chromophores Produced in Reactions of Methylglyoxal with Ammonium Sulfate

    SciTech Connect

    Lin, Peng; Laskin, Julia; Nizkorodov, Sergey A.; Laskin, Alexander

    2015-12-15

    Atmospheric brown carbon (BrC) is an important contributor to light absorption and climate forcing by aerosols. Reactions between small water-soluble carbonyls and ammonia or amines have been identified as one of the potential pathways of BrC formation. However, detailed chemical characterization of BrC chromophores has been challenging and their formation mechanisms are still poorly understood. Understanding BrC formation is impeded by the lack of suitable methods which can unravel the variability and complexity of BrC mixtures. This study applies high performance liquid chromatography (HPLC) coupled to photodiode array (PDA) detector and high resolution mass spectrometry (HRMS) to investigate optical properties and chemical composition of individual BrC components produced through reactions of methylglyoxal (MG) and ammonium sulfate (AS), both of which are abundant in the atmospheric environment. A direct relationship between optical properties and chemical composition of 30 major BrC chromophores was established. Nearly all of these chromophores are nitrogen-containing compounds that account for >70% of the overall light absorption by the MG+AS system in the 300-500 nm range. These results suggest that reduced-nitrogen organic compounds formed in reactions between atmospheric carbonyls and ammonia/amines are important BrC chromophores. It is also demonstrated that improved separation of BrC chromophores by HPLC will significantly advance understanding of BrC chemistry.

  11. Performance of DFT Methods in the Calculation of Optical Spectra of TCF-Chromophores

    SciTech Connect

    Andzelm, Jan; Rinderspacher, Berend C.; Rawlett, Adam M.; Dougherty, Joseph; Baer, Roi; Govind, Niranjan

    2009-10-01

    We present electronic structure calculations of the ultraviolet/visible (UV-Vis) spectra of highly active push-pull chromophores containing tricyanofuran (TCF) acceptor group. In particular, we have applied the recently developed long-range corrected Baer-Neuhauser-Livshits (BNL) exchange-correlation functional. The performance of this functional compares favorably with other density functional theory (DFT) approaches, including the CAM-B3LYP functional. The accuracy of UV-Vis results for these molecules is best at low values of attenuation parameters (γ) for both BNL and CAM-B3LYP functionals. The optimal value of γ is different for the charge-transfer (CT) and π-π* excitations. The BNL and PBE0 exchange correlation functionals capture the CT states particularly well while the π-π* excitations are less accurate and system dependent. Chromophore conformations, which considerably affect the molecular hyperpolarizability, do not significantly influence the UV-Vis spectra on average. As expected, the color of chromophores is a sensitive function of modifications to its conjugated framework, and is not significantly affected by increasing aliphatic chain length linking a chromophore to a polymer. For selected push-pull aryl-chromophores, we find a significant dependence of absorption spectra on the strength of diphenylaminophenyl donors.

  12. Synthesis and properties of nonlinear optical chromophore containing alkoxy-substituted phenylene as conjugation bridge

    NASA Astrophysics Data System (ADS)

    Kim, Dong Wook; Yoon, Sung Cheol; Lim, Jong-Sun; Lee, Changjin

    2007-07-01

    We designed and synthesized a push-pull type chromophore (St-TCF) containing phenylene ring as a conjugation bridge. Bulky alkyl chain was substituted into the phenylene bridge to minimize intermolecular interaction of the neighbor molecules and to enhance solubility of the chromophore in solvents and polymer host. The chemical structure and purity were verified by 1H NMR, 1H-1H COSY, 13C NMR, DEPT and Mass spectroscopy. The NMR spectra showed that we obtained the chromophore in a trans conformation. In spite of the bulky alkyl chains, St-TCF exhibited fairly high melting point of 167 °C. The chromophore was thermally stable up to 200 °C in the nitrogen atmosphere. The relatively high melting point and decomposition on-set may be attributable to the rigid phenylene ring. The chromophore was blended with an optically transparent polymer host and then the macroscopic electro-optic activity was evaluated. In a preliminary result, the polymer films containing St-TCF as a concentration of 50 wt% exhibited as large as 20-24 pm/V electro-optic coefficient at 1.55 μ.

  13. The terminal phycobilisome emitter, LCM: A light-harvesting pigment with a phytochrome chromophore.

    PubMed

    Tang, Kun; Ding, Wen-Long; Höppner, Astrid; Zhao, Cheng; Zhang, Lun; Hontani, Yusaku; Kennis, John T M; Gärtner, Wolfgang; Scheer, Hugo; Zhou, Ming; Zhao, Kai-Hong

    2015-12-29

    Photosynthesis relies on energy transfer from light-harvesting complexes to reaction centers. Phycobilisomes, the light-harvesting antennas in cyanobacteria and red algae, attach to the membrane via the multidomain core-membrane linker, L(CM). The chromophore domain of L(CM) forms a bottleneck for funneling the harvested energy either productively to reaction centers or, in case of light overload, to quenchers like orange carotenoid protein (OCP) that prevent photodamage. The crystal structure of the solubly modified chromophore domain from Nostoc sp. PCC7120 was resolved at 2.2 Å. Although its protein fold is similar to the protein folds of phycobiliproteins, the phycocyanobilin (PCB) chromophore adopts ZZZssa geometry, which is unknown among phycobiliproteins but characteristic for sensory photoreceptors (phytochromes and cyanobacteriochromes). However, chromophore photoisomerization is inhibited in L(CM) by tight packing. The ZZZssa geometry of the chromophore and π-π stacking with a neighboring Trp account for the functionally relevant extreme spectral red shift of L(CM). Exciton coupling is excluded by the large distance between two PCBs in a homodimer and by preservation of the spectral features in monomers. The structure also indicates a distinct flexibility that could be involved in quenching. The conclusions from the crystal structure are supported by femtosecond transient absorption spectra in solution. PMID:26669441

  14. The terminal phycobilisome emitter, LCM: A light-harvesting pigment with a phytochrome chromophore

    PubMed Central

    Tang, Kun; Ding, Wen-Long; Höppner, Astrid; Zhao, Cheng; Zhang, Lun; Hontani, Yusaku; Kennis, John T. M.; Gärtner, Wolfgang; Scheer, Hugo; Zhou, Ming; Zhao, Kai-Hong

    2015-01-01

    Photosynthesis relies on energy transfer from light-harvesting complexes to reaction centers. Phycobilisomes, the light-harvesting antennas in cyanobacteria and red algae, attach to the membrane via the multidomain core-membrane linker, LCM. The chromophore domain of LCM forms a bottleneck for funneling the harvested energy either productively to reaction centers or, in case of light overload, to quenchers like orange carotenoid protein (OCP) that prevent photodamage. The crystal structure of the solubly modified chromophore domain from Nostoc sp. PCC7120 was resolved at 2.2 Å. Although its protein fold is similar to the protein folds of phycobiliproteins, the phycocyanobilin (PCB) chromophore adopts ZZZssa geometry, which is unknown among phycobiliproteins but characteristic for sensory photoreceptors (phytochromes and cyanobacteriochromes). However, chromophore photoisomerization is inhibited in LCM by tight packing. The ZZZssa geometry of the chromophore and π-π stacking with a neighboring Trp account for the functionally relevant extreme spectral red shift of LCM. Exciton coupling is excluded by the large distance between two PCBs in a homodimer and by preservation of the spectral features in monomers. The structure also indicates a distinct flexibility that could be involved in quenching. The conclusions from the crystal structure are supported by femtosecond transient absorption spectra in solution. PMID:26669441

  15. Acquired retinal folds in the cat.

    PubMed

    MacMillan, A D

    1976-06-01

    Retinal folds were found in 5 cats. The apparent cause of the folding was varied: in 1 cat the folds appeared after a localized retinal detachment; in 2 cats the condition accompanied other intraocular abnormalities associated with feline infectious peritonitis; 1 cat had active keratitis, and the retinal changes were thought to have been injury related; and 1 cat, bilaterally affected, had chronic glomerulonephritis. PMID:945253

  16. Angiographic results of retinal-retinal anastomosis and retinal-choroidal anastomosis after treatments in eyes with retinal angiomatous proliferation

    PubMed Central

    Saito, Masaaki; Iida, Tomohiro; Kano, Mariko; Itagaki, Kanako

    2012-01-01

    Background The purpose of this study was to evaluate the angiographic results of retinal-retinal anastomosis (RRA) and retinal-choroidal anastomosis (RCA) for eyes with retinal angiomatous proliferation (RAP) after treatment with intravitreal bevacizumab injections as monotherapy or intravitreal bevacizumab combined with photodynamic therapy. Methods In this interventional, consecutive case series, we retrospectively reviewed five naïve eyes from four patients (mean age 80 years) treated with three consecutive monthly intravitreal bevacizumab (1.25 mg/0.05 mL) injections as initial treatment, and followed up for at least 3 months. In cases with over 3 months of follow-up and having recurrence of RAP or leakage by fluorescein angiography, retreatment was performed with a single intravitreal bevacizumab injection and photodynamic therapy. Results Indocyanine green angiography showed RRA in three eyes with subretinal neovascularization and RCA in two eyes with choroidal neovascularization at baseline. At 3 months after baseline (month 3), neither the RRA nor RCA was occluded in any eye on indocyanine green angiography. Retreatment with intravitreal bevacizumab plus photodynamic therapy was performed in three eyes at months 3 (persistent leakage on fluorescein angiography), 6, and 7 (recurrence of RAP lesion), which achieved obvious occlusion of the RRA and RCA. Mean best-corrected visual acuity improved from 0.13 to 0.21 at month 3 (P = 0.066). No complications or systemic adverse events were noted. Conclusion Although intravitreal bevacizumab for RAP was effective in improving visual acuity during short-term follow-up, intravitreal bevacizumab could not achieve complete occlusion of RRA and RCA, which could lead to recurrence of a RAP lesion and exudation. Retreatment with intravitreal bevacizumab plus photodynamic therapy ultimately achieved complete occlusion of the RRA and RCA. PMID:22969283

  17. Photocatalytic Water Splitting with the Acridine Chromophore: A Computational Study.

    PubMed

    Liu, Xiaojun; Karsili, Tolga N V; Sobolewski, Andrzej L; Domcke, Wolfgang

    2015-08-20

    The hydrogen-bonded acridine-water complex is considered as a model system for the exploration of photochemical reactions which can lead to the splitting of water into H(•) and OH(•) radicals. The vertical excitation energies of the lowest singlet and triplet excited states of the complex were calculated with the CASSCF/CASPT2 and ADC(2) ab initio electronic-structure methods. In addition to the well-known excited states of the acridine chromophore, excited states of charge-transfer character were identified, in which an electron is transferred from the p orbital of the H2O molecule to the π* orbital of acridine. The low-energy barriers which separate these reactive charge-transfer states from the spectroscopic states of the acridine-water complex have been characterized by the calculation of two-dimensional relaxed potential-energy surfaces as functions of the H atom-transfer coordinate and the donor (O)-acceptor (N) distance. When populated, these charge-transfer states drive the transfer of a proton from the water molecule to acridine, which results in the acridinyl-hydroxyl biradical. The same computational methods were employed to explore the photochemistry of the (N-hydrogenated) acridinyl radical. The latter possesses low-lying (about 3.0 eV) ππ* excited states with appreciable oscillator strengths in addition to a low-lying dark ππ* excited state. The bound potential-energy functions of the ππ* excited states are predissociated by the potential-energy function of an excited state of πσ* character which is repulsive with respect to the NH stretching coordinate. The dissociation threshold of the πσ* state is about 2.7 eV and thus below the excitation energies of the bright ππ* states. The conical intersections of the πσ* state with the ππ* excited states and with the electronic ground state provide a mechanism for the direct and fast photodetachment of the H atom from the acridinyl radical. These computational results indicate that the H2

  18. Retinal Cell Degeneration in Animal Models

    PubMed Central

    Niwa, Masayuki; Aoki, Hitomi; Hirata, Akihiro; Tomita, Hiroyuki; Green, Paul G.; Hara, Akira

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. PMID:26784179

  19. Retinal Effects Of Blue Light Exposure

    NASA Astrophysics Data System (ADS)

    Ham, William T.; Mueller, Harold A.; Ruffolo, J. J.

    1980-10-01

    Recent research has shown that blue light exposure is an important factor in certain types of retinal injury. The mammalian ocular media transmits the spectral band 400-1400 nm to the retina. The short wavelengths (400-550 nm) produce a photochemical or actinic type of damage, while the longer wavelengths (550-1400 nm) produce thermal damage. Distinction between the two types of retinal damage are discussed briefly and the importance of the blue light effect for solar retinitis and eclipse blindness is emphasized. The significance of blue light retinal injury is summarized for various environmental and occupational exposures.

  20. Retinal Macroglial Responses in Health and Disease

    PubMed Central

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

    2016-01-01

    Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies. PMID:27294114

  1. [Novel mechanism for retinal vascular diseases].

    PubMed

    Suzuma, Kiyoshi

    2015-03-01

    I. A new therapeutic target for diabetic retinopathy. Recent reports state that succinate may be an independent retinal angiogenic factor. We evaluated concentrations in vitreous from proliferative diabetic retinopathy (PDR), and found that succinate increased significantly in PDR. Interestingly, levels of succinate from bevacizumab-pre-injected PDR were normal, suggesting that vascular endothelial growth factor (VEGF) had a positive feedback mechanism for succinate since succinate was previously reported to induce VEGF. II. A new understanding of central retinal vein occlusion (CRVO). We evaluated retinal blood flow velocity with laser speckle flowgraphy (LSFG) made in Japan, and found that cases in which both macular edema and retinal blood flow velocity improved after anti-VEGF therapy had better prognosis. In ischemic CRVO at final visit, mean retinal blood velocity was less than 50% of fellow eyes after 1st anti-VEGF therapy, suggesting that those cases might have poor prognosis. LSFG is useful for evaluation and decision in CRVO treatment. III. From exploration for mechanism in retinal vascular diseases to re-vascularization therapy. The standard treatment for retinal non-perfusion area is scatter laser photocoagulation, which is both invasive of the peripheral retina and may prove destructive. Re-vascularization is an ideal strategy for treatment of retinal non-perfusion area. To develop a new methods for re-vascularization in retinal non-perfusion area, we have designed experiments using a retina without vasculature differentiated from induced pluripotent stem(iPS) cells. PMID:25854111

  2. Retinal detachment associated with atopic dermatitis.

    PubMed Central

    Takahashi, M; Suzuma, K; Inaba, I; Ogura, Y; Yoneda, K; Okamoto, H

    1996-01-01

    BACKGROUND: Retinal detachment associated with atopic dermatitis, one of the most common forms of dermatitis in Japan, has markedly increased in Japan in the past 10 years. To clarify pathogenic mechanisms of retinal detachment in such cases, we retrospectively studied clinical characteristics of retinal detachment associated with atopic dermatitis. METHODS: We examined the records of 80 patients (89 eyes) who had retinal detachment associated with atopic dermatitis. The patients were classified into three groups according to lens status: group A, eyes with clear lenses (40 eyes); group B, eyes with cataract (38 eyes), and group C, aphakic or pseudophakic eyes (11 eyes). RESULTS: No significant differences were noted in the ratio of males to females, age distribution, refractive error, or characteristic of retinal detachment among the three groups. The types of retinal breaks, however, were different in eyes with and without lens changes. While atrophic holes were dominant in group A, retinal dialysis was mainly seen in groups B and C. CONCLUSION: These findings suggested that anterior vitreoretinal traction may play an important role in the pathogenesis of retinal breaks in eyes with atopic cataract and that the same pathological process may affect the formation of cataract and tractional retinal breaks in patients with atopic dermatitis. PMID:8664234

  3. The synthesis of new double-donor chromophores with excellent electro-optic activity by introducing modified bridges.

    PubMed

    Yang, Yuhui; Wang, Haoran; Liu, Fenggang; Yang, Dan; Bo, Shuhui; Qiu, Ling; Zhen, Zhen; Liu, Xinhou

    2015-02-28

    A series of chromophores y1–y3 based on the same bis(N,N-diethyl)aniline donor and the tricyanofuran acceptor (TCF) linked together via the modified thiophene π-conjugation with different isolated groups have been synthesized and systematically investigated in this paper. Density functional theory (DFT) was used to calculate the HOMO–LUMO energy gaps and first-order hyperpolarizability (β) of these chromophores. Besides, to determine the redox properties of these chromophores, cyclic voltammetry (CV) experiments were performed. After introducing the isolation group into the thiophene, reduced energy gaps of 1.03 and 1.02 eV were obtained for chromophores y2 and y3, respectively, much lower compared to chromophore y1 (ΔE = 1.13 eV). These chromophores showed better thermal stability with their decomposition temperatures all above 220 °C. Besides, compared with results obtained from the chromophore (y1) without the isolated group, these new chromophores show better intramolecular charge-transfer (ICT) absorption. Most importantly, the high molecular hyperpolarizability (β) of these chromophores can be effectively translated into large electro-optic (EO) coefficients (r33) in poled polymers. The electro-optic coefficient of poled films containing 25% wt of these new chromophores doped in amorphous polycarbonate (APC) afforded values of 149, 139 and 125 pm V(−1) at 1310 nm for chromophores y1–y3, respectively. Besides, when the concentration was increased, the film containing chromophores y1 and y3 showed obvious phase separation, while the film with chromophore y2 showed the maximum r33 value of 146 pm V(−1). Moreover, the electro-optic film prepared with these new chromophores showed greater stability. High r33 values indicated that the double donors of the bis(N,N-diethyl)aniline unit can efficiently improve the electron-donating ability and the isolated groups on the thiophene bridge can reduce intermolecular electrostatic interactions, thus

  4. The effects of oxygen concentration and light intensity on the photostability of zwitterionic chromophores

    SciTech Connect

    Raymond, S. G.; Williams, G. V. M.; Lochocki, B.; Bhuiyan, M. D. H.; Kay, A. J.; Quilty, J. W.

    2009-06-01

    Photostability measurements at different oxygen partial pressures and light intensities have been made on host-guest films containing amorphous polycarbonate and an organic chromophore with a high second order nonlinear optical figure of merit. We find that the photodegradation quantum efficiency dramatically increases with increasing oxygen partial pressure. At very low oxygen partial pressures (8x10{sup -6} bar) the average number of photons required to photodegrade a chromophore is as high as 2x10{sup 8} at 655 nm. The photodegradation quantum efficiency in air is observed to decrease with increasing optical intensity. We show that this is due to a reduced oxygen content in the film caused by chromophore photodegradation rather than ground state bleaching. There is an anomalous increase and then decrease in the photoluminescence intensity that cannot easily be explained.

  5. Detection of Cellulose-Derived Chromophores by Ambient Ionization-MS.

    PubMed

    Schedl, Andreas; Korntner, Philipp; Zweckmair, Thomas; Henniges, Ute; Rosenau, Thomas; Potthast, Antje

    2016-01-19

    The detection of individual chromophores that contribute to the overall discoloration of paper ("yellowing") is a challenge because those substances are only present in very small amounts. In this research, two analytical approaches based on ambient ionization techniques, namely, desorption electrospray ionization and paper spray, both coupled to mass spectrometry, are compared to each other with regard to their suitability for detecting acetylated cellulosic key chromophores. The paper spray approach proved to be the more sensitive and versatile method. Subsequently, paper spray (PS)-mass spectrometry was applied to model papers and historical papers in which the acetylated chromophores were detected successfully. Independent accurate mass measurements confirmed the results obtained from reference compounds, model samples, and real-world specimens. PMID:26691171

  6. First-Principles Studies of the Excited States of Chromophore Monomers and Dimers

    NASA Astrophysics Data System (ADS)

    Hamed, Samia; Sharifzadeh, Sahar; Neaton, Jeffrey

    2015-03-01

    Elucidation of the energy transfer mechanism in natural photosynthetic systems remains an exciting challenge. Through the careful analysis of excited states on individual chromophores and dimers - and the predictive first-principles methods used to compute them - we are building towards an understanding of the nature of excitation transfer among arrays of chromophores embedded in protein environments. Excitation energies, transition dipoles, and natural transition orbitals for the important low-lying singlet and triplet states of experimentally-relevant chromophores are obtained from first-principles time-dependent density functional theory (TDDFT) and many body perturbation theory. The effect of the Tamm-Dancoff approximation and the performance of several exchange-correlation functionals, including an optimally-tuned range-separated hybrid, are evaluated with TDDFT, and compared to MBPT calculations and experiments. This work has been supported by the DOE; computational resources have been provided by NERSC.

  7. Chromophore-Based Luminescent Metal-Organic Frameworks as Lighting Phosphors.

    PubMed

    Lustig, William P; Wang, Fangming; Teat, Simon J; Hu, Zhichao; Gong, Qihan; Li, Jing

    2016-08-01

    Energy-efficient solid-state-lighting (SSL) technologies are rapidly developing, but the lack of stable, high-performance rare-earth free phosphors may impede the growth of the SSL market. One possible alternative is organic phosphor materials, but these can suffer from lower quantum yields and thermal instability compared to rare-earth phosphors. However, if luminescent organic chromophores can be built into a rigid metal-organic framework, their quantum yields and thermal stability can be greatly improved. This Forum Article discusses the design of a group of such chromophore-based luminescent metal-organic frameworks with exceptionally high performance and rational control of the important parameters that influence their emission properties, including electronic structures of chromophore, coligands, metal ions, and guest molecules. PMID:27244591

  8. Measurement of chromophores density using high Q-factor silica microspheres

    NASA Astrophysics Data System (ADS)

    Kandas, Ishac; Shehata, Nader; Daengngam, Chalongrat; Ashry, Islam; Xu, Yong

    2016-01-01

    This work investigates the relationship between the Q factor of a silica microsphere coated with nonlinear optical molecules and the surface density of the nonlinear molecules. Two types of nonlinear molecules are studied: poly{1-[p-(3‧-carboxy-4‧-hydroxyphenylazo) benzenesulfonamido]-1,2-ethandiyl} (PCBS), and Procion Brown MX-GRN (PB). In our experiments, we coat silica microspheres with ionic self-assembled multilayer films with different thicknesses as well as with different PCBS/PB chromophores densities. The Q factors of the coated microspheres are measured to be within the range of 106 to 107, which can be attributed to the optical absorption of the coated chromophores. This work can be used to experimentally determine the effective density of chromophores assembled on the silica microsphere. It may also find applications in chemical/biological sensing.

  9. Synthesis and photophysics of a red-light absorbing supramolecular chromophore system.

    PubMed

    Rombouts, Jeroen A; Ravensbergen, Janneke; Frese, Raoul N; Kennis, John T M; Ehlers, Andreas W; Slootweg, J Chris; Ruijter, Eelco; Lammertsma, Koop; Orru, Romano V A

    2014-08-11

    In search of supramolecular antenna systems for light-harvesting applications, we report on a short and effective synthesis of a fused NDI-zinc-salphen-based chromophore (salphen = bis-salicylimide phenylene) and its photophysical properties. A supramolecular recognition motif is embedded into the chromophoric π-system of this compound. The fused π-chromophore behaves as one pigment, absorbs light between 600 and 750 nm and displays a modest Stokes shift. Upon binding pyridines, the compound (DATZnS) does not change its redox potentials, does not undergo any internal excited state quenching and does not appreciably alter its excited state lifetime. These notable properties define DATZnS as an alternative to porphyrin-based components used in supramolecular light-harvesting architectures. PMID:24965936

  10. Chemical modification of glass surface with a monolayer of nonchromophoric and chromophoric methacrylate terpolymer

    NASA Astrophysics Data System (ADS)

    Janik, Ryszard; Kucharski, Stanisław; Sobolewska, Anna; Barille, Regis

    2010-11-01

    The methacrylate terpolymers, a nonchromophoric and chromophoric one, containing 2-hydroxyethyl groups were reacted with 3-isocyanatopropyltriethoxysilane to obtain reactive polymers able to form covalent bonding with -SiOH groups of the glass surface via triethoxysilane group condensation. Chemical modification of the Corning 2949 glass plates treated in this way resulted in increase of wetting angle from 11° to ca. 70-73°. Determination of ellipsometric parameters revealed low value of the substrate refractive index as compared with that of bulk Corning 2949 glass suggesting roughness of the surface. The AFM image of the bare glass surface and that modified with terpolymer monolayer confirmed this phenomenon. Modification of the glass with the terpolymer monolayer made it possible to create the substrate surface well suited for deposition of familiar chromophore film by spin-coating. The chromophore polymer film deposited onto the modified glass surface was found to be resistant to come unstuck in aqueous solution.

  11. Microwave assisted synthesis, spectroscopic studies and non linear optical properties of bis-chromophores.

    PubMed

    Khan, Salman A; Razvi, M A N; Bakry, Ahmed H; Afzal, S M; Asiri, Abdullah M; El-Daly, Samy A

    2015-02-25

    Bis chromophores were synthesized by the terephthalaldehyde with (4-nitrophenyl) acetonitrile/(4-flurophenyl) acetonitrile under microwave irradiation. Bis-chromophores were obtained in good to excellent yields. The structures of bis-chromophores were established by FT-IR, (1)H NMR, (13)C NMR, EI-MS and elemental analyses. Physical chemical properties such as singlet absorption, extinction coefficient, stokes shift, oscillator strength and dipole moment, were investigated by UV-Vis and fluorescence spectroscopy measurements. Further we also measured the nonlinear refractive index and nonlinear absorption coefficients of these compounds using the single beam z-scan technique with a cw argon ion laser at 514.5 nm at different concentrations in DMSO solvent. The third order nonlinear susceptibility was estimated from these measurements and it shows high nonlinearity. The high negative refractive index makes these compounds suitable for optical limiting application. PMID:25300042

  12. Effect of Structural Modifications on the Self-Assembly of Oligoprolines Conjugated with Sterically Demanding Chromophores.

    PubMed

    Lewandowska, Urszula; Zajaczkowski, Wojciech; Pisula, Wojciech; Ma, Yingjie; Li, Chen; Müllen, Klaus; Wennemers, Helma

    2016-03-01

    Conjugates between oligoprolines and sterically demanding perylene monoimides (PMIs) form hierarchical supramolecular self-assemblies. The influence of the length and stereochemistry at the attachment site between the peptide backbone and the chromophore on the self-assembly properties of the conjugates was explored. Comparison between oligoprolines bearing 4R- or 4S-configured azidoprolines (Azp) for the conjugation with the PMIs revealed that diastereoisomers with 4R configuration guide the self-assembly consistently better than conjugates with 4S configuration. Elongating the peptide chain beyond nine proline residues or introducing structural "errors", by altering the absolute configuration of one stereogenic center at the outside of the functionalizable oligoproline helix, lowered the efficacy of self-assembly significantly, both in solution phase and in the solid state. The results showed how subtle structural modifications allow for tuning the self-assembly of chromophores and provided further design principles for the development of peptide-chromophore conjugates into nanostructured materials. PMID:26891419

  13. Quantum coherence effects in natural light-induced processes: cis-trans photoisomerization of model retinal under incoherent excitation.

    PubMed

    Tscherbul, Timur V; Brumer, Paul

    2015-12-14

    We present a theoretical study of quantum coherence effects in the primary cis-trans photoisomerization of retinal in rhodopsin induced by incoherent solar light. Using the partial secular Bloch-Redfield quantum master equation approach based on a two-state two-mode linear vibronic coupling model of the retinal chromophore [S. Hahn and G. Stock, J. Phys. Chem. B, 2000, 104, 1146-1149], we show that a sudden turn-on of incoherent pumping can generate substantial Fano coherences among the excited states of retinal. These coherences are the most pronounced in the regime where the matrix elements of the transition dipole moment between the ground and excited eigenstates are parallel to one another. We show that even when the transition dipole moments are perpendicular (implying the absence of light-induced Fano coherence) a small amount of excited-state coherence is still generated due to the coupling to intramolecular vibrational modes and the protein environment, causing depopulation of the excited eigenstates. The overall effect of the coherences on the steady-state population and on the photoproduct quantum yield is shown to be small; however we observe a significant transient effect on the formation of the trans photoproduct, enhancing the photoreaction quantum yield by ∼11% at 200 fs. These calculations suggest that coupling to intramolecular vibrational modes and the protein environment play an important role in photoreaction dynamics, suppressing oscillations in the quantum yield associated with Fano interference. PMID:26022517

  14. Diacylglycerol O-Acyltransferase Type-1 Synthesizes Retinyl Esters in the Retina and Retinal Pigment Epithelium

    PubMed Central

    Kaylor, Joanna J.; Radu, Roxana A.; Bischoff, Nicholas; Makshanoff, Jacob; Hu, Jane; Lloyd, Marcia; Eddington, Shannan; Bianconi, Tran; Bok, Dean; Travis, Gabriel H.

    2015-01-01

    Retinyl esters represent an insoluble storage form of vitamin A and are substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment epithelium (RPE). The major retinyl-ester synthase in RPE cells is lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent retinyl-ester synthase activity has been observed in RPE homogenates but the protein responsible has not been identified. Here we show that diacylglycerol O-acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including RPE and Müller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in dgat1 -/- mice has no effect on retinal anatomy or the ultrastructure of photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in dgat1 -/- mice were also normal. However, the normal build-up of all-trans-retinyl esters (all-trans-RE’s) in the RPE during the first hour after a deep photobleach of visual pigments in the retina was not seen in dgat1 -/- mice. Further, total retinyl-ester synthase activity was reduced in both dgat1 -/- retina and RPE. PMID:25974161

  15. Chemistry and molecular physiology of vision: light-sensitive protein rhodopsin

    NASA Astrophysics Data System (ADS)

    Ostrovsky, Mikhail A.; Feldman, Tatyana B.

    2012-11-01

    The review concerns literature data on the structure, functions and molecular simulation of rhodopsin. The mechanisms of the spectral tuning of visual pigments, photoisomerization of the rhodopsin chromophore group (11-cis-retinal moiety) and the formation of the physiologically active state of rhodopsin as a G-protein-coupled receptor are considered. Particular attention is given to the rhodopsin visual cycle and pathogenetic consequences of its impairment. A knowledge of the structure and photochemistry of rhodopsin was shown to be of importance for the use in nanotechnology of the future. The bibliography includes 219 references.

  16. Antitumor enediyne chromoprotein C-1027: mechanistic investigation of the chromophore-mediated self-decomposition pathway.

    PubMed

    Inoue, Masayuki; Usuki, Toyonobu; Lee, Nayoung; Hirama, Masahiro; Tanaka, Toshiyuki; Hosoi, Fumihito; Ohie, Shinji; Otani, Toshio

    2006-06-21

    C-1027 is an extremely potent antitumor agent that causes double-stranded DNA cleavages. It is a unique small molecule-protein complex composed of a highly reactive enediyne chromophore, which upon binding reacts with its target molecule DNA through radical-mediated hydrogen abstraction and an apoprotein that encapsulates the chromophore serving as its carrier to reach DNA. Although C-1027 has favorable properties as an effective drug delivery system, it slowly self-decomposes due to the reactivity of the chromophore toward the apoprotein. Understanding how the C-1027 destroys itself may enable design of its analogues that overcome this limitation. In this paper, mechanistic insights into the self-reactivity of C-1027 that facilitates its own decomposition are described. We provide evidence that the formation of the Gly96 radical, which promotes the oxidative protein scission and the subsequent chromophore release, is the major pathway for the self-decomposition of C-1027. On the basis of the newly isolated products of the self-decomposition, we propose that the apoprotein effectively protects two different structural elements of the chromophore that are essential for its biological activity: the nine-membered enediyne moiety (necessary for DNA cleavage) and the benzoxazine moiety (necessary for DNA intercalation). Using an engineered apoprotein analogue kinetically more stable toward the chromophore radical, we show that enhanced overall properties can be achieved for the natural C-1027 with respect to stability and antitumor activities. The results present the first example of a rationally designed C-1027 analogue reported to display superior in vitro antitumor activity to the natural C-1027. Our findings may have implications for design of proteins that can stably encapsulate highly reactive small molecules. PMID:16771503

  17. Photoactive energetic materials: linear and nonlinear photochemistry of chromophore linked energetic materials

    NASA Astrophysics Data System (ADS)

    Greenfield, Margo; McGrane, Shawn; Bolme, Cindy; Chavez, David; Veauthier, Jacqueline; Hanson, Susan; Myers, Thomas; Scharff, Jason

    2015-06-01

    In general, conventional molecular explosives are white to off-white in color and only absorb ultraviolet light. A novel approach to synthetically link optically active energetic chromophores to existing molecular energetic materials has resulted in increased photoactivity in the visible (532 nm) region of the electromagnetic spectrum. Tetrazine, an energetic optically active chromophore, which absorbs around 532 nm, has been derivatized with various energetic materials including pentaeythritol tetranitrate (PETN), nitroglycerine (NG) and dinitroazetidine (DNAZ). We report the corresponding photochemistry and photochemical quantum yields of these new materials under various wavelength and intensity regimes.

  18. In-Membrane Chemical Modification (IMCM) for Site-Specific Chromophore Labeling of GPCRs.

    PubMed

    Sušac, Lukas; O'Connor, Casey; Stevens, Raymond C; Wüthrich, Kurt

    2015-12-01

    We present in-membrane chemical modification (IMCM) for obtaining selective chromophore labeling of intracellular surface cysteines in G-protein-coupled receptors (GPCRs) with minimal mutagenesis. This method takes advantage of the natural protection of most cysteines by the membrane environment. Practical use of IMCM is illustrated with the site-specific introduction of chromophores for NMR and fluorescence spectroscopy in the human κ-opioid receptor (KOR) and the human A2A adenosine receptor (A2A AR). IMCM is applicable to a wide range of in vitro studies of GPCRs, including single-molecule spectroscopy, and is a promising platform for in-cell spectroscopy experiments. PMID:26545333

  19. Location of lysine-129 and lysine-40/41 with respect to retinylidene chromophore in bacteriorhodopsin.

    PubMed

    Sonar, S M; Singh, A K

    1991-01-29

    Fluorescence properties of fluorescamine-modified bacteriorhodopsin (BR) have been studied. BR reacts with fluorescamine (1:2 ratio) to give protein (FLBR-I) modified at Lys-129. By making use of citraconic anhydride as a masking reagent, fluorescamine modification of Lys-40/41 in BR has been achieved. Forster's resonance energy transfer studies indicate that the distance between FL-Lys-129 and retinylidene chromophore is 11 A, whereas that between FL-Lys-40/41 and retinylidene chromophore is 24 A. These measured distances have been analysed in terms of BR structure. PMID:1900199

  20. Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor

    PubMed Central

    Acer, Semra; Balcı, Yasemin I; Pekel, Gökhan; Ongun, Tuğba T; Polat, Aziz; Çetin, Ebru N; Yağcı, Ramazan

    2016-01-01

    Objectives: Evaluation of the peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements in children with thalassemia minor. Methods: In this cross-sectional and comparative study, 30 thalassemia minor patients and 36 controls were included. Heidelberg spectral domain optical coherence tomography was used for peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements. Results: There was no statistically significant difference in retinal nerve fiber layer thickness and subfoveal choroidal thickness between the two groups (p > 0.05). There was no correlation between retinal nerve fiber layer thickness and hemoglobin values. Both the arterioral and venular calibers were higher in thalassemia minor group (p < 0.05). Conclusion: There is increased retinal arterioral and venular calibers in children with thalassemia minor compared with controls. PMID:27540484

  1. Retinal fundus imaging in mouse models of retinal diseases.

    PubMed

    Alex, Anne F; Heiduschka, Peter; Eter, Nicole

    2013-01-01

    The development of in vivo retinal fundus imaging in mice has opened a new research horizon, not only in ophthalmic research. The ability to monitor the dynamics of vascular and cellular changes in pathological conditions, such as neovascularization or degeneration, longitudinally without the need to sacrifice the mouse, permits longer observation periods in the same animal. With the application of the high-resolution confocal scanning laser ophthalmoscopy in experimental mouse models, access to a large spectrum of imaging modalities in vivo is provided. PMID:23150359

  2. Spectral Tuning of Deep Red Cone Pigments†

    PubMed Central

    Amora, Tabitha L.; Ramos, Lavoisier S.; Galan, Jhenny F.; Birge, Robert R.

    2008-01-01

    Visual pigments are G-protein-coupled receptors that provide a critical interface between organisms and their external environment. Natural selection has generated vertebrate pigments that absorb light from the far-UV (360 nm) to the deep red (630 nm) while using a single chromophore, in either the A1 (11-cis-retinal) or A2 (11-cis-3,4-dehydroretinal) form. The fact that a single chromophore can be manipulated to have an absorption maximum across such an extended spectral region is remarkable. The mechanisms of wavelength regulation remain to be fully revealed, and one of the least well-understood mechanisms is that associated with the deep red pigments. We investigate theoretically the hypothesis that deep red cone pigments select a 6-s-trans conformation of the retinal chromophore ring geometry. This conformation is in contrast to the 6-s-cis ring geometry observed in rhodopsin and, through model chromophore studies, the vast majority of visual pigments. Nomographic spectral analysis of 294 A1 and A2 cone pigment literature absorption maxima indicates that the selection of a 6-s-trans geometry red shifts M/LWS A1 pigments by ~1500 cm−1 (~50 nm) and A2 pigments by ~2700 cm−1 (~100 nm). The homology models of seven cone pigments indicate that the deep red cone pigments select 6-s-trans chromophore conformations primarily via electrostatic steering. Our results reveal that the generation of a 6-s-trans conformation not only achieves a significant red shift but also provides enhanced stability of the chromophore within the deep red cone pigment binding sites. PMID:18370404

  3. Investigation of chromophore-chromophore interaction by electro-optic measurements, linear dichroism, x-ray scattering, and density-functional calculations

    SciTech Connect

    Apitz, D.; Bertram, R.P.; Benter, N.; Buse, K.; Hieringer, W.; Andreasen, J.W.; Nielsen, M.M.; Johansen, P.M.

    2005-09-01

    Free-beam interferometry and angle-resolved absorption spectra are used to investigate the linear electro-optic coefficients and the linear dichroism in photoaddressable bis-azo copolymer thin films. From the first- and second order parameters deduced, the chromophore orientation distribution is calculated and displayed for several poling temperatures and chromophore concentrations. The influence of dipole-dipole interaction on the overall polymer dynamics is discussed. The first order parameter, and therefore the Pockels effect, peaks for a poling temperature of around 10 deg. C above the glass transition. The decrease of the Pockels effect above this temperature region is triggered by a head-to-tail chromophore orientation, i.e., a transition to a microcrystalline phase, increasing the second order parameter. Comparison of the experimentally observed absorption spectra and those obtained by density-functional calculations support the picture of differently aligned bis-azo dye molecules in a trans,trans configuration. Complementary wide-angle x-ray scattering is recorded to confirm the various kinds of ordering in samples poled at different temperatures.

  4. Argus II retinal prosthesis system: An update.

    PubMed

    Rachitskaya, Aleksandra V; Yuan, Alex

    2016-09-01

    This review focuses on a description of the Argus II retinal prosthesis system (Argus II; Second Sight Medical Products, Sylmar, CA) that was approved for humanitarian use by the FDA in 2013 in patients with retinitis pigmentosa with bare or no light perception vision. The article describes the components of Argus II, the studies on the implant, and future directions. PMID:26855177

  5. Fundus autofluorescence applications in retinal imaging.

    PubMed

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-05-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  6. Fundus autofluorescence applications in retinal imaging

    PubMed Central

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-01-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  7. Retinal cholesterol emboli during diagnostic cardiac catheterization.

    PubMed

    Blanco, V R; Morís, C; Barriales, V; González, C

    2000-11-01

    Retinal embolism is a highly infrequent complication of cardiac catheterization of thrombotic, lipidic, and calcific etiology. We provide the first reported clinical case of retinal embolism caused by cholesterol crystal without systemic adverse effects as a severe complication of diagnostic cardiac catheterization. Cathet. Cardiovasc. Intervent. 51:323-325, 2000. PMID:11066118

  8. Structural Properties and UV-Visible Absorption Spectroscopy of Retinal-pyridyl-CN Re(I) Carbonyl Bipyridine Complex: A Theoretical Study.

    PubMed

    Eng, Julien; Daniel, Chantal

    2015-10-29

    The structural, electronic, and optical properties of the all-trans and five cis conformers of [Re(CO)3(bpy)(ret-pyr-CN)](+) (bpy = 2,2'-bipyridine; ret-pyr-CN = pyridyl-CN-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-2-n)-none-(2,4,6,8-tetraen) were studied in solvent by means of density functional theory (DFT) and time-dependent DFT. The isolated retinal-like chromophore ret-pyr-CN was investigated as well for comparison. By coordination to the complex the two lowest intraligand (IL) states localized on the retinal group are slightly red-shifted from 627 to 690 nm and from 415 to 450 nm, respectively. Several isomerization pathways are open upon irradiation of the Re(I) complex by visible light (400-450 nm), especially to two cis conformers corresponding to the isomerization of the two double bonds of the retinal-like ligand close to the pyridyl group linked to the Re(I) fragment. The metal-to-ligand charge transfer states localized either on the retinal group or on the bpy ligand should play a minor role in the isomerization process itself but could improve its efficiency via ultra-fast intersystem crossing. PMID:26436344

  9. New mouse primary retinal degeneration (rd-3)

    SciTech Connect

    Chang, B.; Hawes, N.L.; Roderick, T.H. ); Heckenlively, J.R. )

    1993-04-01

    A new mouse retinal degeneration that appears to be an excellent candidate for modeling human retinitis pigmentosa is reported. In this degeneration, called rd-3, differentiation proceeds postnatally through 2 weeks, and photoreceptor degeneration starts by 3 weeks. The rod photoreceptor loss is essentially complete by 5 weeks, whereas remnant cone cells are seen through 7 weeks. This is the only mouse homozygous retinal degeneration reported to date in which photoreceptors are initially normal. Crosses with known mouse retinal degenerations rd, Rds, nr, and pcd are negative for retinal degeneration in offspring, and linkage analysis places rd-3 on mouse chromosome 1 at 10 [+-]2.5 cM distal to Akp-1. Homology mapping suggests that the homologous human locus should be on chromosome 1q. 32 refs., 3 figs., 3 tabs.

  10. Retinal pigment epithelium in incontinentia pigmenti.

    PubMed

    Mensheha-Manhart, O; Rodrigues, M M; Shields, J A; Shannon, G M; Mirabelli, R P

    1975-04-01

    An 18-month-old white girl with incontinentia pigmenti presented clinically with leukokoria of the right eye. B-scan ultrasound demonstrated a retrolental mass consistent with a detached retina. Histologic examination of the skin revealed changes compatible with the intermediate verrucous phase of the disease. Microscopic examination of the right eye showed retinal detachment and nodular proliferation of the retinal pigment epithelium. The nodules contained macrophages laden with melanin and lipofuscin. An unusually large amount of lipofuscin was present for a child of this age. The basic pigmentary abnormality may affect the retinal pigment epithelium, resulting in changes in the overlying neurosensory retina that may lead to the retinal dysplasia or retinal detachemnt often associated with this condition. PMID:1119517

  11. The cell stress machinery and retinal degeneration.

    PubMed

    Athanasiou, Dimitra; Aguilà, Monica; Bevilacqua, Dalila; Novoselov, Sergey S; Parfitt, David A; Cheetham, Michael E

    2013-06-27

    Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness. PMID:23684651

  12. Texton-based segmentation of retinal vessels.

    PubMed

    Adjeroh, Donald A; Kandaswamy, Umasankar; Odom, J Vernon

    2007-05-01

    With improvements in fundus imaging technology and the increasing use of digital images in screening and diagnosis, the issue of automated analysis of retinal images is gaining more serious attention. We consider the problem of retinal vessel segmentation, a key issue in automated analysis of digital fundus images. We propose a texture-based vessel segmentation algorithm based on the notion of textons. Using a weak statistical learning approach, we construct textons for retinal vasculature by designing filters that are specifically tuned to the structural and photometric properties of retinal vessels. We evaluate the performance of the proposed approach using a standard database of retinal images. On the DRIVE data set, the proposed method produced an average performance of 0.9568 specificity at 0.7346 sensitivity. This compares well with the best-published results on the data set 0.9773 specificity at 0.7194 sensitivity [Proc. SPIE5370, 648 (2004)]. PMID:17429484

  13. Texton-based segmentation of retinal vessels

    NASA Astrophysics Data System (ADS)

    Adjeroh, Donald A.; Kandaswamy, Umasankar; Odom, J. Vernon

    2007-05-01

    With improvements in fundus imaging technology and the increasing use of digital images in screening and diagnosis, the issue of automated analysis of retinal images is gaining more serious attention. We consider the problem of retinal vessel segmentation, a key issue in automated analysis of digital fundus images. We propose a texture-based vessel segmentation algorithm based on the notion of textons. Using a weak statistical learning approach, we construct textons for retinal vasculature by designing filters that are specifically tuned to the structural and photometric properties of retinal vessels. We evaluate the performance of the proposed approach using a standard database of retinal images. On the DRIVE data set, the proposed method produced an average performance of 0.9568 specificity at 0.7346 sensitivity. This compares well with the best-published results on the data set 0.9773 specificity at 0.7194 sensitivity [Proc. SPIE5370, 648 (2004)].

  14. Fourier transform infrared studies of active-site-methylated rhodopsin. Implications for chromophore-protein interaction, transducin activation, and the reaction pathway.

    PubMed

    Ganter, U M; Longstaff, C; Pajares, M A; Rando, R R; Siebert, F

    1991-03-01

    Fourier transform infrared studies of active-site-methylated rhodopsin (ASMR) show that, as compared to unmodified rhodopsin, the photoreaction is almost unchanged up to the formation of lumirhodopsin. Especially, the deviations are much smaller than those observed for the corresponding intermediates of 13-desmethyl-rhodopsin. In metarhodopsin-I, larger alterations are present with respect to the three internal carboxyl groups. Similar deviations have been observed in meta-I of 13-desmethyl-rhodopsin. This indicates that, in agreement with our previous investigations, these carboxyl groups are located in close proximity to the chromophore. Because this latter pigment is capable, when bleached, of activating transducin, our data provide support for the earlier conclusion that deprotonation of the Schiff base is a prerequisite for transducin activation. The positions of the C = C and C - C stretching modes of the retinal suggest that the redshift observed in ASMR and its photoproducts can be explained by an increased distance of the Schiff base from the counterion(s). It is further shown that the photoreaction does not stop at metarhodopsin-I, but that this intermediate directly decays to a metarhodopsin-III-like species. PMID:2049524

  15. Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.

    PubMed

    Nivison-Smith, Lisa; Zhu, Yuan; Whatham, Andrew; Bui, Bang V; Fletcher, Erica L; Acosta, Monica L; Kalloniatis, Michael

    2014-11-01

    Sildenafil, the active ingredient in Viagra, has been reported to cause transient visual disturbance from inhibition of phosphodiesterase 6 (PDE6), a key enzyme in the visual phototransduction pathway. This study investigated the effects of sildenafil on the rd1(+/-) mouse, a model for carriers of Retinitis Pigmentosa which exhibit normal vision but may have a lower threshold for cellular stress caused by sildenafil due to a heterozygous mutation in PDE6. Sildenafil caused a dose-dependent decrease in electroretinogram (ERG) responses of normal mice which mostly recovered two days post administration. In contrast, rd1(+/-) mice exhibited a significantly reduced photoreceptor and a supernormal bipolar cell response to sildenafil within 1 h of treatment. Carrier mice retinae took two weeks to return to baseline levels suggesting sildenafil has direct effects on both the inner and outer retina and these effects differ significantly between normal and carrier mice. Anatomically, an increase in expression of the early apoptotic marker, cytochrome C in rd1(+/-) mice indicated that the effects of sildenafil on visual function may lead to degeneration. The results of this study are significant considering approximately 1 in 50 people are likely to be carriers of recessive traits leading to retinal degeneration. PMID:25239397

  16. Primary Reactions in Retinal Proteins

    NASA Astrophysics Data System (ADS)

    Diller, R.

    Conversion of sunlight into energy or information and their storage on a chemical level is essential for life on earth. An important family of chromoproteins performing these tasks is that of retinal binding proteins. Prominent examples are rhodopsin (Rh) [1,2] as the visual pigment in vertebrate and invertebrate animals, the archaeal rhodopsins bacteriorhodopsin (BR) [3] as a light driven proton pump, halorhodopsin (HR) [4,5] as a light driven chloride pump, sensory rhodopsin I and II (SRI, SRII) [6] as photoreceptors, and proteorhodopsin (PR) [7] as another bacterial proton pump.

  17. Cellular chromophores and signaling in low level light therapy

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.; Demidova-Rice, Tatiana N.

    2007-02-01

    particular, signaling cascades are initiated via cyclic adenosine monophosphate (cAMP) and nuclear factor kappa B (NF-κB). These signal transduction pathways in turn lead to increased cell proliferation and migration (particularly by fibroblasts), modulation in levels of cytokines, growth factors and inflammatory mediators, and increases in anti-apoptotic proteins. The results of these biochemical and cellular changes in animals and patients include such benefits as increased healing in chronic wounds, improvements in sports injuries and carpal tunnel syndrome, pain reduction in arthritis and neuropathies, and amelioration of damage after heart attacks, stroke, nerve injury and retinal toxicity.

  18. Demarcation laser photocoagulation induced retinal necrosis and rupture resulting in large retinal tear formation.

    PubMed

    Quezada, Carlos; Pieramici, Dante J; Matsui, Rodrigo; Rabena, Melvin; Graue, Federico

    2015-06-01

    Retinal tears after laser photocoagulation are a rare complication that occurs after intense laser. It is talked about among retina specialist occurring particularly at the end of a surgical case while applying endophotocoagulation; to the best our knowledge, there are no reports in the literature of a large retinal tear induced after attempted in-office demarcation laser photocoagulation (DLP) that simulated a giant retinal tear. DLP has been employed in the management of selected cases of macula sparring rhegmatogenous retinal detachment (RRD). Even though extension of the retinal detachment through the "laser barrier" is considered a failure of treatment, few complications have been described with the use of this less invasive retinal detachment repair technique. We describe a case of a high myopic woman who initially was treated with demarcation laser photocoagulation for an asymptomatic retinal detachment associated with a single horseshoe tear and a full thickness large retinal tear was created where the laser was placed. Intense laser photocoagulation resulted in abrupt laser induced retinal necrosis and rupture creating this large retinal break. Proper laser technique should reduce the risks associated with this procedure. PMID:25770055

  19. Chromophoric disorder in conjugated polymers: the cursious case of P3HT

    NASA Astrophysics Data System (ADS)

    Simine, Lena; Rossky, Peter

    The origin of the broad absorption spectrum of conjugated polymers is discussed. Motivated by the open questions posed in the recent experimental literature, we investigate theoretically the chromophoric disorder in single molecule poly(3­hexyl)thiophene (P3HT) at the atomic level using quantum­classical simulations. We reproduce the absorption spectrum and confirm qualitatively the prediction of simplified models ­ the localization length of the first excited state decreases with increasing temperature. Counter to expectation, the same trend is observed for the the average energy of the chromophore: in spite of a shorter localization length, the spectrum of the hot chromophore is red­shifted with respect to its cold counterpart. We trace this peculiarity to the anharmonicity of the underlying torsional potential which allows preferential access to more planar inter­ring conformations at high temperature. The contributions of bending to the transitional energies, the origi n of inhomogeneous broadening and the possibility of classification of the chromophore as planar/twisted/bent atlow and high temperatures are discussed.

  20. Structure-reactivity relationships between fluorescent chromophores and antioxidant activity of grain and sweet sorghum seeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyphenolic structures, such as tannins, are the putative cause of a variety of seed functions including bird/insect resistance and antioxidant activity. Structure-reactivity relationships are necessary to understand the influence of polyphenolic chromophore structures on the tannin content and fr...

  1. Contrasting the Excited-State Dynamics of the Photoactive Yellow Protein Chromophore: Protein versus Solvent Environments

    PubMed Central

    Vengris, Mikas; van der Horst, Michael A.; Zgrablić, Goran; van Stokkum, Ivo H. M.; Haacke, Stefan; Chergui, Majed; Hellingwerf, Klaas J.; van Grondelle, Rienk; Larsen, Delmar S.

    2004-01-01

    Wavelength- and time-resolved fluorescence experiments have been performed on the photoactive yellow protein, the E46Q mutant, the hybrids of these proteins containing a nonisomerizing “locked” chromophore, and the native and locked chromophores in aqueous solution. The ultrafast dynamics of these six systems is compared and spectral signatures of isomerization and solvation are discussed. We find that the ultrafast red-shifting of fluorescence is associated mostly with solvation dynamics, whereas isomerization manifests itself as quenching of fluorescence. The observed multiexponential quenching of the protein samples differs from the single-exponential lifetimes of the chromophores in solution. The locked chromophore in the protein environment decays faster than in solution. This is due to additional channels of excited-state energy dissipation via the covalent and hydrogen bonds with the protein environment. The observed large dispersion of quenching timescales observed in the protein samples that contain the native pigment favors both an inhomogeneous model and an excited-state barrier for isomerization. PMID:15345563

  2. Experimental studies with selected light sources for NIRS of brain tissue: quantifying tissue chromophore concentration

    NASA Astrophysics Data System (ADS)

    Myllylä, Teemu; Korhonen, Vesa; Kiviniemi, Vesa; Tuchin, Valery

    2015-03-01

    Near-infrared spectroscopy (NIRS) based techniques are utilised in quantifying changes of chromophore concentrations in tissue. Particularly, non-invasive in vivo measurements of tissue oxygenation in the cerebral cortex are of interest. The measurement method is based on illuminating tissue and measuring the back-scattered light at wavelengths of interest. Tissue illumination can be realised using different techniques and various light sources. Commonly, lasers and laser diodes (LD) are utilised, but also high-power light emitting diodes (HPLED) are becoming more common. At the moment, a wide range of available narrow-band light sources exists, covering basically the entire spectrum of interest in brain tissue NIRS measurements. In this paper, in the centre of our interest are LDs and HPLEDs, because of their affordability, efficiency in terms of radiant flux versus size and easiness to adopt in in vivo medical applications. We compare characteristics of LDs and HPLEDs at specific wavelengths and their suitability for in vivo quantifying of different tissue chromophore concentration, particularly in cerebral blood flow (CBF). A special focus is on shape and width of the wavelength bands of interest, generated by the LDs and HPLEDs. Moreover, we experimentally study such effects as, spectroscopy cross talk, separability and signal-to-noise ratio (SNR) when quantifying tissue chromophore concentration. Chromophores of our interest are cytochrome, haemoglobin and water. Various LDs and HPLEDs, producing narrow-band wavelengths in the range from 500 nm to 1000 nm are tested.

  3. Color Detection Using Chromophore-Nanotube Hybrid Devices (PReSS/PD2P Talk)

    SciTech Connect

    Zhou, Xinjian

    2009-06-11

    A new solid-state light detection scheme will be discussed in this talk. In our work, single-walled carbon nanotubes transduce the light-induced conformational changes in nearby chromophores into electrical signals. This scheme mimics the way our eyes see the world. Potential applications of such nano-scale light detectors will also be discussed.

  4. Soluble chromophores in marine snow, seawater, sea ice and frost flowers near Barrow, Alaska

    NASA Astrophysics Data System (ADS)

    Beine, Harry; Anastasio, Cort; Domine, Florent; Douglas, Thomas; Barret, Manuel; France, James; King, Martin; Hall, Sam; Ullmann, Kirk

    2012-07-01

    We measured light absorption in 42 marine snow, sea ice, seawater, brine, and frost flower samples collected during the OASIS field campaign between February 27 and April 15, 2009. Samples represented multiple sites between landfast ice and open pack ice in coastal areas approximately 5 km west of Barrow, Alaska. The chromophores that are most commonly measured in snow, H2O2, NO3-, and NO2-, on average account for less than 1% of sunlight absorption in our samples. Instead, light absorption is dominated by unidentified "residual" species, likely organic compounds. Light absorption coefficients for the frost flowers on first-year sea ice are, on average, 40 times larger than values for terrestrial snow samples at Barrow, suggesting very large rates of photochemical reactions in frost flowers. For our marine samples the calculated rates of sunlight absorption and OH production from known chromophores are (0.1-1.4) × 1014 (photons cm-3 s-1) and (5-70) × 10-12 (mol L-1 s-1), respectively. Our residual spectra are similar to spectra of marine chromophoric dissolved organic matter (CDOM), suggesting that CDOM is the dominant chromophore in our samples. Based on our light absorption measurements we estimate dissolved organic carbon (DOC) concentrations in Barrow seawater and frost flowers as approximately 130 and 360 μM C, respectively. We expect that CDOM is a major source of OH in our marine samples, and it is likely to have other significant photochemistry as well.

  5. Production of Chromophoric Dissolved Organic Matter from Mangrove Leaf Litter and Floating Sargassum Colonies

    EPA Science Inventory

    Chromophoric dissolved organic matter (CDOM) strongly absorbs solar radiation in the blue-green and serves as the primary attenuator of water column ultraviolet radiation (UV-R). CDOM interferes with remote sensing of ocean chlorophyll and can control UV-R-induced damage to light...

  6. On the optical absorption of the anionic GFP chromophore in vacuum, solution, and protein.

    PubMed

    Petrone, Alessio; Caruso, Pasquale; Tenuta, Silvia; Rega, Nadia

    2013-12-21

    In spite of the large number of experimental and theoretical studies, the optical absorption trend of the green fluorescent protein (GFP) chromophore in several environments has not been fully understood. We calculated at the same level of time dependent density functional theory the vertical excitation energy of the anionic GFP chromophore in the protein and in ethanol, dioxane, methanol and water solutions. As result, we reproduced for the first time the experimental trend of the absorption peaks with 0.015 eV as the standard deviation of the accuracy. This systematic error allowed us to analyze with confidence the relative weight of several solvation effects on the vertical excitation energy. Experimental trends not correlated with the solvent polarity were therefore explained with a fine balance of different steric and electronic effects on the photophysics of the chromophore. As an indirect and remarkable result, the present analysis confirms that the optical absorption of the chromophore in the gas phase is close to the value of 2.84 eV extrapolated by Dong et al. (J. Am. Chem. Soc., 2006, 128, 12038), and, as a consequence, that the protein environment induces a red shift of 0.23 eV. PMID:24177429

  7. Chemistry of 5,8-dihydroxy-[1,4]-benzoquinone, a key chromophore in aged cellulosics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    2,5-Dihydroxy-[1,4]-benzoquione is one of the three key chromophores found in aged cellulosics. Knowledge of the general reactivity and chemistry of this compound is helpful for a better understanding of cellulose aging and yellowing as well as bleaching of cellulosic materials - processes which als...

  8. Effect of Solvation on Electron Detachment and Excitation Energies of a Green Fluorescent Protein Chromophore Variant.

    PubMed

    Bose, Samik; Chakrabarty, Suman; Ghosh, Debashree

    2016-05-19

    Hybrid quantum mechanics/molecular mechanics (QM/MM) is applied to the fluorinated green fluorescent protein (GFP) chromophore (DFHBDI) in its deprotonated form to understand the solvatochromic shifts in its vertical detachment energy (VDE) and vertical excitation energy (VEE). This variant of the GFP chromophore becomes fluorescent in an RNA environment and has a wide range of applications in biomedical and biochemical fields. From microsolvation studies, we benchmark (with respect to full QM) the accuracy of our QM/MM calculations with effective fragment potential (EFP) as the MM method of choice. We show that while the solvatochromic shift in the VEE is minimal (0.1 eV blue shift) and its polarization component is only 0.03 eV, the effect of the solvent on the VDE is quite large (3.85 eV). We also show by accurate calculations on the solvatochromic shift of the VDE that polarization accounts for ∼0.23 eV and therefore cannot be neglected. The effect of the counterions on the VDE of the deprotonated chromophore in solvation is studied in detail, and a charge-smearing scheme is suggested for charged chromophores. PMID:27116477

  9. Electro-optic properties of hybrid solgel doped with a nonlinear chromophore with large hyperpolarizability.

    PubMed

    Zhang, Hong Xi; Lu, Dong; Peyghambarian, Nasser; Fallahi, Mahmoud; Luo, Jing Dong; Chen, Bao Quan; Jen, Alex K Y

    2005-01-15

    We report the electro-optic properties of hybrid silica solgel doped with a nonlinear chromophore with large hyperpolarizability. Electro-optic coefficients of higher than 30 pm/V have been obtained. Moreover, the electro-optic coefficients have good temporal stability and show promise for the development of high-speed electro-optic devices. PMID:15675685

  10. Chemistry of 5,8-dihydroxy-[1,4]-naphtoquinone, a key chromophore in aged cellulosics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    5,8-Dihydroxy-[1,4]-naphthoquinone (DHNQ) is one of the key chromophores found in aged cellulosics. Cellulose aging and yellowing as well as bleaching of cellulosic materials are key processes in the pulp and paper industries and have considerable economic importance: the knowledge of the general re...

  11. Engineering a genetically-encoded SHG chromophore by electrostatic targeting to the membrane.

    PubMed

    Jinno, Yuka; Shoda, Keiko; Rial-Verde, Emiliano; Yuste, Rafael; Miyawaki, Atsushi; Tsutsui, Hidekazu

    2014-01-01

    Although second harmonic generation (SHG) microscopy provides unique imaging advantages for voltage imaging and other biological applications, genetically-encoded SHG chromophores remain relatively unexplored. SHG only arises from non-centrosymmetric media, so an anisotropic arrangement of chromophores is essential to provide strong SHG signals. Here, inspired by the mechanism by which K-Ras4B associates with plasma membranes, we sought to achieve asymmetric arrangements of chromophores at the membrane-cytoplasm interface using the fluorescent protein mVenus. After adding a farnesylation motif to the C-terminus of mVenus, nine amino acids composing its β-barrel surface were replaced by lysine, forming an electrostatic patch. This protein (mVe9Knus-CVIM) was efficiently targeted to the plasma membrane in a geometrically defined manner and exhibited SHG in HEK293 cells. In agreement with its design, mVe9Knus-CVIM hyperpolarizability was oriented at a small angle (~7.3°) from the membrane normal. Genetically-encoded SHG chromophores could serve as a molecular platform for imaging membrane potential. PMID:25505870

  12. Engineering a genetically-encoded SHG chromophore by electrostatic targeting to the membrane

    PubMed Central

    Jinno, Yuka; Shoda, Keiko; Rial-Verde, Emiliano; Yuste, Rafael; Miyawaki, Atsushi; Tsutsui, Hidekazu

    2014-01-01

    Although second harmonic generation (SHG) microscopy provides unique imaging advantages for voltage imaging and other biological applications, genetically-encoded SHG chromophores remain relatively unexplored. SHG only arises from non-centrosymmetric media, so an anisotropic arrangement of chromophores is essential to provide strong SHG signals. Here, inspired by the mechanism by which K-Ras4B associates with plasma membranes, we sought to achieve asymmetric arrangements of chromophores at the membrane-cytoplasm interface using the fluorescent protein mVenus. After adding a farnesylation motif to the C-terminus of mVenus, nine amino acids composing its β-barrel surface were replaced by lysine, forming an electrostatic patch. This protein (mVe9Knus-CVIM) was efficiently targeted to the plasma membrane in a geometrically defined manner and exhibited SHG in HEK293 cells. In agreement with its design, mVe9Knus-CVIM hyperpolarizability was oriented at a small angle (~7.3°) from the membrane normal. Genetically-encoded SHG chromophores could serve as a molecular platform for imaging membrane potential. PMID:25505870

  13. Chromophore Protonation State Controls Photoswitching of the Fluoroprotein asFP595

    PubMed Central

    Schäfer, Lars V.; Groenhof, Gerrit; Boggio-Pasqua, Martial; Robb, Michael A.; Grubmüller, Helmut

    2008-01-01

    Fluorescent proteins have been widely used as genetically encodable fusion tags for biological imaging. Recently, a new class of fluorescent proteins was discovered that can be reversibly light-switched between a fluorescent and a non-fluorescent state. Such proteins can not only provide nanoscale resolution in far-field fluorescence optical microscopy much below the diffraction limit, but also hold promise for other nanotechnological applications, such as optical data storage. To systematically exploit the potential of such photoswitchable proteins and to enable rational improvements to their properties requires a detailed understanding of the molecular switching mechanism, which is currently unknown. Here, we have studied the photoswitching mechanism of the reversibly switchable fluoroprotein asFP595 at the atomic level by multiconfigurational ab initio (CASSCF) calculations and QM/MM excited state molecular dynamics simulations with explicit surface hopping. Our simulations explain measured quantum yields and excited state lifetimes, and also predict the structures of the hitherto unknown intermediates and of the irreversibly fluorescent state. Further, we find that the proton distribution in the active site of the asFP595 controls the photochemical conversion pathways of the chromophore in the protein matrix. Accordingly, changes in the protonation state of the chromophore and some proximal amino acids lead to different photochemical states, which all turn out to be essential for the photoswitching mechanism. These photochemical states are (i) a neutral chromophore, which can trans-cis photoisomerize, (ii) an anionic chromophore, which rapidly undergoes radiationless decay after excitation, and (iii) a putative fluorescent zwitterionic chromophore. The overall stability of the different protonation states is controlled by the isomeric state of the chromophore. We finally propose that radiation-induced decarboxylation of the glutamic acid Glu215 blocks the

  14. Design, synthesis, characterization and applications of multi-photon absorbing chromophores

    NASA Astrophysics Data System (ADS)

    Zheng, Qingdong

    Recent development in multi-photon based applications including optical power limiting, frequency up-conversion lasing, three-dimensional data storage, two-photon fluorescence microscopy and two-photon photodynamic therapy has benefited a lot from a number of chromophores with large multi-photon absorption. This thesis was focused on the development of novel two- and three-photon active chromophores and their applications. Chapter 1 describes a theoretical background of multi-photon absorption, and recent development of multi-photon based applications. Some molecular design strategies were proposed after a literature review of chromophores with large two-photon absorption. In Chapter 2, a series of stilbazolium salts with varying electron donors and anions were synthesized and characterized. The two-photon absorption and two-photon pumped cavity lasing properties for these dyes were studied by using 1064 nm nano-second laser beam. By using tunable femto-second laser, three-photon pumped cavity-less lasing properties of these dyes have also been comprehensively studied. Four-photon pumped stimulated emission was achieved in some of these stilbazolium dyes. Unsymmetrical emission behaviors under 3- and 4-photon pump conditions for all these stilbazolium dyes were observed, explained and verified. In Chapter 3, DNA was successfully used as a matrix for one-, two-, and three-photon pumped stimulated emission or lasing by intercalating a multi-photon active chromophore. In Chapter 4, it is experimentally shown that both two- and three-photon absorption in a highly concentrated chromophore system can be more efficiently utilized to accomplish optical power limiting and stabilization at laser wavelengths of 1.064 mum and ˜1.3 mum, respectively. In Chapter 5, three novel 1,10-phenanthroline containing pi-conjugated chromophores with varied electron donors were synthesized and characterized together with their corresponding nickel(II) chelated complexes. Large two

  15. Measurement of retinal blood velocity

    NASA Astrophysics Data System (ADS)

    Winchester, Leonard W., Jr.; Chou, Nee-Yin

    2006-02-01

    A fundus camera was modified to illuminate the retina of a rabbit model with low power laser light in order to obtain laser speckle images. A fast-exposure charge-coupled device (CCD) camera was used to capture laser speckle images of the retina. Image acquisition was synchronized with the arterial pulses of the rabbit to ensure that all images are obtained at the same point in the cardiac cycle. The rabbits were sedated and a speculum was inserted to prevent the eyelid from closing. Both albino (New Zealand; pigmented (Dutch belted) rabbits were used in the study. The rabbit retina is almost avascular. The measurements are obtained for choroidal tissue as well as retinal tissue. Because the retina is in a region of high metabolism, blood velocity is strongly affected by blood oxygen saturation. Measurements of blood velocity obtained over a wide range of O II saturations (58%-100%) showed that blood velocity increases with decreasing O II saturation. For most experiments, the left eye of the rabbit was used for laser measurements whereas the right eye served as a control. No observable difference between pre- and post-experimented eye was noted. Histological examinations of retinal tissue subjected to repeated laser measurements showed no indication of tissue damage.

  16. Fixation strategies for retinal immunohistochemistry.

    PubMed

    Stradleigh, Tyler W; Ishida, Andrew T

    2015-09-01

    Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons. PMID:25892361

  17. Fixation Strategies For Retinal Immunohistochemistry

    PubMed Central

    Stradleigh, Tyler W.; Ishida, Andrew T.

    2015-01-01

    Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons. PMID:25892361

  18. Control of the orientational order and nonlinear optical response of the "push-pull" chromophore RuPZn via specific incorporation into densely packed monolayer ensembles of an amphiphilic 4-helix bundle peptide: second harmonic generation at high chromophore densities.

    PubMed

    Gonella, Grazia; Dai, Hai-Lung; Fry, H Christopher; Therien, Michael J; Krishnan, Venkata; Tronin, Andrey; Blasie, J Kent

    2010-07-21

    The macroscopic nonlinear optical response of the "push-pull" chromophore RuPZn incorporated into a single monolayer of the amphiphilic 4-helix bundle peptide (AP0) covalently attached to a solid substrate at high in-plane density has been measured. The second-order susceptibility, chi(zzz), was found to be in the range of approximately 15 x 10(-9) esu, consistent with a coherent sum of the nonlinear contributions from the individual chromophores (beta) as previously measured in isotropic solution through hyper-Rayleigh scattering as well as estimated from theoretical calculations. The microscopic hyperpolarizability of the RuPZn chromophore is preserved upon incorporation into the peptide monolayer, suggesting that the chromophore-chromophore interactions in the densely packed ensemble do not substantially affect the first-order molecular hyperpolarizability. The polarization angle dependence of the second harmonic signal reveals that the chromophore is vectorially oriented in the two-dimensional ensemble. Analysis of the order parameter together with information obtained from grazing incidence X-ray diffraction help in determining the chromophore orientation within the AP0-RuPZn monolayer. Taking into account an average pitch angle of approximately 20 degrees characterizing the coiled-coil structure of the peptide bundle, the width of the bundle's tilt angle distribution should be sigma < or = 20 degrees, resulting in a mean value of the tilt angle 23 degrees < or = theta(0) < or = 37 degrees. PMID:20578696

  19. Layer-by-layer deposited organic/inorganic hybrid multilayer films containing noncentrosymmetrically orientated azobenzene chromophores.

    PubMed

    Kang, En-Hua; Bu, Tianjia; Jin, Pengcheng; Sun, Junqi; Yang, Yanqiang; Shen, Jiacong

    2007-07-01

    Organic/inorganic hybrid multilayer films with noncentrosymmetrically orientated azobenzene chromophores were fabricated by the sequential deposition of ZrO2 layers by a surface sol-gel process and subsequent layer-by-layer (LbL) adsorption of the nonlinear optical (NLO)-active azobenzene-containing polyanion PAC-azoBNS and poly(diallyldimethylammonium chloride) (PDDA). Noncentrosymmetric orientation of the NLO-active azobenzene chromophores was achieved because of the strong repulsion between the negatively charged ZrO(2) and the sulfonate groups of the azobenzene chromophore in PAC-azoBNS. Regular deposition of ZrO(2)/PAC-azoBNS/PDDA multilayer films was verified by UV-vis absorption spectroscopy and quartz crystal microbalance measurements. Both UV-vis absorption spectroscopy and transmission second harmonic generation (SHG) measurements confirmed the noncentrosymmetric orientation of the azobenzene chromophores in the as-prepared ZrO2/PAC-azoBNS/PDDA multilayer films. The square root of the SHG signal (I(2omega)(1/2)) increases with the increase of the azobenzene graft ratio in PAC-azoBNS as the number of deposition cycles of the ZrO(2)/PAC-azoBNS/PDDA films remains the same, while the second-order susceptibility chi(zzz)(2) of the film decreases with the increase of the azobenzene graft ratio. Furthermore, the present method was successfully extended to realize the noncentrosymmetric orientation of azobenzene chromophores in multilayer films when small organic azobenzene compounds with carboxylic acid and/or hydroxyl groups at one end and sulfonate groups at the other end were used. The present method was characterized by its simplicity and flexibility in film preparation, and it is anticipated to be a facile way to fabricate second-order nonlinear optical film materials. PMID:17555337

  20. Modulating LOV Domain Photodynamics with a Residue Alteration outside the Chromophore Binding Site†

    PubMed Central

    Song, Sang-Hun; Freddolino, Peter L.; Nash, Abigail I.; Carroll, Elizabeth C.; Schulten, Klaus; Gardner, Kevin H.; Larsen, Delmar S.

    2011-01-01

    Phototropins, a class of light-activated protein kinases, are essential for several blue light responses in plants and algae, including phototropism. These proteins contain two internal light, oxygen, and voltage sensitive (LOV) domains, which bind flavin chromophores and undergo a reversible photochemical formation of a cysteinyl-flavin adduct as part of the light sensing process. While the photodynamic properties of such photosensory domains are dictated by interactions between the chromophore and surrounding protein, more distant residues can play a significant role as well. Here we explore the role of the Phe434 residue in the photosensory response of the second LOV domain of Avena sativa phototropin 1 (AsLOV2), a model photochemical system for these LOV domains. Phe434 lies over 6 Å from the FMN chromophore in AsLOV2; nevertheless, a F434Y point mutation is likely to change several structural features of the chromophore binding site, as we demonstrate using molecular dynamics simulations. Transient absorption signals spanning 15 decades in time were compared for wildtype AsLOV2 and the F434Y mutant, showing that the latter has significantly altered photodynamics including (i) a faster intersystem crossing leading to triplet formation on a nanosecond time scale, (ii) biphasic formation of adduct state kinetics on the microsecond time scale, and (iii) greatly accelerated ground-state recovery kinetics on a second time scale. We present mechanistic models that link these spectroscopic differences to changes in the configuration of the critical cysteine residue and in the chromophore’s accessibility to solvent and oxygen according to MD trajectories and purging experiments. Taken together, these results demonstrate the importance of residues outside the chromophore-binding pocket in modulating LOV domain photodynamics. PMID:21323358

  1. Synthesis and electro-optic properties of the chromophore-containing NLO polyarylate polymers

    NASA Astrophysics Data System (ADS)

    Ren, Haohui; Peng, Chengcheng; Bo, Shuhui; Fan, Guofang; Xu, Guangming; Zhao, Hui; Zhen, Zhen; Liu, Xinhou

    2014-03-01

    Base on the same two monomers, diphenolic acid (DPA) and isophthaloyl chloride (IPC), three chromophore-containing nonlinear optical (NLO) polyarylate polymers were prepared. A tricyanofuran (TCF)-acceptor type chromophore group was in main-chain (mPAR-chr1), side-chain (sPAR-chr1) and side-chain with a 1,1-bis(4-hydroxyphenyl)-1-phenyl-2,2,2-trifluoroethane (BPAPF) group (sPAR-F-chr1), respectively. The obtained polymers were characterized and evaluated by UV-Vis, 1H NMR, DSC and TGA. All the polymers exhibited good electro-optic (EO) activity. The relationship between EO coefficients (r33) and the chromophore concentration of the three polymers were also characterized and discussed. There were no obvious differences found in EO activity between mPAR-chr1 and sPAR-chr1 polyarylates with the same chromophore. The fluorinated block polyarylate sPAR-F-chr1 has the largest r33 value in these three polyarylates which is 52 pm/V at the wavelength of 1310 nm (which is almost twice the r33 value of normal polymers contained the same chormophore at the same content), when the concentration of chromophore 1 is 18wt.%. 85% of the r33 value was retained in the sPAR-F-chr1 after being heated at 85°C for 600 hours. The polymer sPAR-F-chr1, with good solubility, high Tg (above 200 °C) and side functional group at the same time, may probably be a practical NLO material. These properties make the new polyarylates have potential applications in EO devices such as EO modulators and switches.

  2. Simultaneous control of emission localization and two-photon absorption efficiency in dissymmetrical chromophores

    SciTech Connect

    Tretiak, Sergei

    2009-01-01

    The aim of the present work is to demonstrate that combined spectral tuning of fluorescence and two-photon absorption (TPA) properties of multipolar chromophores can be achieved by introduction of slight electronic chemical dissymmetry. In that perspective, two novel series of structurally related chromophores have been designed and studied: a first series based on rod-like quadrupolar chromophores bearing different electron-donating (D) end groups and a second series based on three-branched octupolar chromophores built from a trigonal donating moiety and bearing various acceptor (A) peripheral groups. The influence of the electronic dissymmetry is investigated by combined experimental and theoretical studies of the linear and nonlinear optical properties of dissymmetric chromophores compared to their symmetrical counterparts. In both types of systems (i.e. quadrupoles and octupoles) experiments and theory reveal that excitation is essentially delocalized and that excitation involves synchronized charge redistribution between the different D and A moieties within the multipolar structure (i.e. concerted intramolecular charge transfer). In contrast, the emission stems only from a particular dipolar subunit bearing the strongest D or A moieties due to fast excitation localization after excitation prior to emission. Hence control of emission characteristics (polarization and emission spectrum) in addition to localization can be achieved by controlled introduction of electronic dissymmetry (i.e. replacement of one of the D or A end-groups by a slightly stronger D{prime} or A{prime} units). Interestingly dissymmetrical functionalization of both quadrupolar and octupolar compounds does not lead to significant loss in TPA responses and can even be beneficial due to the spectral broadening and peak position tuning that it allows. This study thus reveals an original molecular engineering route strategy allowing major TPA enhancement in multipolar structures due to concerted

  3. A mechanical model of retinal detachment

    NASA Astrophysics Data System (ADS)

    Chou, Tom; Siegel, Michael

    2012-08-01

    We present a model of the mechanical and fluid forces associated with exudative retinal detachments where the retinal photoreceptor cells separate, typically from the underlying retinal pigment epithelium (RPE). By computing the total fluid volume flow arising from transretinal, vascular and RPE pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an irreversible, extended retinal delamination. We also investigate localized, blister-like retinal detachments by balancing mechanical tension in the retina with both the retina-RPE adhesion energy and the hydraulic pressure jump across the retina. For detachments induced by traction forces, we find a critical radius beyond which the blister is unstable to growth. Growth of a detached blister can also be driven by inflamed lesions in which the tissue has a higher choroidal hydraulic conductivity, has insufficient RPE pump activity, or has defective adhesion bonds. We determine the parameter regimes in which the blister either becomes unstable to growth, remains stable and finite-sized, or shrinks, allowing possible healing. The corresponding stable blister radius and shape are calculated. Our analysis provides a quantitative description of the physical mechanisms involved in exudative retinal detachments and can help guide the development of retinal reattachment protocols or preventative procedures.

  4. Retinal microvascular network attenuation in Alzheimer's disease

    PubMed Central

    Williams, Michael A.; McGowan, Amy J.; Cardwell, Chris R.; Cheung, Carol Y.; Craig, David; Passmore, Peter; Silvestri, Giuliana; Maxwell, Alexander P.; McKay, Gareth J.

    2015-01-01

    Introduction Cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls. Methods Retinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders. Results Retinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62–0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63–0.97]) were more likely to have AD after appropriate adjustment. Discussion Patients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD. PMID:26634224

  5. Optical Coherence Tomography Angiography in Retinal Diseases

    PubMed Central

    Chalam, K. V.; Sambhav, Kumar

    2016-01-01

    Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

  6. Optical Coherence Tomography Angiography in Retinal Diseases.

    PubMed

    Chalam, K V; Sambhav, Kumar

    2016-01-01

    Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

  7. Purinergic signaling in retinal degeneration and regeneration.

    PubMed

    Reichenbach, Andreas; Bringmann, Andreas

    2016-05-01

    Purinergic signaling is centrally involved in mediating the degeneration of the injured and diseased retina, the induction of retinal gliosis, and the protection of the retinal tissue from degeneration. Dysregulated calcium signaling triggered by overactivation of P2X7 receptors is a crucial step in the induction of neuronal and microvascular cell death under pathogenic conditions like ischemia-hypoxia, elevated intraocular pressure, and diabetes, respectively. Overactivation of P2X7 plays also a pathogenic role in inherited and age-related photoreceptor cell death and in the age-related dysfunction and degeneration of the retinal pigment epithelium. Gliosis of micro- and macroglial cells, which is induced and/or modulated by purinergic signaling and associated with an impaired homeostatic support to neurons, and the ATP-mediated propagation of retinal gliosis from a focal injury into the surrounding noninjured tissue are involved in inducing secondary cell death in the retina. On the other hand, alterations in the glial metabolism of extracellular nucleotides, resulting in a decreased level of ATP and an increased level of adenosine, may be neuroprotective in the diseased retina. Purinergic signals stimulate the proliferation of retinal glial cells which contributes to glial scarring which has protective effects on retinal degeneration and adverse effects on retinal regeneration. Pharmacological modulation of purinergic receptors, e.g., inhibition of P2X and activation of adenosine receptors, may have clinical importance for the prevention of photoreceptor, neuronal, and microvascular cell death in diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration, and glaucoma, respectively, for the clearance of retinal edema, and the inhibition of dysregulated cell proliferation in proliferative retinopathies. This article is part of a Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:25998275

  8. Retinal venous pressure: the role of endothelin.

    PubMed

    Flammer, Josef; Konieczka, Katarzyna

    2015-01-01

    The retinal venous pressure (RVP) can be measured non-invasively. While RVP is equal to or slightly above intraocular pressure (IOP) in healthy people, it is often markedly increased in patients with eye or systemic diseases. Beside a mechanical obstruction, the main cause of such an elevation is a local dysregulation of a retinal vein, particularly a constriction induced by endothelin-1 (ET-1). A local increase of ET-1 can result from a high plasma level, as ET-1 can diffuse from the fenestrated capillaries of the choroid into the optic nerve head (ONH), bypassing the blood retinal barrier. A local increase can also result from increased local production either by a sick neighboring artery or retinal tissue. Generally, the main factors increasing ET-1 are inflammations and hypoxia, either locally or in a remote organ. RVP is known to be increased in patients with glaucoma, retinal vein occlusion (RVO), diabetic retinopathy, high mountain disease, and primary vascular dysregulation (PVD). PVD is the major vascular component of Flammer syndrome (FS). An increase of RVP decreases perfusion pressure, which heightens the risk for hypoxia. An increase of RVP also elevates transmural pressure, which in turn heightens the risk for retinal edema. In patients with RVO, a high level of RVP may not only be a consequence but also a potential cause of the occlusion; therefore, it risks causing a vicious circle. Narrow retinal arteries and particularly dilated retinal veins are known risk indicators for future cardiovascular events. As the major cause for such a retinal venous dilatation is an increased RVP, RVP may likely turn out to be an even stronger predictor. PMID:26504500

  9. Photoactivation-Induced Instability of Rhodopsin Mutants T4K and T17M in Rod Outer Segments Underlies Retinal Degeneration in X. laevis Transgenic Models of Retinitis Pigmentosa

    PubMed Central

    Tam, Beatrice M.; Noorwez, Syed M.; Kaushal, Shalesh; Kono, Masahiro

    2014-01-01

    Retinitis pigmentosa (RP) is an inherited neurodegenerative disease involving progressive vision loss, and is often linked to mutations in the rhodopsin gene. Mutations that abolish N-terminal glycosylation of rhodopsin (T4K and T17M) cause sector RP in which the inferior retina preferentially degenerates, possibly due to greater light exposure of this region. Transgenic animal models expressing rhodopsin glycosylation mutants also exhibit light exacerbated retinal degeneration (RD). In this study, we used transgenic Xenopus laevis to investigate the pathogenic mechanism connecting light exposure and RD in photoreceptors expressing T4K or T17M rhodopsin. We demonstrate that increasing the thermal stability of these rhodopsins via a novel disulfide bond resulted in significantly less RD. Furthermore, T4K or T17M rhodopsins that were constitutively inactive (due to lack of the chromophore-binding site or dietary deprivation of the chromophore precursor vitamin A) induced less toxicity. In contrast, variants in the active conformation accumulated in the ER and caused RD even in the absence of light. In vitro, T4K and T17M rhodopsins showed reduced ability to regenerate pigment after light exposure. Finally, although multiple amino acid substitutions of T4 abolished glycosylation at N2 but were not toxic, similar substitutions of T17 were not tolerated, suggesting that the carbohydrate moiety at N15 is critical for cell viability. Our results identify a novel pathogenic mechanism in which the glycosylation-deficient rhodopsins are destabilized by light activation. These results have important implications for proposed RP therapies, such as vitamin A supplementation, which may be ineffective or even detrimental for certain RP genotypes. PMID:25274813

  10. Photoactivation-induced instability of rhodopsin mutants T4K and T17M in rod outer segments underlies retinal degeneration in X. laevis transgenic models of retinitis pigmentosa.

    PubMed

    Tam, Beatrice M; Noorwez, Syed M; Kaushal, Shalesh; Kono, Masahiro; Moritz, Orson L

    2014-10-01

    Retinitis pigmentosa (RP) is an inherited neurodegenerative disease involving progressive vision loss, and is often linked to mutations in the rhodopsin gene. Mutations that abolish N-terminal glycosylation of rhodopsin (T4K and T17M) cause sector RP in which the inferior retina preferentially degenerates, possibly due to greater light exposure of this region. Transgenic animal models expressing rhodopsin glycosylation mutants also exhibit light exacerbated retinal degeneration (RD). In this study, we used transgenic Xenopus laevis to investigate the pathogenic mechanism connecting light exposure and RD in photoreceptors expressing T4K or T17M rhodopsin. We demonstrate that increasing the thermal stability of these rhodopsins via a novel disulfide bond resulted in significantly less RD. Furthermore, T4K or T17M rhodopsins that were constitutively inactive (due to lack of the chromophore-binding site or dietary deprivation of the chromophore precursor vitamin A) induced less toxicity. In contrast, variants in the active conformation accumulated in the ER and caused RD even in the absence of light. In vitro, T4K and T17M rhodopsins showed reduced ability to regenerate pigment after light exposure. Finally, although multiple amino acid substitutions of T4 abolished glycosylation at N2 but were not toxic, similar substitutions of T17 were not tolerated, suggesting that the carbohydrate moiety at N15 is critical for cell viability. Our results identify a novel pathogenic mechanism in which the glycosylation-deficient rhodopsins are destabilized by light activation. These results have important implications for proposed RP therapies, such as vitamin A supplementation, which may be ineffective or even detrimental for certain RP genotypes. PMID:25274813

  11. Cancer-associated retinopathy with retinal phlebitis.

    PubMed

    Ohnishi, Y; Ohara, S; Sakamoto, T; Kohno, T; Nakao, F

    1993-12-01

    A 50-year-old man with cancer-associated retinopathy was investigated using light and electron microscopy, immunofluorescence studies, and western blotting. He had visual disturbance, ring-like scotoma, and night blindness bilaterally. There were narrowed retinal arterioles and dilated retinal venules. Oral corticosteroid therapy had positive effects. Immunostaining using the patient's serum revealed a positive reaction in the ganglion cell layer of normal retina. Western blotting showed that the patient's serum antibody reacted with normal retinal proteins of 24 and 48 kDa. Multiple metastases were evident at autopsy. PMID:8110675

  12. Retinal isomerization dynamics in dry bacteriorhodopsin films

    NASA Astrophysics Data System (ADS)

    Colonna, Anne; Groma, Géza I.; Vos, Marten H.

    2005-10-01

    The primary photoprocesses in neutral and acid forms of oriented dried bacteriorhodopsin films were investigated by femtosecond absorption spectroscopy. The excitation energy dependence of the signals was used to distinguish photochemistry from processes involving photophysics of photocycle intermediates. Both the kinetics and the quantum yield of all- trans excited state decay by retinal photoisomerization and subsequent J → K transition were found to be very similar as in hydrated environments. Therefore, unlike slower photocycle phases, communication of the retinal with the environment does not play a role in retinal isomerization. Our results are important for understanding recent nonlinear optical applications of such films.

  13. Retinal Stimulation on Rabbit Using Complementary Metal Oxide Semiconductor Based Multichip Flexible Stimulator toward Retinal Prosthesis

    NASA Astrophysics Data System (ADS)

    Tokuda, Takashi; Asano, Ryosuke; Sugitani, Sachie; Taniyama, Mari; Terasawa, Yasuo; Nunoshita, Masahiro; Nakauchi, Kazuaki; Fujikado, Takashi; Tano, Yasuo; Ohta, Jun

    2008-04-01

    The Functionality of a complementary metal oxide semiconductor (CMOS) LSI-based, multichip flexible retinal stimulator was demonstrated in retinal stimulation experiments on rabbits. A 1×4-configured multichip stimulator was fabricated for application to experiments on animals. An experimental procedure including surgical operations was developed, and retinal stimulation was performed with the fabricated multichip stimulator. Neural responses on the visual cortex were successfully evoked by the fabricated stimulator. The stimulator is confirmed to be applicable to acute animal experiments.

  14. Nuclear Migration During Retinal Development

    PubMed Central

    Baye, Lisa M.; Link, Brian A.

    2009-01-01

    In this review we focus on the mechanisms, regulation, and cellular consequences of nuclear migration in the developing retina. In the nervous system, nuclear migration is prominent during both proliferative and post-mitotic phases of development. Interkinetic nuclear migration is the process where the nucleus oscillates from the apical to basal surfaces in proliferative neuroepithelia. Proliferative nuclear movement occurs in step with the cell cycle, with M-phase being confined to the apical surface and G1-, S-, and G2-phases occurring at more basal locations. Later, following cell cycle exit, some neuron precursors migrate by nuclear translocation. In this mode of cellular migration, nuclear movement is the driving force for motility. Following discussion of the key components and important regulators for each of these processes, we present an emerging model where interkinetic nuclear migration functions to distinguish cell fates among retinal neuroepithelia. PMID:17560964

  15. Retinal Adaptation to Object Motion

    PubMed Central

    Ölveczky, Bence P.; Baccus, Stephen A.; Meister, Markus

    2007-01-01

    Summary Due to fixational eye movements, the image on the retina is always in motion, even when one views a stationary scene. When an object moves within the scene, the corresponding patch of retina experiences a different motion trajectory than the surrounding region. Certain retinal ganglion cells respond selectively to this condition, when the motion in the cell’s receptive field center is different from that in the surround. Here we show that this response is strongest at the very onset of differential motion, followed by gradual adaptation with a time course of several seconds. Different subregions of a ganglion cell’s receptive field can adapt independently. The circuitry responsible for differential motion adaptation lies in the inner retina. Several candidate mechanisms were tested, and the adaptation most likely results from synaptic depression at the synapse from bipolar to ganglion cell. Similar circuit mechanisms may act more generally to emphasize novel features of a visual stimulus. PMID:18031685

  16. Regulatory and Economic Considerations of Retinal Drugs.

    PubMed

    Shah, Ankoor R; Williams, George A

    2016-01-01

    The advent of anti-VEGF therapy for neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion and diabetes mellitus has prevented blindness in tens of thousands of people. However, the costs of these drugs are without precedent in ophthalmic drug therapeutics. An analysis of the financial implications of retinal drugs and the impact of the Food and Drug Administration on treatment of retinal disease must include not only an evaluation of the direct costs of the drugs and the costs associated with their administration, but also the cost savings which accrue from their clinical benefit. This chapter will discuss the financial and regulatory issues associated with retinal drugs. PMID:26502165

  17. Retinal vein occlusion: pathophysiology and treatment options

    PubMed Central

    Karia, Niral

    2010-01-01

    This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms. PMID:20689798

  18. Expression Profiling of Developing Zebrafish Retinal Cells.

    PubMed

    Mullally, Madelyn; Albrecht, Caitlin; Horton, Mary; Laboissonniere, Lauren A; Goetz, Jillian J; Chowdhury, Rebecca; Manning, Alicia; Wester, Andrea K; Bose, Quinton; Trimarchi, Jeffrey M

    2016-08-01

    During retinal development, a variety of different types of neurons are produced. Understanding how each of these types of retinal nerve cells is generated is important from a developmental biology perspective. It is equally important if one is interested in how to regenerate cells after an injury or a disease. To gain more insight into how retinal neurons develop in the zebrafish, we performed single-cell mRNA profiling and in situ hybridizations (ISHs) on retinal sections and whole-mount zebrafish. Through the series of ISHs, designed and performed solely by undergraduate students in the laboratory, we were able to retrospectively identify our single-cell mRNA profiles as most likely coming from developing amacrine cells. Further analysis of these profiles will reveal genes that can be mutated using genome editing techniques. Together these studies increase our knowledge of the genes driving development of different cell types in the zebrafish retina. PMID:26982811

  19. Retinal Detachment: Torn or Detached Retina Treatment

    MedlinePlus

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

  20. What Is Next for Retinal Gene Therapy?

    PubMed Central

    Vandenberghe, Luk H.

    2015-01-01

    The field of gene therapy for retinal blinding disorders is experiencing incredible momentum, justified by hopeful results in early stage clinical trials for inherited retinal degenerations. The premise of the use of the gene as a drug has come a long way, and may have found its niche in the treatment of retinal disease. Indeed, with only limited treatment options available for retinal indications, gene therapy has been proven feasible, safe, and effective and may lead to durable effects following a single injection. Here, we aim at putting into context the promise and potential, the technical, clinical, and economic boundaries limiting its application and development, and speculate on a future in which gene therapy is an integral component of ophthalmic clinical care. PMID:25877395

  1. Doppler optical coherence tomography of retinal circulation.

    PubMed

    Tan, Ou; Wang, Yimin; Konduru, Ranjith K; Zhang, Xinbo; Sadda, SriniVas R; Huang, David

    2012-01-01

    Noncontact retinal blood flow measurements are performed with a Fourier domain optical coherence tomography (OCT) system using a circumpapillary double circular scan (CDCS) that scans around the optic nerve head at 3.40 mm and 3.75 mm diameters. The double concentric circles are performed 6 times consecutively over 2 sec. The CDCS scan is saved with Doppler shift information from which flow can be calculated. The standard clinical protocol calls for 3 CDCS scans made with the OCT beam passing through the superonasal edge of the pupil and 3 CDCS scan through the inferonal pupil. This double-angle protocol ensures that acceptable Doppler angle is obtained on each retinal branch vessel in at least 1 scan. The CDCS scan data, a 3-dimensional volumetric OCT scan of the optic disc scan, and a color photograph of the optic disc are used together to obtain retinal blood flow measurement on an eye. We have developed a blood flow measurement software called "Doppler optical coherence tomography of retinal circulation" (DOCTORC). This semi-automated software is used to measure total retinal blood flow, vessel cross section area, and average blood velocity. The flow of each vessel is calculated from the Doppler shift in the vessel cross-sectional area and the Doppler angle between the vessel and the OCT beam. Total retinal blood flow measurement is summed from the veins around the optic disc. The results obtained at our Doppler OCT reading center showed good reproducibility between graders and methods (<10%). Total retinal blood flow could be useful in the management of glaucoma, other retinal diseases, and retinal diseases. In glaucoma patients, OCT retinal blood flow measurement was highly correlated with visual field loss (R(2)>0.57 with visual field pattern deviation). Doppler OCT is a new method to perform rapid, noncontact, and repeatable measurement of total retinal blood flow using widely available Fourier-domain OCT instrumentation. This new technology may improve the

  2. Diode laser contact transscleral retinal photocoagulation: a clinical study.

    PubMed Central

    McHugh, D A; Schwartz, S; Dowler, J G; Ulbig, M; Blach, R K; Hamilton, P A

    1995-01-01

    AIM--To examine the clinical efficacy of contact transscleral retinal photocoagulation with a diode laser. METHODS--Transscleral retinal photocoagulation was performed on 36 eyes. The conditions treated included peripheral retinal breaks associated with retinal detachments (30 eyes) and giant retinal tears (six eyes). Of the 30 eyes with retinal detachments, 28 underwent transscleral photocoagulation to the site of drainage of subretinal fluid in an attempt to reduce the risk of hemorrhage. RESULTS--Threshold lesions were obtained with irradiances of between 95.4 W/cm2 and 191 W/cm2. Satisfactory chorioretinal adhesion was achieved in all eyes with retinal breaks and giant retinal tears. The only significant complications of treatment encountered were punctate choroidal haemorrhages (three eyes). Drainage related choroidal haemorrhage following earlier photocoagulation occurred in two of 28 eyes. CONCLUSIONS--This study confirms the clinical potential of transscleral diode laser photocoagulation in the therapy of surgical retinal conditions. Images PMID:8562540

  3. Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes

    PubMed Central

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Saadane, Aicha; Tonade, Deoye; Samuels, Ivy; Veenstra, Alex; Palczewski, Krzysztof; Kern, Timothy S.

    2016-01-01

    Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. Methods Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. Results Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. Conclusions Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID:27548901

  4. Retinal synaptic regeneration via microfluidic guiding channels.

    PubMed

    Su, Ping-Jung; Liu, Zongbin; Zhang, Kai; Han, Xin; Saito, Yuki; Xia, Xiaojun; Yokoi, Kenji; Shen, Haifa; Qin, Lidong

    2015-01-01

    In vitro culture of dissociated retinal neurons is an important model for investigating retinal synaptic regeneration (RSR) and exploring potentials in artificial retina. Here, retinal precursor cells were cultured in a microfluidic chip with multiple arrays of microchannels in order to reconstruct the retinal neuronal synapse. The cultured retinal cells were physically connected through microchannels. Activation of electric signal transduction by the cells through the microchannels was demonstrated by administration of glycinergic factors. In addition, an image-based analytical method was used to quantify the synaptic connections and to assess the kinetics of synaptic regeneration. The rate of RSR decreased significantly below 100 μM of inhibitor glycine and then approached to a relatively constant level at higher concentrations. Furthermore, RSR was enhanced by chemical stimulation with potassium chloride. Collectively, the microfluidic synaptic regeneration chip provides a novel tool for high-throughput investigation of RSR at the cellular level and may be useful in quality control of retinal precursor cell transplantation. PMID:26314276

  5. Retinal Light Damage: Mechanisms and Protection

    PubMed Central

    Organisciak, Daniel T.; Vaughan, Dana K.

    2009-01-01

    By its action on rhodopsin, light triggers the well-known visual transduction cascade, but can also induce cell damage and death through phototoxic mechanisms -- a comprehensive understanding of which is still elusive despite more than 40 years of research. Herein, we integrate recent experimental findings to address several hypotheses of retinal light damage, premised in part on the close anatomical and metabolic relationships between the photoreceptors and the retinal pigment epithelium. We begin by reviewing the salient features of light damage, recently joined by evidence for retinal remodeling which has implications for the prognosis of recovery of function in retinal degenerations. We then consider select factors that influence the progression of the damage process and the extent of visual cell loss. Traditional, genetically-modified, and emerging animal models are discussed, with particular emphasis on cone visual cells. Exogenous and endogenous retinal protective factors are explored, with implications for light damage mechanisms and some suggested avenues for future research. Synergies are known to exist between our long term light environment and photoreceptor cell death in retinal disease. Understanding the molecular mechanisms of light damage in a variety of animal models can provide valuable insights into the effects of light in clinical disorders and may form the basis of future therapies to prevent or delay visual cell loss. PMID:19951742

  6. Retinal oxygenation via the choroidal circulation.

    PubMed Central

    Landers, M B

    1978-01-01

    The possibility of supplying normal amounts of oxygen to the inner layers of the retina by diffusion from the choroid in the presence of retinal arterial obstruction was studied in cats and rhesus monkeys. While the animals were under general anesthesia, an oxygen electrode was placed in the vitreous cavity immediately adjacent to the retina, and a retinal artery blocker probe was used to occlude various segments of the retina blood supply. The inspired oxygen concentration was alternated between 20% and 100%. The choroidal circulation was intermittently occluded by elevating the intraocular pressure. In all animals it was possible to return the oxygen tension of the innermost retina to normal concentrations or above while the retinal arterial circulation alone was occluded, by having the animal breathe 100% oxygen at one atmosphere pressure. This could not be done when the intraocular pressure was elevated to 85 mm Hg, occluding the choroidal as well as the retinal circulation. The electroretinogram and the visually evoked response were recorded in cats while the retinal circulation was occluded and the inspired oxygen concentration changed from 20% to 100% at one atmosphere pressure. The electroretinogram and the visually evoked response were extinguished by occluding the retinal circulation while the animal was breathing 20% oxygen, and these responses were returned to normal by changing to a 100% inspired oxygen concentration. Images FIGURE 6 PMID:112752

  7. [Gene therapy for inherited retinal dystrophies].

    PubMed

    Côco, Monique; Han, Sang Won; Sallum, Juliana Maria Ferraz

    2009-01-01

    The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these conditions and the patients can expect a progressive loss of vision. Accurate genetic counseling and support for rehabilitation are indicated. Research into the molecular and genetic basis of disease is continually expanding and improving the prospects for rational treatments. In this way, gene therapy, defined as the introduction of exogenous genetic material into human cells for therapeutic purposes, may ultimately offer the greatest treatment for the inherited retinal dystrophies. The eye is an attractive target for gene therapy because of its accessibility, immune privilege and translucent media. A number of retinal diseases affecting the eye have known gene defects. Besides, there is a well characterized animal model for many of these conditions. Proposals for clinical trials of gene therapy for inherited retinal degenerations owing to defects in the gene RPE65, have recently received ethical approval and the obtained preliminary results brought large prospects in the improvement on patient's quality of life. PMID:19820803

  8. Absorbance amplification using chromophore-nanoplasmon coupling for ultrasensitive protein quantification.

    PubMed

    Seo, Sujin; Edwards, Lonna; Logan Liu, Gang

    2015-10-01

    A plasmonic nanoscale Lycurgus cup array (nanoLCA), via near-field interaction with chromophores in commercial colorimetric biochemical assays, can drastically enhance assay sensitivity by over 2 orders of magnitude. A 96-microwell plate modified by placing the plasmonic nanoLCA on the well-bottom was used with the commercial Bradford protein quantification assay. Plasmons on the nanoLCA serve as an energy donor to matched resonance chromophores, and the near-field plasmonic energy coupling effect results in an increase in absorbance value at the plasmonic resonance wavelength. Even with a 5.1-fold reduced sample volume, a limit of detection enhancement factor of 200 is accomplished using the nanoLCA compared to using the conventional Bradford assay without plasmon aid. The nanoLCA-microplate sensing platform is readily scalable to 384- or 1536-microwell plates, which further reduces the sensing volume and boosts detection throughput with the enhanced sensitivity. PMID:26284911

  9. Non-adiabatic dynamics of isolated green fluorescent protein chromophore anion

    SciTech Connect

    Zhao, Li E-mail: pwzhou@dicp.ac.cn E-mail: aihuagao@dicp.ac.cn; Gao, Ai-Hua E-mail: pwzhou@dicp.ac.cn E-mail: aihuagao@dicp.ac.cn; Zhou, Pan-Wang E-mail: pwzhou@dicp.ac.cn E-mail: aihuagao@dicp.ac.cn; Li, Bin E-mail: pwzhou@dicp.ac.cn E-mail: aihuagao@dicp.ac.cn; Han, Ke-Li

    2014-12-21

    On-the-fly ab initio molecular dynamics calculations have been performed to investigate the relaxation mechanism of green fluorescent protein chromophore anion under vacuum. The CASSCF surface hopping simulation method based on Zhu-Nakamura theory is applied to present the real-time conformational changes of the target molecule. The static calculations and dynamics simulation results suggest that not only the twisting motion around bridging bonds between imidazolinone and phenoxy groups but the strength mode of C=O and pyramidalization character of bridging atom are major factors on the ultrafast fluorescence quenching process of the isolated chromophore anion. The abovementioned factors bring the molecule to the vicinity of conical intersections on its potential energy surface and to finish the internal conversion process. A Hula-like twisting pattern is displayed during the relaxation process and the entire decay process disfavors a photoswitching pattern which corresponds to cis-trans photoisomerization.

  10. Blue-coloured highly efficient dye-sensitized solar cells by implementing the diketopyrrolopyrrole chromophore.

    PubMed

    Yum, Jun-Ho; Holcombe, Thomas W; Kim, Yongjoo; Rakstys, Kasparas; Moehl, Thomas; Teuscher, Joel; Delcamp, Jared H; Nazeeruddin, Mohammed K; Grätzel, Michael

    2013-01-01

    The paradigm shift in dye sensitized solar cells (DSCs) - towards donor- π bridge-acceptor (D-π-A) dyes - increases the performances of DSCs and challenges established design principles. Framed by this shifting landscape, a series of four diketopyrrolopyrrole (DPP)-based sensitizers utilizing the donor-chromophore-anchor (D-C-A) motif were investigated computationally, spectroscopically, and fabricated by systematic evaluation of finished photovoltaic cells. In all cases, the [Co(bpy)3](3+/2+) redox-shuttle afforded superior performance compared to I3(-)/I(-). Aesthetically, careful molecular engineering of the DPP chromophore yielded the first example of a high-performance blue DSC - a challenge unmet since the inception of this photovoltaic technology: DPP17 yields over 10% power conversion efficiency (PCE) with the [Co(bpy)3](3+/2+) electrolyte at full AM 1.5 G simulated sun light. PMID:23945746

  11. Investigation of two-photon absorption induced excited state absorption in a fluorenyl-based chromophore.

    PubMed

    Li, Changwei; Yang, Kun; Feng, Yan; Su, Xinyan; Yang, Junyi; Jin, Xiao; Shui, Min; Wang, Yuxiao; Zhang, Xueru; Song, Yinglin; Xu, Hongyao

    2009-12-01

    Two-photon absorption induced excited state absorption in the solution of a new fluorenyl-based chromophore is investigated by a time-resolved pump-probe technique using femtosecond pulses. With the help of an additional femtosecond open-aperture Z-scan technique, numerical simulations based on a three-energy level model are used to interpret the experimental results, and we determine the nonlinear optical parameters of this new chromophore uniquely. Large two-photon absorption cross section and excited state absorption cross section for singlet excited state are obtained, indicating a good candidate for optical limiting devices. Moreover, the influence of two-beam coupling induced energy transfer in neat N,N'-dimethylformamide solvent is also considered, although this effect is strongly restrained by the instantaneous two-photon absorption. PMID:19894682

  12. Multispectral imaging in the extended near-infrared window based on endogenous chromophores

    PubMed Central

    Cao, Qian; Zhegalova, Natalia G.; Wang, Steven T.; Akers, Walter J.

    2013-01-01

    Abstract. To minimize the problem with scattering in deep tissues while increasing the penetration depth, we explored the feasibility of imaging in the relatively unexplored extended near infrared (exNIR) spectral region at 900 to 1400 nm with endogenous chromophores. This region, also known as the second NIR window, is weakly dominated by absorption from water and lipids and is free from other endogenous chromophores with virtually no autofluorescence. To demonstrate the applicability of the exNIR for bioimaging, we analyzed the optical properties of individual components and biological tissues using an InGaAs spectrophotometer and a multispectral InGaAs scanning imager featuring transmission geometry. Based on the differences in spectral properties of tissues, we utilized ratiometric approaches to extract spectral characteristics from the acquired three-dimensional “datacube”. The obtained images of an exNIR transmission through a mouse head revealed sufficient details consistent with anatomical structures. PMID:23933967

  13. Non-adiabatic dynamics of isolated green fluorescent protein chromophore anion.

    PubMed

    Zhao, Li; Zhou, Pan-Wang; Li, Bin; Gao, Ai-Hua; Han, Ke-Li

    2014-12-21

    On-the-fly ab initio molecular dynamics calculations have been performed to investigate the relaxation mechanism of green fluorescent protein chromophore anion under vacuum. The CASSCF surface hopping simulation method based on Zhu-Nakamura theory is applied to present the real-time conformational changes of the target molecule. The static calculations and dynamics simulation results suggest that not only the twisting motion around bridging bonds between imidazolinone and phenoxy groups but the strength mode of C=O and pyramidalization character of bridging atom are major factors on the ultrafast fluorescence quenching process of the isolated chromophore anion. The abovementioned factors bring the molecule to the vicinity of conical intersections on its potential energy surface and to finish the internal conversion process. A Hula-like twisting pattern is displayed during the relaxation process and the entire decay process disfavors a photoswitching pattern which corresponds to cis-trans photoisomerization. PMID:25527960

  14. Influence of a chromophore analogue in the protein cage of a photoactive yellow protein.

    PubMed

    Hamada, Norio; Tan, Zhe; Kanematsu, Yasuo; Inazumi, Naoya; Nakamura, Ryosuke

    2015-09-26

    Time-resolved spectra of a photoactive yellow protein (PYP) containing cyano-p-coumaric acid (CHCA) were recorded. To understand the mechanism of photo-isomerization, an electron-withdrawing CN group was introduced into the PYP to alter the C[double bond, length as m-dash]C double bond character. Free CHCA chromophores in aqueous solution underwent photo-isomerization whereas PYP with a bound CHCA (PYP-CN) exhibited no photocycle at acidic or alkaline pH or in urea and other solutions. Furthermore, no photocycle was observed with PYP mutants after illumination. This phenomenon cannot be fully explained by the electron-withdrawing properties of the CN group. We conclude that the CHCA chromophore in PYP was locked in the protein cage and that the CN group interacted with the protein residues. PMID:26178816

  15. On the midpoint potential of the FAD chromophore in a BLUF-domain containing photoreceptor protein.

    PubMed

    Arents, Jos C; Perez, Marcela Avila; Hendriks, Johnny; Hellingwerf, Klaas J

    2011-01-01

    The redox-midpoint potential of the FAD chromophore in the BLUF domain of anti-transcriptional regulator AppA from Rhodobacter sphaeroides equals ∼-260mV relative to the calomel electrode. Altering the structure of its chromophore-binding pocket through site-directed mutagenesis brings this midpoint potential closer to that of free flavin in aqueous solution. The redox-midpoint potential of this BLUF domain is intermediate between those of LOV domains and Cryptochromes, which may rationalize the primary photochemistry observed in these three flavin-containing photoreceptor families. These results also imply that LOV domains, among the flavin-containing photosensory receptors, are least sensitive to intracellular chemical reduction in the dark. PMID:21110976

  16. Design of Small Intramolecular Singlet Fission Chromophores: An Azaborine Candidate and General Small Size Effects.

    PubMed

    Zeng, Tao; Goel, Prateek

    2016-04-01

    We report the first attempt to design small intramolecular singlet fission chromophores, with the aid of quantum chemistry and explicitly simulating the time evolution of state populations using quantum dynamics method. We start with three previously proposed azaborine-substituted intermolecular singlet fission chromophores. Through analyzing their frontier orbital amplitudes, we select a BN-substituted azulene as the building block. Covalently connecting two such monomers and tuning their relative configuration, we examine three dimers. One dimer is found to be an eminent candidate: the triplet-pair state is quickly formed within 1 ps, and the two triplets are ready to be disentangled. We elucidate the general small size effects in intramolecular singlet fission and focus on specific aspects which should be taken care of when manipulating the fission rate through steric hindrance. PMID:27007577

  17. Depth determination of chromophores in human skin by pulsed photothermal radiometry.

    PubMed

    Milner, T E; Smithies, D J; Goodman, D M; Lau, A; Nelson, J S

    1996-07-01

    We report on the application of pulsed photothermal radiometry (PPTR) to determine the depth of in-vitro and in-vivo subsurface chromophores in biological materials. Measurements provided by PPTR in combination with a nonnegative constrained conjugate-gradient algorithm are used to determine the initial temperature distribution in a biological material immediately following pulsed laser irradiation. Within the experimental error, chromophore depths (50-450 µm) in 55 in-vitro collagen phantoms determined by PPTR and optical low-coherence reflectometry are equivalent. The depths of port-wine-stain blood vessels determined by PPTR correlate very well with their locations found by computer-assisted microscopic observation of histologic sections. The mean blood-vessel depth deduced from PPTR and histologic observation is statistically indistinguishable (p > 0.94). PMID:21102725

  18. Depth determination of chromophores in human skin by pulsed photothermal radiometry

    SciTech Connect

    Milner, T.E. |; Smithies, D.J.; Goodman, D.M.; Nelson, J.S. |; Goodman, D.M.; Lau, A.

    1996-07-01

    We report on the application of pulsed photothermal radiometry (PPTR) to determine the depth of {ital in}-{ital vitro} and {ital in}-{ital vivo} subsurface chromophores in biological materials. Measurements provided by PPTR in combination with a nonnegative constrained conjugate-gradient algorithm are used to determine the initial temperature distribution in a biological material immediately following pulsed laser irradiation. Within the experimental error, chromophore depths (50{endash}450 {mu}m) in 55 {ital in}-{ital vitro} collagen phantoms determined by PPTR and optical low-coherence reflectometry are equivalent. The depths of port-wine-stain blood vessels determined by PPTR correlate very well with their locations found by computer-assisted microscopic observation of histologic sections. The mean blood-vessel depth deduced from PPTR and histologic observation is statistically indistinguishable ({ital p}{lt}0.94). {copyright} {ital 1996 Optical Society of America.}

  19. An Intense Red Jovian Cyclone: Another Key to Finding the Chromophores?

    NASA Astrophysics Data System (ADS)

    Simon-Miller, Amy A.; Carlson, R. W.; Sanchez-Lavega, A.

    2013-10-01

    An intense red cyclone was visible on Jupiter in 1995 and is visible in several Hubble Space Telescope datasets from 1994 through 1995. This cell has a distinctly different spectrum than the Great Red Spot, but is quite similar to the North Equatorial Belt. All three regions show spectral differences from a full-disk Jupiter spectrum, giving new clues to the composition of the color causing compounds, or chromophores, on Jupiter. Principal component analyses show several components and further highlight the differences between regions. Temporal analysis shows that the darkest regions of the NEB are relative constant in color, while the slope of the GRS core may vary slightly. The color difference between regions may be indicative of the same chromophore under different conditions (mixing with white clouds, or longer UV irradiation at higher altitude), although multiple compounds involving NH4SH and hydrocarbons may be needed to explain each spectrum.

  20. PDE-constrained multispectral imaging of tissue chromophores with the equation of radiative transfer

    PubMed Central

    Kim, Hyun Keol; Flexman, Molly; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2010-01-01

    We introduce a transport-theory-based PDE-constrained multispectral model for direct imaging of the spatial distributions of chromophores concentrations in biological tissue. The method solves the forward problem (boundary radiance at each wavelength) and the inverse problem (spatial distribution of chromophores concentrations), in an all-at-once manner in the framework of a reduced Hessian sequential quadratic programming method. To illustrate the code’s performance, we present numerical and experimental studies involving tumor bearing mice. It is shown that the PDE-constrained multispectral method accelerates the reconstruction process by up to 15 times compared to unconstrained reconstruction algorithms and provides more accurate results as compared to the so-called two-step approach to multi-wavelength imaging. PMID:21258511

  1. Laser-Induced Dynamical Chirality and Intramolecular Energy Flow in the CH Chromophore

    SciTech Connect

    Thanopulos, Ioannis

    2007-11-29

    We review the quantum dynamics of intramolecular energy flow during and after coherent infrared multiphoton excitation of the CH organic chromophore. The understanding of the underlying dynamics is of central importance for a wide range of systems in molecular physics, chemistry and biology, due to the experimentally supported assumption that the chromophore dynamics is weakly-dependent on a specific environment, in particular on sub-picosecond time scale. The excitation process due to the interaction with the laser field is studied by computationally monitoring the wave packet motion in the configuration sub-space relevant to femtosecond dynamics, using global analytical potential energy and electric dipole functions previously developed. The features of the intramolecular vibrational energy redistribution and the related dynamical time scales are investigated. In particular, we discuss the generation of dynamical chirality in methane istopomers, the corresponding stereomutation and racemization phenomena on the femtosecond time scale, and their relation to intramolecular vibrational energy redistribution.

  2. Synthesis and nonlinear optical properties of a peripherally functionalized hyperbranched polymer by DR1 chromophores.

    PubMed

    Scarpaci, Annabelle; Blart, Errol; Montembault, Véronique; Fontaine, Laurent; Rodriguez, Vincent; Odobel, Fabrice

    2009-08-01

    The first peripheral postfunctionalization of a hyperbranched polyimide by nonlinear optic chromophores (DR1 derivative) was achieved using two different routes. The first one consists in the esterification of the terminal carboxylic acid groups, whereas the second is based on copper-catalyzed Huisgen reaction of the terminal propargylic ester groups. The resulting polymers display good solubility in classical organic solvents and good filmability because thick films can be prepared (up to 2.7 mum). The second-order nonlinear optical properties were measured by SHG at 1064 nm and we show that these hyperbranched polymers exhibit good poling efficiency and good thermal stability since the electro-optic activity remains stable up to 130 degrees C. These results illustrate the potential of hyperbranched polymers to host second-order nonlinear optical chromophores to replace dendrimers or classical linear polymers generally used in this area. PMID:20355797

  3. Non-adiabatic dynamics of isolated green fluorescent protein chromophore anion

    NASA Astrophysics Data System (ADS)

    Zhao, Li; Zhou, Pan-Wang; Li, Bin; Gao, Ai-Hua; Han, Ke-Li

    2014-12-01

    On-the-fly ab initio molecular dynamics calculations have been performed to investigate the relaxation mechanism of green fluorescent protein chromophore anion under vacuum. The CASSCF surface hopping simulation method based on Zhu-Nakamura theory is applied to present the real-time conformational changes of the target molecule. The static calculations and dynamics simulation results suggest that not only the twisting motion around bridging bonds between imidazolinone and phenoxy groups but the strength mode of C=O and pyramidalization character of bridging atom are major factors on the ultrafast fluorescence quenching process of the isolated chromophore anion. The abovementioned factors bring the molecule to the vicinity of conical intersections on its potential energy surface and to finish the internal conversion process. A Hula-like twisting pattern is displayed during the relaxation process and the entire decay process disfavors a photoswitching pattern which corresponds to cis-trans photoisomerization.

  4. Regeneration of Light-Harvesting Complexes via Dynamic Replacement of Photodegraded Chromophores.

    PubMed

    Zhang, Hanyu; Pan, Jing; Ghimire, Srijana; Bork, Matthew A; Riccitelli, Molly M; McMillin, David R; Choi, Jong Hyun

    2015-04-22

    All-synthetic molecular donor-acceptor complexes are designed, which are capable of counteracting the effect of photoinduced degradation of donor chromophores. Anionic gallium protoporphyrin IX (GaPP) and semiconducting carbon nanotube (CNT) are used as a model donor-acceptor complex, which is assembled using DNA oligonucleotides. The GaPP-DNA-CNT complex produces an anodic photocurrent in a photoelectrochemical cell, which steadily decays due to photo-oxidation. By modulating the chemical environment, we showed that the photodegraded chromophores may be dissociated from the complex, whereas the DNA-coated carbon nanotube acceptors are kept intact. Reassociation with fresh porphyrins leads to the full recovery of GaPP absorption and photocurrents. This strategy could form a basis for improving the light-harvesting performance of molecular donor-acceptor complexes and extending their operation lifetime. PMID:25848806

  5. Synthesis of a novel organic nonlinear optical chromophore and the Testing for µg β Value

    NASA Astrophysics Data System (ADS)

    Han, Li-Kun; Jiang, Ya-Dong; Li, Wei; Cai, Yuan

    2007-01-01

    A novel second-order nonlinear optical chromophore (DCDHF-2-V) was synthesized from 3-Hydroxy-3-methyl-2-butanae, propanedinitrile and 4-diethylaminobenzaldehyde by aldol condensation reaction. Molecular structural characterization was investigated by elemental analysis, FTIR, and 1H-NMR spectra. The melting point obtained from DSC thermogram was almost 251 °C, and the compound shows a thermal stability up to 270 °C. Second-order NLO properties of the chromophore were measured by solvatochromic method. From the quantum-mechanical two-level model, it can be obtained that the µg β value of DCDHF-2-V is 6520 × 10-48esu at the wavelength of 1064 nm.

  6. Selective destruction of protein function by chromophore-assisted laser inactivation

    SciTech Connect

    Jay, D.G.

    1988-08-01

    Chromophore-assisted laser inactivation of protein function has been achieved. After a protein binds a specific ligand or antibody conjugated with malachite green (C.I. 42,000), it is selectively inactivated by laser irradiation at a wavelength of light absorbed by the dye but not significantly absorbed by cellular components. Ligand-bound proteins in solution and on the surfaces of cells can be denatured without other proteins in the same samples being affected. Chromophore-assisted laser inactivation can be used to study cell surface phenomena by inactivating the functions of single proteins on living cells, a molecular extension of cellular laser ablation. It has an advantage over genetics and the use of specific inhibitors in that the protein function of a single cell within the organism can be inactivated by focusing the laser beam.

  7. Broadband continuous-wave technique to measure baseline values and changes in the tissue chromophore concentrations

    PubMed Central

    Yeganeh, Hadi Zabihi; Toronov, Vladislav; Elliott, Jonathan T.; Diop, Mamadou; Lee, Ting-Yim; St. Lawrence, Keith

    2012-01-01

    We present a broad-band, continuous-wave spectral approach to quantify the baseline optical properties of tissue and changes in the concentration of a chromophore, which can assist to quantify the regional blood flow from dynamic contrast-enhanced near-infrared spectroscopy data. Experiments were conducted on phantoms and piglets. The baseline optical properties of tissue were determined by a multi-parameter wavelength-dependent data fit of a photon diffusion equation solution for a homogeneous medium. These baseline optical properties were used to find the changes in Indocyanine green concentration time course in the tissue. The changes were obtained by fitting the dynamic data at the peak wavelength of the chromophore absorption, which were used later to estimate the cerebral blood flow using a bolus tracking method. PMID:23162714

  8. A DNA-Fullerene Conjugate as a Template for Supramolecular Chromophore Assemblies: Towards DNA-Based Solar Cells.

    PubMed

    Ensslen, Philipp; Gärtner, Stefan; Glaser, Konstantin; Colsmann, Alexander; Wagenknecht, Hans-Achim

    2016-01-26

    A fullerene was covalently attached to a (dA)20 template that serves as structural scaffold to self-assemble an ordered and mixed array of ethynyl-pyrene- and ethynyl-Nile-red-nucleoside conjugates. Fluorescence spectroscopy revealed evidence for energy transfer between the two different chromophores. Moreover, fluorescence quenching is significantly enhanced by the attached fullerene in mixed assemblies of different chromophore ratios. This indicates exciton dissociation by electron transfer from the photo-generated exciton on the chromophore stack to the fullerene. The fullerene-DNA-conjugate was integrated as a photo-active layer in solar cells that showed charge-carrier generation in the spectral regime of all three components of the conjugate. This work clearly demonstrates that DNA is suitable as structural element for chromophore assemblies in future organic optoelectronic devices, such as solar cells. PMID:26689149

  9. PHOTOREACTIVITY OF CHROMOPHORIC DISSOLVED ORGANIC MATTER (CDOM) DERIVED FROM DECOMPOSITION OF VARIOUS VASCULAR PLANT AND ALGAL SOURCES

    EPA Science Inventory

    Chromophoric dissolved organic matter (CDOM) in aquatic environments is derived from the microbial decomposition of terrestrial and microbial organic matter. Here we present results of studies of the spectral properties and photoreactivity of the CDOM derived from several organi...

  10. Energy transfer pathways among phycobilin chromophores and fluorescence emission spectra of the phycobilisome core at 293 and 77 K.

    PubMed

    Stadnichuk, V I; Lukashev, E P; Yanyushin, M F; Zlenko, D V; Muronez, E M; Stadnichuk, I N; Krasilnikov, P M

    2015-01-01

    Energy transfer pathways between phycobiliproteins chromophores in the phycobilisome (PBS) core of the cyanobacterium Synechocystis sp. PCC 6803 were investigated. The computer 3D model of the PBS core with determination of chromophore to chromophore distance was created. Our kinetic equations based on this model allowed us to describe the relative intensities of the fluorescence emission of the short(peaked at 665 nm) and long-wavelength (peaked at 680 nm) chromophores in the PBS core at low and room temperatures. The difference of emissions of the PBS core at 77 and 293 K are due to the back energy transfer, which is observed at room temperature and is negligible at 77 K. PMID:26728735

  11. Optical Ground-Based Spectra of Jupiter and Saturn: An Exploration of Giant Planet Chromophores

    NASA Astrophysics Data System (ADS)

    Chanover, Nancy J.; Simon-Miller, A. A.; Hudson, R. L.; Loeffler, M. J.

    2013-10-01

    We present and interpret ground-based optical spectra of Jupiter and Saturn recently acquired in an effort to characterize candidate coloring agents, or chromophores, in the atmospheres of the gas giant planets of our solar system. Surprisingly, despite hundreds of years of observations, we still do not know the identity of the trace chemical compounds that color the atmospheres of the giant planets. Previous analyses have attempted to identify a specific chemical that is responsible for the colors, but none has yet been conclusively proven. We acquired spatially resolved optical spectra of various regions in the atmospheres of both Jupiter and Saturn in February 2013 using the Dual Imaging Spectrograph (DIS) on the Astrophysical Research Consortium's 3.5-meter telescope at Apache Point Observatory. The spectra cover the range of 300-1000 nm, with a spectral resolution of R ~ 1200. For the observations of both Jupiter and Saturn, we used DIS with the 6 arcminute long slit aligned with the planets' latitudinal bands and stepped the slit north-south to build up a spectral image cube with spectra at all locations on the planet. This enables the extraction of subapertures within the slit corresponding to specific locations, e.g. the Great Red Spot on Jupiter, during the data reduction process. We compare the optical spectra of various colored regions in the giant planet atmospheres to laboratory data of candidate chromophores. The characterization of chromophore materials will provide insight into the upper tropospheric dynamics and circulation patterns on Jupiter and Saturn that provide a stable environment for the creation and/or sustenance of chromophores. This will help further our understanding of the different evolutionary pathways of the gas giant planets of our solar system, providing a process-oriented view of their variations in cloud colors.

  12. Excited-State Intramolecular Proton Transfer in a Blue Fluorescence Chromophore Induces Dual Emission.

    PubMed

    Wu, Dan; Guo, Wei-Wei; Liu, Xiang-Yang; Cui, Ganglong

    2016-08-01

    Compared with green fluorescence protein (GFP) chromophores, the recently synthesized blue fluorescence protein (BFP) chromophore variant presents intriguing photochemical properties, for example, dual fluorescence emission, enhanced fluorescence quantum yield, and ultra-slow excited-state intramolecular proton transfer (ESIPT; J. Phys. Chem. Lett., 2014, 5, 92); however, its photochemical mechanism is still elusive. Herein we have employed the CASSCF and CASPT2 methods to study the mechanistic photochemistry of a truncated BFP chromophore variant in the S0 and S1 states. Based on the optimized minima, conical intersections, and minimum-energy paths (ESIPT, photoisomerization, and deactivation), we have found that the system has two competitive S1 relaxation pathways from the Franck-Condon point of the BFP chromophore variant. One is the ESIPT path to generate an S1 tautomer that exhibits a large Stokes shift in experiments. The generated S1 tautomer can further evolve toward the nearby S1 /S0 conical intersection and then jumps down to the S0 state. The other is the photoisomerization path along the rotation of the central double bond. Along this path, the S1 system runs into an S1 /S0 conical intersection region and eventually hops to the S0 state. The two energetically allowed S1 excited-state deactivation pathways are responsible for the in-part loss of fluorescence quantum yield. The considerable S1 ESIPT barrier and the sizable barriers that separate the S1 tautomers from the S1 /S0 conical intersections make these two tautomers establish a kinetic equilibrium in the S1 state, which thus results in dual fluorescence emission. PMID:27128380

  13. Imidazole as a parent π-conjugated backbone in charge-transfer chromophores

    PubMed Central

    Kulhánek, Jiří

    2012-01-01

    Summary Research activities in the field of imidazole-derived push–pull systems featuring intramolecular charge transfer (ICT) are reviewed. Design, synthetic pathways, linear and nonlinear optical properties, electrochemistry, structure–property relationships, and the prospective application of such D-π-A organic materials are described. This review focuses on Y-shaped imidazoles, bi- and diimidazoles, benzimidazoles, bis(benzimidazoles), imidazole-4,5-dicarbonitriles, and imidazole-derived chromophores chemically bound to a polymer chain. PMID:22423270

  14. Utilizing coupled-oscillator photophysics to elaborate chromophores with exceptional molecular hyperpolarizabilities

    NASA Astrophysics Data System (ADS)

    Uyeda, H. T.; Miloradovic, Ivan R.; Zhao, Yuxia; Wostyn, Kurt; Asselberghs, Inge; Clays, Koen J.; Persoons, Andre P.; Therien, Michael J.

    2003-11-01

    The syntheses and electrooptic properties of a family of nonlinear optical chromophores are described. Typically, these species feature an ethyne-elaborated, highly polarizable porphyrinic component, and metal polypyridyl complexes that serve as integral donor and acceptor elements. The frequency dependence of the dynamic hyperpolarizability of a wide-range of these chromophores, that vary widely with respect to their electronic structure, was determined from hyper-Rayleigh light scattering (HRS) measurements carried out at fundamental incident irradiation wavelengths (λinc) of 830, 1064, and 1300 nm. These data show that: (i) Coupled oscillator photophysics and metal-mediated cross-coupling can be exploited to elaborate high βλ supermolecules that exhibit significant excited-state electronic communication between their respective pigment building blocks; (ii) High-stability metal polypyridyl compounds constitute an attractive alternative to electron releasing dialkyl- and diarylamino groups, the most commonly used donor moieties in a wide-range of established NLO dyes, and long-recognized to be the moiety that often limits the thermal stability of such compounds; (iii) This design strategy clearly enables ready elaboration of extraordinarily large βλ chromophores at telecommunication-relevant wavelengths; and (iv) Multiple charge-transfer (CT) transitions within a single chromophore can be designed to have transition dipole moments of the same or opposite sign; because the sign of the resonance enhancement factor is frequency dependent, appropriate engineering of the relative contributions of these CT states at a given wavelength provides a new means to regulate the magnitude of dynamic hyperpolarizabilities.

  15. Ultraviolet light absorbers having two different chromophors in the same molecule

    DOEpatents

    Vogl, O.; Li, S.

    1983-10-06

    This invention relates to novel ultraviolet light absorbers having two chromophors in the same molecule, and more particularly to benzotriazole substituted dihydroxybenzophenones and acetophenones. More particularly, this invention relates to 3,5-(di(2H-benzotriazole-2-yl))-2,4-dihydroxybenzophenone and 3,5-(di(2H-benzotriazole-2-yl))-2,4-dihydroxyacetophenone which are particularly useful as an ultraviolet light absorbers.

  16. Donor-acceptor organo-imido polyoxometalates: high transparency, high activity redox-active NLO chromophores.

    PubMed

    Al-Yasari, Ahmed; Van Steerteghem, Nick; El Moll, Hani; Clays, Koen; Fielden, John

    2016-02-21

    We show that polyoxometalates (POMs) are an excellent redox-active acceptor on which to base high performance 2(nd) order non-linear optical (NLO) chromophores. This is demonstrated through three new organoimido-Lindqvist derivatives with HRS β0-values exceeding those of any dipolar organic system with comparable donor, π-system and absorption profile. Thus, organoimido POMs may provide a new generation of high performance, high transparency, and potentially redox-switchable NLO materials. PMID:26815652

  17. Long-term outcomes in patients undergoing vitrectomy for retinal detachment due to viral retinitis

    PubMed Central

    Almeida, David RP; Chin, Eric K; Tarantola, Ryan M; Tegins, Elizabeth O; Lopez, Christopher A; Boldt, Herbert Culver; Gehrs, Karen M; Sohn, Elliott H; Russell, Stephen R; Folk, James C; Mahajan, Vinit B

    2015-01-01

    Purpose To determine the outcomes in patients with rhegmatogenous retinal detachment (RRD) secondary to viral retinitis. Patients and methods This was a retrospective, consecutive, noncomparative, interventional case series of 12 eyes in ten patients with RRD secondary to viral retinitis. Results of vitreous or aqueous biopsy, effect of antiviral therapeutics, time to retinal detachment, course of visual acuity, and anatomic and surgical outcomes were investigated. Results There were 1,259 cases of RRD during the study period, with 12 cases of RRD secondary to viral retinitis (prevalence of 0.95%). Follow-up was available for a mean period of 4.4 years. Varicella zoster virus was detected in six eyes, herpes simplex virus in two eyes, and cytomegalovirus in two eyes. Eight patients were treated with oral valacyclovir and two patients with intravenous acyclovir. Lack of optic nerve involvement correlated with improved final visual acuity of 20/100 or greater. Pars plana vitrectomy (n=12), silicone-oil tamponade (n=11), and scleral buckling (n=10) provided successful anatomic retinal reattachment in all cases, with no recurrent retinal detachment and no cases of hypotony during the follow-up period. Conclusion Varicella zoster virus was the most frequent cause of viral retinitis, and lack of optic nerve involvement was predictive of a favorable visual acuity prognosis. Vitrectomy with silicone-oil tamponade and scleral buckle placement provided stable anatomical outcomes. PMID:26229423

  18. Electroretinographic effects of retinal dragging and retinal folds in eyes with familial exudative vitreoretinopathy

    PubMed Central

    Yaguchi, Yukari; Katagiri, Satoshi; Fukushima, Yoko; Yokoi, Tadashi; Nishina, Sachiko; Kondo, Mineo; Azuma, Noriyuki

    2016-01-01

    We evaluated the retinal function of retinal dragging (Rdrag) and radial retinal folds (Rfolds) in eyes with familial exudative vitreoretinopathy (FEVR) using full-field electroretinography (ERG). Seventeen eyes of nine patients with FEVR who had Rdrag or Rfolds were retrospectively studied. Eyes were classified into four groups according to the severity of the retinal alterations: Group 1, without Rdrag or Rfolds (5 eyes); Group 2, with Rdrag (4 eyes); Group 3, with Rfolds (6 eyes); and Group 4, with Rfolds in which all major retinal vessels were involved (2 eyes). The amplitudes of all ERG components and the implicit times of the photopic a- and b-waves and 30-Hz flicker responses were decreased or prolonged as the severity of the retinal alterations increased (P < 0.01). The photopic negative response was most severely affected and nearly undetectable in all eyes in Groups 3 and 4, although the other ERG components were detectable in all eyes in Group 3 and one eye in Group 4. These results suggest the decrease of retinal functions was correlated with the degree of severity of Rdrag and Rfolds in eyes with FEVR. In addition, the function of the retinal ganglion cells appears to be more severely affected compared with the others. PMID:27456314

  19. Excited-State Proton-Transfer-Induced Trapping Enhances the Fluorescence Emission of a Locked GFP Chromophore

    PubMed Central

    2016-01-01

    The chemical locking of the central single bond in core chromophores of green fluorescent proteins (GFPs) influences their excited-state behavior in a distinct manner. Experimentally, it significantly enhances the fluorescence quantum yield of GFP chromophores with an ortho-hydroxyl group, while it has almost no effect on the photophysics of GFP chromophores with a para-hydroxyl group. To unravel the underlying physical reasons for this different behavior, we report static electronic structure calculations and nonadiabatic dynamics simulations on excited-state intramolecular proton transfer, cis–trans isomerization, and excited-state deactivation in a locked ortho-substituted GFP model chromophore (o-LHBI). On the basis of our previous and present results, we find that the S1 keto species is responsible for the fluorescence emission of the unlocked o-HBI and the locked o-LHBI species. Chemical locking does not change the parts of the S1 and S0 potential energy surfaces relevant to enol–keto tautomerization; hence, in both chromophores, there is an ultrafast excited-state intramolecular proton transfer that takes only 35 fs on average. However, the locking effectively hinders the S1 keto species from approaching the keto S1/S0 conical intersections so that most of trajectories are trapped in the S1 keto region for the entire 2 ps simulation time. Therefore, the fluorescence quantum yield of o-LHBI is enhanced compared with that of unlocked o-HBI, in which the S1 excited-state decay is efficient and ultrafast. In the case of the para-substituted GFP model chromophores p-HBI and p-LHBI, chemical locking hardly affects their efficient excited-state deactivation via cis–trans isomerization; thus, the fluorescence quantum yields in these chromophores remain very low. The insights gained from the present work may help to guide the design of new GFP chromophores with improved fluorescence emission and brightness. PMID:26744782

  20. Crystal structure of phototoxic orange fluorescent proteins with α tryptophan-based chromophore

    DOE PAGESBeta

    Pletneva, Nadya V.; Pletnev, Vladimir Z.; Sarkisyan, Karen S.; Gorbachev, Dmitry A.; Egorov, Evgeny S.; Mishin, Alexander S.; Lukyanov, Konstantin A.; Dauter, Zbigniew; Pletnev, Sergei

    2015-12-23

    Phototoxic fluorescent proteins represent a sparse group of genetically encoded photosensitizers that could be used for precise light-induced inactivation of target proteins, DNA damage, and cell killing. Only two such GFP-based fluorescent proteins (FPs), KillerRed and its monomeric variant SuperNova, were described up to date. We present a crystallographic study of their two orange successors, dimeric KillerOrange and monomeric mKiller-Orange, at 1.81 and 1.57 Å resolution, respectively. They are the first orange-emitting protein photosensitizers with a tryptophan-based chromophore (Gln65-Trp66-Gly67). Same as their red progenitors, both orange photosensitizers have a water-filled channel connecting the chromophore to the β-barrel exterior and enablingmore » transport of ROS. In both proteins, Trp66 of the chromophore adopts an unusual trans-cis conformation stabilized by H-bond with the nearby Gln159. This trans-cis conformation along with the water channel was shown to be a key structural feature providing bright orange emission and phototoxicity of both examined orange photosensitizers.« less

  1. Crystal structure of phototoxic orange fluorescent proteins with α tryptophan-based chromophore

    SciTech Connect

    Pletneva, Nadya V.; Pletnev, Vladimir Z.; Sarkisyan, Karen S.; Gorbachev, Dmitry A.; Egorov, Evgeny S.; Mishin, Alexander S.; Lukyanov, Konstantin A.; Dauter, Zbigniew; Pletnev, Sergei

    2015-12-23

    Phototoxic fluorescent proteins represent a sparse group of genetically encoded photosensitizers that could be used for precise light-induced inactivation of target proteins, DNA damage, and cell killing. Only two such GFP-based fluorescent proteins (FPs), KillerRed and its monomeric variant SuperNova, were described up to date. We present a crystallographic study of their two orange successors, dimeric KillerOrange and monomeric mKiller-Orange, at 1.81 and 1.57 Å resolution, respectively. They are the first orange-emitting protein photosensitizers with a tryptophan-based chromophore (Gln65-Trp66-Gly67). Same as their red progenitors, both orange photosensitizers have a water-filled channel connecting the chromophore to the β-barrel exterior and enabling transport of ROS. In both proteins, Trp66 of the chromophore adopts an unusual trans-cis conformation stabilized by H-bond with the nearby Gln159. This trans-cis conformation along with the water channel was shown to be a key structural feature providing bright orange emission and phototoxicity of both examined orange photosensitizers.

  2. Crystal Structure of Phototoxic Orange Fluorescent Proteins with a Tryptophan-Based Chromophore

    PubMed Central

    Pletneva, Nadya V.; Pletnev, Vladimir Z.; Sarkisyan, Karen S.; Gorbachev, Dmitry A.; Egorov, Evgeny S.; Mishin, Alexander S.; Lukyanov, Konstantin A.; Dauter, Zbigniew; Pletnev, Sergei

    2015-01-01

    Phototoxic fluorescent proteins represent a sparse group of genetically encoded photosensitizers that could be used for precise light-induced inactivation of target proteins, DNA damage, and cell killing. Only two such GFP-based fluorescent proteins (FPs), KillerRed and its monomeric variant SuperNova, were described up to date. Here, we present a crystallographic study of their two orange successors, dimeric KillerOrange and monomeric mKillerOrange, at 1.81 and 1.57 Å resolution, respectively. They are the first orange-emitting protein photosensitizers with a tryptophan-based chromophore (Gln65-Trp66-Gly67). Same as their red progenitors, both orange photosensitizers have a water-filled channel connecting the chromophore to the β-barrel exterior and enabling transport of ROS. In both proteins, Trp66 of the chromophore adopts an unusual trans-cis conformation stabilized by H-bond with the nearby Gln159. This trans-cis conformation along with the water channel was shown to be a key structural feature providing bright orange emission and phototoxicity of both examined orange photosensitizers. PMID:26699366

  3. Visible light and near infrared-responsive chromophores for drug delivery-on-demand applications

    PubMed Central

    Linsley, Chase S.; Quach, Viola Y.; Agrawal, Gaurav; Hartnett, Elyse; Wu, Benjamin M.

    2016-01-01

    The need for temporal-spatial control over the release of biologically active molecules has motivated efforts to engineer novel drug delivery-on-demand strategies actuated via light irradiation. Many systems, however, have been limited to in vitro proof-of-concept due to biocompatibility issues with the photo-responsive moieties or the light wavelength, intensity and duration. To overcome these limitations, this paper describes a light actuated drug delivery-on-demand strategy that uses visible and near infrared (NIR) light and biocompatible chromophores: cardiogreen, methylene blue and riboflavin. All 3 chromophores are capable of significant photothermal reaction upon exposure to NIR and visible light, and the amount of temperature change is dependent upon light intensity, wavelength as well as chromophore concentration. Pulsatile release of bovine serum albumin (BSA) from thermally-responsive hydrogels was achieved over 4 days. These findings have the potential to translate light actuated drug delivery-on-demand systems from the bench to clinical applications that require explicit control over the presentation of biologically active molecules. PMID:26423655

  4. The structure of the chromophore within DsRed, a red fluorescent protein from coral.

    PubMed

    Gross, L A; Baird, G S; Hoffman, R C; Baldridge, K K; Tsien, R Y

    2000-10-24

    DsRed, a brilliantly red fluorescent protein, was recently cloned from Discosoma coral by homology to the green fluorescent protein (GFP) from the jellyfish Aequorea. A core question in the biochemistry of DsRed is the mechanism by which the GFP-like 475-nm excitation and 500-nm emission maxima of immature DsRed are red-shifted to the 558-nm excitation and 583-nm emission maxima of mature DsRed. After digestion of mature DsRed with lysyl endopeptidase, high-resolution mass spectra of the purified chromophore-bearing peptide reveal that some of the molecules have lost 2 Da relative to the peptide analogously prepared from a mutant, K83R, that stays green. Tandem mass spectrometry indicates that the bond between the alpha-carbon and nitrogen of Gln-66 has been dehydrogenated in DsRed, extending the GFP chromophore by forming C==N==C==O at the 2-position of the imidazolidinone. This acylimine substituent quantitatively accounts for the red shift according to quantum mechanical calculations. Reversible hydration of the C==N bond in the acylimine would explain why denaturation shifts mature DsRed back to a GFP-like absorbance. The C==N bond hydrolyses upon boiling, explaining why DsRed shows two fragment bands on SDS/PAGE. This assay suggests that conversion from green to red chromophores remains incomplete even after prolonged aging. PMID:11050230

  5. Chromophores from photolyzed ammonia reacting with acetylene: Application to Jupiter's Great Red Spot

    NASA Astrophysics Data System (ADS)

    Carlson, R. W.; Baines, K. H.; Anderson, M. S.; Filacchione, G.; Simon, A. A.

    2016-08-01

    The high altitude of Jupiter's Great Red Spot (GRS) may enhance the upward flux of gaseous ammonia (NH3) into the high troposphere, where NH3 molecules can be photodissociated and initiate a chain of chemical reactions with downwelling acetylene molecules (C2H2). These reactions, experimentally studied earlier by (Ferris and Ishikawa [1987] Nature 326, 777-778) and (Ferris and Ishikawa [1988] J. Amer. Chem. Soc. 110, 4306-4312), produce chromophores that absorb in the visible and ultraviolet regions. In this work we photolyzed mixtures of NH3 and C2H2 using ultraviolet radiation with a wavelength of 214 nm and measured the spectral transmission of the deposited films in the visible region (400-740 nm). From these transmission data we estimated the imaginary indices of refraction. Assuming that ammonia grains at the top of the GRS clouds are coated with this material, we performed layered sphere and radiative transfer calculations to predict GRS reflection spectra. Comparison of those results with observed and previously unreported Cassini visible spectra and with true-color images of the GRS show that the unknown GRS chromophore is spectrally consistent with the coupled NH3-C2H2 photochemical products produced in our laboratory experiments. Using high-resolution mass spectrometry and infrared spectroscopy we infer that the chromophore-containing residue is composed of aliphatic azine, azo, and diazo compounds.

  6. Crystal Structure of Phototoxic Orange Fluorescent Proteins with a Tryptophan-Based Chromophore.

    PubMed

    Pletneva, Nadya V; Pletnev, Vladimir Z; Sarkisyan, Karen S; Gorbachev, Dmitry A; Egorov, Evgeny S; Mishin, Alexander S; Lukyanov, Konstantin A; Dauter, Zbigniew; Pletnev, Sergei

    2015-01-01

    Phototoxic fluorescent proteins represent a sparse group of genetically encoded photosensitizers that could be used for precise light-induced inactivation of target proteins, DNA damage, and cell killing. Only two such GFP-based fluorescent proteins (FPs), KillerRed and its monomeric variant SuperNova, were described up to date. Here, we present a crystallographic study of their two orange successors, dimeric KillerOrange and monomeric mKillerOrange, at 1.81 and 1.57 Å resolution, respectively. They are the first orange-emitting protein photosensitizers with a tryptophan-based chromophore (Gln65-Trp66-Gly67). Same as their red progenitors, both orange photosensitizers have a water-filled channel connecting the chromophore to the β-barrel exterior and enabling transport of ROS. In both proteins, Trp66 of the chromophore adopts an unusual trans-cis conformation stabilized by H-bond with the nearby Gln159. This trans-cis conformation along with the water channel was shown to be a key structural feature providing bright orange emission and phototoxicity of both examined orange photosensitizers. PMID:26699366

  7. Minimal domain of bacterial phytochrome required for chromophore binding and fluorescence

    PubMed Central

    Rumyantsev, Konstantin A.; Shcherbakova, Daria M.; Zakharova, Natalia I.; Emelyanov, Alexander V.; Turoverov, Konstantin K.; Verkhusha, Vladislav V.

    2015-01-01

    Fluorescent proteins (FP) are used to study various biological processes. Recently, a series of near-infrared (NIR) FPs based on bacterial phytochromes was developed. Finding ways to improve NIR FPs is becoming progressively important. By applying rational design and molecular evolution we have engineered R. palustris bacterial phytochrome into a single-domain NIR FP of 19.6 kDa, termed GAF-FP, which is 2-fold and 1.4-fold smaller than bacterial phytochrome-based NIR FPs and GFP-like proteins, respectively. Engineering of GAF-FP involved a substitution of 15% of its amino acids and a deletion of the knot structure. GAF-FP covalently binds two tetrapyrrole chromophores, biliverdin (BV) and phycocyanobilin (PCB). With the BV chromophore GAF-FP absorbs at 635 nm and fluoresces at 670 nm. With the PCB chromophore GAF-FP becomes blue-shifted and absorbs at 625 nm and fluoresces at 657 nm. The GAF-FP structure has a high tolerance to small peptide insertions. The small size of GAF-FP and its additional absorbance band in the violet range has allowed for designing a chimeric protein with Renilla luciferase. The chimera exhibits efficient non-radiative energy transfer from luciferase to GAF-FP, resulting in NIR bioluminescence. This study opens the way for engineering of small NIR FPs and NIR luciferases from bacterial phytochromes. PMID:26679720

  8. Dynamics and two-photon absorption properties of chromophore functionalized semiconductor nanoparticles

    NASA Astrophysics Data System (ADS)

    Varaganti, Shankar; Gessesse, Mathias; Obare, Sherine O.; Ramakrishna, Guda

    2009-08-01

    Two photon absorption cross-sections and fluorescence dynamics of Riboflavin, Fluorescein 548, Coumarin 519 and Quinizarin adsorbed onto reactive (TiO2) and non-reactive (ZrO2) semiconductor nanoparticles have been investigated. These dye molecules are chosen because of their inherently different anchoring groups with which they can bind to semiconductor nanoparticles giving a handle to probe the influence of anchoring group as well as molecule-nanoparticle electronic coupling on the two-photon absorption and nonlinear optical properties. Two-photon excited fluorescence technique has been utilized to monitor the two photon absorption cross-sections and the dynamics of singlet states are followed with femto second fluorescence upconversion. Interesting cross-section trends have been observed where the TPA cross-section of chromophore on ZrO2 surface is similar or lower to that of the free dye while the cross-sections seem to be higher on the surface of reactive TiO2 nanoparticle surface. Fluorescence upconversion investigations were able to probe the electronic interactions of the chromophore with semiconductor nanoparticle and also the adsorption of the chromophores on the surface of the nanoparticle.

  9. Temporal Fluctuations in Excimer-Like Interactions between π-Conjugated Chromophores.

    PubMed

    Stangl, Thomas; Wilhelm, Philipp; Schmitz, Daniela; Remmerssen, Klaas; Henzel, Sebastian; Jester, Stefan-S; Höger, Sigurd; Vogelsang, Jan; Lupton, John M

    2015-04-16

    Inter- or intramolecular coupling processes between chromophores such as excimer formation or H- and J-aggregation are crucial to describing the photophysics of closely packed films of conjugated polymers. Such coupling is highly distance dependent and should be sensitive to both fluctuations in the spacing between chromophores as well as the actual position on the chromophore where the exciton localizes. Single-molecule spectroscopy reveals these intrinsic fluctuations in well-defined bichromophoric model systems of cofacial oligomers. Signatures of interchromophoric interactions in the excited state--spectral red shifting and broadening and a slowing of photoluminescence decay--correlate with each other but scatter strongly between single molecules, implying an extraordinary distribution in coupling strengths. Furthermore, these excimer-like spectral fingerprints vary with time, revealing intrinsic dynamics in the coupling strength within one single dimer molecule, which constitutes the starting point for describing a molecular solid. Such spectral sensitivity to sub-Ångström molecular dynamics could prove complementary to conventional FRET-based molecular rulers. PMID:26263130

  10. Fiber optic-based fluorescence detection system for in vivo studies of exogenous chromophore pharmacokinetics

    NASA Astrophysics Data System (ADS)

    Doiron, Daniel R.; Dunn, J. B.; Mitchell, W. L.; Dalton, Brian K.; Garbo, Greta M.; Warner, Jon A.

    1995-05-01

    The detection and quantification of the concentration of exogenous chromophores in-vivo by their fluorescence is complicated by many physical and geometrical parameters. Measurement of such signals is advantageous in determining the pharmacokinetics of photosensitizers such as those used in photodynamic therapy (PDT) or to assist in the diagnosis of tissue histological state. To overcome these difficulties a ratio based fiber optic contact fluorometer has been developed. This fluorescence detection system (FDS) uses the ratio of the fluorescence emission peak of the exogenous chromophore to that of endogenous chromophores, i.e. autofluorescence, to correct for a variety of parameters affecting the magnitude of the measured signals. By doing so it also minimizes the range of baseline measurements prior to exogenous drug injection, for various tissue types. Design of the FDS and results of its testing in animals and patients using the second generation photosensitizer Tin ethyletiopurpurin (SnET2) are presented. These results support the feasibility and usefulness of the Ratio FDS system.

  11. Mutational analysis of a higher plant antenna protein provides identification of chromophores bound into multiple sites

    PubMed Central

    Bassi, Roberto; Croce, Roberta; Cugini, Daniela; Sandonà, Dorianna

    1999-01-01

    The chromophore-binding properties of the higher plant light-harvesting protein CP29 have been studied by using site-directed mutagenesis of pigment-binding residues. Overexpression of the apoproteins in bacteria was followed by reconstitution in vitro with purified pigments, thus obtaining a family of mutant CP29 proteins lacking individual chromophore-binding sites. Biochemical characterization allowed identification of the eight porphyrins and two xanthophyll-binding sites. It is shown that the four porphyrin-binding sites (A1, A2, A4, and A5) situated in the central, twofold-symmetrical domain of the protein are selective for Chl-a, whereas the four peripheral sites (A3, B3, B5, and B6) have mixed Chl-a–Chl-b specificity. Within a site, porphyrin coordination by glutamine increases affinity for Chl-b as compared with glutamate. Xanthophyll site L1 is occupied by lutein, whereas site L2 can bind violaxanthin or neoxanthin. The protein is relatively stable when site L2 site is empty, suggesting that xanthophylls can be exchanged during operation of xanthophyll cycle-dependent photoprotection mechanism. Differential absorption spectroscopy allowed determination of transition energy levels for individual chromophores, thus opening the way to calculation of energy-transfer rates between Chl in higher plant antenna proteins. PMID:10468561

  12. The structure of the chromophore within DsRed, a red fluorescent protein from coral

    PubMed Central

    Gross, Larry A.; Baird, Geoffrey S.; Hoffman, Ross C.; Baldridge, Kim K.; Tsien, Roger Y.

    2000-01-01

    DsRed, a brilliantly red fluorescent protein, was recently cloned from Discosoma coral by homology to the green fluorescent protein (GFP) from the jellyfish Aequorea. A core question in the biochemistry of DsRed is the mechanism by which the GFP-like 475-nm excitation and 500-nm emission maxima of immature DsRed are red-shifted to the 558-nm excitation and 583-nm emission maxima of mature DsRed. After digestion of mature DsRed with lysyl endopeptidase, high-resolution mass spectra of the purified chromophore-bearing peptide reveal that some of the molecules have lost 2 Da relative to the peptide analogously prepared from a mutant, K83R, that stays green. Tandem mass spectrometry indicates that the bond between the alpha-carbon and nitrogen of Gln-66 has been dehydrogenated in DsRed, extending the GFP chromophore by forming —C⩵N—C⩵O at the 2-position of the imidazolidinone. This acylimine substituent quantitatively accounts for the red shift according to quantum mechanical calculations. Reversible hydration of the C⩵N bond in the acylimine would explain why denaturation shifts mature DsRed back to a GFP-like absorbance. The C⩵N bond hydrolyses upon boiling, explaining why DsRed shows two fragment bands on SDS/PAGE. This assay suggests that conversion from green to red chromophores remains incomplete even after prolonged aging. PMID:11050230

  13. Chromophores from photolyzed ammonia reacting with acetylene: Application to Jupiters Great Red Spot

    NASA Technical Reports Server (NTRS)

    Carlson, Robert W.; Baines, Kevin H.; Anderson, M. S.; Filacchione, G.; Simon, A. A.

    2016-01-01

    The high altitude of Jupiter's Great Red Spot (GRS) may enhance the upward flux of gaseous ammonia (NH3 ) into the high troposphere, where NH3 molecules can be photodissociated and initiate a chain of chemical reactions with downwelling acetylene molecules (C2H2 ). These reactions, experimentally studied earlier by (Ferris and Ishikawa [1987] Nature 326, 777-778) and (Ferris and Ishikawa [1988] J. Amer. Chem. Soc. 110, 4306-4312), produce chromophores that absorb in the visible and ultraviolet regions. In this work we photolyzed mixtures of NH3 and C2H2 using ultraviolet radiation with a wavelength of 214 nm and measured the spectral transmission of the deposited films in the visible region (400-740 nm). From these transmission data we estimated the imaginary indices of refraction. Assuming that ammonia grains at the top of the GRS clouds are coated with this material, we performed layered sphere and radiative transfer calculations to predict GRS reflection spectra. Comparison of those results with observed and previously unreported Cassini visible spectra and with true-color images of the GRS show that the unknown GRS chromophore is spectrally consistent with the coupled NH3-C2H2 photochemical products produced in our laboratory experiments. Using high-resolution mass spectrometry and infrared spectroscopy we infer that the chromophore-containing residue is composed of aliphatic azine, azo, and diazo compounds.

  14. Minimal domain of bacterial phytochrome required for chromophore binding and fluorescence.

    PubMed

    Rumyantsev, Konstantin A; Shcherbakova, Daria M; Zakharova, Natalia I; Emelyanov, Alexander V; Turoverov, Konstantin K; Verkhusha, Vladislav V

    2015-01-01

    Fluorescent proteins (FP) are used to study various biological processes. Recently, a series of near-infrared (NIR) FPs based on bacterial phytochromes was developed. Finding ways to improve NIR FPs is becoming progressively important. By applying rational design and molecular evolution we have engineered R. palustris bacterial phytochrome into a single-domain NIR FP of 19.6 kDa, termed GAF-FP, which is 2-fold and 1.4-fold smaller than bacterial phytochrome-based NIR FPs and GFP-like proteins, respectively. Engineering of GAF-FP involved a substitution of 15% of its amino acids and a deletion of the knot structure. GAF-FP covalently binds two tetrapyrrole chromophores, biliverdin (BV) and phycocyanobilin (PCB). With the BV chromophore GAF-FP absorbs at 635 nm and fluoresces at 670 nm. With the PCB chromophore GAF-FP becomes blue-shifted and absorbs at 625 nm and fluoresces at 657 nm. The GAF-FP structure has a high tolerance to small peptide insertions. The small size of GAF-FP and its additional absorbance band in the violet range has allowed for designing a chimeric protein with Renilla luciferase. The chimera exhibits efficient non-radiative energy transfer from luciferase to GAF-FP, resulting in NIR bioluminescence. This study opens the way for engineering of small NIR FPs and NIR luciferases from bacterial phytochromes. PMID:26679720

  15. Temperature dependence and the dispersion of nonlinear optical properties of chromophore-containing polyimide thin films

    SciTech Connect

    Gorkovenko, A. I.; Plekhanov, A. I.; Simanchuk, A. E.; Yakimanskiy, A. V.; Nosova, G. I.; Solovskaya, N. A.; Smirnov, N. N.

    2014-12-14

    Detailed investigations of the quadratic nonlinear response of a series of new polyimides with covalently attached chromophore DR13 are performed by the Maker fringes method in the range of fundamental wavelength from 850 to 1450 nm. Polymer films with thickness of 100–400 nm were spin-coated on glass substrates and corona poled. For these materials, the maximum values of the second harmonic generation coefficients d{sub 33} are 80–120 pm/V. A red shift of the nonlinear response dispersion with respect to the linear absorption spectrum was observed for the DR13 chromophore. The temperature dependences of linear absorption and nonlinear coefficients d{sub 33} for studied structures are observed. It was found that the temperature changes of the absorption spectra lead to appreciable contribution to the value of the nonlinear coefficient d{sub 33}. The demonstrated high temperature stability (up to 120 °C) of chromophore-containing polyimide thin films makes it possible to eliminate the degradation of their nonlinear optical properties in the future applications of such structures.

  16. Minimal domain of bacterial phytochrome required for chromophore binding and fluorescence

    NASA Astrophysics Data System (ADS)

    Rumyantsev, Konstantin A.; Shcherbakova, Daria M.; Zakharova, Natalia I.; Emelyanov, Alexander V.; Turoverov, Konstantin K.; Verkhusha, Vladislav V.

    2015-12-01

    Fluorescent proteins (FP) are used to study various biological processes. Recently, a series of near-infrared (NIR) FPs based on bacterial phytochromes was developed. Finding ways to improve NIR FPs is becoming progressively important. By applying rational design and molecular evolution we have engineered R. palustris bacterial phytochrome into a single-domain NIR FP of 19.6 kDa, termed GAF-FP, which is 2-fold and 1.4-fold smaller than bacterial phytochrome-based NIR FPs and GFP-like proteins, respectively. Engineering of GAF-FP involved a substitution of 15% of its amino acids and a deletion of the knot structure. GAF-FP covalently binds two tetrapyrrole chromophores, biliverdin (BV) and phycocyanobilin (PCB). With the BV chromophore GAF-FP absorbs at 635 nm and fluoresces at 670 nm. With the PCB chromophore GAF-FP becomes blue-shifted and absorbs at 625 nm and fluoresces at 657 nm. The GAF-FP structure has a high tolerance to small peptide insertions. The small size of GAF-FP and its additional absorbance band in the violet range has allowed for designing a chimeric protein with Renilla luciferase. The chimera exhibits efficient non-radiative energy transfer from luciferase to GAF-FP, resulting in NIR bioluminescence. This study opens the way for engineering of small NIR FPs and NIR luciferases from bacterial phytochromes.

  17. AAV Mediated GDNF Secretion From Retinal Glia Slows Down Retinal Degeneration in a Rat Model of Retinitis Pigmentosa

    PubMed Central

    Dalkara, Deniz; Kolstad, Kathleen D; Guerin, Karen I; Hoffmann, Natalie V; Visel, Meike; Klimczak, Ryan R; Schaffer, David V; Flannery, John G

    2011-01-01

    Mutations in over 80 identified genes can induce apoptosis in photoreceptors, resulting in blindness with a prevalence of 1 in 3,000 individuals. This broad genetic heterogeneity of disease impacting a wide range of photoreceptor functions renders the design of gene-specific therapies for photoreceptor degeneration impractical and necessitates the development of mutation-independent treatments to slow photoreceptor cell death. One promising strategy for photoreceptor neuroprotection is neurotrophin secretion from Müller cells, the primary retinal glia. Müller glia are excellent targets for secreting neurotrophins as they span the entire tissue, ensheath all neuronal populations, are numerous, and persist through retinal degeneration. We previously engineered an adeno-associated virus (AAV) variant (ShH10) capable of efficient and selective glial cell transduction through intravitreal injection. ShH10-mediated glial-derived neurotrophic factor (GDNF) secretion from glia, generates high GDNF levels in treated retinas, leading to sustained functional rescue for over 5 months. This GDNF secretion from glia following intravitreal vector administration is a safe and effective means to slow the progression of retinal degeneration in a rat model of retinitis pigmentosa (RP) and shows significant promise as a gene therapy to treat human retinal degenerations. These findings also demonstrate for the first time that glia-mediated secretion of neurotrophins is a promising treatment that may be applicable to other neurodegenerative conditions. PMID:21522134

  18. Toward high-resolution optoelectronic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Palanker, Daniel; Huie, Philip; Vankov, Alexander; Asher, Alon; Baccus, Steven

    2005-04-01

    It has been already demonstrated that electrical stimulation of retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. Current retinal implants provide very low resolution (just a few electrodes), while several thousand pixels are required for functional restoration of sight. We present a design of the optoelectronic retinal prosthetic system that can activate a retinal stimulating array with pixel density up to 2,500 pix/mm2 (geometrically corresponding to a visual acuity of 20/80), and allows for natural eye scanning rather than scanning with a head-mounted camera. The system operates similarly to "virtual reality" imaging devices used in military and medical applications. An image from a video camera is projected by a goggle-mounted infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. Such a system provides a broad field of vision by allowing for natural eye scanning. The goggles are transparent to visible light, thus allowing for simultaneous utilization of remaining natural vision along with prosthetic stimulation. Optical control of the implant allows for simple adjustment of image processing algorithms and for learning. A major prerequisite for high resolution stimulation is the proximity of neural cells to the stimulation sites. This can be achieved with sub-retinal implants constructed in a manner that directs migration of retinal cells to target areas. Two basic implant geometries are described: perforated membranes and protruding electrode arrays. Possibility of the tactile neural stimulation is also examined.

  19. Interventions for asymptomatic retinal breaks and lattice degeneration for preventing retinal detachment

    PubMed Central

    Wilkinson, Charles P

    2015-01-01

    Background Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these lesions frequently is recommended, in spite of the fact that the effectiveness of this therapy is unproven. Objectives The objective of this review was to assess the effectiveness and safety of techniques used to treat asymptomatic retinal breaks and lattice degeneration for the prevention of retinal detachment. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February 2014), PubMed (January 1948 to February 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in

  20. Amyloidosis in Retinal Neurodegenerative Diseases.

    PubMed

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer's disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer's patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer's patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a "window" to the brain. PMID:27551275

  1. Evolution of vertebrate retinal photoreception

    PubMed Central

    Lamb, Trevor D.

    2009-01-01

    Recent findings shed light on the steps underlying the evolution of vertebrate photoreceptors and retina. Vertebrate ciliary photoreceptors are not as wholly distinct from invertebrate rhabdomeric photoreceptors as is sometimes thought. Recent information on the phylogenies of ciliary and rhabdomeric opsins has helped in constructing the likely routes followed during evolution. Clues to the factors that led the early vertebrate retina to become invaginated can be obtained by combining recent knowledge about the origin of the pathway for dark re-isomerization of retinoids with knowledge of the inability of ciliary opsins to undergo photoreversal, along with consideration of the constraints imposed under the very low light levels in the deep ocean. Investigation of the origin of cell classes in the vertebrate retina provides support for the notion that cones, rods and bipolar cells all originated from a primordial ciliary photoreceptor, whereas ganglion cells, amacrine cells and horizontal cells all originated from rhabdomeric photoreceptors. Knowledge of the molecular differences between cones and rods, together with knowledge of the scotopic signalling pathway, provides an understanding of the evolution of rods and of the rods' retinal circuitry. Accordingly, it has been possible to propose a plausible scenario for the sequence of evolutionary steps that led to the emergence of vertebrate photoreceptors and retina. PMID:19720653

  2. Multi-MHz retinal OCT

    PubMed Central

    Klein, Thomas; Wieser, Wolfgang; Reznicek, Lukas; Neubauer, Aljoscha; Kampik, Anselm; Huber, Robert

    2013-01-01

    We analyze the benefits and problems of in vivo optical coherence tomography (OCT) imaging of the human retina at A-scan rates in excess of 1 MHz, using a 1050 nm Fourier-domain mode-locked (FDML) laser. Different scanning strategies enabled by MHz OCT line rates are investigated, and a simple multi-volume data processing approach is presented. In-vivo OCT of the human ocular fundus is performed at different axial scan rates of up to 6.7 MHz. High quality non-mydriatic retinal imaging over an ultra-wide field is achieved by a combination of several key improvements compared to previous setups. For the FDML laser, long coherence lengths and 72 nm wavelength tuning range are achieved using a chirped fiber Bragg grating in a laser cavity at 419.1 kHz fundamental tuning rate. Very large data sets can be acquired with sustained data transfer from the data acquisition card to host computer memory, enabling high-quality averaging of many frames and of multiple aligned data sets. Three imaging modes are investigated: Alignment and averaging of 24 data sets at 1.68 MHz axial line rate, ultra-dense transverse sampling at 3.35 MHz line rate, and dual-beam imaging with two laser spots on the retina at an effective line rate of 6.7 MHz. PMID:24156052

  3. Amyloidosis in Retinal Neurodegenerative Diseases

    PubMed Central

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  4. Intrinsically photosensitive retinal ganglion cells.

    PubMed

    Do, Michael Tri Hoang; Yau, King-Wai

    2010-10-01

    Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors. PMID:20959623

  5. Acetylene-derived strong organic acceptors for planar and nonplanar push-pull chromophores.

    PubMed

    Kivala, Milan; Diederich, François

    2009-02-17

    Though investigated for decades, interest in push-pull chromophores (D-pi-A), strong electron donors (D) connected by pi-conjugating spacers to strong electron acceptors (A), continues to grow. Such chromophores are of substantial interest for optoelectronic devices such as waveguides. Also, strong donors and acceptors form bimolecular charge-transfer (CT) complexes and salts, some of which exhibit electrical conductivity and magnetic behavior. Furthermore, strong organic acceptors are increasingly explored as dopants in the fabrication of organic light-emitting diodes (OLEDs) and solar cells. This Account describes systematic efforts pursued over the past decade in our laboratory to generate new families of organic electron acceptors (A) and conjugate them via pi-spacers to electron donors (D) under formation of push-pull systems with intense intramolecular CT interactions and high third-order optical nonlinearities. First, we describe donor-acceptor-substituted tetraethynylethenes (TEEs). In these chromophores, the peripherally attached p-nitrophenyl acceptors and N,N-dimethylanilino donors behave as nearly independent redox centers. Acetylenic scaffolding using TEE building blocks produces large all-carbon sheets, such as perethynylated dehydroannulenes, expanded radialenes, and radiaannulenes with potent electron-acceptor properties. Arylated TEEs act as molecular switches allowing two-way photochemical interconversion that is not perturbed by thermal isomerization pathways. Upon sequential substitution of the acetylene moieties in TEEs, we formed another family of potent acceptors, the cyanoethynylethenes (CEEs). Donor-substituted CEEs are planar CT chromophores with very high third-order optical nonlinearities. Their high environmental stability allows for the formation of thin films by vapor-phase deposition. Through careful analysis of the physicochemical properties of CEEs, we established useful guidelines for evaluating and tuning the optical gap in

  6. Evaluation and management of pediatric rhegmatogenous retinal detachment

    PubMed Central

    Wenick, Adam S.; Barañano, David E.

    2012-01-01

    Pediatric rhegmatogenous retinal detachments are rare, accounting for less than ten percent of all rhegmatogenous retinal detachments. While most retinal detachments in the adult population are related to posterior vitreous detachment, pediatric retinal detachment are often related to trauma or an underlying congenital abnormalities or genetic syndrome. The anatomy of pediatric eyes, the often late presentation of the disease, and the high incidence of bilateral pathology in children all pose significant challenges in the management of these patients. We discuss the epidemiology of pediatric rhegmatogenous retinal detachment, review the genetic syndromes associated with a high incidence of retinal detachment, and examine other common causes of retinal detachment in this age group. We then outline an approach to evaluation and management and describe the expected outcomes of repair of retinal detachment in the pediatric population. PMID:23961003

  7. Retinal imaging with virtual reality stimulus for studying Salticidae retinas

    NASA Astrophysics Data System (ADS)

    Schiesser, Eric; Canavesi, Cristina; Long, Skye; Jakob, Elizabeth; Rolland, Jannick P.

    2014-12-01

    We present a 3-path optical system for studying the retinal movement of jumping spiders: a visible OLED virtual reality system presents stimulus, while NIR illumination and imaging systems observe retinal movement.

  8. Four-wavelength retinal vessel oximetry

    NASA Astrophysics Data System (ADS)

    Drewes, Jonathan Jensen

    1999-11-01

    This dissertation documents the design and construction of a four-wavelength retinal vessel oximeter, the Eye Oximeter (EOX). The EOX scans low-powered laser beams (at 629, 678, 821 and 899 nm) into the eye and across a targeted retinal vessel to measure the transmittance of the blood within the vessel. From the transmittance measurements, the oxygen saturation of the blood within the vessel is computed. Retinal vessel oxygen saturation has been suggested as a useful parameter for monitoring a wide range of conditions including occult blood loss and a variety of ophthalmic diseases. An artificial eye that simulates the geometry of a human retinal vessel was constructed and used to calibrate the EOX saturation measurement. A number of different oximetry equations were developed and tested. From measurements made on whole human blood in the artificial eye, an oximetry equation that places a linear wavelength dependance on the scattering losses (3% decrease from 629 to 899 nm) is found to best calibrate the EOX oxygen saturation measurement. This calibration also requires that an adjustment be made to the absorption coefficient of hemoglobin at 629 nm that has been reported in the literature. More than 4,000 measurements were made in the eyes of three human subjects during the development of the EOX. Applying the oximetry equation developed through the in vitro experiments to human data, the average human retinal venous oxygen saturation is estimated to be 0.63 +/- 0.07 and the average human retinal arterial oxygen saturation is 0.99 +/- 0.03. Furthermore, measurements made away from the optic disk resulted in a larger variance in the calculated saturation when compared to measurements made on the optic disk. A series of EOX experiments using anesthetized swine helped to verify the sensitivity of the EOX measurement of oxygen saturation. It is found that the calibration in swine differed from the calibration in the artificial eye. An empirical calibration from the

  9. Jules Gonin. Pioneer of retinal detachment surgery.

    PubMed

    Wolfensberger, Thomas J

    2003-12-01

    Before the turn of the 20th century, eyes with a retinal detachment were considered doomed. Contrary to other branches of ophthalmology, such as cataract extraction, the surgical treatment of retinal detachment was still in its infancy, and the surgical success rates were less than five percent. From 1902 to 1921 Jules Gonin almost single handedly changed the landscape of retinal detachment surgery forever. He recognised that the retinal break was the cause--and not the consequence as it was largely believed at the time--of the retinal detachment, and that the treatment had at all costs to comprise the closure of the break by cauterisation. He named the procedure ignipuncture, as he cauterised the retina through the sclera with a very hot pointed instrument. Despite rigorously detailed clinical observations and increasing success rates, his discovery was not readily accepted and sometimes openly opposed by a large part of the ophthalmic establishment. It was not until 1929 that he received worldwide acclaim at the International Ophthalmological Congress in Amsterdam for his surgical technique. His legacy lives on in the eye hospital in Lausanne that bears his name, in the Gonin Medal awarded by the International Council of Ophthalmology every four years for the highest achievement in ophthalmology, and in a street named after him, the very street that he used to walk from his home to the hospital every day. PMID:14750617

  10. Synthesis and optical properties of a crosslinkable polymer system containing TCF and TCP chromophores with excellent electro-optic activity and thermal stability

    NASA Astrophysics Data System (ADS)

    Chen, Zhuo; Bo, Shuhui; Zhen, Zhen; Liu, Xinhou

    2012-10-01

    Crosslinkable polymer with side-chain system was investigated to increase the content of NLO chromophores and improve the stability of oriented chromophores. In this work, a series of crosslinkable copolymers which beared different concentrations of chromophores with the tricyanofurane (TCF) acceptor and a kind of crosslinkable copolymers beared chromophores with dendritic tricyanopyrroline (TCP) acceptor were successfully synthesized and characterized. The crosslinked EO polymers which beared chromophores with the tricyanofurane (TCF) acceptor revealed the highest EO coefficient (r33) of 47.0 pm/V at 1310 nm, which was similar with the r33 of uncrosslinked systems. Compared to the uncrosslinked EO polymer systems, the crosslinked ones exhibited significantly enhanced temporal stability. Keywords: Nonlinear optics; Crosslinkable system; Chromophore-containing copolymers; Side-chain; Crosslinking reaction; Thermally stable polymer

  11. Low Vision Rehabilitation of Retinitis Pigmentosa. Practice Report

    ERIC Educational Resources Information Center

    Rundquist, John

    2004-01-01

    Retinitis pigmentosa is a rod-cone dystrophy, commonly genetic in nature. Approximately 60-80% of those with retinitis pigmentosa inherit it by an autosomal recessive transmission (Brilliant, 1999). There have been some reported cases with no known family history. The symptoms of retinitis pigmentosa are decreased acuity, photophobia, night…

  12. Retinas in a Dish Peek into Inherited Retinal Degeneration.

    PubMed

    Duong, Thu T; Vasireddy, Vidyullatha; Mills, Jason A; Bennett, Jean

    2016-06-01

    Human retinal degeneration can cause blindness, and the lack of relevant model systems has made identifying underlying mechanisms challenging. Parfitt et al. (2016) generate three-dimensional retinal tissue from patient-derived induced pluripotent stem cells to identify how CEP290 mutations cause retinal degeneration, and show an antisense approach can correct disease-associated phenotypes. PMID:27257755

  13. Acute Variations in Retinal Vascular Oxygen Content in a Rabbit Model of Retinal Venous Occlusion

    PubMed Central

    Saati, Saloomeh; Martin, Gabriel; Chader, Gerald; Humayun, Mark S.

    2012-01-01

    Purpose To study the variation in intravascular oxygen saturation (oximetry) during an acute retinal vein occlusion (RVO) using hyperspectral computed tomographic spectroscopy based oximetry measurements. Methods Thirty rabbits were dilated and anesthetized for experiments. Baseline oximetry measurements were made using a custom-made hyperspectral computed tomographic imaging spectrometer coupled to a fundus camera. RVO were induced using argon green laser following an intravenous injection of Rose Bengal. RVO induction was confirmed by fluorescein angiography. Retinal oximetry measurements were repeated in arterial and venous branches one hour after RVO induction and up to 4 weeks afterwards. Comparison of retinal oximetry before and after vein occlusion was made using the Student T-test. Results One hour after RVO induction, we observed statistically significant reductions in the intravascular oxygen saturation in temporal retinal arteries (85.1±6.1% vs. 80.6±6.6%; p<0.0001) and veins (71.4±5.5% vs. 64.0±4.7%; p<0.0001). This decrease was reversible in animals that spontaneously recannulated the vein occlusion. There were no statistically significant differences in oxygen saturation in the nasal control arteries and veins before and after temporal vein RVO induction. Conclusions We demonstrate, for the first time, acute changes in the intravascular oxygen content of retinal vessels 1 hour after RVO. These changes are reversible upon spontaneous recannulation of retinal vessels. This study demonstrates that hyperspectral computer tomographic spectroscopy based oximetry can detect physiological variations in intravascular retinal oxygen saturation. The study also provides the first qualitative and quantitative evidence of the variation in retinal vascular oxygen content directly attributable to an acute retinal vein occlusion. PMID:23185567

  14. Repetitive magnetic stimulation improves retinal function in a rat model of retinal dystrophy

    NASA Astrophysics Data System (ADS)

    Rotenstreich, Ygal; Tzameret, Adi; Levi, Nir; Kalish, Sapir; Sher, Ifat; Zangen, Avraham; Belkin, Michael

    2014-02-01

    Vision incapacitation and blindness associated with retinal dystrophies affect millions of people worldwide. Retinal degeneration is characterized by photoreceptor cell death and concomitant remodeling of remaining retinal cells. Repetitive Magnetic Stimulation (RMS) is a non-invasive technique that creates alternating magnetic fields by brief electric currents transmitted through an insulated coil. These magnetic field generate action potentials in neurons, and modulate the expression of neurotransmitter receptors, growth factors and transcription factors which mediate plasticity. This technology has been proven effective and safe in various psychiatric disorders. Here we determined the effect of RMS on retinal function in Royal College of Surgeons (RCS) rats, a model for retinal dystrophy. Four week-old RCS and control Spargue Dawley (SD) rats received sham or RMS treatment over the right eye (12 sessions on 4 weeks). RMS treatment at intensity of at 40% of the maximal output of a Rapid2 stimulator significantly increased the electroretinogram (ERG) b-wave responses by up to 6- or 10-fold in the left and right eye respectively, 3-5 weeks following end of treatment. RMS treatment at intensity of 25% of the maximal output did not significant effect b-wave responses following end of treatment with no adverse effect on ERG response or retinal structure of SD rats. Our findings suggest that RMS treatment induces delayed improvement of retinal functions and may induce plasticity in the retinal tissue. Furthermore, this non-invasive treatment may possibly be used in the future as a primary or adjuvant treatment for retinal dystrophy.

  15. Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

    NASA Technical Reports Server (NTRS)

    Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

    2003-01-01

    Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

  16. Quantum Chemical Benchmark Studies of the Electronic Properties of the Green Fluorescent Protein Chromophore. 1. Electronically Excited and Ionized States of the Anionic Chromophore in the Gas Phase.

    PubMed

    Epifanovsky, Evgeny; Polyakov, Igor; Grigorenko, Bella; Nemukhin, Alexander; Krylov, Anna I

    2009-07-14

    We present the results of quantum chemical calculations of the electronic properties of the anionic form of the green fluorescent protein chromophore in the gas phase. The vertical detachment energy of the chromophore is found to be 2.4-2.5 eV, which is below the strongly absorbing ππ* state at 2.6 eV. The vertical excitation of the lowest triplet state is around 1.9 eV, which is below the photodetachment continuum. Thus, the lowest bright singlet state is a resonance state embedded in the photodetachment continuum, whereas the lowest triplet state is a regular bound state. Based on our estimation of the vertical detachment energy, we attribute a minor feature in the action spectrum as due to the photodetachment transition. The benchmark results for the bright ππ* state demonstrated that the scaled opposite-spin method yields vertical excitation within 0.1 eV (20 nm) from the experimental maximum at 2.59 eV (479 nm). We also report estimations of the vertical excitation energy obtained with the equation-of-motion coupled cluster with the singles and doubles method, a multireference perturbation theory corrected approach MRMP2 as well as the time-dependent density functional theory with range-separated functionals. Expanding the basis set with diffuse functions lowers the ππ* vertical excitation energy by 0.1 eV at the same time revealing a continuum of "ionized" states, which embeds the bright ππ* transition. PMID:26610014

  17. Automated retinal layer segmentation and characterization

    NASA Astrophysics Data System (ADS)

    Luisi, Jonathan; Briley, David; Boretsky, Adam; Motamedi, Massoud

    2014-05-01

    Spectral Domain Optical Coherence Tomography (SD-OCT) is a valuable diagnostic tool in both clinical and research settings. The depth-resolved intensity profiles generated by light backscattered from discrete layers of the retina provide a non-invasive method of investigating progressive diseases and injury within the eye. This study demonstrates the application of steerable convolution filters capable of automatically separating gradient orientations to identify edges and delineate tissue boundaries. The edge maps were recombined to measure thickness of individual retinal layers. This technique was successfully applied to longitudinally monitor changes in retinal morphology in a mouse model of laser-induced choroidal neovascularization (CNV) and human data from age-related macular degeneration patients. The steerable filters allow for direct segmentation of noisy images, while novel recombination of weaker segmentations allow for denoising post-segmentation. The segmentation before denoising strategy allows the rapid detection of thin retinal layers even under suboptimal imaging conditions.

  18. Computer-aided retinal photocoagulation system

    NASA Astrophysics Data System (ADS)

    Barrett, Steven F.; Wright, Cameron H.; Jerath, Maya R.; Lewis, R. Stephen; Dillard, Bryan C.; Rylander, Henry G.; Welch, Ashley J.

    1996-01-01

    Researchers at the University of Texas at Austin's Biomedical Engineering Laser Laboratory and the U.S. Air Force Academy's Department of Electrical Engineering are developing a computer-assisted prototype retinal photocoagulation system. The project goal is to rapidly and precisely automatically place laser lesions in the retina for the treatment of disorders such as diabetic retinopathy and retinal tears while dynamically controlling the extent of the lesion. Separate prototype subsystems have been developed to control lesion parameters (diameter or depth) using lesion reflectance feedback and lesion placement using retinal vessels as tracking landmarks. Successful subsystem testing results in vivo on pigmented rabbits using an argon continuous wave laser are presented. A prototype integrated system design to simultaneously control lesion parameters and placement at clinically significant speeds is provided.

  19. Primary Vitreoretinal Lymphoma Masquerading as Refractory Retinitis

    PubMed Central

    Zloto, Ofira; Elkader, Amir E. Abd; Fabian, Ido Didi; Vishnevskia-Dai, Vicktoria

    2015-01-01

    Purpose To report a case of a patient with primary vitreoretinal lymphoma masquerading as retinitis. Methods Retrospective review of the patient's clinical, histopathological and imaging records. Results Cytopathology was negative for malignancy, and preliminary polymerase chain reaction results supported the diagnosis of varicella zoster virus retinitis. Therefore, the patient was treated with antiviral therapy. However, under this treatment, the retinitis progressed. As a result, primary vitreoretinal lymphoma was suspected, and empirical treatment with intravitreal methotrexate injections was started. Under this treatment, the ocular features improved. Five months after initial ocular presentation and ocular resolution, the patient presented with central nervous system lymphoma. Conclusion This case should raise the awareness of the variable clinical presentations, the challenging diagnosis and treatment of primary vitreoretinal lymphoma. All cases should be continuously systemically evaluated. PMID:26557084

  20. Autophagy in light-induced retinal damage.

    PubMed

    Chen, Yu; Perusek, Lindsay; Maeda, Akiko

    2016-03-01

    Vision is reliant upon converting photon signals to electrical information which is interpreted by the brain and therefore allowing us to receive information about our surroundings. However, when exposed to excessive light, photoreceptors and other types of cells in the retina can undergo light-induced cell death, termed light-induced retinal damage. In this review, we summarize our current knowledge regarding molecular events in the retina after excessive light exposure and mechanisms of light-induced retinal damage. We also introduce works which investigate potential roles of autophagy, an essential cellular mechanism required for maintaining homeostasis under stress conditions, in the illuminated retina and animal models of light-induced retinal damage. PMID:26325327

  1. Shedding New Light on Retinal Protein Photochemistry

    NASA Astrophysics Data System (ADS)

    Wand, Amir; Gdor, Itay; Zhu, Jingyi; Sheves, Mordechai; Ruhman, Sanford

    2013-04-01

    The ultrafast spectroscopic investigation of novel retinal proteins challenges existing notions concerning the course of primary events in these natural photoreceptors. We review two illustrations here. The first demonstrates that changes in the initial retinal configuration can alter the duration of photochemistry by nearly an order of magnitude in Anabaena sensory rhodopsin, making it as rapid as the ballistic photoisomerization in visual pigments. This prompted a reinvestigation of the much studied bacteriorhodopsin, leading to a similar trend as well, contrary to earlier reports. The second involves the study of xanthorhodopsin, an archaeal proton pump that includes an attached light-harvesting carotenoid. Pump-probe experiments demonstrate the efficient transfer of energy from carotenoid to retinal, providing a first glimpse at a cooperative multichromophore function, which is probably characteristic of many other proteins as well. Finally, we discuss measures required to advance our knowledge from kinetics to mode-specific dynamics concerning this expanding family of biological photoreceptors.

  2. Molecular biology of retinal ganglion cells.

    PubMed Central

    Xiang, M; Zhou, H; Nathans, J

    1996-01-01

    Retinal ganglion cells are the output neurons that encode and transmit information from the eye to the brain. Their diverse physiologic and anatomic properties have been intensively studied and appear to account well for a number of psychophysical phenomena such as lateral inhibition and chromatic opponency. In this paper, we summarize our current view of retinal ganglion cell properties and pose a number of questions regarding underlying molecular mechanisms. As an example of one approach to understanding molecular mechanisms, we describe recent work on several POU domain transcription factors that are expressed in subsets of retinal ganglion cells and that appear to be involved in ganglion cell development. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8570601

  3. Retinoschisis transposition following a retinal detachment repair

    PubMed Central

    McVeigh, Katherine; Keller, Johannes; Haynes, Richard J.

    2015-01-01

    Objective: The authors have observed this phenomenon of translocation of the schisis cavity in a few previous cases and aim to report this unusual finding. Method: A patient with known superotemporal retinoschisis developed a distinctly separate inferotemporal retinal detachment in his left eye. This was repaired with a vitrectomy, cryotherapy and C2F6 tamponade under local anaesthetic. Following surgery, the retinoschisis was found in the inferonasal quadrant of the eye and remained stable as the gas dispersed. Result: We hypothesise that the tamponading agent compressed the viscous fluid within the area of schisis, displacing the area of schisis circumferentially. Conclusion: This case emphasises that as long as the retinal breaks are properly sealed, no intervention is required with the schisis during rhegmatogenous retinal detachment surgery.

  4. [Muscular Dystrophies Involving the Retinal Function].

    PubMed

    Jägle, H

    2016-03-01

    Muscular dystrophies are rare disorders, with an incidence of approx. 20 in 100 000. Some dystrophies also affect retinal or optic nerve function. In such cases, the ophthalmological findings may be critical for differential diagnosis or patient counseling. For example in Duchenne muscular dystrophy, where the alteration in retinal function seems to reflect cerebral involvement. Other important forms are mitochondrial and metabolic disorders, such as the Kearns-Sayre syndrome and the Refsum syndrome. Molecular genetic analysis has become a major tool for differential diagnosis, but may be complex and demanding. This article gives an overview of major muscular dystrophies involving retinal function and their genetic origin, in order to guide differential diagnosis. PMID:27011029

  5. Prospects for retinal gene replacement therapy.

    PubMed

    Smith, Alexander J; Bainbridge, James W; Ali, Robin R

    2009-04-01

    Inherited retinal degeneration, which includes conditions such as retinitis pigmentosa and Leber congenital amaurosis (LCA), affects approximately 1/3000 of the population in the Western world. It is characterized by loss of vision and results from mutations in any one of >100 different genes. There are currently no effective treatments, but many of the genes have now been identified and their functions elucidated, providing a major impetus to develop gene-based treatments. Preliminary results from three clinical trials indicate that the treatment of a form of LCA by gene therapy can be safe and effective. Here, we discuss the potential for treating other forms of retinal degeneration by gene therapy, focusing on the gene defects that are likely to be the most amenable to treatment. PMID:19303164

  6. Dystroglycan is required for proper retinal layering.

    PubMed

    Lunardi, Andrea; Cremisi, Federico; Dente, Luciana

    2006-02-15

    Dystroglycan (DG) is a transmembrane receptor linking the extracellular matrix to the internal cytoskeleton. Its structural function has been mainly characterized in muscle fibers, but DG plays signaling and developmental roles also in different tissues and cell types. We have investigated the effects of dystroglycan depletion during eye development of Xenopus laevis. We have injected a specific morpholino (Mo) antisense oligonucleotide in the animal pole of one dorsal blastomere of embryos at four cells stage. Mo-mediated loss of DG function caused disruption of the basal lamina layers, increased apoptosis and reduction of the expression domains of specific retinal markers, at early stages. Later in development, morphants displayed unilateral ocular malformations, such as microphtalmia and retinal delayering with photoreceptors and ganglion cells scattered throughout the retina or aggregated in rosette-like structures. These results recall the phenotypes observed in specific human diseases and suggest that DG presence is crucial at early stages for the organization of retinal architecture. PMID:16406325

  7. Integrated computer-aided retinal photocoagulation system

    NASA Astrophysics Data System (ADS)

    Barrett, Steven F.; Wright, Cameron H. G.; Oberg, Erik D.; Rockwell, Benjamin A.; Cain, Clarence P.; Jerath, Maya R.; Rylander, Henry G., III; Welch, Ashley J.

    1996-05-01

    Successful retinal tracking subsystem testing results in vivo on rhesus monkeys using an argon continuous wave laser and an ultra-short pulse laser are presented. Progress on developing an integrated robotic retinal laser surgery system is also presented. Several interesting areas of study have developed: (1) 'doughnut' shaped lesions that occur under certain combinations of laser power, spot size, and irradiation time complicating measurements of central lesion reflectance, (2) the optimal retinal field of view to achieve simultaneous tracking and lesion parameter control, and (3) a fully digital versus a hybrid analog/digital tracker using confocal reflectometry integrated system implementation. These areas are investigated in detail in this paper. The hybrid system warrants a separate presentation and appears in another paper at this conference.

  8. Retinal Oximetry in a Healthy Japanese Population

    PubMed Central

    Nakano, Yuki; Shimazaki, Takeru; Kobayashi, Nobuko; Miyoshi, Yukiko; Ono, Aoi; Kobayashi, Mamoru; Shiragami, Chieko; Hirooka, Kazuyuki; Tsujikawa, Akitaka

    2016-01-01

    Purpose To establish the normative database of retinal oximetry using Oxymap T1 in a healthy Japanese population, and study the reproducibility of the measurements in Japanese. Methods We measured oxygen saturation in the major retinal vessels with Oxymap T1 in 252 eyes of 252 healthy Japanese subjects. Fundus images acquired using Oxymap T1 were processed using built-in Oxymap Analyzer software. Reproducibility of retinal oximetry was investigated using 20 eyes of 20 healthy subjects. Results The mean retinal oxygen saturation of 4 quadrants in healthy Japanese was 97.0 ± 6.9% in arteries and 52.8 ± 8.3% in veins. The mean arteriovenous difference in oxygen saturation was 44.2 ± 9.2%. Both arterial and venous oxygen saturation were significantly lower in the temporal side of the retina, especially in the temporal-inferior vessels. However, the arteriovenous difference in oxygen saturation was limited in the 4 quadrants. Interphotograph, intervisit, and interevaluator intraclass correlation coefficients were 0.936–0.979, 0.809–0.837, and 0.732–0.947, respectively. In the major retinal arteries, oxygen saturation increased with age (r = 0.18, p<0.01), at a rate of 0.67% per 10 years. However, venous oxygen saturation showed no correlation with age. Conclusions This study provides the normative database for the Japanese population. The arterial saturation value appears to be higher than other previous studies. Mean retinal oximetry in 4 quadrants with Oxymap T1 has high reproducibility. PMID:27434373

  9. Protease nexin-1 regulates retinal vascular development.

    PubMed

    Selbonne, Sonia; Francois, Deborah; Raoul, William; Boulaftali, Yacine; Sennlaub, Florian; Jandrot-Perrus, Martine; Bouton, Marie-Christine; Arocas, Véronique

    2015-10-01

    We recently identified protease nexin-1 (PN-1) or serpinE2, as a possibly underestimated player in maintaining angiogenic balance. Here, we used the well-characterized postnatal vascular development of newborn mouse retina to further investigate the role and the mechanism of action of PN-1 in physiological angiogenesis. The development of retinal vasculature was analysed by endothelial cell staining with isolectin B4. PN-1-deficient (PN-1(-/-)) retina displayed increased vascularization in the postnatal period, with elevated capillary thickness and density, compared to their wild-type littermate (WT). Moreover, PN-1(-/-) retina presented more veins/arteries than WT retina. The kinetics of retinal vasculature development, retinal VEGF expression and overall retinal structure were similar in WT and PN-1(-/-) mice, but we observed a hyperproliferation of vascular cells in PN-1(-/-) retina. Expression of PN-1 was analysed by immunoblotting and X-Gal staining of retinas from mice expressing beta-galactosidase under a PN-1 promoter. PN-1 was highly expressed in the first week following birth and then progressively decreased to a low level in adult retina where it localized on the retinal arteries. PCR arrays performed on mouse retinal RNA identified two angiogenesis-related factors, midkine and Smad5, that were overexpressed in PN-1(-/-) newborn mice and this was confirmed by RT-PCR. Both the higher vascularization and the overexpression of midkine and Smad5 mRNA were also observed in gastrocnemius muscle of PN-1(-/-) mice, suggesting that PN-1 interferes with these pathways. Together, our results demonstrate that PN-1 strongly limits physiological angiogenesis and suggest that modulation of PN-1 expression could represent a new way to regulate angiogenesis. PMID:26109427

  10. Reading Visual Braille with a Retinal Prosthesis

    PubMed Central

    Lauritzen, Thomas Z.; Harris, Jordan; Mohand-Said, Saddek; Sahel, Jose A.; Dorn, Jessy D.; McClure, Kelly; Greenberg, Robert J.

    2012-01-01

    Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2–4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients. PMID:23189036

  11. Preservation of retinotopic map in retinal degeneration.

    PubMed

    Xie, John; Wang, Gene-Jack; Yow, Lindy; Humayun, Mark S; Weiland, James D; Cela, Carlos J; Jadvar, Hossein; Lazzi, Gianluca; Dhrami-Gavazi, Elona; Tsang, Stephen H

    2012-05-01

    Retinal degenerations trigger the loss of photoreceptors and cause the remaining de-afferented neural retina to undergo remodeling. Concerns over this potential retinal synaptic reorganization following visual loss have raised questions regarding the usefulness of visual restoration via retinal electrical stimulation. We have used quantitative positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) to objectively evaluate the connection between the retina and the primary visual cortex under both light and transcorneal electrical stimulation (TcES) in five subjects with retinal degeneration (RD) who have had more than ten years of light-perception-only best visual acuity and five age-matched normal-sighted controls. All subjects underwent quantitative PET with FDG as the metabolic tracer during stimulation of the right eye under both light stimulation condition and transcorneal electrical stimulation (TcES) using ERG-Jet contact lens electrode. Cortical activation maps from each stimulation condition were obtained using statistical parametric mapping. TcES phosphene threshold current and qualitative visual cortex activation from both stimulation conditions were compared between the two subject groups. Average phosphene threshold current was 0.72 ± 0.18 mA for the five normal-sighted controls and 3.08 ± 2.01 mA for the retinal degenerative subjects. Phosphene threshold current was significantly higher in retinal degenerative subjects compared to normal-sighted controls (p < 0.05). We found both light stimulation and TcES resulted in retinotopically mapped primary visual cortex activation in both groups. In addition, the patterns of early visual area activation between the two subject groups are more similar during TcES than light stimulation. Our findings suggest primary visual cortex continues to maintain its retinotopy in RD subjects despite prolonged visual loss. PMID:22685713

  12. Metamorphopsia Associated with Branch Retinal Vein Occlusion

    PubMed Central

    Manabe, Koichiro; Tsujikawa, Akitaka; Osaka, Rie; Nakano, Yuki; Fujita, Tomoyoshi; Shiragami, Chieko; Hirooka, Kazuyuki; Uji, Akihito; Muraoka, Yuki

    2016-01-01

    Purpose To apply M-CHARTS for quantitative measurements of metamorphopsia in eyes with acute branch retinal vein occlusion (BRVO) and to elucidate the pathomorphology that causes metamorphopsia. Methods This prospective study consisted of 42 consecutive patients (42 eyes) with acute BRVO. Both at baseline and one month after treatment with ranibizumab, metamorphopsia was measured with M-CHARTS, and the retinal morphological changes were examined with optical coherence tomography. Results At baseline, metamorphopsia was detected in the vertical and/or horizontal directions in 29 (69.0%) eyes; the mean vertical and horizontal scores were 0.59 ± 0.57 and 0.52 ± 0.67, respectively. The maximum inner retinal thickness showed no association with the M-CHARTS score, but the M-CHARTS score was correlated with the total foveal thickness (r = 0.43, p = 0.004), the height of serous retinal detachment (r = 0.31, p = 0.047), and the maximum outer retinal thickness (r = 0.36, p = 0.020). One month after treatment, both the inner and outer retinal thickness substantially decreased. However, metamorphopsia persisted in 26 (89.7%) of 29 eyes. The posttreatment M-CHARTS score was not correlated with any posttreatment morphological parameters. However, the posttreatment M-CHARTS score was weakly correlated with the baseline total foveal thickness (r = 0.35. p = 0.024) and closely correlated with the baseline M-CHARTS score (r = 0.78, p < 0.001). Conclusions Metamorphopsia associated with acute BRVO was quantified using M-CHARTS. Initial microstructural changes in the outer retina from acute BRVO may primarily account for the metamorphopsia. PMID:27123642

  13. [Retinal vein occlusion: an interdisciplinary approach].

    PubMed

    Hatz, Katja; Martinez, Maria

    2016-01-01

    Retinal vein occlusion provide a common cause of significant visual reduction but also late ocular complications. The medical care of these patients pursue two goals: On the one hand vision threatening complications need to be identified and treated, and on the other hand treatable risk factors are need to be identified and treated. This paper summarizes the common ophthalmological therapeutic approaches as well as recommended medical evaluations carried out by the general practitioner. This supports the interdisciplinary approach in evaluating and treating retinal vein occlusions by ophthalmologists and the general practitioners/specialist in internal medicine. PMID:26982647

  14. Laser speckle analysis of retinal vascular dynamics

    PubMed Central

    Neganova, Anastasiia Y; Postnov, Dmitry D; Jacobsen, Jens Christian B.; Sosnovtseva, Olga

    2016-01-01

    Studies of vascular responses are usually performed on isolated vessels or on single vessels in vivo. This allows for precise measurements of diameter or blood flow. However, dynamical responses of the whole microvascular network are difficult to access experimentally. We suggest to use full-field laser speckle imaging to evaluate vascular responses of the retinal network. Image segmentation and vessel recognition algorithms together with response mapping allow us to analyze diameter changes and blood flow responses in the intact retinal network upon systemic administration of the vasoconstrictor angiotensin II, the vasodilator acetylcholine or on the changing level of anesthesia in in vivo rat preparations.

  15. The effect of bulky groups on the electro-optic coefficient r33 of a pyridine-donor nonlinear optical chromophore

    NASA Astrophysics Data System (ADS)

    Quilty, J. W.; Thomas, D. G.; Clarke, D. J.; Breukers, R. D.

    2016-04-01

    The effect of bulky groups attached to pyridine-donor chromophores on the electro-optic coefficient r33 of host-guest polymers was measured by modulation ellipsometry. Overall, the experimental results indicated no significant beneficial effect of the bulky groups on r33 . The maximum r33 achieved was just under 6 pm/V for the plain chromophore, compared with the expected 20 pm/V based on the molecular properties. Decomposition of the chromophore absorption band revealed significant aggregation, with the monomer fraction estimated to be marginally less than 1 / 3 for all chromophores studied. We attribute the lower achieved r33 values to increased molecular aggregation.

  16. A comprehensive picture of the ultrafast excited-state dynamics of retinal.

    PubMed

    Flender, Oliver; Scholz, Mirko; Hölzer, Jonas; Oum, Kawon; Lenzer, Thomas

    2016-06-01

    All-trans retinal is the chromophore of microbial rhodopsins initiating energy conversion and cellular signalling by subpicosecond photoinduced switching. Here, we provide detailed UV-Vis transient absorption experiments to disentangle the complex photochemistry of this polyene, which is governed by its terminal aldehyde group. After photoexcitation to the S2((1)Bu(+)) state, the system exhibits polarity-dependent branching, populating separate S1((1)Ag(-)) and intramolecular charge transfer (ICT) species. In all solvents, population of a singlet nπ* state from S1 is observed which represents the precursor of the T1 triplet state. While triplet formation dominates in nonpolar solvents (67% quantum yield), it is dramatically reduced in polar solvents (4%). The channel closes completely upon replacing the aldehyde by a carboxyl group, due to an energetic up-shift of (1)nπ*. In that case, internal conversion via the ICT species becomes the main pathway, with preferential formation of the initially excited isomer. PMID:27188764

  17. Modulating the electronic structure of chromophores by chemical substituents for efficient energy transfer: application to fluorone.

    PubMed

    Sand, Andrew M; Liu, Claire; Valentine, Andrew J S; Mazziotti, David A

    2014-08-01

    Strong electron correlation within a quasi-spin model of chromophores was recently shown to enhance exciton energy transfer significantly. Here we investigate how the modulation of the electronic structure of the chromophores by chemical substitution can enhance energy-transfer efficiency. Unlike previous work that does not consider the direct effect of the electronic structure on exciton dynamics, we add chemical substituents to the fluorone dimer to study the effect of electron-donating and electron-withdrawing substituents on exciton energy transfer. The exciton dynamics are studied from the solution of a quantum Liouville equation for an open system whose model Hamiltonian is derived from excited-state electronic structure calculations. Both van der Waals energies and coupling energies, arising from the Hellmann-Feynman force generated upon transferring the dimers from infinity to a finite separation, are built into the model Hamiltonian. Though these two effects are implicitly treated in dipole-based models, their explicit and separate treatment as discussed here is critical to forging the correct connection with the electronic structure calculations. We find that the addition of electron-donating substituents to the fluorone system results in an increase in exciton-transfer rates by factors ranging from 1.3-1.9. The computed oscillator strength is consistent with the recent experimental results on a larger heterodimer system containing fluorone. The oscillator strength increases with the addition of electron-donating substituents. Our results indicate that the study of chromophore networks via electronic structure will help in the future design of efficient synthetic light-harvesting systems. PMID:25062094

  18. Wavelength optimization for rapid chromophore mapping using spatial frequency domain imaging

    NASA Astrophysics Data System (ADS)

    Mazhar, Amaan; Dell, Steven; Cuccia, David J.; Gioux, Sylvain; Durkin, Anthony J.; Frangioni, John V.; Tromberg, Bruce J.

    2010-11-01

    Spatial frequency-domain imaging (SFDI) utilizes multiple-frequency structured illumination and model-based computation to generate two-dimensional maps of tissue absorption and scattering properties. SFDI absorption data are measured at multiple wavelengths and used to fit for the tissue concentration of intrinsic chromophores in each pixel. This is done with a priori knowledge of the basis spectra of common tissue chromophores, such as oxyhemoglobin (ctO2Hb), deoxyhemoglobin (ctHHb), water (ctH2O), and bulk lipid. The quality of in vivo SFDI fits for the hemoglobin parameters ctO2Hb and ctHHb is dependent on wavelength selection, fitting parameters, and acquisition rate. The latter is critical because SFDI acquisition time is up to six times longer than planar two-wavelength multispectral imaging due to projection of multiple-frequency spatial patterns. Thus, motion artifact during in vivo measurements compromises the quality of the reconstruction. Optimal wavelength selection is examined through matrix decomposition of basis spectra, simulation of data, and dynamic in vivo measurements of a human forearm during cuff occlusion. Fitting parameters that minimize cross-talk from additional tissue chromophores, such as water and lipid, are determined. On the basis of this work, a wavelength pair of 670 nm/850 nm is determined to be the optimal two-wavelength combination for in vivo hemodynamic tissue measurements provided that assumptions for water and lipid fractions are made in the fitting process. In our SFDI case study, wavelength optimization reduces acquisition time over 30-fold to 1.5s compared to 50s for a full 34-wavelength acquisition. The wavelength optimization enables dynamic imaging of arterial occlusions with improved spatial resolution due to reduction of motion artifacts.

  19. Chromophore-labelled, luminescent platinum complexes: syntheses, structures, and spectroscopic properties.

    PubMed

    Stacey, Oliver J; Ward, Benjamin D; Coles, Simon J; Horton, Peter N; Pope, Simon J A

    2016-06-21

    Ligands based upon 4-carboxamide-2-phenylquinoline derivatives have been synthesised with solubilising octyl hydrocarbon chains and tethered aromatic chromophores to give naphthyl (), anthracenyl () and pyrenyl () ligand variants, together with a non-chromophoric analogue () for comparison. (1)H NMR spectroscopic studies of the ligands showed that two non-interchangeable isomers exist for and while only one isomer exists for and . Supporting DFT calculations on suggest that the two isomers may be closely isoenergetic with a relatively high barrier to exchange of ca. 100 kJ mol(-1). These new ligands were cyclometalated with Pt(ii) to give complexes [Pt()(acac)] (acac = acetylacetonate). The spectroscopically characterised complexes were studied using multinuclear NMR spectroscopy including (195)Pt{(1)H} NMR studies which revealed δPtca. -2785 ppm for [Pt()(acac)]. X-ray crystallographic studies were undertaken on [Pt()(acac)] and [Pt()(acac)], each showing the weakly distorted square planar geometry at Pt(ii); the structure of [Pt()(acac)] showed evidence for intermolecular Pt-Pt interactions. The UV-vis. absorption studies show that the spectral profiles for [Pt()(acac)] are a composite of the organic chromophore centred bands and a broad (1)MLCT (5d → π*) band (ca. 440 nm) associated with the complex. Luminescence studies showed that complexes [Pt()(acac)] are dual emissive with fluorescence characteristic of the tethered fluorophore and long-lived phosphorescence attributed to (3)MLCT emission. In the case of the pyrenyl derivative, [Pt()(acac)], the close energetic matching of the (3)MLCT and (3)LCpyr excited states led to an elongation of the (3)MLCT emission lifetime (τ = 42 μs) under degassed solvent conditions, suggestive of energy transfer processes between the two states. PMID:27241625

  20. Structural Evidence for a Dehydrated Intermediate in Green Fluorescent Protein Chromophore Biosynthesis

    SciTech Connect

    Pletneva, Nadya V.; Pletnev, Vladimir Z.; Lukyanov, Konstantin A.; Gurskaya, Nadya G.; Goryacheva, Ekaterina A.; Martynov, Vladimir I.; Wlodawer, Alexander; Dauter, Zbigniew; Pletnev, Sergei

    2010-11-03

    The acGFPL is the first-identified member of a novel, colorless and non-fluorescent group of green fluorescent protein (GFP)-like proteins. Its mutant aceGFP, with Gly replacing the invariant catalytic Glu-222, demonstrates a relatively fast maturation rate and bright green fluorescence ({lambda}{sub ex} = 480 nm, {lambda}{sub em} = 505 nm). The reverse G222E single mutation in aceGFP results in the immature, colorless variant aceGFP-G222E, which undergoes irreversible photoconversion to a green fluorescent state under UV light exposure. Here we present a high resolution crystallographic study of aceGFP and aceGFP-G222E in the immature and UV-photoconverted states. A unique and striking feature of the colorless aceGFP-G222E structure is the chromophore in the trapped intermediate state, where cyclization of the protein backbone has occurred, but Tyr-66 still stays in the native, non-oxidized form, with C{sup {alpha}} and C{sup {beta}} atoms in the sp{sup 3} hybridization. This experimentally observed immature aceGFP-G222E structure, characterized by the non-coplanar arrangement of the imidazolone and phenolic rings, has been attributed to one of the intermediate states in the GFP chromophore biosynthesis. The UV irradiation ({lambda} = 250-300 nm) of aceGFP-G222E drives the chromophore maturation further to a green fluorescent state, characterized by the conventional coplanar bicyclic structure with the oxidized double Tyr-66 C{sup {alpha}} = C{sup {beta}} bond and the conjugated system of {pi}-electrons. Structure-based site-directed mutagenesis has revealed a critical role of the proximal Tyr-220 in the observed effects. In particular, an alternative reaction pathway via Tyr-220 rather than conventional wild type Glu-222 has been proposed for aceGFP maturation.

  1. Associated depression in pseudophakic patients with intraocular lens with and without chromophore

    PubMed Central

    Mendoza-Mendieta, María Elena; Lorenzo-Mejía, Ana Aurora

    2016-01-01

    Background With aging, the crystalline lens turns yellowish, which increases the absorption of wavelengths in the blue electromagnetic spectrum, reducing their photoreception in the retina. Since these wavelengths are the main stimulus in the regulation of the circadian rhythm, progressive reduction in their transmission is associated with chronic sleep disturbances and depression in elderly patients. Cataract extraction improves circadian photoreception at any age. However, lenses that block blue waves have 27% to 38% less melatonin suppression than lenses that block only ultraviolet (UV) rays. Purpose To assess the depression symptoms in subjects who have had bilateral phacoemul-sification and intraocular lens (IOL) implants, one group with yellow chromophore IOLs and the other group with transparent IOLs were compared. Setting Association to Prevent Blindness in Mexico (APEC), Hospital “Dr Luis Sánchez Bulnes”. Design This was an observational, cross-sectional, and single-center study. Materials and methods Twenty-six subjects between 60 and 80 years of age, with a history of bilateral phacoemulsification and placement of the same type of IOL in both eyes from 4 to 12 months prior to the study, who attended the follow-up visits and agreed to participate in this study, and provided signed informed consent were included in the study. They were asked to answer the short version of the 15-item Geriatric Depression Scale. Results The average age of the study participants was 72.5±5.94 years. The group without chromophore included 46.1% (n=12) of the patients and the group with chromophore included 53.9% (n=14) of the patients (P=0.088). Conclusion In the group of patients with IOLs that block the passage of blue light, the depression rate was 21.4%, a rate similar to that observed in the elderly population, whereas no patients in the group with transparent IOLs had depression. PMID:27099465

  2. Review: R28 retinal precursor cells: The first 20 years

    PubMed Central

    2014-01-01

    The R28 retinal precursor cell line was established 20 years ago, originating from a postnatal day 6 rat retinal culture immortalized with the 12S E1A (NP-040507) gene of the adenovirus in a replication-incompetent viral vector. Since that time, R28 cells have been characterized and used for a variety of in vitro and in vivo studies of retinal cell behavior, including differentiation, neuroprotection, cytotoxicity, and light stimulation, as well as retinal gene expression and neuronal function. While no cell culture is equivalent to the intact eye, R28 cells continue to provide an important experimental system for the study of many retinal processes. PMID:24644404

  3. Retinal arterial occlusive disease in systemic lupus erythematosus.

    PubMed

    Gold, D; Feiner, L; Henkind, P

    1977-09-01

    Four patients with systemic lupus erythematosus (SLE) developed an unusual form of occlusive retinal arterial disease. The most prominent clinical features of this disorder were deposition of yellow-white material in retinal arterial walls and evidence of multifocal retinal arterial occlusion. Fluorescein angiographic findings included nonperfusion of the obstructed arteries and the retinal capillary beds fed by them, and fluorescein leakage at the sites of involvement of the retinal arteries. This ocular complication of SLE is presumably a manifestation of the widespread systemic vascular problems seen in this disorder. It may be more common in patients with lupus involving the CNS. PMID:901267

  4. Twisted Thiophene-Based Chromophores with Enhanced Intramolecular Charge Transfer for Cooperative Amplification of Third-Order Optical Nonlinearity.

    PubMed

    Teran, Natasha B; He, Guang S; Baev, Alexander; Shi, Yanrong; Swihart, Mark T; Prasad, Paras N; Marks, Tobin J; Reynolds, John R

    2016-06-01

    Exploiting synergistic cooperation between multiple sources of optical nonlinearity, we report the design, synthesis, and nonlinear optical properties of a series of electron-rich thiophene-containing donor-acceptor chromophores with condensed π-systems and sterically regulated inter-aryl twist angles. These structures couple two key mechanisms underlying optical nonlinearity, namely, (i) intramolecular charge transfer, greatly enhanced by increased electron density and reduced aromaticity at chromophore thiophene rings and (ii) a twisted chromophore geometry, producing a manifold of close-lying excited states and dipole moment changes between ground and excited states that are nearly twice that of untwisted systems. Spectroscopic, electrochemical, and nonlinear Z-scan measurements, combined with quantum chemical calculations, illuminate relationships between molecular structure and mechanisms of enhancement of the nonlinear refractive index. Experiment and calculations together reveal ground-state structures that are strongly responsive to the solvent polarity, leading to substantial negative solvatochromism (Δλ ≈ 10(2) nm) and prevailing zwitterionic/aromatic structures in the solid state and in polar solvents. Ground-to-excited-state energy gaps below 2.0 eV are obtained in condensed π-systems, with lower energy gaps for twisted versus untwisted systems. The real part of the second hyperpolarizability in the twisted structures is much greater than the imaginary part, with the highest twist angle chromophore giving |Re(γ)/Im(γ)| ≈ 100, making such chromophores very promising for all-optical-switching applications. PMID:27232098

  5. The biliverdin chromophore binds covalently to a conserved cysteine residue in the N-terminus of Agrobacterium phytochrome Agp1.

    PubMed

    Lamparter, Tilman; Carrascal, Montserrat; Michael, Norbert; Martinez, Enriqueta; Rottwinkel, Gregor; Abian, Joaquin

    2004-03-30

    Phytochromes are widely distributed biliprotein photoreceptors. Typically, the chromophore becomes covalently linked to the protein during an autocatalytic lyase reaction. Plant and cyanobacterial phytochromes incorporate bilins with a ring A ethylidene side chain, whereas other bacterial phytochromes utilize biliverdin as chromophore, which has a vinyl ring A side chain. For Agrobacterium phytochrome Agp1, site-directed mutagenesis provided evidence that biliverdin is bound to cysteine 20. This cysteine is highly conserved within bacterial homologues, but its role as attachment site has as yet not been proven. We therefore performed mass spectrometry studies on proteolytic holopeptide fragments. For that purpose, an Agp1 expression vector was re-engineered to produce a protein with an N-terminal affinity tag. Following proteolysis, the chromophore co-purified with a ca. 5 kDa fragment during affinity chromatography, showing that the attachment site is located close to the N-terminus. Mass spectrometry analyses performed with the purified chromopeptide confirmed the role of the cysteine 20 as biliverdin attachment site. We also analyzed the role of the highly conserved histidine 250 by site-directed mutagenesis. The homologous amino acid plays an important but yet undefined role in plant phytochromes and has been proposed as chromophore attachment site of Deinococcus phytochrome. We found that in Agp1, this amino acid is dispensable for covalent attachment, but required for tight chromophore-protein interaction. PMID:15035636

  6. Self-Assembled Light-Harvesting System from Chromophores in Lipid Vesicles.

    PubMed

    Sahin, Tuba; Harris, Michelle A; Vairaprakash, Pothiappan; Niedzwiedzki, Dariusz M; Subramanian, Vijaya; Shreve, Andrew P; Bocian, David F; Holten, Dewey; Lindsey, Jonathan S

    2015-08-13

    Lipid vesicles are used as the organizational structure of self-assembled light-harvesting systems. Following analysis of 17 chromophores, six were selected for inclusion in vesicle-based antennas. The complementary absorption features of the chromophores span the near-ultraviolet, visible, and near-infrared region. Although the overall concentration of the pigments is low (~1 μM for quantitative spectroscopic studies) in a cuvette, the lipid-vesicle system affords high concentration (≥10 mM) in the bilayer for efficient energy flow from donor to acceptor. Energy transfer was characterized in 13 representative binary mixtures using static techniques (fluorescence-excitation versus absorptance spectra, quenching of donor fluorescence, modeling emission spectra of a mixture versus components) and time-resolved spectroscopy (fluorescence, ultrafast absorption). Binary donor-acceptor systems that employ a boron-dipyrrin donor (S0 ↔ S1 absorption/emission in the blue-green) and a chlorin or bacteriochlorin acceptor (S0 ↔ S1 absorption/emission in the red or near-infrared) have an average excitation-energy-transfer efficiency (ΦEET) of ~50%. Binary systems with a chlorin donor and a chlorin or bacteriochlorin acceptor have ΦEET ∼ 85%. The differences in ΦEET generally track the donor-fluorescence/acceptor-absorption spectral overlap within a dipole-dipole coupling (Förster) mechanism. Substantial deviation from single-exponential decay of the excited donor (due to the dispersion of donor-acceptor distances) is expected and observed. The time profiles and resulting ΦEET are modeled on the basis of (Förster) energy transfer between chromophores relatively densely packed in a two-dimensional compartment. Initial studies of two ternary and one quaternary combination of chromophores show the enhanced spectral coverage and energy-transfer efficacy expected on the basis of the binary systems. Collectively, this approach may provide one of the simplest designs for

  7. Torsional Motion of the Chromophore Catechol following the Absorption of Ultraviolet Light

    NASA Astrophysics Data System (ADS)

    Young, J. D.; Staniforth, M.; Paterson, M. J.; Stavros, V. G.

    2015-06-01

    The ability to probe energy flow in molecules, following the absorption of ultraviolet light, is crucial to unraveling photophysical phenomena. Here we excite a coherent superposition of vibrational states in the first excited electronic state (S1 ) in catechol, resulting in a vibrational wave packet. The observed quantum beats, assigned to superpositions of the low-frequency, and strongly mixed, O-H torsional mode τ2 , elegantly demonstrate how changes in geometry upon photoionization from the S1 state to the ground state of the cation (D0 ) enables one to probe energy flow at the very early stages of photoexcitation in this biological chromophore.

  8. A Miniaturized Therapeutic Chromophore for Multiple Metal Pollutant Sensing, Pathological Metal Diagnosis and Logical Computing.

    PubMed

    Rout, Bhimsen

    2016-01-01

    The efficacy of a miniaturized unimolecular analytic system is illustrated. The easily accessible therapeutic chromophore "temoporfin", which responds differentially to bound metals at multiple wavelengths of Q-band absorption using chemometric analysis, expeditiously detects and discriminates a wide range of metals regarded as priority pollutants in water and hence may also be used for diagnosis of medically relevant metals in human urine. The molecule was further investigated as an electronic logic device, e.g. keypad lock device, to authorize multiple highly secure chemical passwords for information protection. PMID:27271817

  9. Optical and Near-IR Spectral Comparison with Chromophore Candidates in the Jovian Atmosphere

    NASA Astrophysics Data System (ADS)

    Thelen, Alexander; Chanover, Nancy; Miller, Charles; Loeffler, Mark; Hudson, Reggie; Simon, Amy

    2014-11-01

    Large atmospheric features, such as the belts, zones, and storms that make up Jupiter’s atmosphere remain colored by an unidentified chemical compound (or set of compounds). Optical reflectance spectra of Jupiter’s atmosphere in the literature show few spectral features in the blue (shortwards of 500 nm), unlike the red portion of the spectrum which is dominated by the methane absorption spectrum. The prevailing spectral slope and dearth of molecular absorption features in the blue are attributed to absorption by coloring compounds, or chromophores, in the upper Jovian atmosphere. While both organic and inorganic candidate compounds have been proposed, few laboratory studies have been conducted at temperatures and pressures appropriate for local Jupiter conditions to determine the identity of the chromophores responsible for coloring these large atmospheric features such as Jupiter’s Great Red Spot. In this study, we analyzed ground-based optical spectra and near-IR spectral image cubes of Jupiter for comparison with laboratory data of a potential chromophore compound. Optical spectra 330-450 nm in the blue, ~570-690 nm in the red) were obtained between December 2013 and February 2014 with the Dual Imaging Spectrograph, mounted on the Astrophysical Research Consortium 3.5-meter telescope at Apache Point Observatory. Near-infrared (1.25-2.5 μm) spectra of various locations in Jupiter’s atmosphere were obtained from spectral image cubes taken with the New Horizons Linear Etalon Imaging Spectral Array during the early 2007 Jupiter flyby. The combination of these two data sets allowed us to identify specific regions in the Jovian atmosphere with distinct coloration. We compare these ground- and space-based observations to laboratory spectra from the Cosmic Ice Laboratory at NASA’s Goddard Space Flight Center. Thin films of NH4SH were exposed to varying amounts of ionizing radiation at Jovian temperature conditions, thereby enabling us to evaluate NH4SH as a

  10. Simultaneous recovery of chromophore concentrations and ultrasound velocity by spectrally resolved photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Yuan, Zhen; Zhang, Qizhi; Grobmyer, Stephen; Jiang, Huabei

    2009-02-01

    We describe a new spectral approach for inversion of photoacoustic data with multi-wavelength pulsed laser illumination. Multi-spectral PAT provides a means of recovery of different chromophore concentrations and ultrasound velocity simultaneously and directly by incorporating prior spectral information into the image reconstruction process. It is demonstrated from simulation tests and small animal experiments that the multi-parameter recovery based on multispectral PAT is reliable and accurate. The reconstructed multiple parameter images may provide us a key tool to quantify physiological function, disease progression, or response to intervention.

  11. Synthesis, structure, and excimer formation of vesicular assemblies carrying 1- or 2-naphthyl chromophores

    SciTech Connect

    Sisido, Masahiki; Sato, Yasuhiko; Sasaki, Hiroki; Imanishi, Yukio )

    1990-01-01

    New chromophoric amphiphiles consisting of optically active 1- or 2-naphthylalanines, each carrying two long alkyl chains and an ammonium ion, were synthesized. These amphiphiles were found to form vesicular structures in aqueous dispersion, and those having two octadecyl chains showed a gel-liquid crystalline transition around room temperature. UV and CD spectra showed exciton-type interactions for the 2-naphthyl amphiphiles in a high-energy excited state but no dimers or higher aggregates of the naphthyl groups in the ground state. Fluorescence spectra showed monomer and excimer emissions. The circularly polarized fluorescence spectra showed a positive signal at the excimer emission, indicating a chiral excimer configuration.

  12. Synthesis of several novel multifunctionalized chromophores for second-order NLO

    NASA Astrophysics Data System (ADS)

    Luo, Jingdong; Zhan, Caimao; Qin, Jingui

    1998-08-01

    4-[4-disubstituted-amino-phenylazo]-(alpha) - cyanocinnamates with two or more functional groups (such as hydroxyl, allyl) at both ends of the molecule to be used as novel chromophores for second-order NLO polymeric materials are synthesized by diazonium coupling and Knoevenagel condensation. In this two-step method, the tediousness of functionalization at the electron-acceptor end is avoided by selecting (alpha) -cyanoacrylate as electron-acceptor. The products are easy to purify, and the whole procedure is simple and time-saving, which facilitates the choice of polymer system for effective hardened NLO lattice in a broader range.

  13. NIR bacteriochlorin chromophores accessed by Heck and Sonogashira cross-coupling reactions on a tetrabromobacteriochlorin derivative.

    PubMed

    de Assis, Francisco F; Ferreira, Marco A B; Brocksom, Timothy J; de Oliveira, Kleber T

    2016-01-28

    The synthesis of a new tetrabromobacteriochlorin BCBr4 is reported having the 3,4-dibromo-1H-pyrrole-2-carbaldehyde (10) as the major precursor. The BCBr4 was successfully employed in Pd cross-coupling reactions with methyl acrylate, phenyl acetylene and 4-ethynylanisole. In all three cases, the desired tetra-coupled products were obtained in good to excellent yields, and present a significant red shift in the UV-Vis bands above 800 nm. DFT and TD-DFT theoretical analyses of the NIR bacteriochlorin chromophores were performed in order to evaluate the effect of β substitution on their electronic structures. PMID:26676846

  14. A Miniaturized Therapeutic Chromophore for Multiple Metal Pollutant Sensing, Pathological Metal Diagnosis and Logical Computing

    PubMed Central

    Rout, Bhimsen

    2016-01-01

    The efficacy of a miniaturized unimolecular analytic system is illustrated. The easily accessible therapeutic chromophore “temoporfin”, which responds differentially to bound metals at multiple wavelengths of Q-band absorption using chemometric analysis, expeditiously detects and discriminates a wide range of metals regarded as priority pollutants in water and hence may also be used for diagnosis of medically relevant metals in human urine. The molecule was further investigated as an electronic logic device, e.g. keypad lock device, to authorize multiple highly secure chemical passwords for information protection. PMID:27271817

  15. A Miniaturized Therapeutic Chromophore for Multiple Metal Pollutant Sensing, Pathological Metal Diagnosis and Logical Computing

    NASA Astrophysics Data System (ADS)

    Rout, Bhimsen

    2016-06-01

    The efficacy of a miniaturized unimolecular analytic system is illustrated. The easily accessible therapeutic chromophore “temoporfin”, which responds differentially to bound metals at multiple wavelengths of Q-band absorption using chemometric analysis, expeditiously detects and discriminates a wide range of metals regarded as priority pollutants in water and hence may also be used for diagnosis of medically relevant metals in human urine. The molecule was further investigated as an electronic logic device, e.g. keypad lock device, to authorize multiple highly secure chemical passwords for information protection.

  16. Chronic Myeloid Leukaemia Presenting as Bilateral Retinal Haemorrhages with Multiple Retinal Infiltrates

    PubMed Central

    Barot, Rakesh K.; Gohel, Devadatta Jayantilal; Bhagat, Nupur

    2016-01-01

    Chronic Myeloid Leukaemia (CML) causes retinopathy manifesting as venous dilation and tortuosity, perivascular sheathing, retinal haemorrhages, microaneurysms, cotton-wool spots and optic nerve infiltration. Retina is the most commonly involved intraocular structure in CML. However, retinal involvement is a rare form of presentation of CML and few cases have been reported. We report a case of CML presenting as unilateral sudden visual loss. Fundus showed multiple white centered retinal haemorrhages in both eyes with unilateral macular oedema. Blood work-up showed raised WBC count, high platelet count and low Haemoglobin. Cytological analysis of bone marrow biopsy confirmed Philadelphia chromosome. After a course of Imatinib, visual acuity improved and haemorrhages resolved with normalization of macular thickness. In our case, patient presented early, leading to early detection producing better visual prognosis. This highlights the importance of detailed hematological work up in patients with retinal involvement to rule out leukaemic retinopathy.

  17. Probing how initial retinal configuration controls photochemical dynamics in retinal proteins

    NASA Astrophysics Data System (ADS)

    Wand, A.; Rozin, R.; Eliash, T.; Friedman, N.; Jung, K. H.; Sheves, M.; Ruhman, S.

    2013-03-01

    The effects of the initial retinal configuration and the active isomerization coordinate on the photochemistry of retinal proteins (RPs) are assessed by comparing photochemical dynamics of two stable retinal ground state configurations (all-trans,15-anti vs. 13-cis,15-syn), within two RPs: Bacteriorhodopsin (BR) and Anabaena Sensory Rhodopsin (ASR). Hyperspectral pump-probe spectroscopy shows that photochemistry starting from 13-cis retinal in both proteins is 3-10 times faster than when started in the all-trans state, suggesting that the hastening is ubiquitous to microbial RPs, regardless of their different biological functions and origin. This may also relate to the known disparity of photochemical rates between microbial RPs and visual pigments. Importance and possible underlying mechanisms are discussed as well.

  18. Retinal Detachment Associated with AIDS-Related Cytomegalovirus Retinitis: Risk Factors in a Resource-Limited Setting

    PubMed Central

    Yen, Michael; Chen, Jenny; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Vichitvejpaisal, Pornpattana; Ausayakhun, Sakarin; Jirawison, Choeng; Shantha, Jessica; Holland, Gary N; Heiden, David; Margolis, Todd P; Keenan, Jeremy D

    2014-01-01

    Purpose To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. Design Case-control study. Methods Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. Results Patients with a retinal detachment were more likely than controls to have low visual acuity (OR, 1.24 per line of worse vision on the logMAR scale; 95%CI, 1.16-1.33) and bilateral disease (OR, 2.12; 95%CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95%CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95%CI, 1.41-4.94). Conclusion Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment. PMID:25448999

  19. PKC/MAPK signaling suppression by retinal pericyte conditioned medium prevents retinal endothelial cell proliferation.

    PubMed

    Kondo, Tetsu; Hosoya, Ken-Ichi; Hori, Satoko; Tomi, Masatoshi; Ohtsuki, Sumio; Terasaki, Tetsuya

    2005-05-01

    Little is known about the regulation mechanism of endothelial cell proliferation by retinal pericytes. The purpose of this study was to elucidate the suppression mechanism of retinal capillary endothelial cell growth by soluble factors derived from retinal pericytes. Conditioned medium of retinal pericytes (rPCT1-CM) suppressed ischemia-induced retinal neovascularization. The growth and DNA synthesis of TR-iBRB2 cells, a conditionally immortalized rat retinal capillary endothelial cell line, were suppressed in a concentration-dependent manner by concentrated rPCT1-CM. The number of human cultured endothelial cells was also reduced by rPCT1-CM. These results provide the first evidence that CM from the cultivation of pericytes alone can inhibit retinal neovascularization in vivo and in vitro. Although the growth reduction of TR-iBRB2 cells was only partly reversed by treatment of rPCT1-CM with antibodies to transforming growth factor-beta1, it was completely lost by heat-treatment of rPCT1-CM, suggesting that anti-angiogenic factors are soluble proteins. The levels of expression of G1/S-phase-related proteins, such as cyclin D1, cyclin-dependent kinase (cdk)4, cdk6, and proliferating cell nuclear antigen, were reduced and a cdk inhibitor, p21(Cip1), was induced in rPCT1-CM-treated TR-iBRB2 cells. Moreover, phosphorylated p44/42 mitogen-activated protein kinase (p44/42 MAPK) in TR-iBRB2 cells was reduced by rPCT1-CM treatment and phosphorylated protein kinase C (PKC)alpha/betaII, which is upstream of p44/42 MAPK, was also suppressed. In conclusion, CM from retinal pericytes suppresses PKC-p44/42 MAPK signaling, inhibits endothelial cell growth, and prevents retinal neovascularization. Anti-angiogenic factors derived from retinal pericytes are likely to play a critical role in the regulation of retinal endothelial cell growth. PMID:15499572

  20. Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan

    PubMed Central

    Chen, San-Ni; Hwang, Jiunn-Feng; Wu, Wen-Chuan

    2016-01-01

    This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. PMID:26909812