MICROCIRCULATION, Issue 1 2007
C. N. SCHOLFIELD
ABSTRACT Control of ocular blood flow occurs predominantly at the level of the retinal and choroidal arterioles. The present article provides an overview of the Ca2 + handling mechanisms and plasmalemmal ion channels involved in the regulation of retinal and choroidal arteriolar smooth muscle tone. Increases in global intracellular free Ca2 + ([Ca2 +]i) involve multiple mechanisms, including agonist-dependent release of Ca2 + from intracellular stores through activation of the inositol trisphosphate (IP3) pathway. Ca2 + enters by voltage-dependent L-type Ca2 + channels and novel dihydropyridine-sensitive store-operated nonselective cation channels. Ca2 + extrusion is mediated by plasmalemmal Ca2 + -ATPases and through Na+/Ca2+ exchange. Local Ca2 + transients (Ca2 + sparks) play an important excitatory role, acting as the building blocks for more global Ca2 + signals that can initiate vasoconstriction. K+ and Cl, channels may also affect cell function by modulating membrane potential. The precise contribution of each of these mechanisms to the regulation of retinal and choroidal perfusion in vivo warrants future investigation. [source]

Alpha-retinals as Rhodopsin Chromophores,Preference for the 9- Z Configuration and Partial Agonist Activity,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2008
Yajie Wang
The visual pigment rhodopsin, the photosensory element of the rod photoreceptor cell in the vertebrate retina, shows in combination with an endogenous ligand, 11- Z retinal, an astonishing photochemical performance. It exhibits an unprecedented quantum yield (0.67) in a highly defined and ultrafast photoisomerization process. This triggers the conformational changes leading to the active state Meta(rhodopsin) II. Retinal is covalently bound to Lys-296 of the protein opsin in a protonated Schiff base. The resulting positive charge delocalization over the terminal part of the polyene chain of retinal creates a conjugation defect that upon photoexcitation moves to the opposite end of the polyene. Shortening the polyene as in 4,5-dehydro,5,6-dihydro (alpha), 5,6-dihydro or 7,8-dihydro-analogs might facilitate photoisomerization of a 9- Z and a 11- Z bond. Here we describe pigment analogs generated with bovine opsin and 11- Z or 9- Z 4,5-dehydro,5,6-dihydro-retinal that were further characterized by UV,Vis and FTIR spectroscopy. The preference of opsin for native 11- Z retinal over the 9- Z isomer is reversed in 4,5-dehydro,5,6-dihydro-retinal. 9- Z 4,5-dehydro,5,6-dihydro-retinal readily generated a photosensitive pigment. This modification has no effect on the quantum yield, but affects the Batho,blueshifted intermediate (BSI) equilibrium and leads to a strong decrease in the G-protein activation rate because of a downshift of the pKa of the Meta I,Meta II equilibrium. [source]

Rhodopsin Regeneration is Accelerated via Noncovalent 11- cis Retinal,Opsin Complex,A Role of Retinal Binding Pocket of Opsin,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2008
Hiroyuki Matsumoto
The regeneration of bovine rhodopsin from its apoprotein opsin and the prosthetic group 11- cis retinal involves the formation of a retinylidene Schiff base with the , -amino group of the active lysine residue of opsin. The pH dependence of a Schiff base formation in solution follows a typical bell-shaped profile because of the pH dependence of the formation and the following dehydration of a 1-aminoethanol intermediate. Unexpectedly, however, we find that the formation of rhodopsin from 11- cis retinal and opsin does not depend on pH over a wide pH range. These results are interpreted by the Matsumoto and Yoshizawa (Nature258 [1975] 523) model of rhodopsin regeneration in which the 11- cis retinal chromophore binds first to opsin through the , -ionone ring, followed by the slow formation of the retinylidene Schiff base in a restricted space. We find the second-order rate constant of the rhodopsin formation is 6100 ± 300 mol,1 s,1 at 25°C over the pH range 5,10. The second-order rate constant is much greater than that of a model Schiff base in solution by a factor of more than 107. A previous report by Pajares and Rando (J Biol Chem264 [1989] 6804) suggests that the lysyl ,-NH2 group of opsin is protonated when the , -ionone ring binding site is unoccupied. The acceleration of the Schiff base formation in rhodopsin is explained by stabilization of the deprotonated form of the lysyl ,-NH2 group which might be induced when the , -ionone ring binding site is occupied through the noncovalent binding of 11- cis retinal to opsin at the initial stage of rhodopsin regeneration, followed by the proximity and orientation effect rendered by the formation of noncovalent 11- cis retinal,opsin complex. [source]

9- cis Retinal Increased in Retina of RPE65 Knockout Mice with Decrease in Coat Pigmentation,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006
Jie Fan
The protein RPE65 is essential for the generation of the native chromophore, 11- cis retinal, of visual pigments. However, the Rpe65 knockout (Rpe65 -1- ) mouse shows a minimal visual response due to the presence of a pigment, isorhodopsin, formed with 9- cis retinal. Isorhodopsin accumulates linearly with prolonged dark-rearing of the animals. The majority of Rpe65 -/- mice have an agouti coat color. A tan coat color subset of Rpe65 -/- mice was found to have an enhanced visual response as measured by electroretinograms. The enhanced response was found to be due to increased levels of 9- cis retinal and isorhodopsin pigment levels. Animals of both coat colors reared in cyclic light have minimal levels of regenerated pigment and show photoreceptor degeneration. On dark-rearing, pigment accumulates and photoreceptor degeneration is decreased. In the tan Rpe65 -/- mice, the level of photoreceptor degeneration is less than in the agouti animals, which have an increased pigment and decreased free opsin level. Therefore, photoreceptor damage correlates with the amount of the apoprotein present, supporting findings that the activity from unregenerated opsin can lead to photoreceptor degeneration. [source]

Retinal and Optic Nerve Diseases

ARTIFICIAL ORGANS, Issue 11 2003
Eyal Margalit
Abstract:, A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device. [source]

1263: Symptoms and signs of posterior uveitis

ACTA OPHTHALMOLOGICA, Issue 2010
M KHAIRALLAH
Purpose Posterior uveitis (PU) is an important anatomic form of uveitis in which the primary site of inflammation is the choroid or retina, with or without subsequent vitreous involvement. Methods Review of symptoms and signs of PU. Results The onset of PU can be sudden or less frequently insidious. Most common ocular symptoms include blurred vision, loss of vision, and floaters. Some patients with PU may have no symptoms, especially if inflammatory process is asymmetric. PU is usually associated with vitritis that can vary from mild to severe. Vitritis should be graded according to standardized grading systems. Other vitreous changes may include vitreous strands, vitreous hemorrhage, vitreous traction, and posterior vitreous detachment. Retinal and/or choroidal inflammation can be focal, multifocal, or more diffuse. It is important to distinguish between active and inactive chorioretinal disease. Retinal vasculitis can occur in the setting of several PU entities. It can involve retinal veins or arteries. It appears as focal, multifocal, or diffuse vascular cuffing or sheathing. Other retinal vasculitic changes include retinal hemorrhages, retinal vascular occlusion, retinal/optic disc neovascularization, and aneurysms. Maculopathy is common patients with PU. It may result from direct inflammatory infiltration, macular edema, serous retinal detachment, retinal ischemia, epiretinal membrane, or macular hole. Optic nerve involvement that can occur in association with PU include optic disc hyperemia/edema, optic neuritis, neuroretinitis, optic disc exudate, and optic disc granuloma. Conclusion Clinical examination is a key step in the diagnostic approach to PU. Clinician should be aware of the array of ocular symptoms of signs and their importance in orienting the differential diagnosis. [source]

2126: Retinal and cortical functions in adult mice lacking cannabinoid receptors

ACTA OPHTHALMOLOGICA, Issue 2010
C CASANOVA
Purpose Cannabinoid receptor type 1 (CB1R) has been localized in the adult retina of rodents. It is expressed in cones, horizontal, bipolar, some amacrine and ganglion cells. The expression of the cannabinoid receptor type 2 (CB2R) mRNA in the retina of adult rats was also reported. The goal of the present study was to investigate the functional roles of CB1R and CB2R in the retina by comparing retinal electrophysiological responses and cortical optical signals in normal and genetically modified mice. Methods Experiments were conducted on four different groups of C57BL/6 mice: CB1R wild type (WT), CB1R knockout (KO), CB2R WT and KO. Scotopic electroretinograms (ERG) luminance-response functions and photopic ERGs were recorded. In a subset of CB1 groups, intrinsic signals acquired by optical brain imaging were used to determine spatial frequency, contrast sensitivity and retinotopic maps in the visual cortex. Results The CB1R KO retina showed a stronger photopic response. No differences were observed for scotopic responses. For the CB2R groups, the scotopic b-wave response was stronger in the KO mice. No differences could be seen between visual cortices maps with respect to SF and contrast sensitivity. Retinotopic maps differed only along the azimuth. Significant differences were observed between hemodynamic response functions. Conclusion These results indicate that CB receptors can play a regulatory effect on the neurovascular coupling at the retinal and cortical levels and on the functional organization of the mice visual cortex along the azimuth Axis.(NSERC) [source]

Retinal and optic nerve oxygenation and carbonic anhydrase inhibition

ACTA OPHTHALMOLOGICA, Issue 2009
M LA COUR
Purpose To study the effects of carbonic anhydrase inhibition on porcine retinal and optic nerve oxygenation under physiological conditions and in experimental models of ischemia. Methods Polarographic oxygen electrodes were used to measure the oxygen tension in the vitreous 500 microns in front of the optic nerve and retina. Retinal ischemia was produced by diathermia of the superior arcade vein, producing a branch retinal vein occlusion, BRVO. Optic nerve ischemia was produced by intravenous administration of 100 mg Indomethacin intravenously. Results One week after induction of BRVO, the oxygen tension over BRVO affected retina was significantly decreased by 29%. Administration of the carbonic anhydrase inhibitor dorzolamide (500 mg) caused a significant increase in the oxygen tension over BRVO affected retina, and in effect restored this tension to normal values (n=5). Intravenous administration of 300 mg Indomethacin caused a decrease of optic nerve oxygen tension by 41%. Subsequent administration of 500 mg dorzolamide increased the optic nerve oxygen tension, albeit not to normal levels (n=6). Conclusion Carbonic anhydrase inhibition increases the oxygen tension in the retina and optic nerve. In BRVO affected retina, carbonic anhydrase inhibition restores oxygen tension to normal levels. [source]

Complete reconstruction of the retinal laminar structure from a cultured retinal pigment epithelium is triggered by altered tissue interaction and promoted by overlaid extracellular matrices

DEVELOPMENTAL NEUROBIOLOGY, Issue 14 2009
Fusako Kuriyama
Abstract The retina regenerates from retinal pigment epithelial (RPE) cells by transdifferentiation in the adult newt and Xenopus laevis when it is surgically removed. This was studied under a novel culture condition, and we succeeded, for the first time, in developing a complete retinal laminar structure from a single epithelial sheet of RPE. We cultured a Xenopus RPE monolayer sheet isolated from the choroid on a filter cup with gels overlaid and found that the retinal tissue structure differentiated with all retinal layers present. In the culture, RPE cells isolated themselves from the culture substratum (filter membrane), migrated, and reattached to the overlaid gel, on which they initiated transdifferentiation. This was exactly the same as observed during in vivo retina regeneration of X. laevis. In contrast, when RPE monolayers were cultured similarly without isolation from the choroid, RPE cells proliferated, but remained pigmented instead of transdifferentiating, indicating that alteration in tissue interaction triggers transdifferentiation. We then examined under the conventional tissue culture condition whether altered RPE-choroid interaction induces Pax6 expression. Pax6 was upregulated in RPE cells soon after they were removed from the choroid, and this expression was not dependent of FGF2. FGF2 administration was needed for RPE cells to maintain Pax6 expression. From the present results, in addition to our previous ones, we propose a two-step mechanism of transdifferentiation: the first step is a reversible process and is initiated by the alteration of the cell-extracellular matrix and/or cell,cell interaction followed by Pax6 upregulation. FGF2 plays a key role in driving RPE cells into the second step, during which they differentiate into retinal stem cells. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source]

Distribution of neurotrophin-3 during the ontogeny and regeneration of the lizard (Gallotia galloti) visual system

DEVELOPMENTAL NEUROBIOLOGY, Issue 1 2008
E. Santos
Abstract We have previously described the spontaneous regeneration of retinal ganglion cell axons after optic nerve (ON) transection in the adult Gallotia galloti. As neurotrophin-3 (NT-3) is involved in neuronal differentiation, survival and synaptic plasticity, we performed a comparative immunohistochemical study of NT-3 during the ontogeny and regeneration (after 0.5, 1, 3, 6, 9, and 12 months postlesion) of the lizard visual system to reveal its distribution and changes during these events. For characterization of NT-3+ cells, we performed double labelings using the neuronal markers HuC-D, Pax6 and parvalbumin (Parv), the microglial marker tomato lectin or Lycopersicon esculentum agglutinin (LEA), and the astroglial markers vimentin (Vim) and glial fibrillary acidic protein (GFAP). Subpopulations of retinal and tectal neurons were NT-3+ from early embryonic stages to adulthood. Nerve fibers within the retinal nerve fiber layer, both plexiform layers and the retinorecipient layers in the optic tectum (OT) were also stained. In addition, NT-3+/GFAP+ and NT-3+/Vim+ astrocytes were detected in the ON, chiasm and optic tract in postnatal and adult lizards. At 1 month postlesion, abundant NT-3+/GFAP+ astrocytes and NT-3,/LEA+ microglia/macrophages were stained in the lesioned ON, whereas NT-3 became downregulated in the experimental retina and OT. Interestingly, at 9 and 12 months postlesion, the staining in the experimental retina resembled that in control animals, whereas bundles of putative regrown fibers showed a disorganized staining pattern in the OT. Altogether, we demonstrate that NT-3 is widely distributed in the lizard visual system and its changes after ON transection might be permissive for the successful axonal regrowth. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source]

Overview of retinoid metabolism and function

DEVELOPMENTAL NEUROBIOLOGY, Issue 7 2006
Rune Blomhoff
Abstract Retinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all- trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all- trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra-nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein-coupled transmembrane receptors called opsins. These receptors function as light-driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin-bound 11- cis -retinal is isomerized to all- trans -retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all- trans retinol to all- trans retinal and all- trans retinoic acid, and esterification of all- trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all- trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 606,630, 2006 [source]

A high-throughput on-line microdialysis-capillary assay for D -serine

ELECTROPHORESIS, Issue 7-8 2003
Kylie B. O'Brien
Abstract A high-throughput method is described for the analysis of D -serine and other neurotransmitters in tissue homogenates. Analysis is performed by microdialysis-capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection in a sheath flow detection cell. Sample pretreatment is not required as microdialysis sampling excludes proteins and cell fragments. Primary amines are derivatized on-line with o -phthaldialdehyde (OPA) in the presence of ,-mercaptoethanol followed by on-line CE-LIF analysis. Under the separation conditions described here, D -serine is resolved from L -serine and other primary amines commonly found in biological samples. Each separation requires less than 22 s. Eliminating the need for sample pretreatment and performing the high-speed CE analysis on-line significantly reduces the time required for D -serine analysis when compared with traditional methods. This method has been used to quantify D -serine levels in larval tiger salamander retinal homogenates, as well as dopamine, ,-amino- n -butyric acid (GABA), glutamate and L -aspartate. D -serine release from an intact retina was also detected. [source]

Proteorhodopsin photosystem gene clusters exhibit co-evolutionary trends and shared ancestry among diverse marine microbial phyla

ENVIRONMENTAL MICROBIOLOGY, Issue 4 2007
Jay McCarren
Summary Since the recent discovery of retinylidene proteins in marine bacteria (proteorhodopsins), the estimated abundance and diversity of this gene family has expanded rapidly. To explore proteorhodopsin photosystem evolutionary and distributional trends, we identified and compared 16 different proteorhodopsin-containing genome fragments recovered from naturally occurring bacterioplankton populations. In addition to finding several deep-branching proteorhodopsin sequences, proteorhodopsins were found in novel taxonomic contexts, including a betaproteobacterium and a planctomycete. Approximately one-third of the proteorhodopsin-containing genome fragments analysed, as well as a number of recently reported marine bacterial whole genome sequences, contained a linked set of genes required for biosynthesis of the rhodopsin chromophore, retinal. Phylogenetic analyses of the retinal biosynthetic genes suggested their co-evolution and probable coordinated lateral gene transfer into disparate lineages, including Euryarchaeota, Planctomycetales, and three different proteobacterial lineages. The lateral transfer and retention of genes required to assemble a functional proteorhodopsin photosystem appears to be a coordinated and relatively frequent evolutionary event. Strong selection pressure apparently acts to preserve these light-dependent photosystems in diverse marine microbial lineages. [source]

Free fatty acids exert a greater effect on ocular and skin blood flow than triglycerides in healthy subjects

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2004
M. Bayerle-Eder
Abstract Background, Free fatty acids (FFAs) and triglycerides (TGs) can cause vascular dysfunction and arteriosclerosis. Acute elevation of plasma FFA and TG concentration strongly increase ocular and skin blood flow. This study was designed to discriminate whether FFA or TG independently induce hyperperfusion by measuring regional and systemic haemodynamics. Methods, In a balanced, randomized, placebo-controlled, double-blind, three-way, crossover study nine healthy subjects received either Intralipid® (Pharmacia and Upjohn, Vienna, Austria) with heparin, Intralipid® alone or placebo control. Pulsatile choroidal blood flow was measured with laser interferometry, retinal blood flow and retinal red blood cell velocity with laser Doppler velocimetry, and skin blood flow with laser Doppler flowmetry during an euglycaemic insulin clamp. Results, A sevenfold increase of FFA during Intralipid®/heparin infusion was paralleled by enhanced choriodal, retinal, and skin blood flow by 17 ± 4%, 26 ± 5% (P < 0·001), and 47 ± 19% (P = 0·03) from baseline, respectively. In contrast, a mere threefold increase of FFA by infusion of Intralipid® alone did not affect outcome parameters, despite the presence of plasma TG levels of 250,700 mg dL,1; similar to those obtained during combined Intralipid®/heparin infusion. Systemic haemodynamics were not affected by drug infusion. Conclusions, Present findings demonstrate a concentration-dependent increase in ocular and skin blood flow by FFA independently of elevated TG plasma concentrations. As vasodilation of resistance vessels occur rapidly, FFA may play a role in the development of continued regional hyperperfusion and deteriorate microvascular function. [source]

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

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007
Helia B. Schonthaler
Abstract An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11- cis -retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all- trans to 11- cis -retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11- cis -retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all- trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11- cis -retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11- cis -retinal for cone vision. [source]

The specificity of alcohol dehydrogenase with cis -retinoids

FEBS JOURNAL, Issue 9 2004
Activity with 11- cis -retinol, localization in retina
Studies in knockout mice support the involvement of alcohol dehydrogenases ADH1 and ADH4 in retinoid metabolism, although kinetics with retinoids are not known for the mouse enzymes. Moreover, a role of alcohol dehydrogenase (ADH) in the eye retinoid interconversions cannot be ascertained due to the lack of information on the kinetics with 11- cis -retinoids. We report here the kinetics of human ADH1B1, ADH1B2, ADH4, and mouse ADH1 and ADH4 with all- trans -, 7- cis -, 9- cis -, 11- cis - and 13- cis -isomers of retinol and retinal. These retinoids are substrates for all enzymes tested, except the 13- cis isomers which are not used by ADH1. In general, human and mouse ADH4 exhibit similar activity, higher than that of ADH1, while mouse ADH1 is more efficient than the homologous human enzymes. All tested ADHs use 11- cis -retinoids efficiently. ADH4 shows much higher kcat/Km values for 11- cis -retinol oxidation than for 11- cis -retinal reduction, a unique property among mammalian ADHs for any alcohol/aldehyde substrate pair. Docking simulations and the kinetic properties of the human ADH4 M141L mutant demonstrated that residue 141, in the middle region of the active site, is essential for such ADH4 specificity. The distinct kinetics of ADH4 with 11- cis -retinol, its wide specificity with retinol isomers and its immunolocalization in several retinal cell layers, including pigment epithelium, support a role of this enzyme in the various retinol oxidations that occur in the retina. Cytosolic ADH4 activity may complement the isomer-specific microsomal enzymes involved in photopigment regeneration and retinoic acid synthesis. [source]

Bacteriorhodopsin-Monolayer-Based Planar Metal,Insulator,Metal Junctions via Biomimetic Vesicle Fusion: Preparation, Characterization, and Bio-optoelectronic Characteristics,

ADVANCED FUNCTIONAL MATERIALS, Issue 8 2007
D. Jin
Abstract A reliable and reproducible method for preparing bacteriorhodopsin (bR)-containing metal,biomolecule,monolayer-metal planar junctions via vesicle fusion tactics and soft deposition of Au top electrodes is reported. Optimum monolayer and junction preparations, including contact effects, are discussed. The electron-transport characteristics of bR-containing membranes are studied systematically by incorporating native bR or artificial bR pigments derived from synthetic retinal analogues, into single solid-supported lipid bilayers. Current,voltage (I,V) measurements at ambient conditions show that a single layer of such bR-containing artificial lipid bilayers pass current in solid electrode/bilayer/solid electrode structures. The current is passed only if retinal or its analogue is present in the protein. Furthermore, the preparations show photoconductivity as long as the retinal can isomerize following light absorption. Optical characterization suggests that the junction photocurrents might be associated with a photochemically induced M-like intermediate of bR. I,V measurements along with theoretical estimates reveal that electron transfer through the protein is over four orders of magnitude more efficient than what would be estimated for direct tunneling through 5,nm of water-free peptides. Our results furthermore suggest that the light-driven proton-pumping activity of the sandwiched solid-state bR monolayer contributes negligibly to the steady-state light currents that are observed, and that the orientation of bR does not significantly affect the observed I,V characteristics. [source]

The network behind spatio-temporal patterns: building low-complexity retinal models in CNN based on morphology, pharmacology and physiology

INTERNATIONAL JOURNAL OF CIRCUIT THEORY AND APPLICATIONS, Issue 2 2001
Csaba Rekeczky
Abstract In this paper, a vertebrate retina model is described based on a cellular neural network (CNN) architecture. Though largely built on the experience of previous studies, the CNN computational framework is considerably simplified: first-order RC cells are used with space-invariant nearest-neighbour interactions only. All non-linear synaptic connections are monotonic continuous functions of the pre-synaptic voltage. Time delays in the interactions are continuous represented by additional first-order cells. The modelling approach is neuromorphic in its spirit relying on both morphological and pharmacological information. However, the primary motivation lies in fitting the spatio-temporal output of the model to the data recorded from biological cells (tiger salamander). In order to meet a low-complexity (VLSI) implementation framework some structural simplifications have been made. Large-neighbourhood interaction (neurons with large processes), furthermore inter-layer signal propagation are modelled through diffusion and wave phenomena. This work presents novel CNN models for the outer and some partial models for the inner (light adapted) retina. It describes an approach that focuses on efficient parameter tuning and also makes it possible to discuss adaptation, sensitivity and robustness issues on retinal ,image processing' from an engineering point of view. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Using 1,3-butadiene and 1,3,5-hexatriene to model the cis-trans isomerization of retinal, the chromophore in the visual pigment rhodopsin

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4-5 2002
Fredrik Blomgren
Abstract The short polyenes 1,3-butadiene and 1,3,5-hexatriene are used to model the cis-trans isomerization of the protonated Schiff base of retinal (PSBR) in rhodopsin (Rh). We employed the complete active space self-consistent field (CASSCF) method for calculation of the potential energy surfaces (PESs) in C2 symmetry. In the calculations, the central bond was twisted from 0 to 180° in the first singly excited singlet state (Sse), i.e., the state dominated by a configuration with one electron excited from HOMO to LUMO. It was found that the PES of 1,3-butadiene has a maximum whereas the PES of 1,3,5-hexatriene has a minimum for a twist angle of 90°. This is explained by a shift in border of single and double bonds in the Sse state. The first step in the cis-trans isomerization of PSBR, which is the formation of the C6C7 (see Scheme 1 for numbering) twisted PSBR in the first excited singlet state (S1), inside the protein binding pocket of the visual pigment Rh is modeled using crystal coordinates and the calculations performed on 1,3-butadiene and 1,3,5-hexatriene. More specifically, a plausible approximate structure is calculated in a geometric way for the C6C7 90° twisted PSBR, which fits into the protein binding pocket in the best possible way. It has been shown earlier that PSBR has an energy minimum for this angle in S1. The CASSCF method was used to investigate the wave function of the calculated structure of PSBR. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002 [source]

Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures

JOURNAL OF ANATOMY, Issue 4 2005
Niall Patton
Abstract The retinal and cerebral microvasculatures share many morphological and physiological properties. Assessment of the cerebral microvasculature requires highly specialized and expensive techniques. The potential for using non-invasive clinical assessment of the retinal microvasculature as a marker of the state of the cerebrovasculature offers clear advantages, owing to the ease with which the retinal vasculature can be directly visualized in vivo and photographed due to its essential two-dimensional nature. The use of retinal digital image analysis is becoming increasingly common, and offers new techniques to analyse different aspects of retinal vascular topography, including retinal vascular widths, geometrical attributes at vessel bifurcations and vessel tracking. Being predominantly automated and objective, these techniques offer an exciting opportunity to study the potential to identify retinal microvascular abnormalities as markers of cerebrovascular pathology. In this review, we describe the anatomical and physiological homology between the retinal and cerebral microvasculatures. We review the evidence that retinal microvascular changes occur in cerebrovascular disease and review current retinal image analysis tools that may allow us to use different aspects of the retinal microvasculature as potential markers for the state of the cerebral microvasculature. [source]

The role of early neural activity in the maturation of turtle retinal function

JOURNAL OF ANATOMY, Issue 4 2001
EVELYNE SERNAGOR
In the developing vertebrate retina, ganglion cells fire spontaneous bursts of action potentials long before the eye becomes exposed to sensory experience at birth. These early bursts are synchronised between neighbouring retinal ganglion cells (RGCs), yielding unique spatiotemporal patterns: ,waves' of activity sweep across large retinal areas every few minutes. Both at retinal and extraretinal levels, these embryonic retinal waves are believed to guide the wiring of the visual system using hebbian mechanisms of synaptic strengthening. In the first part of this review, we recapitulate the evidence for a role of these embryonic spontaneous bursts of activity in shaping developing complex receptive field properties of RGCs in the turtle embryonic retina. We also discuss the role of visual experience in establishing RGC visual functions, and how spontaneous activity and visual experience interact to bring developing receptive fields to maturation. We have hypothesised that the physiological changes associated with development reflect modifications in the dendritic arbours of RGCs, the anatomical substrate of their receptive fields. We demonstrate that there is a temporal correlation between the period of receptive field expansion and that of dendritic growth. Moreover, the immature spontaneous activity contributes to dendritic growth in developing RGCs. Intracellular staining of RGCs reveals, however, that immature receptive fields only rarely show direct correlation with the layout of the corresponding dendritic tree. To investigate the possibility that not only the presence of the spontaneous activity, but even the precise spatiotemporal patterns encoded in retinal waves might contribute to the refinement of retinal neural circuitry, first we must clarify the mechanisms mediating the generation and propagation of these waves across development. In the second part of this review, we present evidence that turtle retinal waves, visualised using calcium imaging, exhibit profound changes in their spatiotemporal patterns during development. From fast waves sweeping across large retinal areas and recruiting many cells on their trajectory at early stages, waves become slower and eventually stop propagating towards hatching, when they become stationary patches of neighbouring coactive RGCs. A developmental switch from excitatory to inhibitory GABAA responses appears to mediate the modification in spontaneous activity patterns while the retina develops. Future chronic studies using specific spatiotemporal alterations of the waves will shed a new light on how the wave dynamics help in sculpting retinal receptive fields. [source]

Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2001
Keisuke Mori
In this study, we investigated whether overexpression of pigment epithelium-derived factor (PEDF) by gene transfer can inhibit neovascularization by testing its effect in three different models of ocular neovascularization. Intravitreous injection of an adenoviral vector encoding PEDF resulted in expression of PEDF mRNA in the eye measured by RT-PCR and increased immunohistochemical staining for PEDF protein throughout the retina. In mice with laser-induced rupture of Bruch's membrane, choroidal neovascularization was significantly reduced after intravitreous injection of PEDF vector compared to injection of null vector or no injection. Subretinal injection of the PEDF vector resulted in prominent staining for PEDF in retinal pigmented epithelial cells and strong inhibition of choroidal neovascularization. In two models of retinal neovascularization (transgenic mice with increased expression of vascular endothelial growth factor (VEGF) in photoreceptors and mice with oxygen-induced ischemic retinopathy), intravitreous injection of null vector resulted in decreased neovascularization compared to no injection, but intravitreous injection of PEDF vector resulted in further inhibition of neovascularization that was statistically significant. These data suggest that sustained increased intraocular expression of PEDF by gene therapy might provide a promising approach for treatment of ocular neovascularization. © 2001 Wiley-Liss, Inc. [source]

Color Doppler sonography of orbital and vertebral arteries in migraineurs without aura

JOURNAL OF CLINICAL ULTRASOUND, Issue 6 2003
Simay Altan Kara MD
Abstract Purpose The objective of this study was to investigate whether the retrobulbar hemodynamics in the ophthalmic (OA), posterior ciliary (PCA), central retinal (CRA), and vertebral (VA) arteries are affected in migraineurs without aura. Methods The eyes of migraineurs without aura and those of healthy control subjects were evaluated during both headache and headache-free periods. Retrobulbar and vertebral blood flow velocities in the OA, PCA, CRA, and the extracranial part of the VA were measured bilaterally using color Doppler sonography. The peak systolic and end-diastolic flow velocities and the pulsatility (PI) and resistance (RI) indices were determined for all arteries. Results In total, we enrolled 30 migraineurs and 31 healthy control subjects. Statistically significant differences between headache-free migraineurs and control subjects were observed in the PI and RI of both right and left PCAs and in the RI of both right and left CRAs. The PI and RI of the left VA of the migraineurs were significantly lower during both headache and headache-free periods than were those of the control subjects. Among the migraineurs, the peak systolic and end-diastolic velocities of the left VA were increased during headache periods relative to those found during the headache-free periods. Conclusions The retrobulbar circulation and flow hemodynamics in the left VA may be altered in both headache and headache-free periods in migraineurs without aura. The differences found between migraineurs and control subjects may implicate autonomic dysfunction in migraineurs. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:308,314, 2003 [source]

Retinoid metabolism in the small intestine during development of liver cirrhosis

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2009
Sathish Kumar Natarajan
Abstract Background and Aims:, Retinoids are important mediators of cellular differentiation and proliferation in various epithelia of the body including the small intestine. Though alterations in intestinal epithelial cell proliferation have been noted in liver cirrhosis, mechanisms involved in the process are not well understood. This study examined the levels of various retinoids and retinoid-metabolizing enzymes in the small intestine during development of liver cirrhosis. Methods:, Four groups of animals were used (control, phenobarbitone control, thioacetamide and carbon tetrachloride treatment). Twice-weekly intragastric or i.p. administration of carbon tetrachloride or thioacetamide, respectively, produced liver cirrhosis after 3 months, which was confirmed through histology and serum markers. Retinoid levels were measured by high-performance liquid chromatography. Results:, A decrease in the levels of retinal, retinoic acid and retinol was evident in the intestine by 3 months, when cirrhosis was evident histologically, and these remained low until 6 months. A decrease in the activities of retinaldehyde oxidase, retinaldehyde reductase and retinol dehydrogenase was also seen in intestine from cirrhotic rats. Conclusion:, These results suggest that altered retinoid metabolism in the intestine of cirrhotic rats might have an influence on changes in intestinal epithelial cell differentiation, seen in liver cirrhosis. [source]

Kinetic and mechanistic studies on the inhibition of free radical-initiated polymerization of styrene by ,-carotene and ,-tocopherol

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 6 2002
Zhaolong Li
Abstract The inhibition of free radical-initiated polymerization of styrene by ,-carotene (,C) and ,-tocopherol (TOH) was studied by dilatometry. The polymerization was initiated by 2,2,-azobis(isobutyronitrile) at 50,°C in chlorobenzene and inhibited by ,C and/or TOH. It was found that ,C and TOH could efficiently inhibit the polymerization, either used individually or in combination, and a significant synergistic effect was observed when they were used in combination. It is proposed that retinal, which is the principal oxidation product of ,C, may be involved in the synergistic inhibition reaction of ,C and TOH. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Structural Features of the NAD-Dependent In Situ Retinoic Acid Supply System in Esophageal Mucosa

ALCOHOLISM, Issue 2010
Hirokazu Yokoyama
Background:, We previously reported that an NAD-dependent in situ retinoic acid supply system, which comprises some isoforms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and provides retinoic acid from retinol via a 2-step oxidation process, exists in the rat esophagus. Herein, their isoforms responsible for the pathway and its localization in the rat esophagus was examined. Methods:, The expressions of mRNAs of various isoforms of ADH and ALDH were examined in the fraction mainly comprising mucosal layer of the rat esophagus by RT-PCR. Expression levels of Class IV ADH and ALDH 1A1 were compared between the fractions and that mainly comprising muscle layer of the rat esophagus by quantitative PCR. The catalytic activities producing retinoic acid from retinal were compared between the 2 fractions and its optimum pH was also determined. Results:, Classes I, III, and IV ADHs and ALDHs 1A1 and 3A1 were predominant isoforms in the rat esophageal mucosa. The expression levels of mRNA of Class IV ADH and ALDH 3A1 were significantly higher in the mucosal than in the muscle layer. Consistently, the catalytic activities producing retinoic acid from retinal were significantly higher in the former than the latter. The optimum pH of the process was 9.0. Conclusions:, Considering the affinities for retinol and retinal of ADHs and ALDHs expressed in the rat esophagus, the NAD-dependent in situ retinoic acid supply system in the rat esophagus is thought to comprise Class IV ADH and ALDH 1A1. In the rat esophagus, the system exists predominantly in the mucosal layer. [source]

Interferon-induced retinopathy and its risk in patients with diabetes and hypertension undergoing treatment for chronic hepatitis C virus infection

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
J. D. PANETTA
Summary Background, Ocular complications are amongst many side-effects of interferon based therapy for hepatitis C virus (HCV) infection. Some suggest that diabetic and hypertensive patients are at increased risk of these complications. Aim, To determine the frequency of ophthalmological complications related to interferon use. Methods, Retrospective analysis of patients undergoing HCV treatment with pegylated interferon ,-2a, ,-2b or consensus interferon plus ribavirin between 2005 and 2007. All patients underwent a baseline eye examination and any visual complaints during treatment prompted a repeat examination. Data recorded included HCV genotype, treatment duration, interferon type, pre-treatment and on treatment visual complaints, known ocular pathology, and retinal findings at baseline and at follow-up. Results, Of 183 patients, 29 (16%) had diabetes and 85 (46%) had hypertension. Seventy-one (38%) received interferon ,-2a, 100 (55%) ,-2b, and 12 (7%) consensus interferon. Seven (3.8%) had retinal changes on follow-up and treatment was discontinued in 3 (1.6%). Of seven with ocular changes two had hypertension and one had both hypertension and diabetes. Conclusion, The incidence of symptomatic retinopathy in HCV patients undergoing interferon therapy appears low and treatment cessation is rarely needed. Furthermore, patients with hypertension and diabetes may not be at higher risk for interferon-induced retinopathy. [source]

Cellular Physiology of Retinal and Choroidal Arteriolar Smooth Muscle Cells

Lipofuscin and Macular Degeneration

NUTRITION REVIEWS, Issue 10 2003
George Wolf DPhil
The accumulation of the autofluorescent pigment lipofuscin in the retina that occurs with aging has been explained as a side effect of the visual cycle. It occurs when two molecules of all- trans -retinal condense with one molecule of phosphatidylethanolamine in the discs of the rod outer segments, and is followed by uptake into retinal pigment epithelium (RPE) and conversion to the stable A2E, a pyridinium bisretinoid that is toxic to RPE cells. The accumulation of A2E, the major component of lipofuscin causes RPE cell apoptosis, thereby explaining age-related macular degeneration and macular degeneration characteristic of Stargardt disease. The drug isotretinoin (13- cis - retinoic acid) prevents accumulation of A2E in mice by slowing down the visual cycle and might therefore be used to prevent macular degeneration. [source]

Technical Note: Method for estimating volume of subretinal fluid in cases of localized retinal detachment by OCT ophthalmoscopy

OPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 5 2007
Hideto Nakajima
Abstract The volume of the subretinal fluid can be used to assess the condition of different types of retinal and macular disorders. The purpose of this report is to introduce a method to measure the volume of the subretinal fluid with the images of the optical coherence tomography (OCT) Ophthalmoscope in three cases of central serous chorioretinopathy and one case of retinal pigment epithelial detachment. We used the topography-mode program of the OCT Ophthalmoscope and measured the average height of the retinal detachment. By multiplying the size of the area of the retinal detachment and the average height of the retinal detachment, the volume of subretinal fluid could be determined. Examples are given to show the results of volume measurement of subretinal fluid in cases of localized retinal detachments. [source]