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  • Two opsin genes from the vetch aphid, Megoura viciae.

    27 November 2018

    The cDNAs of two opsins (Megopsin1 and Megopsin2) from the vetch aphid, Megoura viciae, have been sequenced and encoded for gene products with 378 and 371 amino acid residues, respectively. Phylogenetic analysis reveals that Megopsin1 falls into the insect long-wavelength opsin group and Megopsin2 is a member of the insect UV-wavelength opsins. Both opsins share the key features of G-protein-coupled receptors and the specific motifs of photopigments. In situ hybridization demonstrated that the transcripts of Megopsin1 and Megopsin2 were expressed in the retinula cells of the compound eyes.

  • Thresholds for masking responses to light in three strains of retinally degenerate mice.

    27 November 2018

    Mutant mice with retinal degeneration (rd/rd) were given 1-h pulses of light of varying brightness at times of the night when they would normally be active. The mutant mice showed a significantly greater inhibition of locomotor activity to light (negative masking) than wildtype controls. Lack of impairment, or even enhancement of negative masking suggests that this response may depend on sparing in retinally degenerate mice of the same receptor type that mediates clock resetting, because synchronization of the circadian system is known to be unimpaired in these mutants. With very dim light pulses, mutants did not change their activity, but wildtypes actually became more active (positive masking). Positive and negative masking appear to depend on different sensory and central processes.

  • Neither functional rod photoreceptors nor rod or cone outer segments are required for the photic inhibition of pineal melatonin.

    27 November 2018

    Pineal melatonin production is rapidly suppressed by light. In mammals, the photoreceptors mediating this response are ocular; however, definitive information regarding their nature and precise location is absent. In an attempt to define these photoreceptors, we examined the sensitivity of pineal melatonin production to inhibition by controlled irradiance monochromatic green light (lambda max 509 nm) in C3H mice bearing either of two mutations affecting the retina: retinal degeneration (rd), a disruption of rod phototransduction, and retinal degeneration slow (rds), an ablation of photoreceptor outer segments. Diurnal profiles of pineal melatonin content were similar in both mutant genotypes and in wild-type mice; melatonin peaked between 3-5 h before lights on. All three genotypes exhibited irradiance dependent inhibition of pineal melatonin content; 2.6 x 10(-2) microwatts/cm2 509 nm light induced complete suppression in all three genotypes, whereas lower irradiances were ineffective in all cases. Bilateral enucleation abolished responses even to 6 microwatts/cm2 509 nm light. These results demonstrate that the process of irradiance detection for pineal melatonin inhibition is buffered against considerable loss of photoreceptive capacity and that neither rod photoreceptors nor rod or cone outer segments are required for mediating this response in mice.

  • Differential expression of interphotoreceptor retinoid-binding protein, opsin, cellular retinaldehyde-binding protein, and basic fibroblastic growth factor.

    27 November 2018

    The mRNA for rat interphotoreceptor retinoid-binding protein (IRBP) consists of 5.2 kb and 6.4 kb transcripts which are expressed early during retinal development. Here, we characterized rat IRBP cDNA and genomic clones, determined the mechanism generating the two transcripts and compared their expression to mRNAs for opsin, cellular retinaldehyde-binding protein (CRAlBP) and basic fibroblast growth factor (bFGF). We found that human and rat IRBPs have a high degree of sequence homology (86% amino acid identity over the fourth repeat). RNA-PCR studies and Northern blot analysis, showed that the 6.4 kb mRNA has a longer 3'-untranslated region (UTR) than the 5.2 kb message. Both IRBP transcripts, but not the mRNA for opsin are present in the neonatal and adult pineal. During development, the mRNAs for IRBP and opsin reach one-half of their maximal levels by P5 and P11, respectively. The ratio of the two IRBP mRNAs remains constant throughout life. In contrast, the ratio of the longest to the shortest opsin mRNA decreases between E19 and 1 year of age. Immunohistochemistry demonstrated a marked increase in the amount of IRBP in the interphotoreceptor matrix between P1 and P9 corresponding to the enhanced expression of this mRNA. Up-regulation of opsin mRNA expression during the second postnatal week corresponds to the emergence of the outer segments. The temporal expression of CRAlBP is similar to IRBP while bFGF is not expressed until after photoreceptor differentiation is complete. In summary, two 3'-transcription termination sites explain the difference in IRBP mRNA sizes. The different temporal and tissue specific patterns of IRBP and opsin expression suggest that separate mechanisms control the expression of these two genes. The expression patterns of IRBP and CRAlBP are consistent with the role of vitamin A as a morphogen and bFGF in neuronal maintenance.

  • Immunocytochemical markers revealing retinal and pineal but not hypothalamic photoreceptor systems in the Japanese quail.

    27 November 2018

    The retinal proteins opsin, alpha-transducin, S-antigen and interstitial retinol-binding protein (IRBP) are essential for the processes of vision. By use of immunocytochemistry we have employed antibodies directed against these "photoreceptor proteins" in an attempt to identify the photoreceptor systems (retina, pineal and deep brain) of the Japanese quail. Opsin immunostaining was identified within many outer (basal portion) and inner segments of retinal photoreceptor cells and limited numbers of photoreceptor perikarya. Opsin immunostaining was also demonstrated in limited numbers of pinealocytes with all parts of these cells being immunoreactive. These results differ from previous observations. In contrast to the results obtained with the antibody against opsin, S-antigen and alpha-transducin immunostaining was seen throughout the entire outer segments and many photoreceptor perikarya of the retina, in the pineal organ immunostaining was seen in numerous pinealocytes in all follicles. These results conform to previous findings in birds. In addition, IRBP has been demonstrated for the first time in the avian retina and pineal organ. These findings underline the structural and functional similarities between the retina and pineal organ and provide additional support for a photoreceptive role of the avian pineal. No specific staining was detected in any other region of the brain in the Japanese quail; the hypothalamic photoreceptors of birds remain unidentified.

  • Rod photopigment deficits in albinos are specific to mammals and arise during retinal development.

    27 November 2018

    Adult albino mammals have specific retinal defects, including reduced numbers of rod photoreceptors. To examine when this rod deficit arises and whether it exists in nonmammalian albinos, we have used absorbance spectrophotometry to measure photopigment levels in dark-adapted eyes taken from three groups of pigmented and albino animals: adult rodents (rats and mice), developing rats, and mature Xenopus frogs. Rhodopsin concentrations were consistently and significantly reduced in mammalian albinos compared to their wild-type counterparts from before the time of eye opening, but photopigment levels were similar in frogs of both pigmentation phenotypes. The results strongly suggest that deficits in the rod cell population arise early in development of the mammalian albino retina, but do not generalize to nonmammalian mutants lacking retinal melanin.

  • Transgenic ablation of rod photoreceptors alters the circadian phenotype of mice.

    27 November 2018

    The impact of photoreceptor loss on the circadian system was examined by utilizing a transgenic mouse model (rdta) in which rod photoreceptors were specifically ablated. These mice were able to phase-shift their circadian locomotor behaviour in response to light, but features of this circadian behaviour were markedly altered. The amplitude of circadian responses to light were approximately 2.5 greater, the circadian period (tau) was reduced (c. 20 min) and the total duration of activity (alpha) was increased (c. 50 min) when compared to wild type (+/+) and rd/rd mice (retinal degeneration, mice which also lack rod photoreceptors) of the same genetic background. The pattern of Fos expression in the suprachiasmatic nuclei (the site of the primary circadian clock in mammals) was indistinguishable between +/+ and rdta mice. However, Fos expression in the retina suggested that rod loss in rdta mice resulted in a functional reorganization of the retina and the constitutive activation of a population of retinal ganglion cells. Although it has been known for several years that the entraining photoreceptors of mammals are ocular, and that rod photoreceptors are not required for light regulation of the clock, these are the first data to show that features of the circadian phenotype (amplitude of the phase response curve, alpha, tau) can be influenced by photoreceptor ablation. These data support the hypothesis that the circadian phenotype of mammals is the product of an interaction between the suprachiasmatic nuclei and the retina. Thus, mammals which show an altered circadian behaviour can no longer be assumed to have defects associated only with specific clock genes; genes that affect photoreceptor survival may also modify circadian behaviour.

  • Seeing the light...in a new way.

    27 November 2018

    Research over the past decade has shown that the rods and cones are not the only photoreceptors of the eye. There also exists a population of directly light sensitive ganglion cells that act as brightness detectors and regulate a wide variety of different photosensory tasks, including the regulation of 24-h circadian clocks, synthesis of the hormone melatonin, pupil size and behaviour. These receptors may even help modulate our mood and sense of well-being.

  • Photoentrainment in mammals: a role for cryptochrome?

    27 November 2018

    There is growing evidence in support of the hypothesis that, in mammals, photoreceptive tasks are segregated into those associated with creating a detailed visual image of the environment and those involved in the photic regulation of temporal biology. The hypothesis that this segregation extends to the use of different photoreceptors remains unproven, but published reports from several mammalian species that circadian photoentrainment survives a degree of retinal degeneration sufficient to induce visual blindness suggest that this may be so. This has lead to speculation that mammals might employ a dedicated 'circadian photoreceptor' distinct from the rod and cone cells of the visual system. The location and nature of this putative circadian photoreceptor has become a matter of conjecture. The latest candidates to be put forward as potential circadian photopigments are the mammalian cryptochrome proteins (CRY1 and 2), putative vitamin-B2 based photopigments. To date, published experimental evidence falls short of a definitive demonstration that these proteins form the basis of circadian photoreception in mammals. Consequently, this review aims to assess their suitability for this task in light of what we know regarding the biology of the cyrptochromes and the nature of mammalian photoentrainment.

  • Melanopsin (Opn4) positive cells in the cat retina are randomly distributed across the ganglion cell layer.

    27 November 2018

    A rare type of rodent retinal ganglion cell expresses melanopsin (Opn4), the majority of which project to the suprachiasmatic nuclei. Many of these cells are directly light sensitive and appear to regulate the circadian system in the absence of rod and cone photoreceptors. However, the rodent retina contains no overt regions of specialization, and the different ganglion cell types are hard to distinguish. Consequently, attempts to distinguish the distribution of melanopsin ganglion cells in relation to regions of retinal specialization or subtype have proved problematic. Retinal cells with a common function tend to be regularly distributed. In this study, we isolate cat melanopsin and label melanopsin expressing cells using in situ hybridization. The labelled cells were all confined to the ganglion cell layer, their density was low, and their distribution was random. Melanopsin containing cells showed no clear center-to-periphery gradient in their distribution and were comprised of a relatively uniform cellular population.

  • NIHR LCRN Studies

    30 June 2016

    The Critical Care Research Group undertakes a number of studies that are adopted by the NIHR local research network portfolio.

  • HAVEN

    10 May 2016

    The HAVEN project is funded by the Health Innovation Challenge Fund, a joint venture supported by the Wellcome Trust and the Department of Health.

  • HAVEN

    10 May 2016

    The HAVEN project is funded by the Health Innovation Challenge Fund, a joint venture supported by the Wellcome Trust and the Department of Health.

  • OXVASC Study

    15 January 2013

  • Preventing a Stroke

    15 January 2013

  • Research results

    15 January 2013

  • Useful Links

    15 January 2013

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    15 January 2013

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    15 January 2013

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    15 January 2013

  • Oxford Vascular Study

    26 August 2016

    CPSD

    The Oxford Vascular Study (OxVasc) investigates vascular diseases (e.g. strokes, heart attacks) in patients registered with eight general practices in Oxfordshire. We run a rapid-access clinic for patients with suspected Transient Ischaemic Attacks (TIAs) or minor strokes.

  • OPTIMA

    26 August 2016

    CPSD

    The Oxford Project to Investigate Memory and Ageing (OPTIMA) started in 1988 and the last LEAD participants were seen in March 2015. We are no longer recruiting to any of the cohorts. However, we are currently creating the OPTIMA Legacy Resource from which data collected from the OPTIMA cohorts is available and samples are biobanked and available. Brain tissue is available as part of the Brains For Dementia Research (BDR) collection.

  • Models of Brain Decision Networks

    21 July 2014

    DCN

    Our group uses computer simulations and mathematical analyses to understand the information processing and activity dynamics of brain networks underlying decision making. We use these models to investigate how neural circuits work in the healthy state, how their dynamics deteriorate in neurological disorders, and how their dynamics and information processing may be best restored by treatments.

  • Anaesthesia Neuroimaging Research Group

    26 November 2018

    NDA

    Our group uses multimodal neuroimaging to understand the changes in the brain under anaesthesia and during altered states of consciousness.

  • Translational Molecular Neuroscience Group

    14 February 2018

    NDCN

    Drug discovery in neuroscience is very challenging but the need is greater than ever. Perhaps the most important factor for successfully developing an effective therapy, is the identification of human disease relevant drug targets. Our group aims to elucidate the pathophysiological basis of human neurological disorders from genetic molecular networks to complex neural systems using human genetics, human models and human tissue wherever possible.

  • Congenital Myasthenia Service

    15 January 2013

    DCN

    We provide a nationally commissioned specialised service for the diagnosis and management of children and adults in whom a congenital myasthenic syndrome is suspected.

  • Breathe Oxford

    13 May 2014

    NDA

  • Cognitive and Motivational Disorders

    6 July 2018

    DCN NDCN

    Our group studies changes in motivation, memory and decision-making that occur in neurological disease. We combine behavioural, neuroimaging, and pharmacological experiments to apply cognitive neuroscience to clinical problems.

  • Oxford University Global Surgery Group

    1 August 2018

    The Oxford University Global Surgery Group brings together Medical Sciences Division clinicians in surgery, anaesthesia, obstetrics and gynaecology with an interest in global surgical issues.

  • Oxford Epilepsy Research Group

    2 April 2014

    DCN

    We are a forward-looking dynamic group interested in all aspects of clinical and experimental epileptology with an emphasis on clinically relevant research. The Group draws together all relevant disciplines across Oxford University Hospitals and the University of Oxford.