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  • An immunocytochemical study of encephalic photoreceptors in three species of lamprey.

    27 November 2018

    The extraretinal and extrapineal photoreceptors of three species of adult lamprey, sea lamprey (Petromyzon marinus), river lamprey (Lampetra fluviatilis) and silver lamprey (Ichthyomyzon unicuspis) were studied using antibodies raised against photoreceptor rod and cone opsins, alpha-transducin and arrestin. In all three species cells in the pineal organ (P), parapineal organ (PP), nucleus preopticus (T5), nucleus commissurae postopticae (D8), nucleus ventralis hypothalami (D10) and nucleus dorsalis hypothalami (D11) were labelled by one or more of the anti-opsin antibodies. In addition, anti-arrestin antibodies labelled cells within the D8 and anti-alpha-transducin antibodies labelled cells within the pineal complex and hypothalamus (primarily D8 and/or D10). A more variable and species dependent pattern of opsin, arrestin and alpha-transducin labelling was observed within the nucleus commissurae postinfundibularis (D12) in an area comprising the nucleus dorsalis thalami pars subhabenularis (D4sh) and nucleus dorsalis thalami pars caudalis/nucleus commissurae posterioris (D4c/M1), and in the proximity of the second Müller cells in the ventrocaudal diencephalon (2.MZ/M6). The majority of the neurons labelled within the pineal and parapineal organs and hypothalamus were periventricular with clear cerebrospinal fluid contacts (CSF-contacting neurons). Labelled neurons in the epithalamic (D4sh and D4c/M1) and caudal diencephalon (2.MZ/M6) had no obvious ventricular contacts. We speculate that the "primitive" vertebrate brain of lampreys represents an ancestral condition in which different populations of encephalic photoreceptors are associated with different behavioural and physiological responses. Image-forming vision needs an eye, but irradiance detection does not require a specialised organ. Rather the photoreceptors could be closely associated with their effector systems within the brain.

  • The spatio-temporal pattern of photoreceptor degeneration in the aged rd/rd mouse retina.

    27 November 2018

    Photoreceptor degeneration in the retina of the rd/rd (retinal degeneration) mice has been studied using immunocytochemistry with antisera against cone- and rod-opsin. The rd/rd mice exhibited different regional specific rates of degeneration for rods and cones. As early as postnatal day 25, cells labelled with the rod-opsin and cone-opsin antisera disappeared preferently from the central retina. Whereas in the inferior half of the retina, degeneration subsequently proceeded towards the periphery, this did not occur in the dorsal hemisphere. By the age of 100 days, many cells immunoreactive for the cone-opsin antiserum and a few cells immunoreactive for the rod-opsin antiserum were located in an area of the dorsal retina. The ventral retina lacked labelled elements at this age. Finally, rd/rd mice at one year or 600 days of age contained a similar number of cone-opsin immunopositive cells (approximately 2000-2800 cells), occupying almost the same area in the retina as that found at 100 days of age. A photoreceptor candidate for the entrainment of non-visual photoreception probably remains in the cone population in aged rd/rd mice.

  • The photoreceptive capacity of the developing pineal gland and eye of the golden hamster (Mesocricetus auratus).

    27 November 2018

    Anatomical and physiological studies have suggested that the pineal gland of neonatal mammals has a photoreceptive capacity. Using the golden hamster (Mesocricetus auratus) as our model, we applied biochemical approaches to look for a functional photopigment within the pineal during early development. Immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) were used to localize and quantify opsin, and high-performance liquid chromatography (HPLC) to identify photopigment chromophore (11-cis and all-trans retinaldehyde) in the developing eye and pineal. For HPLC analysis, retinaldehydes were converted to their corresponding retinoid oximes. Eluted retinoids were identified by comparison with standard vitamin A1 retinoid oxime isomers on the basis of relative elution sequence and characteristic absorbance spectra. Both immunocytochemistry and ELISA suggested an increase in the opsin content of the pineal during the first week of life. In the eye, 11-cis retinaldehyde was first detected between days 3 and 5 after birth. In three separate extractions, and using a considerable excess of pineal tissue, we failed to identify chromophore within the pineal during the first week of postnatal development. The appearance of 11-cis retinaldehyde within the eye between postnatal days 3-5 is consistent with the hypothesis that retinol isomerase activity is coordinated with outer segment development. The failure to identify chromophore within the neonatal pineal suggests that this gland lacks a functional opsin-based photopigment. These data contradict physiological evidence suggesting that the neonatal pineal of mammals contains photoreceptors.

  • Analysis of immunohistochemical label of Fos protein in the suprachiasmatic nucleus: comparison of different methods of quantification.

    27 November 2018

    The induction of the proto-oncogene c-fos, and its phosphoprotein product Fos, has been extensively used to study the effects of light on the circadian pacemaker in the suprachiasmatic nucleus (SCN). Experimental approaches to the quantification of Fos induction have mainly been based on immunohistochemistry and subsequent measure of Fos immunoreactivity (IR) in sections of the SCN. In this study, the authors compare several methods of quantification using optical density image analysis or counts of Fos-IR labeled cells. To assess whether optical density measures using image analysis reflect the amount of Fos in brain tissue, the authors developed standards of known concentrations of Fos protein in an agar matrix. The agar standards were sectioned and treated simultaneously with sections of the SCN from animals exposed to different levels of irradiance. Optical density was found to be proportional to the quantity of Fos in the sections, indicating that this measure accurately reflects relative levels of Fos protein induction. Quantification by optical density analysis allows an objective measure in which the various parameters, conditions of illumination, and threshold can be maintained constant throughout the analysis. Counting cells by visual observation is more subjective because threshold values cannot be precisely defined and can vary according to the observer, illumination, degree of label, and other factors. In addition, cell counts involving direct visual observation, automated cell counts, or stereological methods do not take into account the difference in the density of label between cells, thus giving equal weight to lightly or densely stained cells. These measures are more or less weakly correlated with measures of optical density and thus do not accurately reflect the amount of bound Fos protein in the tissue sections. In contrast, labeled surface area as measured by image analysis shows a linear relationship with optical density. The main outcome of this study is that computer-assisted image analysis provides an accurate and rapid method to determine the relative amount of Fos protein in the SCN and the effects of light on intracellular signaling mechanisms involved in the circadian clock.

  • Visual pigments and oil droplets in diurnal lizards: a comparative study of Caribbean anoles.

    27 November 2018

    We report microspectrophotometric (MSP) data for the visual pigments and oil droplets of 17 species of Caribbean anoline lizard known to live in differing photic habitats and having distinctly different dewlap colors. The outgroup Polychrus marmoratus was also examined to gain insight into the ancestral condition. Except for Anolis carolinensis, which is known to use vitamin A(2) as its visual pigment chromophore, all anoline species examined possessed at least four vitamin-A(1)-based visual pigments with maximum absorbance (lambda(max)) at 564, 495, 455 and 365 nm. To the previously reported visual pigments for A. carolinensis we add an ultraviolet-sensitive one with lambda(max) at 365 nm. Five common classes of oil droplet were measured, named according to apparent color and associated with specific cone classes - yellow and green in long-wavelength-sensitive (LWS) cones, green only in medium-wavelength-sensitive (MWS) cones and colorless in short-wavelength-sensitive (SWS) and ultraviolet-sensitive (UVS) cones. MSP data showed that the colorless droplet in the SWS cone had significant absorption between 350 and 400 nm, while the colorless droplet in the UVS cone did not. The pattern for Polychrus marmoratus was identical to that for the anoles except for the presence of a previously undescribed visual cell with a rod-like outer segment, a visual pigment with a lambda(max) of 497 nm and a colorless oil droplet like that in the UVS cones. These findings suggest that anoline visual pigments, as far as they determine visual system spectral sensitivity, are not necessarily adapted to the photic environment or to the color of significant visual targets (e.g. dewlaps).

  • 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.

  • OxPPOPS Hernia

    15 January 2013

  • OxPPOPS Breast Cancer

    15 January 2013

  • SILENCE

    13 April 2016

    The Sleep in the Intensive Care Unit: Lowering Elements of Noise in the Critical Care Environment (SILENCE) research programme is funded by a feasibility study grant awarded by the NIHR Research for Patient Benefit scheme, and is sponsored by the University of Oxford. Final results are expected late 2018.

  • SILENCE

    13 April 2016

  • SILENCE

    13 April 2016

    The SILENCE programme is a series of linked research projects. Updates on progress will be posted here.

  • SILENCE

    13 April 2016

  • SILENCE

    21 April 2017

    Contact details for the SILENCE research programme

  • Non-contact vital signs monitoring

    20 September 2016

    The non-contact vital signs monitoring (NVSM) study is a joint collaboration between the Department of Engineering, the Nuffield Department of Clinical Neurosciences, and Oxehealth Ltd.

  • NVSM

    25 October 2016

    Significant project milestones will be displayed here

  • NVSM

    20 September 2016

    Contact details for the non-contact vital signs monitoring research team

  • Retinal Cell Biology and Degeneration

    15 January 2013

    NLO

    The discovery of a novel inner retinal photoreceptor cell, driving non-visual functions, has had a significant impact on the retinal neuroscience field. My research focuses on understanding the physiology and function of these photosensitive retinal ganglion cells.

  • Oxford Smart Specs Research Group

    13 June 2014

    DCN NLO

    We are developing a set of 'smart' electronic glasses (‘smart specs’) to enhance sight for the visually impaired.

  • Vision Group

    13 February 2014

    FMRIB NLO

    We use brain imaging techniques to investigate the human visual system, both in its normal state and in disease and disorder.

  • FMRIB P.A.I.N Group

    19 January 2015

    FMRIB NDA

    The Pain Analgesia/Anaesthesia Imaging Neuroscience group is a multidisciplinary team of scientists and clinicians. We research how the human central nervous system generates and modulates painful experiences in acute and chronic settings.

  • NeuroMetrology Lab

    13 April 2016

    DCN NDCN

    Our objective is to develop ways of accurately measuring neurological disorders such as Parkinson's disease.

  • Glioma Neurosurgery Research Group

    11 February 2016

    FMRIB NDCN

    Our research aims to understand the characteristics of individual brain tumours, combining cutting edge brain imaging, molecular neuropathology and neurosurgical techniques to develop personalized approaches for first-line cancer surgery.

  • Parkinson’s Neuropathology Group

    23 February 2016

    DCN

    We study why certain neuronal populations are vulnerable to neurodegeneration in Parkinson’s disease brain and whether pathological changes seen in the peripheral tissues mirror or precede what is ultimately seen in the brain, and how this can be used to develop biomarkers.

  • Neuro-Endocrinology Research Group

    11 February 2016

    DCN

    This cross-disciplinary research group links neuropathology, endocrinology and molecular genetics to explore how the genetics and epigenetics of pituitary tumours influences clinical characteristics and to identify targets for therapeutic intervention.

  • Large Artery Disease

    26 August 2016

    CPSD

    CPSD runs several research studies looking into the causes, investigation, and management of large artery atherosclerosis, carotid stenosis, vertebral artery disease and intracranial atherosclerosis.