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  • 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.

  • Opsin-like immunoreactivity in the circadian pacemaker neurons and photoreceptors of the eye of the opisthobranch mollusc Bulla gouldiana.

    27 November 2018

    Circadian pacemaker cells in the eyes of the opisthobranch mollusc Bulla gouldiana generate a near 24-h rhythm in the frequency of optic nerve impulses. Previous electrophysiological studies suggest that these basal retinal neurons are intrinsically photosensitive and transduce light signals that shift the phase of their pacemaker mechanism. To test whether the pacemaker neurons contain opsin-like proteins, several polyclonal antibodies that recognize opsins of vertebrate photoreceptors have been tested on histological sections of the eye and on the neurons in primary cell culture. The antibodies label both the pacemaker cells and the large distal photoreceptors that surround the lens. Immunoblot analyses of the proteins of the eye have identified a single band at 62+/-4 kDa. These opsin antibodies may label the photopigment used in the entrainment of the circadian pacemaker.

  • The regulation of circadian clocks by light in fruitflies and mice.

    27 November 2018

    A circadian clock has no survival value unless biological time is adjusted (entrained) to local time and, for most organisms, the profound changes in the light environment provide the local time signal (zeitgeber). Over 24 h, the amount of light, its spectral composition and its direction change in a systematic way. In theory, all of these features could be used for entrainment, but each would be subject to considerable variation or 'noise'. Despite this high degree of environmental noise, entrained organisms show remarkable precision in their daily activities. Thus, the photosensory task of entrainment is likely to be very complex, but fundamentally similar for all organisms. To test this hypothesis we compare the photoreceptors that mediate entrainment in both flies and mice, and assess their degree of convergence. Although superficially different, both organisms use specialized (employing novel photopigments) and complex (using multiple photopigments) photoreceptor mechanisms. We conclude that this multiplicity of photic inputs, in highly divergent organisms, must relate to the complex sensory task of using light as a zeitgeber.

  • Circadian rhythms: Something to cry about?

    27 November 2018

    Recent studies suggest that a class of proteins known as cryptochromes have an evolutionarily conserved role in the entrainment of circadian rhythms to the night-day cycle. While the evidence reported is intriguing, the notion that cryptochromes have the same role in all species requires further investigation.

  • A novel rod-like opsin isolated from the extra-retinal photoreceptors of teleost fish.

    27 November 2018

    We have isolated a novel opsin from the pineal complex of Atlantic salmon (Salmo salar) and from the brain of the puffer fish (Fugu rubripes). These extra-retinal opsins share approximately 74% identity at the nucleotide and amino acid level with rod-opsins from the retina of these species. By PCR, we have determined that the novel rod-like opsin is not expressed in the salmon retina, and the retinal rod-opsin is not expressed in the salmon pineal. Phylogenetic analysis suggests that the rod-like opsins arose from a gene duplication event approximately 205 million years ago, a time of considerable adaptive radiation of the bony fish. In view of the large differences in the coding sequences of the pineal/brain rod-like opsins, their extra-retinal sites of expression, and phylogenetic position we have termed these novel opsins 'extra-retinal rod-like opsins' (ERrod-like opsins). We speculate that the differences between retinal rod-opsins and ERrod-like opsins have arisen from their differing photosensory roles and/or genetic drift after the gene duplication event in the Triassic.

  • The persistence of cone photoreceptors within the dorsal retina of aged retinally degenerate mice (rd/rd): implications for circadian organization.

    27 November 2018

    Rod- and cone-opsin specific antibodies were used in an attempt to immunolabel remaining photoreceptor cells in the mutant rd (retinal degeneration) mouse retina. We identified a region-specific distribution in the pattern of photoreceptor degeneration, with the dorsal retina showing markedly less photoreceptor degeneration than the ventral retina. All rod and cone immunoreactive cells disappeared in the ventral retina by 100-120 days of age. By contrast, both cone and a small number of rod immunopositive cells were identified in the dorsal retina at this time. By 200 days all rod immunoreactive cells had disappeared. At 360 days numerous cone immunoreactive cells remained within a restricted region of the dorsal retina. As rd mice show unattenuated circadian responses to light, these remaining photoreceptor cells within the dorsal retina become candidates for the regulation of circadian physiology by light.

  • 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

  • ABCD Tool

    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.