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  • Interstitial retinol-binding protein and cellular retinal-binding protein in the mammalian pineal.

    27 November 2018

    Antibodies against bovine interstitial retinol-binding protein (IRBP) and cellular retinal-binding protein (CRA1BP) were used in immunochemical and immunocytochemical studies of the pineal glands of cattle, hamsters and rats (RCS and RCS-rdy+). On immunoblots, IRBP (Mr 144,000) was identified in cattle, hamster and rat pineal extracts. The abundance of IRBP in bovine pineals was 33 +/- 6 ng.mg-1 (mean +/- SD, n = 12) soluble protein. RCS (Royal College of Surgeons) rat pineals gave a strong IRBP reaction on immunoblots, even when virtually no IRBP could be found in the eye due to photoreceptor degeneration. In the hamster retina IRBP immunostaining was distributed throughout the entire interphotoreceptor matrix and the outer segment layer. The pineal also showed strong IRBP-like immunostaining scattered uniformly throughout the gland. Other hamster brain regions showed no specific immunostaining; however, an immunoreactive protein with the same Mr as IRBP was detected on Western blots of bovine cerebral cortex, spinal cord and brainstem soluble proteins. Immunoreactive proteins at lower Mr were also detected in these tissues. CRA1BP immunoreactivity (Mr about 32,000) was observed in immunoblots of bovine, hamster and rat pineal proteins. These findings suggest that some mammalian pinealocytes are related to the retinal cells that contain CRA1BP (i.e. pigment epithelium, Muller cells) while others are related to the photoreceptors, which synthesize IRBP.

  • Photoperiodism in birds.

    27 November 2018

    Birds show a circadian rhythm in melatonin secretion and, as expected, the pattern of output changes with photoperiod. Somewhat surprisingly then, in view of the mechanisms in mammals, birds do not seem to use this seasonal message in the photoperiodic control of reproduction. Some further experiments are needed, however, because in birds the pineal gland is not the only source of melatonin. Another difference from mammals is that birds detect the photoperiodic light not with the retina but by brain photoreceptors, which probably lie in the hypothalamus. An action spectrum for these receptors has now been obtained for the quail and this shows a peak absorption at 492 nm, suggesting that the photoreceptor is rhodopsin-based. The sensitivity of the brain receptors to 500 nm light was calculated at 2 X 10(4) photons mm-2s-1. For light to induce the photoperiodic response it must be interpreted by the bird's clock as a long day. This happens if the light falls 12-20 h after dawn and coincides with a rhythm of photosensitivity. The subsequent neuroendocrine response to the light signal is both precise and relatively long-term. A single 4 h light pulse initiates a wave of gonadotropin secretion lasting for 10 days. The light stimulus can be replaced by a brief (2 min) daily electrical stimulus given to the hypothalamus 10-12 h after dawn. Over the next few years it should be possible to disentangle further the neural processes involved.

  • Opsin-like immunoreaction in the retinae and pineal organs of four mammalian species.

    27 November 2018

    Opsin-like immunoreactivity was observed in the retinae and pineal organs of the mouse, rat and guinea pig, and the pineal organ of the cat. In the retina the immunoreaction was restricted to photoreceptor cells, which displayed immunostaining in their perikarya and outer and inner segments. Distinct pinealocytes endowed with characteristic processes were labelled in the pineal organs of the mouse and cat. However, in the cat the number of immunoreactive pinealocytes was very limited. In the pineal organs of the rat and guinea pig immunoreaction was very weak and diffuse. No immunoreaction was observed when the antibody was preabsorbed with purified bovine (rhod)opsin. These findings are in accord with the results of previous studies indicating molecular similarities between retinal photoreceptors and pinealocytes in mammals.

  • A green cone-like pigment in the 'blind' mole-rat Spalax ehrenbergi: functional expression and photochemical characterization.

    27 November 2018

    The degenerate subcutaneous eye of the blind mole rat belonging to the Spalax ehrenbergi superspecies has been shown to contain a long wavelength sensitive (LWS) cone pigment. Baculovirus expression of this LWS pigment and subsequent IMAC purification yields a photosensitive protein, that according to absorbance maximum (530 +/- 2 nm), kinetics of late phototransitions, and transducin activation, has all characteristics of a functional green cone pigment. The absorbance spectrum of the Spalax pigment is strongly red-shifted relative to the very homologous mouse, rabbit and rat green cone pigments (508-510 nm). Also in contrast to the rodent pigments, the Spalax pigment exhibits anion-dependent spectral properties, displaying a 12 nm blue-shift upon substitution of chloride ions by nitrate ions. Finally, the slow part of the photocascade deviates in some aspects from that of sighted mammals. The possible relevance of these findings for the evolutionary adaptation of Spalax to a subterranean ecotope is discussed.

  • Placing ocular mutants into a functional context: a chronobiological approach.

    27 November 2018

    The behavior of mammals is characterized by a 24-h cycle of rest and activity which is a fundamental adaption to the solar cycle of light and darkness. The pacemaker of this circadian clock is localized in the ventral part of the hypothalamus, the so-called suprachiasmatic nuclei (SCN), and is entrained by light signals mediated by the eye. The eye is directly connected via the retinohypothalamic tract (RHT) to the SCN. Light that reaches the retina elicits glutamate release at the synaptic terminals of the RHT and influences the neurons in the SCN in a manner that alters the behavioral state of the animal. A light pulse that reaches the retina at the beginning of the night elicits a delay of the clock phase, whereas a light pulse that reaches the retina at the end of the dark period leads to an advance of the clock phase. This advance or delay can be quantified by measuring the change in onset of wheel-running activity. Such measurements have, and continue to provide, a remarkably powerful assay of how light is detected and transduced to regulate circadian rhythms. The methods used for such measurements in mice are described in the following article.

  • Vitamin A2-based visual pigments in fully terrestrial vertebrates.

    27 November 2018

    As part of a broad study of the ocular and extraocular photoreceptors of reptiles, we have used high performance liquid chromatography (HPLC) to identify the retinoids present in whole eye extracts of the arboreal lizard Anolis carolinensis and the non-arboreal ruin lizard Podarcis sicula. Unexpectedly, only vitamin A2-derived chromophore was detected in Anolis, while a mixture of vitamin A1- and vitamin A2-derived chromophores was detected in Podarcis. These are the first examples of fully terrestrial vertebrates using vitamin A2-derived chromophore for visual pigment generation. Furthermore, microspectrophotometric (MSP) data for Anolis show a class of photoreceptor having a visual pigment with maximum absorbance at about 625 nm, some 40 nm further into the red than has been found in any terrestrial vertebrate examined to date.

  • Immunohistochemical demonstration of marked changes in the LHRH system of photosensitive and photorefractory European starlings (Sturnus vulgaris).

    27 November 2018

    Immunocytochemistry was used to determine the effects of photoperiod on the LHRH neurosecretory system in the brain of male European starlings. In this species, as in other birds, reproduction is triggered by long daylengths but continued exposure leads to photorefractoriness and to a complete shut-down of the reproductive system. These effects are thought to be mediated through changes in the secretion of LHRH. In starlings exposed to a photoperiod of 11 h light:13 h darkness (11L:13D) and with fully developed testes there was strong immunostaining of both LHRH perikarya (n = 522 +/- 43 S.E.M.) and fibres. Photosensitive short-day (8L:16D) starlings with undeveloped testes had an almost identical distribution of strongly immunoreactive perikarya (n = 523 +/- 62) but there were fewer fibres. In the median eminence, fibre number was reduced significantly (P less than 0.01) by some 30%. In long-day (18L:6D) photorefractory starlings with fully regressed testes there was an even more obvious change in the LHRH system. Perikarya were only weakly immunoreactive and there was a significant (P less than 0.01) reduction in mean diameter from 10 to 6.5 micron. In addition, there was a significant (P less than 0.05) reduction in cell number (312 +/- 62), although this may well result from the fact that some weakly stained cells fell below the limits of resolution and could not be counted. LHRH fibres disappeared almost entirely from the median eminence, and were not visible elsewhere in the brain. The higher neural pathways regulating photorefractoriness induced by long days are unknown but clearly both production of LHRH in the perikarya and release/storage of LHRH in the terminals is being profoundly modified.

  • Oxford Persisting Post-Operative Pain Study

    15 January 2013

    NDA

    The aim of OxPPOPS is to identify the incidence and predictive factors for the development of persistent pain after surgery. We have just finished recruiting a cohort of patients having planned caesarean sections.

  • Cognitive Neurology Research Group

    4 March 2013

    DCN

    We want to understand how - and why - brain function can be disturbed to lead to inattention, poor memory and abnormal decision making. Our aim is to develop new treatments for these conditions across a range of neurological disorders.

  • Neuroanatomy and Cognition Group

    15 January 2013

    DCN

    Our projects study cognitive/psychiatric disorders and comparative evolutionary neuroscience. We are interested in the relationship between brain structure and function in disease, development and aging - particularly related to language and social cognition.

  • Epilepsy Imaging Research Group

    14 February 2013

    FMRIB

    Combining state-of-the-art brain imaging methods, we aim to understand how functional networks in the brain respond and adapt to epilepsy and epilepsy-associated lesions.

  • Clinical Ophthalmology Research Group

    15 January 2013

    NLO

    We are developing gene therapy and stem cell treatments for retinal diseases

  • Retinal Neurobiology and Optogenetics Group

    15 January 2013

    NLO

    Our research focuses on light dependent signalling in the retina and brain, including visual and non-visual light detection. We are also examining novel opsin photopigments and exploring their applications to optogenetics.

  • Retinal Degeneration and Gene Identification

    15 January 2013

    NLO

    Our work involves the identification and characterisation of genes that play a role in the retina, including both visual and non-image forming tasks such as the detection of light for the entrainment of the circadian system.

  • Molecular Neurodegeneration Research Group

    11 March 2014

    DCN

    Our aim is to understand fundamental biological processes that could inform the development of targeted therapies and innovative biomarkers in neurodegenerative and neurogenetic disorders.