Hisako Ikeda

Tumour necrosis factor causes an increase in axonal transport of protein and demyelination in the mouse optic nerve

Abstract An increase in fast axonal transport of protein by the optic nerve was found in mice following a single combined injection of human recombinant tumour necrosis factor alpha (rTNF) and [3H]proline into the vitreous chamber. Demyelination was observed in optic nerve fibres arising from the eyes of mice which received a single rTNF injection. No such changes were detected when heat-inactivated rTNF was injected with the label. The effects of intravitreal injection of rTNF on the pathophysiology of mouse optic nerve resembled those found in mice infected with Semliki Forest virus (SFV), an animal model of multiple sclerosis. We suggest that TNF could mediate at lease some of the pathophysiological changes found in SFV-infected mice and may provide a clue concerning the disease mechanism in multiple sclerosis.

Anatomical, electrophysiological and pigmentary aspects of vision in the bush baby: An interpretative study

Abstract An attempt is made to interpret the spectral sensitivity of the dark-adapted bush baby ( Galago crassicaudatus agisymbanus , Coquerel) as a function of the light-absorbing properties of its visual pigment, and the reflectivity and fluorescence of its golden-coloured tapetum. The following observations and measurements have been made: 1. The retina is typically nocturnal. 2. The fine structure of the tapetum is described. 3. The spectral sensitivity curve between 420 and 600 nm has been determined on nine animals by an electrophysiological method. 4. The lens absorption is maximal at 385 nm (density = 0.9), but at 420 nm has a density of 0.1 and a negligible absorption beyond 520 nm. 5. The visual pigment is a substantially homogeneous retinene 1 -based chromoprotein of γ max = 501 nm . The “nominal” retinal density of the pigment is 0.16, and its effective density in the photoreceptors is 0.4. 6. The relative reflectance of the tapetum and the absorptive properties of the tapetal pigment have been measured. The pigment is a derivative of isoalloxazine (probably riboflavin) and exists in situ in the form of crystal plates. Within the framework of certain assumptions it is concluded that tapetal fluorescence does contribute to the visual sensitivity of the bush baby, thus confirming the prediction of Pirie (1959).

The spectral sensitivity of the pigeon (Columba livia)

Abstract The pigeons retinal function has been studied by electroretinography. The duplex nature and the cone-predominancy of the retina have been demonstrated by the ERG waveform, by the effects of stimulus intensity, by the position of the retina stimulated, and by darkadaptation. The scotopic spectral sensitivity was determined with small b-waves evoked by a stimulus inclined at 30° to the optical axis in fully dark-adapted eyes. The scotopic spectral sensitivity curve has its maximum at 502 mμ and is in close agreement with the absorption spectrum of the pigeons rod pigment. The sensitivity curves obtained from the ERG evoked by the light directed along the optical axis of the retina did not fit the rod pigment curve. Furthermore, a change in the spectral distribution of the sensitivity from the scotopic to photopic (the Purkinje shift) was observed when the response criterion value for determining the sensitivity was changed from a scotopic b-wave range to photopic b-wave range. The photopic sensitivity was determined by 40 c/s flicker ERG elicited by axial stimuli. The sensitivity curve was in fair agreement with the absorption spectrum of the pigeons cone pigment ( λ max = 544 mμ ). The effect of the oil droplets and the discrepancies between the photopic sensitivity curve ( λ max = 547 mμ ) and the photopic dominator curve ( λ max = 580 mμ ) otbained by the earlier workers are discussed. Another spectral sensitivity curve having its maximum at 605 mμ was obtained after selective adaptation to 547 mμ light. This suggests the possibility of a third pigment in the pigeon retina. Two narrow-bandwidth spectral sensitivity curves that were in good agreement with the green and red modulators reported in the ganglion cell spike of the pigeon by Donner were found. One, which corresponded to Donners green modulator, was obtained with high amplitude b-waves evoked axially. The other, which corresponded to Donners red modulator, was obtained with the ERG off-response. This indicates that the ERG of the pigeon shares the spectral properties of the ganglion cells.

New components of the mammalian receptor potential and their relation to visual photochemistry

Abstract The photoreversal potential, associated with the photoregeneration of rhodopsin, resists cooling but disappears when the stimulus flash has brought equilibrium between rhodopsin and its bleached products. In contrast, the positive portion of the ERP (which is the only portion present below 5°C) increases in amplitude if the stimuli photoregenerate rhodopsin. and is present at photochemical equilibrium. Both the positive and negative portions of the ERP are similarly affected by photoregeneration. In the cold eye, where rhodopsin is bleached to metarhodopsin I, the photoreversal is still present. The isolated mammalian pigment epithelium and choroid produces a rapid corneo-negative potential superficially similar to the photoreversal potential, but which is photostable. This potential is much larger in pigmented eyes and probably requires the presence of melanin for its production. It does not resist cooling, and disappears, revealing a positive component. The ERP is shown to originate in an irreversible thermal process later than the primary photoexcitation. It is suggested that the photoreversal potential is the electrical correlate of the formation of rhodopsin from excited photoproducts. Certain differences between the positive ERP in dark- and light-adaptation suggest that this potential contains an additional component, analogous to the photoreversal potential. associated with net bleaching (photolysis).

Effects of hereditary degeneration of the retina on the early receptor potential and the corneo-fundal potential of the rat eye

(1) The base level of the corneo-fundal potential in normal rats matures by 60 days. (2) The light induced changes in potential mature by 30 days. (3) There is no correlation between the potential changes and rhodopsin synthesis. (4) In dystrophic rats the base level of the corneo-fundal potential is normal till 20 days (when retinal degeneration begins), but then stops growing. (5) at 60 days (when the pigment epithelium degenerates) it falls abruptly. (6) The light induced changes are supernormal before 18 days, but decline to zero by 35 days. (7) The early receptor potential (ERP) of normal rats matures by 25 days. (8) In dystrophic rats the ERP is supernormal before the 20th day, but then declines. (9) The amplitude changes indicate that the ERP is only developed by normally organized outer limbs. (10) In dystrophic animals with supernormal ERPs the ERG is already depressed, indicating different sites of origin for ERP, and a- and b-waves.

Early abnormalities of retinal dopamine pathways in rats with hereditary retinal dystrophy

AbstractThe dopaminergic pathway that affects rod-driven horizontal cells has been studied in the Royal College of Surgeons (RCS) rat during the period preceding photoreceptor degeneration (postnatal day 17–24). The experiments were performed by intracellular recording from single horizontal cells in vitro. Horizontal cells from the recessive control animals (postnatal day 17–24) were depolarized by dopamine (10µM) and hyperpolarized by the D1 antagonist SCH 23 390 (10µM). In contrast, cells from age-matched dystrophic retinas, though depolarized by dopamine, were unaffected by SCH 23390 (10–100µM), suggesting a significant reduction in the level of endogenous dopamine release. Histologic examination for catecholaminergic neurons revealed no differences in either the cell number or anatomy between the retinas of the control and dystrophic animals. Furthermore, perfusion of the control retinas with melatonin (500 nM–1µM) yielded responses characteristic of the dystrophic type. In the period preceding degeneration, the RCS retina thus displays a discrete abnormality in dopaminergic pathways, such that there is a gross reduction in endogenous dopamine release below that required to activate D1 receptors. Since melatonin levels have been shown to be high in these retinas, we propose that abnormalities in the dopamine-melatonin systems give rise to an electrophysiologic deficit in the postphotoreceptoral retina of the RCS rat. Abbreviations: DA — dopamine, RCS — Royal College of Surgeons.

Effects of light-adaptation on the early receptor potential

Abstract In the dark-adapted eyes of albino rats, the amplitude of the early receptor potential (ERP) decreases with successive flashes, but does not disappear. Instead it reaches an equilibrium level, which is higher in dead eyes, and depends on the intensity of the short wave component in the stimulus flash. After equilibrium to white light has been reached, insertion of a filter, which absorbs blue wavelengths but which only slightly reduces the effectiveness of the flash in evoking the ERP, causes a progressive decline to a new equilibrium. When the filter is removed, the responses progressively increase once again. The latter effect is best seen in the dead eye, light-adapted by short exposures to tungsten light. Parallel extractions of dark- and light-adapted retinae show that the ERP amplitude is related to the quantity of rhodopsin in the retinae. The difference spectra of solutions from light-adapted eyes indicates that they contain isorhodopsin. It is concluded that the test flashes used in evoking the ERP cause photoregeneration of pigment, thus preventing complete bleaching and disappearance of the ERP. This in turn implies that in the eye metarhodopsin is relatively stable. The appearance of a new very rapid negative potential is associated with photoregeneration.

Electrophysiological properties of neurones following mild and acute retinal ischaemia

Early electrophysiological changes following acute retinal ischaemia were studied by recording single or multiunit retinal ganglion cells and the electroretinogram (ERG) in barbiturate anaesthetized cats. Retinal ischaemia was initiated photochemically by platelet aggregation in retinal vessels which had been irradiated with monochromatic green light following an intravenous injection of Rose Bengal dye. No physiologically active ganglion cells were found within, or close to, the irradiated sites with chorioretinal oedema. On the other hand, in the areas 5-20 degrees away from the irradiation sites, ganglion cells had abnormally raised spontaneous (background) firing which obscured visually driven firing. The retinal areas where no physiologically active ganglion cells were found showed histopathological changes which are similar to those described for glutamate-induced retinal damage. Retinal areas where depolarized retinal ganglion cells were located, however, showed only minor vacuolation of the ganglion cell fibre layer. Early global electrophysiological changes following photochemically induced retinal vascular lesion were consistent with those predicted from the findings in the single cell study. Vascular lesions produced with high irradiation energy (10-30 J), which promote extensive chorioretinal oedema, resulted in gradual loss of visually responsive ganglion cells. Lesions produced by low-energy irradiation (2 J), causing slight narrowing of the blood columns in the vessels, on the other hand, resulted in significant increases in the amplitude and the implicit time of the ERG b-wave and the background firing of multiunit retinal ganglion cells. Electrophysiological changes associated with mild retinal ischaemia are analogous to physiological effects associated with exogenous glutamate or blockade of glutamate uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-NMDA type excitatory amino acid receptors mediate rod input to horizontal cells in the isolated rat retina

The actions of excitatory amino acid agonists and antagonists on rod driven horizontal cells were studied in the isolated retina of the rat. Horizontal cells were depolarised by L-glutamate, kainate and quisqualate but not by N-methyl-D-aspartate (NMDA). The broad band excitatory amino acid antagonist, kynurenate and the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), hyperpolarised horizontal cells, blocking the light responses and also the effects of agonists. In contrast, the competitive NMDA antagonists, 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) and 2-amino-5-phosphono-pentanoate (AP5) were without effect. Thus, rat horizontal cells possess excitatory amino acid receptors of the non-NMDA type and these mediate their rod driven inputs.

Diurnal variations in the electroretinographic c-wave and retinal melatonin content in rats with inherited retinal dystrophy

The inability of retinal pigment epithelium to phagocytose shed photoreceptor disks is a cause of retinal degeneration in the Royal College of Surgeons rat; retinal pigment epithelial phagocytosis and disk shedding are regulated by the diurnal rhythm of retinal melatonin level. The diurnal rhythms of the electroretinogram (particularly that of the retinal pigment epithelial potential, the electroretinographic c-wave) and retinal melatonin content were thus investigated in Royal College of Surgeons rats from postnatal day 17 to 24, the period preceding retinal degeneration. The amplitudes of both the b- and c-waves of the electroretinogram fell significantly during the peak time of rod disk shedding and rose after the time of expected light off in the control and dystrophic rats. While the b-wave rhythms did not differ between the two strains, diurnal changes in the c-wave were significantly less distinct in the dystrophic rats than in controls. This difference may reflect lack of phagocytosis in dystrophic rats. Furthermore, the ERG c-wave was significantly larger and prolonged, and the retinal melatonin content higher, in dystrophic rats of this age group than in controls. It appears that retinal melatonin metabolism may play an important role in the maintenance of retinal pigment epithelial and photoreceptor function.