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[Glial and neuronal cellular changes in the glaucomatous human retina].

The purpose of the present study was analysis of the cellular response to glaucoma in the human retina. Retinal strips obtained from two enucleated eyes with therapy-resistant, absolute glaucoma were explanted and cultured in vitro. The morphology of the remaining cell populations was assessed with the DiI method in non-cultured, formalin-fixed retinal tissue from both retinas. We found immunohistochemically identifiable glia cells migrating out from the explants and glial processes formed on the substrate. Labelling of representative retinal areas with the fluorescent dye DiI applied to the nerve fiber layer resulted in delineation of growth cone-bearing glial processes, of occasional non-atrophied ganglion cells, and of amacrines and horizontal cells in deeper layers of the retina. The results demonstrate that glaucoma leads both to selective damage of ganglion cells and to a glial proliferation characterized by the formation of processes both in the retina and following explantation.

Culture Techniques↗

Most calretinin-containing amacrine cells in the rabbit retina co-localize glycine.

Calretinin-containing retinal amacrine cells are heterogeneous with regard to their neurochemical properties. In the rabbit retina, about 90% of them contain glycine, as evidenced in the present study by double-label immunocytochemistry. In a previous report, we showed that a small population of amacrine cells contains both gamma-aminobutyric acid and calretinin. In this study, we further identified this cell population by means of known secondary markers. However, none of the markers we tested (choline acetyltransferase, serotonin accumulation, NADPH-diaphorase, vasoactive intestinal polypeptide) co-localized with calretinin. A small population (1%) of the cells in the ganglion cell layer contains both calretinin and glycine. Since calretinin-positive cells in the ganglion cell layer have been identified as ganglion cells based on soma size and presence of calretinin-positive axons in the optic nerve fiber layer, this population may represent a class of ganglion cell which contains glycine. Our results, together with those of other studies, suggest that calretinin is not a general marker of any of the well-known amacrine cell types in the mammalian retina. Rather, calretinin, just as other calcium-binding proteins, is distributed in a species-specific manner. At the same time it appears that, as shown for horizontal cells, one or more of the major buffer-type calcium-binding proteins of the EF-hand family is present in most of the retinal amacrine cells.

Animals↗

Modulation of perch connexin35 hemi-channels by cyclic AMP requires a protein kinase A phosphorylation site.

Retinal neurons are coupled via gap junctions, which function as electrical synapses that are gated by ambient light conditions. Gap junctions connecting either horizontal cells or AII amacrine cells are inhibited by the neurotransmitter dopamine, via the activation of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway. Fish connexin35 (Cx35) and its mouse ortholog, Cx36, are good candidates to undergo dopaminergic modulation, because they have been detected in the inner plexiform layer of the retina, where Type II amacrine cells establish synaptic contacts. We have taken advantage of the ability of certain connexins to form functional connexons (hemi-channels), when expressed in Xenopus oocytes, to investigate whether pharmacological elevation of cAMP modulates voltage-activated hemi-channel currents in single oocytes. Injection of perch Cx35 RNA into Xenopus oocytes induced outward voltage-dependent currents that were recorded at positive membrane potentials. Incubation of oocytes with 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), a membrane permeable cAMP analog, resulted in a dose-dependent and reversible inhibition of hemi-channel currents at the more positive voltage steps. In contrast, treatment with 8-Br-cAMP did not have any effect on hemi-channel currents induced by skate Cx35. Amino acid sequence comparison of the two fish connexins revealed, in the middle cytoplasmic loop of perch Cx35, the presence of a PKA consensus sequence that was absent in the skate connexin. The results obtained with two constructs in which the putative PKA phosphorylation site was either suppressed (perch Cx35R108Q) or introduced (skate Cx35Q108R) indicate that it is responsible for the inhibition of hemi-channel currents. These studies demonstrate that perch Cx35 is a target of the cAMP/PKA signaling pathway and identify a consensus PKA phosphorylation site that is required for channel gating.

8-Bromo Cyclic Adenosine Monophosphate↗

Projection from the superficial layers of the tectum to the pretectal complex in the cat.

The projection from the superficial layers of the tectum to the pretectal complex in the cat was examined using the retrograde transport of wheat germ agglutinin-horseradish peroxidase. Restricted injections were made into different parts of the pretectum. Neurons in the superior colliculus were found to be arranged in a mediolateral array that corresponds to the rostromedial to caudolateral array of their axon projections to the nucleus of the optic tract and posterior pretectal nucleus. These results suggest that similar parts of the retinotopic maps present in the pretectum and superior colliculus are connected. The labeled cells in the superior colliculus were located within the deep part of stratum griseum superficiale and the superficial part of stratum opticum, and were composed of multipolar cells, vertical fusiform cells and horizontal cells. We conclude from this study that the cells of origin in the superior colliculus originate in the same region to which the contralateral retinal Y-cells project and that have also the morphological diversity, as do other tecto-thalamic neurons.

Animals↗

Expression of glutamate receptor genes in the mammalian retina: the localization of GluR1 through GluR7 mRNAs.

Seven distinct cDNAs encoding functional subunits of the AMPA/kainate-type glutamate receptors have been recently cloned. This in situ hybridization study was done to determine which subunits are expressed in the retina and, where possible, which neurons express them. Hybridization of 35S-UTP-labeled cRNA probes with transverse sections revealed that mRNAs for all seven receptor subunits (GluR1-GluR7) are expressed in both cat and rat retinas. GluR1 and GluR2 produced labeling over the entire inner nuclear layer (INL) and ganglion cell layer (GCL). GluR3-GluR7 have more limited distributions, indicative of expression by only a subset of neurons. All of the subunits are expressed by the cells at the inner edge of the INL, where amacrine cells reside, yet the layers with the horizontal, bipolar, and ganglion cells contain different subsets of subunits. These findings suggest that these glutamate receptor subunits are employed at many of the retinal synapses, including the photoreceptor input to the outer plexiform layer and the bipolar cell's contacts with the processes at the INL. It is also possible that some glial cells in the INL express some of the subunits. Since different combinations of GluR1-GluR3 have been shown to play an important role in the calcium permeability in response to glutamate, we investigated whether single cells coexpressed those subunits. By hybridizing adjacent semithin (1 micron) sections of the cat retina with probes for GluR1-GluR3, it was possible to observe coexpression of all three subunits, or of pairs of these subunits, in cells within the INL and GCL.

Animals↗

Cellular mechanisms for color-coding in holostean retinas and the evolution of color vision.

Electrophysiological recording and microspectrophotometry were used to analyze retinal function in representatives of the two surviving genera of holostean grade fish--the bowfin (Amia calva) and gars (Lepisosteus sp.). The properties of the cone photopigments, horizontal cells and ganglion cells show that these holostean retinas have cellular mechanisms for color vision which are fundamentally similar to those previously described for teleosts, turtle and mammals. These findings suggest that trichromatic receptor systems and opponent color-coding mechanisms may have evolved in primitive Neopterygii or more ancient fish, before the advent of teleosts. In conjunction with other recent data on living representatives of primitive fishes, these findings also add renewed plausibility for the view that vertebrate color vision could have taken a common origin some 400 million years ago from an ancestral aquatic jawed vertebrate.

Action Potentials↗

Synaptogenesis in the retina of the cat.

We have studied the development of synapses in the retina of the cat from E(embryonic day)21 to adulthood. The inner plexiform layer (IPL) could be distinguished by E36, but at this age no synapses had formed, although compact processes had formed in the IPL and membrane specialisations had developed in adjacent processes. Conventional synapses form in the IPL from E45 and become increasingly numerous and differentiated over subsequent weeks. Extracellular space and cellular debris were prominent during the formation of these synapses. The conventional synapses appear to form principally between amacrine cells until E56, when ganglion cell dendrites could be identified as postsynaptic processes. Ribbon synapses characteristic of bipolar cells were identified around birth, suggesting that bipolar cells do not form synapses until that age. The outer plexiform layer (OPL) could be distinguished in central retina at E56. Extracellular space, debris of degenerating cells and mounds of agranular vesicles were prominent at this age but synapses were not observed until E59, when cone pedicles formed ribbon synapses onto horizontal cell processes. The first synapses clearly formed by spherules, also onto horizontal cells, were seen at E62. The central process of the postsynaptic triad, considered to be the dendrite of a bipolar cell, was first observed in both cone pedicles and rod spherules around birth, again suggesting that bipolar cells do not enter into synaptic arrangements until that age. Synaptogenesis in the OPL shows a strong centro-peripheral gradient; its initial stages were observed centrally in the late E50's but synapse formation was not complete in the retinal periphery until P(postnatal day)7 or later. We could not detect a centro-peripheral gradient in the formation of conventional synapses in the IPL, but the formation of ribbon synapses in this layer began centrally at birth and in the mid-periphery at P5. In summary, the first synapses to form in the retina are those which spread information laterally within the plexiform layers, between amacrine cells and from receptor to horizontal cells. The cells which carry information centrally, in particular bipolar cells, enter into synaptic arrangements considerably later. Further, retinal cells seem to form synapses in a distinct sequence: first amacrines, then receptors and lastly bipolar cells.

Animals↗

Cellular remodeling in mammalian retina: results from studies of experimental retinal detachment.

Retinal detachment, the separation of the neural retina from the retinal pigmented epithelium, starts a cascade of events that results in cellular changes throughout the retina. While the degeneration of the light sensitive photoreceptor outer segments is clearly an important event, there are many other cellular changes that have the potential to significantly effect the return of vision after successful reattachment. Using animal models of detachment and reattachment we have identified many cellular changes that result in significant remodeling of the retinal tissue. These changes range from the retraction of axons by rod photoreceptors to the growth of neurites into the subretinal space and vitreous by horizontal and ganglion cells. Some neurite outgrowths, as in the case of rod bipolar cells, appear to be directed towards their normal presynaptic target. Horizontal cells may produce some directed neurites as well as extensive outgrowths that have no apparent target. A subset of reactive ganglion cells all fall into the latter category. Muller cells, the radial glia of the retina, undergo numerous changes ranging from proliferation to a wholesale structural reorganization as they grow into the subretinal space (after detachment) or vitreous after reattachment. In a few cases have we been able to identify molecular changes that correlate with the structural remodeling. Similar changes to those observed in the animal models have now been observed in human tissue samples, leading us to conclude that this research may help us understand the imperfect return of vision occurring after successful reattachment surgery. The mammalian retina clearly has a vast repertoire of cellular responses to injury, understanding these may help us improve upon current therapies or devise new therapies for blinding conditions.

Animals↗

Evidence for the involvement of purinergic P2X receptors in outer retinal processing.

Extracellular ATP mediates fast excitatory neurotransmission in many regions of the central nervous system through activation of P2X receptors. Although several P2X receptor subunits have been identified in the mammalian retina, little is known about the functional role of these receptors in retinal signalling. The purpose of the present study was to investigate whether purinergic P2X(7) receptors are involved in outer retinal processing by assessing receptor localization, degradation of extracellular ATP and the effect of functional activation of P2X(7) receptors on the electroretinogram (ERG). Using light and electron microscopy, we demonstrated that P2X(7) receptors are expressed postsynaptically on horizontal cell processes as well as presynaptically on photoreceptor synaptic terminals in both the rat and marmoset retina. Using an enzyme cytochemical method, we showed that ecto-ATPases are active in the outer plexiform layer of the rat retina, providing a mechanism by which purinergic synaptic transmission can be rapidly terminated. Finally, we evaluated the role of P2X(7) receptors in retinal function by assessing changes to the ERG response of rats after intravitreal delivery of the P2X(7) receptor agonist benzoyl benzoyl ATP (BzATP). Intravitreal injection of BzATP resulted in a sustained increase (up to 58%) in the amplitude of the photoreceptor-derived a-wave of the ERG. In contrast, BzATP caused a transient reduction in the rod- and cone-derived postreceptoral responses. These results provide three lines of evidence for the involvement of extracellular purines in outer retinal processing.

Adenosine Triphosphatases↗

The emergence of GABA-accumulating neurons during retinal histogenesis in the embryonic chick.

The emergence of GABA-accumulating neurons was studied from stages 29 to 40 during retinal histogenesis in the chick, covering embryonic (E) days E6-E14, using autoradiographic analysis following incubation of isolated retinas with [3H]GABA (2 microM). Analysis was restricted to central retina which is more advanced in its differentiation than the periphery. On E6 numerous mitotic figures were present along the scleral border of the unstratified neuroepithelium. Specific localization of [3H]GABA was associated initially with somata situated in middle regions of the retinal expanse. Occasionally contiguous pairs of labeled cells were seen. The inner plexiform layer makes its appearance during E7; at that time silver grains were present over cell bodies located in the ganglion cell layer and the proximal portion of the inner nuclear layer, those of probable amacrine cells. As retinal stratification continued, more cells were observed to have elaborated membrane systems for GABA uptake with varying degrees of affinity. By E8, although dividing, non-labeled cells were in close proximity, GABA-labeled cells were observed in positions of horizontal cells. By E14, the pattern of label distribution appeared essentially similar to that reported for adult retina, i.e. [3H]GABA labeling was observed over horizontal cells and their processes, subpopulations of amacrine cells which appear to ramify extensively across the inner plexiform layer, selected perikarya of the ganglion cell layer, and the nerve fiber layer. In addition, a subpopulation of labeled photoreceptors, some identified as cones by virtue of oil droplets, was observed. Thus, preferential accumulation of GABA appears during E6, prior to formation of either inner or outer plexiform layers. The localization of [3H]GABA demonstrates that ganglion and amacrine cell bodies are labeled initially, followed by horizontal cells. Specific accumulation of [3H]muscimol, a potent agonist of GABA receptors, appears about E12 over cells located in proximal regions of the inner nuclear layer; these somata later ramify in sublaminae 2 and 4 of the inner plexiform layer.

Animals↗

Differentiation of ganglion cells and amacrine cells in the rat retina: correlation with expression of HuC/D and GAP-43 proteins.

In order to understand the development of retinal cells, we have studied the temporal expression of HuC/D protein in embryonic, postnatal and adult rat retina. During development and in the adult retina, practically all cell somata in the ganglion cell layer and the vast majority of conventional amacrine cells in the inner nuclear layer displayed HuC/D immunoreactivity. Most but not all ganglion cells expressed HuC/D at embryonic day 15, suggesting a delay between final mitosis and the initiation of HuC/D expression. Immunoreactivity for HuC/D was also evident in developing but not mature horizontal cells. Combined immunohistochemical visualization of HuC/D protein and the growth-associated protein (GAP-43) showed a distinct localization of GAP-43 in a specific compartment close to the somato-dendritic region of developing HuC/D-positive cell somata. The localization of GAP-43 immunoreactivity to a specific soma compartment became less evident during maturation. Immunoreactivity for HuC/D and GAP-43 was also discernible in horizontal cells at postnatal day 14. In the adult retina, most GAP-43 immunoreactivity was seen in the inner plexiform layer. Detailed analysis showed that HuC/D and GAP-43 expression is restricted to subsets of retinal neurons during development and in the mature retina. Thus, GAP-43 appears to be correlated with initial steps of differentiation and outgrowth of dendritic processes in HuC/D-positive ganglion and amacrine cells.

Amacrine Cells↗

A common mammalian plan of accessory optic system organization revealed in all primates.

The accessory optic system (AOS), which was described as early as 1870 by Gudden, constitutes a distinct midbrain visual pathway in all classes of vertebrates. In non-primate mammals, retinal fibres of this system project to a set of three nuclei: the dorsal (DTN), the lateral (LTN) and the medial (MTN) terminal nuclei. Whereas all AOS cells respond to the slow motion of large visual stimuli, the neurons are tuned to complementary directions of movement: horizontal temporo-nasal direction for the DTN, vertical up and down for the LTN and vertical down for the MTN. It has thus been suggested that these nuclei establish a system of retinal coordinates for the detection of whole field motion. As the AOS provides direct and indirect pathways to both oculomotor and vestibular structures, each of these nuclei is thought to be an essential link in the co-ordination of eye and head movements in relation to movement within the visual-field. One problem for the generalization of this theory is that the medial terminal nucleus has never been found in primates. In this report we establish both the existence of this nucleus and its afferent input from the retina in all major groups of primates (prosimians, New and Old World monkeys and apes), indicating a common anatomical plan of organization of the AOS in mammals.

Animals↗

Synaptic connections linking cones and horizontal cells in the retina of the pikeperch (Stizostedion vitreum).

Cones and horizontal cells of the pikeperch retina were studied with morphological and physiological techniques. Gap junctions were observed between cone pedicles and basal processes emitted by neighboring cones. Intracellular recordings showed that the light-evoked hyperpolarizing cone response was enhanced by light falling upon neighboring receptors within a radius of 50 microns. We suggest that the network of gap junctions between cones mediates the summative lateral interaction described. Three sub-classes of horizontal cells (H1, H2, H3) send dendrites to cones; H1 and H2 cells appear to contact twin cones, exclusively or preferentially, whereas H3 cells appear to synapse only with single cones. Horizontal cells of the same sub-class are joined by gap junctions between dendrites or at the lateral faces of perikarya. These unions extend over several micron 2 and as seen in transmission electron microscopy consist of patches of close apposition alternating with areas of membrane separation, folding and occasional zonulae adherents. Freeze-fracture profiles of horizontal gap junctions show localized areas of dense particle aggregation on the P-face and pits on the E-face flanked by regions of unspecialized membrane. These morphological findings provide support for the known spatial and color-coding properties of pikeperch horizontal cells.

Animals↗

Postnatal development of 3H-GABA-accumulating cells in rabbit retina.

Light and electron microscopic autoradiography demonstrates that 3H-GABA is accumulated by horizontal cells in neonatal rabbit retina but not in the adult. A specific population of horizontal cells appears to be mature at birth and they avidly accumulate 3H-GABA during a 15-minute incubation period in vitro. Uptake into horizontal cells is not observed after the fifth postnatal day; 3H-GABA-accumulating horizontal cell bodies and their processes are the first identifiable components that clearly mark the future location of the outer plexiform layer at birth and as such, may be considered pioneering elements. Our observations raise the interesting possibility that the pioneering horizontal cell may provide structural and/or chemical factors necessary for the subsequent development of the outer plexiform layer of the retina. Labeling patterns of other retinal cells also show varying degrees of change during development. A population of amacrine cells accumulate 3H-GABA at birth. These cells show little change in their morphological or 3H-GABA uptake properties from birth to adulthood. Müller cells show weak accumulation of 3H-GABA at birth. Subsequent to this time, labeling of Müller cells is significantly more robust, resulting in Müller cell domination of retinal autoradiographic patterns in more mature retinas. Every cell body in the ganglion cell layer accumulates 3H-GABA at birth. The number of labeled cells declines during postnatal development, resulting in a very limited adult population. We conclude that the ability of retinal cells to accumulate 3H-GABA does not remain constant during postnatal development; rather each cell population displays a unique maturation sequence that results in a dramatic developmental shift in the number and types of GABA-accumulating cells present in the retina.

Age Factors↗

Glutamate receptor subunit GluR2 and NMDAR1 immunoreactivity in the retina of macaque monkeys with experimental glaucoma does not identify vulnerable neurons.

Excitatory amino acid neurotoxicity has been proposed as a mechanism underlying selective neuronal death in glaucoma. The relationships between the cellular distribution of glutamate receptor subunit proteins GluR2 and NMDAR1 and the vulnerability of restricted retinal neuron subpopulations was explored in experimental glaucoma in macaque monkeys, produced by treating the trabecular meshwork in one eye with argon or diode laser burns. Immunostaining of retinal segments was performed using specific monoclonal antibodies to the GluR2 and NMDAR1 subunit proteins as well as neurofilament protein. The distribution of immunoreactivity was qualitatively assessed in the retina, and ganglion cells were counted in the paracentral and peripheral regions of each retinal segment. Immunoreactivity for both of these glutamate receptor subunit proteins was widely distributed in most retinal neuron types in control eyes and was colocalized with neurofilament protein in ganglion cells. In the glaucomatous eyes, densities of GluR2- and NMDAR1-immunoreactive ganglion cells were dramatically reduced compared to unaffected fellow eyes, but GluR2- and NMDAR1-immunoreactive populations of horizontal, bipolar, and amacrine cells were not affected. These data parallel previous observations on the selective vulnerability of ganglion cells in this experimental model of glaucoma. However, GluR2 and NMDAR1 subunits do not constitute cell type-specific markers of vulnerability in glaucoma as they are present in neurons prone to degeneration as well as in resistant ones. While retinal pathology in glaucoma involves excitotoxic mechanisms that may be related to glutamate receptor subunits regulating calcium fluxes, the specific pattern of neuronal vulnerability clearly depends on other cellular characteristics such as morphology, connectivity, and other aspects of the neurochemical phenotype.

Animals↗

Contribution of rod, on-bipolar, and horizontal cell light responses to the ERG of dogfish retina.

Simultaneous extracellular ERG and intracellular recordings from horizontal and ON-bipolar cells were obtained from the dark-adapted retina of the dogfish. The light intensity-peak response relation (IR) and time course of on-bipolar cell responses closely resembled that of the ERG b-wave, but only at low light intensities [<10 rhodopsin molecules bleached per rod (Rh*)]. Block of on-bipolar cell responses with 50 microM 2-amino-4-phosphonobutyrate (APB) abolished the b-wave and unmasked a vitreal-negative wave. Subtraction from the control ERG resulted in the isolation of a vitreal-positive ERG with an IR which matched that of on-bipolar cells over the full range of light intensities. The D.C. component of the ERG arises as a result of sustained depolarization of on-bipolar cells in response to long (>0.5 s) dim light stimuli, or following bright light flashes. The IR of horizontal cells and the vitreal-negative wave unmasked by APB could be matched by scaling at low light intensities (<5 Rh*). However, horizontal cell responses saturated at about 30 Rh*, while the vitreal-negative wave continued to increase in amplitude. The time course of horizontal cell membrane current with dim flashes could be matched to the rising phase of the vitreal-negative wave, assuming that the delay in generating the voltage response in horizontal cells is due to their long (100 ms) membrane time constant. Blocking post-photoreceptor activity resulted in a much smaller vitreal-negative wave than that unmasked by APB alone. We conclude that the b-wave arises from on-bipolar cell depolarization, while the leading edge of the a-wave is a composite of the change in extracellular voltage drop across the rod layer and a component (proximal PIII) reflecting a decrease in extracellular K+ as horizontal cell synaptic channels close with light.

Animals↗

[The eye and nutrition].

PURPOSE: To examine the effect of vitamins and trace elements on ocular tissue. MATERIALS AND METHODS: Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B12, C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyser, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens. RESULTS: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus. Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B12 deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B12 was found to be related to the circadian rhythm in the retina. Deficiencies of Zn, Cu, Mn, and vitamins A, B12, and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers. In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer. Zn seemed to be necessary for corneal epithelial cell wound healing. DISCUSSION: Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance. CONCLUSION: Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B12, C, and E are necessary for maintenance of cellular structure and metabolism.

Animals↗

[A 50-year-old man with metamorphopsia and optic nerve swelling].

We report a 50-year-old male having metamorphopsia associated with retinal edema. He was well until one month prior to the present admission when he developed occipital headache and backache. Three weeks later, he noted a sudden onset of twisting of visual images. On admission, he was in no acute distress with well preserved general conditions. Only neurological abnormalities were bilateral papilledema, retinal edema and horizontal nystagmus with a rotatory component. Routine blood chemistries were unremarkable. The CSF contained 28 cells/cmm with 60% consisting of large atypical cells. Cranial CT scans revealed no mass, however, the magnified orbital CT showed bilateral swelling of the optic nerve. He was treated with ventriculoperitoneal shunt and Ommaya tube placement through which methotrexate, cytarabine and prednisolone were administered. He was also treated with systemic cisplatin, mitomycin-C and 5-fluorouracil. With these therapy, his headache, metamorphopsia and papilledema improved. He was discharged for out-patient follow-up, however, he had to admitted again because of progressive difficulty of gait and loss of appetite. On admission, he complained of severe backache, and his gait disturbance appeared to be in part due to his backache. A slight weakness was noted in all four limbs with loss of deep reflexes. Mentally he was alert and cranial nerves appeared intact without papilledema. But nuchal rigidity was noted. Cranial CT scan revealed attenuation of all the cortical sulci and marked diffuse low density changes in the cerebral white matter, and his chest film revealed a ring-shape shadow in his left lung field. He deteriorated progressively with terminal gastrointestinal hemorrhage. He expired three weeks after his second admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗