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V H Perry

Publications and source records attributed to V H Perry.

At least 181 records · Page 10Linked to original sources

Localization and function of tissue macrophages.

The rat monoclonal antibody F4/80 defines a plasma membrane glycoprotein of about 160 kilodaltons that is expressed by mature mouse macrophages. The antigen has been used to define macrophage distribution within the mouse (normal adult, embryo, infection models) by cytochemistry and quantitative immunochemical analysis. Macrophages migrate into fetal and adult haemopoietic and other tissues in an ordered sequence. The surface properties of 'fixed' macrophages isolated from various organs (bone marrow, liver, spleen) are distinct from those of circulating monocytes or free cells (peritoneal and pleural cavities, alveolar) and may play a role in local adhesion and trophic interactions with other cells.

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Cell death in the retinal ganglion cell layer during optic nerve regeneration for the frog Rana pipiens.

Cell number in the retinal ganglion cell layer of adult Rana pipiens was estimated from cresyl stained wholemounts. Values for normal animals ranged from 466,000 to 643,000 but differences between sides of individual animals varied by 9% or less. During optic nerve regeneration, following unilateral extracranial optic nerve crush, cell numbers in experimental retinae fell compared to their unoperated partners with the majority of the loss taking place between 56 and 84 days; by 200 day only half the cell complement remained. Since retrograde transport of horseradish peroxidase labelled 87% of cells in the normal ganglion cell layer, most of the loss during regeneration must have been from the ganglion cell population.

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Effect of neonatal optic nerve transection on some classes of amacrine cells in the rat retina.

An optic nerve section of the right eye of rat pups was carried out and the retina of the left and right eyes analyzed eight weeks later. Immunocytochemical studies for the localization of tyrosine-hydroxylase, choline acetyltransferase and substance P in amacrine cells revealed no qualitative differences in the distribution of the cell bodies or dendrites for the right and left retinas. Biochemical analysis showed a higher level of choline acetyltransferase, dopamine and glutamate decarboxylase in the right than in the left retina, though the glutamate decarboxylase difference was statistically insignificant. The biochemical difference is thought to reflect the differences in the protein or wet weight content of the retinas due to degeneration of the ganglion cells. It is concluded that destruction of the ganglion cells has no obvious effect upon the development or survival of some classes of amacrine cells.

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Ganglion cells in retinae transplanted to newborn rats.

Cells projecting out of retinal transplants placed over the tectum of newborn rats were studied by labelling with horseradish peroxidase 1 month or more after transplantation. Using this technique, it was found that only cells with the dendritic characteristics of ganglion cells were labelled and, furthermore, that the major classes of ganglion cells seen in normal retinae were also present in the transplants. The cell body size histograms of ganglion cells in normal and transplanted retinae compared closely with each other. Dendritic trees were closely confined by the limits of the inner plexiform layer, and if that layer was folded or distorted, they were themselves frequently abnormal. While axons usually coursed over the surface of the retinal transplants, they quite often followed an anomalous course crossing the individual layers. It appears, therefore, that this transplantation procedure has relatively little impact on the ability of ganglion cells to develop many of their characteristic morphological features. Whether the different functional responses of the various ganglion cell classes are also preserved after transplantation is a matter for further investigation.

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Lesion-induced myelin formation in the retina.

In the normal rat retina ganglion cell axons are not myelinated until they enter the optic nerve. After a lesion to the retina made via the sclera and choroid, Schwann cells invade the retina and myelinate ganglion cell axons. The lesion-induced myelin formation is most conspicuous in animals operated between the day of birth and 20 days of age. A lesion to the retina made from the vitread surface does not produce Schwann cell invasion. We suggest that the Schwann cells migrate into the retina from extraocular structures via the sclera. These observations provide a valuable system for the study of interactions between CNS axons and Schwann cells.

Age Factors↗

The ganglion cell and cone distributions in the monkey's retina: implications for central magnification factors.

The distribution of cones and ganglion cells was determined in whole-mounted monkey retinae. Ganglion cell density along the horizontal meridian was asymmetric, being up to three times greater in nasal retina. A similar but smaller asymmetry occurred with cones. The total number of ganglion cells varied from 1.4 to 1.8 X 10(6), agreeing well with counts of optic nerve axons. The variation of ganglion cell density with eccentricity indicates the magnification factor (MF) of the retina. This was compared with MF at the dorsal lateral geniculate nucleus and at striate cortex, revealing that the relative representation of the fovea increases substantially in both thalamus and cortex.

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Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain.

Macrophages and microglia in the developing and adult mouse brain have been identified by immunohistochemical localization of the macrophage-specific antigen F4/80 and monoclonal antibodies to the FcIgG1/2b (2.4G2) and type-three complement (Mac-1) receptors. In the adult mouse there are two classes of F4/80-positive cells; those associated with the choroid plexus, ventricles and leptomeninges and the microglia. The cells bearing Fc and complement receptors are indistinguishable, by their morphology and distribution, from those revealed by F4/80. During development macrophages invade the brain and can be followed through a series of transitional forms as they differentiate to become microglia. Macrophage invasion occurs when naturally dying cells are observed in large numbers and this is consistent with the idea that dying neurons and axons provide a stimulus for macrophage infiltration. Our results provide strong support for the hypothesis that the microglia are derived from monocytes and show that microglia possess receptors which would allow them to play a part in the immune defence of the nervous system.

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The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages associated with epithelia.

The tissue distribution of the murine macrophage-specific antigen F4/80 has been analysed using an immunohistochemical technique. The antigen is observed on all known macrophage populations (including Kupffer cells and bronchoalveolar macrophages) and is absent from any cell types that are definitely not mononuclear phagocytes. Microglial cells from brain express F4/80. F4/80+ macrophages observed associated with epithelia can be divided into two categories, intraepithelial and periepithelial. The former includes epidermal Langerhans cells and cells with similar morphology in other stratified squamous epithelia (cervix, oesophagus), pseudostratified epithelium (trachea), transitional epithelium of urinary bladder, and simple epithelia lining various ducts (salivary gland, common bile duct, tracheobronchial gland). Periepithelial F4/80+ cells, apparently spread immediately below the basal lamina, are associated with simple epithelia throughout the gastrointestinal, respiratory, and male and female reproductive tract as well as the brain ependyma. A major class of periepithelial F4/80+ cells is associated with capillaries throughout the microcirulation. The role of these macrophage populations in control of epithelial function is discussed.

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Is Thy-1 expressed only by ganglion cells and their axons in the retina and optic nerve?

The distribution of Thy-1 in the retina and optic nerve has been examined immunohistochemically, and compared to that of the astrocytic marker glial fibrillary acidic protein. The axons and cell bodies of ganglion cells were found to be Thy-1 positive as were processes within the inner plexiform layer. Transection of the optic nerve in the neonatal rat results in the rapid degeneration of the ganglion cells but some Thy-1 staining remains in the inner plexiform layer. We have estimated using an immunoassay of normal and optic nerve transected retinae that about 70% of the Thy-1 in the retina is on ganglion cells and their axons and the remainder is on cells which contribute processes to the inner plexiform layer, presumably amacrine, bipolar or Müller cells. In the optic nerve the Thy-1 was found to be limited to the fascicles of optic nerve fibres and the intrafascicular spaces, containing astrocytes and their processes, were not stained. Axotomy of the adult nerve, which produced axonal degeneration and astrocytic proliferation, led to a loss of over 95% of the Thy-1 from the nerve. We found no evidence that the astrocytes of the retina or optic nerve were Thy-1 positive in normal animals or during degeneration.

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Retinal ganglion cells that project to the dorsal lateral geniculate nucleus in the macaque monkey.

Horseradish peroxidase was deposited in the optic nerve to retrogradely label and reveal the dendritic form of all classes of ganglion cell, or it was injected into the dorsal lateral geniculate nucleus to reveal only those classes projecting to the thalamus. The results were compared with those of the accompanying paper in which the ganglion cells projecting to the midbrain are selectively revealed. Two major classes of ganglion cells are described, the P alpha and P beta cells. For both classes dendritic field size increases with eccentricity from the fovea and there is no overlap in the two classes at any given eccentricity. Cell body size shows a similar mean difference but with a slight overlap. Both cell bodies and dendritic fields are larger along the temporal horizontal meridian than the nasal horizontal meridian, for P alpha and for P beta cells, but these differences are reduced when naso-temporal differences in ganglion cell density are taken into account, that is, size correlates closely with density. Injections restricted to the parvocellular layers of the lateral geniculate nucleus labelled almost exclusively P beta cells, whereas injections confined to the magnocellular layers labelled almost exclusively P alpha cells. As midbrain injections label no P beta cells and few P alpha cells it can be shown that about 80% of ganglion cells are P beta cells projecting to parvocellular lateral geniculate nucleus, and that about 10% are P alpha cells projecting to magnocellular layers. The coverage factor, that is the number of cells covering each point on the retina, varied from 1.9-2.3 for P beta cells, and from 2-7 for P alpha cells. Comparing the results with those of comparable investigations on cats and rabbits shows a much clearer segregation of the terminal targets of different classes of ganglion cell in monkeys, the greatest difference being the absence in the monkey of a projection to the geniculate from gamma- and epsilon-like cells. Further, axons which branch and innervate both thalamus and midbrain are rare in monkeys but common in other mammals. Comparing the results with those from physiological investigations suggests that the P beta cells correspond to colour-opponent cells, whereas P alpha cells correspond to the achromatic broad-band magnocellular cells.

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Retinal ganglion cells that project to the superior colliculus and pretectum in the macaque monkey.

Horseradish peroxidase was injected into the superior colliculus or pretectum or both in order to label, by retrograde axoplasmic transport, the retinal ganglion whose cells axons innervate the dorsal midbrain. The dendrites of ganglion cells were sufficiently well-labelled to reveal their overall morphological characteristics. It was therefore possible to compare the number and form of ganglion cells projecting to the midbrain with the total population of ganglion cells as revealed by optic nerve injections, and with ganglion cells labelled by injections in the lateral geniculate nucleus. We found that not more than 10% of all retinal ganglion cells project to the superior colliculus in the macaque monkey. This percentage varies little over the retina, being about 6% of all ganglion cells near the fovea and increasing slightly with eccentricity. The superior colliculus does not receive a projection from P beta cells and only a few P alpha cells terminate there. The majority of cells which project to the superior colliculus have a small- to medium-sized cell body and sparsely branched dendritic tree. We have called them P gamma and P epsilon cells by analogy with the gamma cells and epsilon cells in the cat's retina. Anatomically the P gamma and P epsilon cells are heterogeneous, which would be consistent with the physiological heterogeneity found for ganglion cells which project to the midbrain in monkeys.

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The postnatal reduction of the uncrossed projection from the nasal retina in the cat.

We have investigated the postnatal reduction of the uncrossed projection from the nasal retina in the cat by injecting horseradish peroxidase into one optic tract of kittens and cats and retrogradely labeling the cells in the ipsilateral retina that have an uncrossed projection to the brain. The newborn kitten has over 600 uncrossed cells in the nasal retina. The number is reduced to about one-quarter of that value by postnatal day 10. The two adult cats examined had 75 and 100 of these ipsilaterally projecting nasal cells. They are distributed all across the nasal retina, and most have the morphology characteristic of gamma cells. A lesion in one optic tract in the newborn kitten results in an increase in the number of cells from the nasal retina with an ipsilateral projection at maturity. There are more of these cells in the region that has been depleted of ganglion cells by the lesion. This excess consists mostly of gamma and epsilon cells. These findings indicate that competitive factors play a role in the elimination of inappropriate ganglion cell projections in the cat, and that this process contributes to the precision of the nasotemporal division of the retina.

Amidines↗

Postnatal changes in retinal ganglion cell and optic axon populations in the pigmented rat.

The number of ganglion cells in the retina of the postnatal rat has been examined. We estimated both the number of axons in the optic nerve and the number of cells which can be retrogradely labelled with horseradish peroxidase from injections into the brain. In the retina of the newborn rat there are at least twice as many ganglion cells as in the adult rat. By retrograde labelling of the ganglion cells and following transection of their axons 24-48 hrs later we can find no evidence that ganglion cells withdraw their axon without degeneration of the patent cell body. We have found that the excess ganglion cells are lost over the first ten postnatal days and during this period we observe pyknotic nuclei in the ganglion cell layer. From our estimates of the total number of neurones in the ganglion cell layer and the number of ganglion cells found at different ages we conclude that the migration of amacrine cells into the ganglion cell layer occurs in the first five postnatal days.

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Retrograde and anterograde-transneuronal degeneration in the parabigeminal nucleus following tectal lesions in developing rats.

Degenerative effects in the parabigeminal nucleus were studied in adult rats that had received lesions of the superior colliculus at different postnatal ages. Unilateral lesions lead to complete degeneration of the dorsal and ventral divisions of the parabigeminal nucleus, which connect reciprocally with the damaged tectum, and produce effects on the middle division which receives afferents from the ipsilateral and projects to the contralateral tectum. On the side contralateral to the lesion there was a reduction in the cross-sectional area of the division as a consequence of retrograde degeneration, except in rats operated on at birth or when adults; ipsilateral to the lesion there was a reduction in the cross-sectional area of the division as a result of anterograde-transneuronal degeneration, except in animals operated on when adults. The reduction in cross-sectional area is partly due to a decrease in the number of neurones in the middle division. The maximal effects in both cases occurred in animals operated on at 10 days after birth, and the sensitivity to retrograde degeneration follows a U-shaped curve. Bilateral tectal lesions performed at birth or 5 days after birth produce virtually complete degeneration of the whole parabigeminal nuclei. Anterograde radioautographic tracing showed that all parabigeminal divisions received topographically organized projections from the ipsilateral superior colliculus. Ipsilateral projections from the dorsal and ventral divisions and crossed projections from the middle division were identified in the tectum of newborn rats with fluorescent retrograde tracers. Possible explanations for the cases in which tectal lesions failed to produce an effect on the architecture of the middle division include increased resistance to axonal damage and regulative processes over natural neuronal death. The results also indicate that the two forms of degeneration are additive with regard to the whole population of developing parabigeminal neurones.

Age Factors↗

Massive retinotectal projection in rats.

Retinal ganglion cells were labeled with horseradish peroxidase injected into the superior colliculus of normal pigmented rats. It is shown that virtually all ganglion cells with crossed axons project to the tectum, thus including all cell types described so far in the rat. The results contrast with the conclusion that only one-third of the ganglion cell population project to the tectum in normal hamsters.

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Immunohistochemical localization of a macrophage-specific antigen in developing mouse retina: phagocytosis of dying neurons and differentiation of microglial cells to form a regular array in the plexiform layers.

In the developing mouse retina degenerating neurons can be observed initially in the ganglion cell layer followed by a phase of cell death in the inner nuclear layer. Using an immunohistochemical method to localize the mouse macrophage specific antigen F4/80, we show that macrophages migrate from the vascular supply overlying the developing retina and phagocytose the degenerating neurons. The macrophages subsequently differentiate to become the microglia of the retina and form a regularly spaced distribution across the retina in the inner and outer plexiform layers. These experiments provide strong evidence for the mesodermal origin of central nervous system microglia.

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