Biomedical subjects

G Jeffery

Publications and source records attributed to G Jeffery.

At least 37 records · Page 2Linked to original sources

PubMed1998

Retinal nerve fibre layer polarimetry: histological and clinical comparison.

AIMS: To compare histological thickness of the retinal nerve fibre layer in the primate with retardation measurements obtained in vivo using the Mark II Nerve Fiber Analyzer (NFA, Laser Diagnostic Technologies, San Diego, USA). METHODS: Scanning laser polarimetry was performed on both eyes of a healthy anaesthetised adult primate (Macaca mulatta). The retinal nerve fibre layer thickness was measured in the eye with the best polarimetry image. A nerve fibre layer thickness map was scaled and aligned to a retardation map to permit correlation of retardation and thickness measurements. RESULTS: Retinal nerve fibre layer thickness measurements could be satisfactorily aligned with corresponding retardation values at 216 locations. The overall correlation coefficient for nerve fibre layer thickness and retardation was r = 0.70 (n = 216, p < 0.001). Regional comparison showed the best correlation (r = 0.76, n = 45, p < 0.001) occurred inferior to the optic disc. Less positive but still highly significant correlations were seen superiorly and temporally (r = 0.52, n = 26, p = 0.007 and r = 0.49, n = 86, p = < 0.001 respectively), with the lowest correlation occurring at the nasal aspect of the disc (r = 0.06, n = 67, p = 0.64). CONCLUSIONS: In the primate eye, retinal nerve fibre layer thickness shows a positive correlation with retardation measurements obtained with the nerve fibre analyser. However, since the correlation coefficient varied around the optic disc, further evaluation of the device is advised before its routine clinical use.

Animals↗

PubMed1997

Correction of retinal abnormalities found in albinism by introduction of a functional tyrosinase gene in transgenic mice and rabbits.

The factors that regulate normal retinal development remain obscure. However, it is known that elements in the retinal pigment epithelium are critical. When melanin is absent there is a reduction in rods, the central retina fails to develop fully and there is a systematic distortion in the chiasmatic projection to the brain. It has been demonstrated using transgenic mice that the chiasmatic abnormality is controlled by the tyrosinase gene, which is the key enzyme in melanin synthesis. Here we examine whether the two retinal deficits are regulated by this gene. We have examined the distribution of photoreceptors in an albino mouse strain in which a functional tyrosinase gene has been inserted and compared these transgenics with albino and wild type mice. In albinos, rod photoreceptors were reduced by approximately 30%, but were normal in the transgenics. Cone numbers were unchanged. Cell density in the ganglion cell layer was examined in transgenic rabbits, in which albinism had also been rescued with the tyrosinase gene. Normal rabbits have a steep gradient in cell density between central and peripheral retina. Cell density was abnormally low in the central retina in albinos, but normal in the transgenics. Hence, the tyrosinase gene is responsible for each of the retinal deficits associated with albinism. However, it is not clear whether this is due to the absence of melanin or whether the key agent is an associated cell product.

Albinism, Ocular↗

PubMed1997

The albino retina: an abnormality that provides insight into normal retinal development.

Albino mammals have specific deficits in their retinae and in the pattern of decussation at their optic chiasm, demonstrating that a melanin-related agent is crucial for normal development of the visual system. Although much attention has been paid to chiasmatic abnormality over the past 30 years, little progress has been made in understanding the abnormality. There has now been a shift of attention towards an analysis of the developing albino retina, which is providing significant advances in our understanding of the role played by this melanin-related agent. It is now possible to identify one candidate substance that emanates from the synthetic pathway of melanin that plays a key role in regulating retinal development.

Animals↗

PubMed1996

Cellular localisation of metabotropic glutamate receptors in the mammalian optic nerve: a mechanism for axon-glia communication.

It has been proposed that neurotransmitter signalling can occur between axons and glia in the mammalian optic nerve in the absence of synaptic specialisations, and that this may be glutamate mediated. Here, the cellular distribution of five metabotropic glutamate receptors (mGluR's 1a, 1b, 1c, 2/3 and 5) have been assessed in the rat optic pathway using specific antibodies. Positive immunoreactivity is found for mGluR2/3 and 5. Both are found in axons, although only mGluR5 is present in the majority of these. Strong immunoreactivity for mGluR2/3 is found in cells in the optic pathway and thalamus. The cellular morphology and distribution is consistent with their being astrocytes. Examination of brain sections stained for mGluR2/3 is consistent with this notion, with many cells having end-feet processes terminating on blood vessels or the pial surface. The axonal immunoreactivity could represent the presence of these receptors on axons, but it is more probable that the receptor protein synthesised in the ganglion cell soma is being transported to the cell terminal in sufficient concentration to be revealed by immunohistochemistry. The reason for the axon-astrocyte signalling is unclear, and may be associated with metabolic coupling. In development, communication between axons and glia mediates a range of functions including pathway selection and myelination. It is probable that in the adult this form of signalling underpins a range of functions that have yet to be described.

Animals↗

PubMed1996

Delayed neurogenesis in the albino retina: evidence of a role for melanin in regulating the pace of cell generation.

Melanin or an associated product in the retinal pigment epithelium (RPE) regulates retinal maturation, because in albino mammals the central retina is underdeveloped and there is a cell specific deficit in the rod population. Further, retinal projections through the chiasm are disrupted systematically. Here we test the hypothesis that melanin influences the birth dates of cells in the ganglion cell layer of the rat. [3H]Thymidine was injected at stages between E12 and E21 into mothers carrying both pigmented and albino fetuses. The animals were examined at maturity. Both pigmentation genotypes showed a centre to periphery pattern of cell production. Injections at E12 resulted in similar patterns of labelling in central regions. But from E14 labelled cells in the albinos were consistently closer to the central retina than those in their pigmented litter mates, suggesting a temporal lag in the centre to periphery pattern of cell production. By E21 there was little or no label in the pigmented animals, but it persisted in albinos, being similar in distribution to that in pigmented animals injected at E19. These results are consistent with the notion that melanin, or more likely an affiliated agent, in the RPE plays a role in regulating mitosis in the neural retina, possibly by influencing an aspect of the cell cycle. This may be the origin of the abnormalities found in the adult.

Animals↗

PubMed1996

PNS features of rodent optic nerve axons.

Peripheral nerves undulate together, giving them a wavelike appearance. This axonal pattern is also found in one region of the central nervous system, the optic nerve. Undulations provide a degree of compliance, as when a nerve is stretched, they are pulled straight. In the peripheral nervous system, undulations are thought to be conditional on the presence of extrafascicular collagen, which is also present between fascicles in the mammalian optic nerve. The pattern of undulations is described in the rat optic nerve and is related to the nerve's fascicular configuration and the regions between the fascicles, the extrafascicular matrix. The stage at which the undulations appear is determined to ascertain whether they are an intrinsic feature of optic axons or whether they emerge in association with the development of other events. The waves could be traced across the width of the nerve. Their pattern was not altered at fascicular boundaries, where axon groups are segregated. The periodicity of the undulations was constant between the eye and the middle of the nerve's length. Here fascicular divisions are present. Close to the chiasm, where the glial organisation changes and fascicles disappear, the periodicity of the undulations lengthened. They disappeared in the chiasm. Although collagen is a major component of the mammalian optic nerve's extrafascicular matrix, it was not present in the rat. Hence, the wavelike trajectory is independent of connective tissue. The waves are not present during early development and hence not an intrinsic feature of these axons. They appear behind the eye at late prenatal stages, emerging in association with glia in the extrafascicular matrix. They develop caudally, mirroring glial maturation. It is probable that the glia are maturing astrocytes that provide a scaffold for this feature of optic axon trajectory.

Animals↗

PubMed1995

Development of the chiasm of a marsupial, the quokka wallaby.

We have previously shown that the mature optic chiasm of a marsupial is divided morphologically into three regions, two lateral regions in which ipsilaterally projecting axons are confined and a central region containing only contralaterally projecting axons. By contrast, in the chiasms of eutherian (placental) mammals studied to date, there is no tripartite configuration. Ipsilaterally and contralaterally projecting axons from each eye are mixed in the caudal nerve and in each hemichiasm and encounter axons from the opposite eye near the midline of the chiasm. Here, we show that, unlike eutherians, marsupials have astrocytic processes in high concentrations in lateral regions of the nerve and rostral chiasm. Early in development, during the period when optic axons are growing through the chiasm, many intrachiasmatic cells are seen with densities five to eight times higher in lateral than in central chiasmatic regions. Such cells continue to be added to all chiasmatic regions; later in development, considerably more are added centrally, as the chiasm increases in volume. In the mature chiasm, cell densities are similar in all regions. By contrast to the marsupial, cell addition in the chiasm of a placental mammal, the ferret, is almost entirely restricted to later developmental stages, after axons have grown through the chiasm, and there are no obvious spatial variations in the distribution of cells during the period examined. During development, similar to the adult marsupial, ipsilaterally projecting axons do not approach the chiasmatic midline but remain confined laterally. We propose that the cells generated early and seen in high densities in the lateral chiasmatic regions of the marsupial may play a role in guiding retinal axons through this region of pathway selection. These data suggest that there is not a common pattern of developmental mechanisms that control the path of axons through the chiasm of different mammals.

Animals↗

PubMed1995

The human optic nerve: fascicular organisation and connective tissue types along the extra-fascicular matrix.

Fibres in the mammalian optic nerve are arranged into fascicles between which there is an extra-fascicular matrix containing connective tissue, a feature similar to that found in association with fibres in peripheral nerves, but not otherwise found in the CNS. The relationship between these major features of the nerve architecture are not known. We have addressed this question by examining the fascicular organisation of the optic nerve and the distribution of connective tissue and specific collagen types in the human. We have also examined the spatial development of connective tissue in the human nerve to determine when and from where it originates. Fibres are grouped into fascicles at all locations along the nerve, except intracranially, close to the chiasm where this pattern is lost. Relatively large fascicular numbers are found directly behind the eye and in the region of the optic canal, but decline in the mid-orbital segment of the nerve. Connective tissue is present in the extra-fascicular matrix throughout the fasciculated segment, but in many cases it does not fully encircle fascicles. The proportion of matrix occupied by connective tissue is similar along the length of the nerve (approximately 60%). Within the matrix, collagen types I, III, IV, V and VI are present throughout fasciculated regions. Staining for types V and VI appeared relatively weak compared with that for the other types. Although the collagen types in the nerve are similar to those at the lamina cribrosa and in peripheral nerves, they did not appear to be differentially distributed as in regions of the PNS. Connective tissue enters the nerve at a number of wide-spread locations early in development, consistent with the notion that it enters the nerve with the blood supply. It is present within the matrix before it is established at the lamina cribrosa.

Aged↗

PubMed1994

Melanin and the regulation of mammalian photoreceptor topography.

Melanin, or products directly associated with it, regulates the maturation of the neural retina because in hypopigmented mammals the central retina fails to develop fully. To determine whether this deficit is reflected in the distribution of photoreceptors, their topography has been studied in the retinae of normally reared pigmented and albino ferrets and animals reared under reduced light conditions. In both strains, the general distribution of rods and cones was similar to that in the cat, cone density peaking in the central retina and rod density peaking in an annulus around the area centralis. The cone population was organized in the form of an orderly mosaic whose regularity was measured at a wide range of retinal eccentricities. No differences were found in cone numbers or their mosaic distribution between pigmented and albino strains, either at the area centralis or at more peripheral regions. In both cases order within the cone mosaic was independent of density or retinal eccentricity. In the albinos there was a significant deficit in the number of rods at all retinal locations when compared with rod numbers in the pigmented animals. There were no differences between normally reared and dark-reared animals in this respect either within or between the strains. Therefore, the albino gene must have a selective and specific effect on the development of this cell type in the outer retina. Ganglion cells and rods are both affected by the albino gene, while cones are not. Because cones and ganglion cells are generated during the same period and rods are generated later, the albino gene cannot be acting during a particular developmental time window. Because the cone mosaic was normal in the albinos, in spite of a large rod deficit, the factors that regulate the spacing of cones cannot depend in any significant manner upon the later generation and subsequent addition of rods to the outer retina.

Albinism↗

PubMed1994

Correction of abnormal retinal pathways found with albinism by introduction of a functional tyrosinase gene in transgenic mice.

In albino mammals the pattern of connections between the eye and the brain is systematically disrupted at the optic chiasm, with a proportion of axons that should project ipsilaterally being rerouted to the contralateral hemisphere of the brain. Albino mice carry a mutation at the c-locus, which encodes the tyrosinase gene. Tyrosinase is the key enzyme in melanin synthesis. In this study we have used transgenic mice generated from an albino strain in which a functional tyrosinase transgene within a yeast artificial chromosome has been inserted. We have examined the chiasmatic pathways in these and control animals and have demonstrated that the abnormality is corrected in the tyrosinase transgenic mice. The results of this study identify the key element in this abnormality. The establishment of the transgenic model provides a unique tool with which to investigate the way in which melanin shapes this region of the developing mammalian visual system.

Albinism↗

PubMed1994

Is abnormal retinal development in albinism only a mammalian problem? Normality of a hypopigmented avian retina.

The central retina in hypopigmented mammals is underdeveloped. In the outer retina this deficit is confined to rods. Also, many ganglion cells in temporal regions project inappropriately to the contralateral hemisphere. This study addresses the question of whether pigment-related abnormalities occur in the central retina of a non-mammal, the bird. Birds have a highly developed central retina, but unlike most mammals they do not have a significant uncrossed retinal projection. Consequently, examination of the retinae of hypopigmented birds will reveal whether there is a relationship between the two abnormalities. Also if one of the primary effects of albinism is centred on rods, then albino birds may not show a deficit, because their retinae are cone dominated. Retinae from normally pigmented and two forms of hypopigmented budgerigars (Melopsittacus undulatus) were studied. Measurements of layer thickness, cell density and cell size were made at a range of locations in the ganglion cell layer and in the inner and the outer nuclear layers. Estimates of cone numbers were also made. Each strain of bird had an area of increased retinal layer thickness in dorso-temporal regions, but not a fovea. Although there were variations in the measurements undertaken between the strains, none were pigment related or consistent with the abnormality found in the central retina in albino mammals. Consequently, the underdevelopment of the central retina seen in hypopigmented mammals does not occur in this bird. There are two possible explanations for this result. First, normal mammalian retinal development may depend partly on time-dependent interactions in the maturation of the retinal pigment epithelium and the neural retina. Although there is a common time table for the development of the mammalian visual system when expressed in terms of the caecal period, which is between conception and eye opening, the pace of retinal development in birds is accelerated, which may alter interactions between these regions. Second, as the bird retina is cone dominated, any deficits in albino strains may be relatively minor.

Albinism↗

PubMed1992

Translaminar deficits in the retinae of albinos.

The central retina in albino mammals is poorly developed. There is a general reduction in ganglion cell density compared with the normal animal, and there are irregularities in the center to periphery gradient in ganglion cell density. It is not known whether, and if so to what extent, this abnormality is associated with deficits in other retinal layers. In this study the distribution of cells in the ganglion cell layer has been determined in horizontally sectioned eyes from pigmented and albino ferrets. This was undertaken to define the location of the region of highest cell density and the relative cell gradients around it. Detailed counts and measurements were then undertaken to determine the cell density within, and thickness of, the inner and the outer nuclear layers in these animals. All the albino animals had an abnormal distribution of cells in the ganglion cell layer in the central retina when compared with pigmented animals. The extent of this abnormality was variable. No differences between pigmented and albino animals could be found in the packing density of cells within the inner or the outer nuclear layer. However, in the pigmented animals there was a clear increase in the thickness of these layers associated with the region of highest density in the ganglion cell layer. This feature was absent in the albino animals, where the gradient in layer thickness was less marked and frequently contained irregularities. These abnormalities were most obvious in the outer nuclear layer.

Albinism↗

PubMed1992

Distinctive pattern of organisation in the retinofugal pathway of a marsupial: I. Retina and optic nerve.

The nasotemporal division in the retina and the pattern of crossed and uncrossed axons in the optic nerve were determined in an Australian marsupial, a wallaby, Setonix brachyurus (the quokka), following unilateral horseradish peroxidase injections into primary visual centres. The gross morphology of the nerve was also examined. Ipsilaterally projecting ganglion cells were restricted to the temporal retina, whereas those that project contralaterally were located in all retinal regions. The morphological study of the nerve showed that fasciculation patterns, evident along much of the length of the nerve, became indistinct centrally and were replaced in the prechiasmatic region by dorsoventrally oriented fissures. In this prechiasmatic region, axons were oriented in two directions. Whereas the majority were aligned centroperipherally with the long axis of the nerve, a proportion were aligned dorsoventrally in the fissures. Labelling with HRP revealed that uncrossed axons were restricted to the lateral region of the optic nerve and possibly to discrete fascicles, whereas those destined to cross at the chiasm occupied all regions of the nerve but were less dense on the lateral side. This spatial distribution of crossed and uncrossed projections did not change along the length of the nerve. These results demonstrate that fibre organisation in the marsupial optic nerve is different than that found in eutherian mammals.

Animals↗

PubMed1992

Distinctive pattern of organisation in the retinofugal pathway of a marsupial: II. Optic chiasm.

In the mammalian optic chiasm retinal axons from each eye divide into two populations, those that decussate and those that remain uncrossed. In eutherian (placental) mammals, the separation of these pathways is not reflected in the structure of the chiasm. The two populations from each eye are mixed through each hemichiasm, segregating only at the midline, where the uncrossed projection turns back. In this study the optic chiasm of a marsupial, the wallaby, Setonix brachyurus (quokka) has been investigated with staining and neuronal tracing techniques. The chiasm of this mammal is quite different from that of eutherian mammals. In coronal section it can be morphologically subdivided into three regions, a central body in which fasciculated groups of axons from each eye interdigitate across the midline, and two distinct lateral regions, one on each side, which contain the uncrossed retinal projections. In the rostral chiasm the lateral regions are separated from the main body of the chiasm by vertically oriented fibre-free regions. Caudally, the lateral regions increase in size and become less distinct as increasing numbers of contralaterally projecting axons that have crossed the midline project into them. However, the two populations remain predominantly segregated in this region. As the lateral regions develop, the central body of the chiasm becomes thinner and finally detaches at the midline to form the two optic tracts. The routes taken by retinal axons through the eutherian and marsupial chiasm appear to be fundamentally different. Therefore, the developmental factors that determine the laterality of retinal projections are likely to show significant differences in the two mammalian groups.

Animals↗

PubMed1992

The mosaic of alpha cells in the cat retina is not dependent on axon terminal interactions during development.

Alpha ganglion cells in the cat retina are distributed in a regular array. It has been proposed that the development of this mosaic pattern is achieved by class-specific interactions between the dendrites and/or axon terminals of neighbouring alpha cells, but the relative contributions that are made by each of these factors to the regularity of the mosaic remain unclear. An opportunity to address this question is provided by a comparative study of the distribution of alpha cells across the nasotemporal division of normally pigmented and Siamese cat retinae. In this strip of retina the alpha cell population divides its axon terminals between the two sides of the brain. Hence, the potential for interactions between axon terminals of alpha cells whose somata are adjacent within this region of the retina is undermined. This situation is exacerbated in Siamese cats because they have a congenital abnormality in this region, which results in an abnormally wide nasotemporal division. In this study the regularity of the alpha cell mosaic has been analysed at a wide range of eccentricities, including the nasotemporal division. In normally pigmented cats the nasotemporal division was visualised directly following unilateral horseradish peroxidase injections into the thalamus. In Siamese cats, the location of the abnormally wide nasotemporal division was inferred from electrophysiological recordings undertaken in their striate cortices. In both strains of cat the regularity of the alpha cell mosaic was shown to be largely independent of their density or retinal location. Furthermore, in the normals, the separate mosaics for ipsilaterally or contralaterally projecting alpha cells within the nasotemporal division were found to be no more or less regular than that for the combined population. This finding implies that there is no disturbance in their order across the discontinuity formed by their separate chiasmatic routes. Similar results were obtained from within the abnormal nasotemporal division of the Siamese cat. It is concluded that terminal interactions play an insignificant role in the formation of the adult alpha cell mosaic, the regularity of which is probably established by class-specific intraretinal interactions.

Animals↗

PubMed1992

The fascicular organisation of the cat optic nerve.

Mammalian optic nerve axons are organised within a fascicular framework. This pattern changes between the eye and the chiasm. For most of the length of the nerve fascicular patterns are apparent, but close to the chiasm, in a region of major fibre rearrangement, the fascicular configuration is lost. It is not known how this change occurs, or whether there are less obvious systematic changes in the number of fascicles or their geometry along the length of the nerve. In this study these questions have been addressed at successive locations along the length of the cat optic nerve. The number of fascicles varied depending upon the location examined. A relatively high number were found behind the eye. The number declined in the mid-orbital portion before increasing again in the region of the optic canal. Further caudally there was a progressive change in the pattern of fasciculation, with a loss of fascicular structure medially. The remaining fascicles became concentrated around the inferotemporal periphery of the nerve. There was no fascicular organisation at the point at which the two nerves fused at the chiasm. Although the number of fascicles varied along the length of the nerve their geometric pattern did not change.

Animals↗

PubMed1991

Evaluation of the influence of optic stalk melanin on the chiasmatic pathways in the developing rodent visual system.

In a number of mammalian species, fibre outgrowth in the developing retinofugal pathway is coincident with the presence of melanin in the retinal part of the optic stalk. The presence of melanin is transient in this developing system and has been proposed to play a role in the guidance of retinofugal fibres. Further, it has been suggested that this stalk melanin accounts for the differences between the size of the uncrossed retinal component in pigmented and nonpigmented strains. However, a recent study showed that there is no melanin in the optic stalk of Manchester rats during fibre outgrowth. Since such rats supposedly have a normal pigment distribution and a normal pattern of decussation at the optic chiasm, this finding appears to undermine the suggested role played by stalk melanin in establishing the laterality of retinal fibre projections in other mammalian species. The aim of this study was to re-evaluate the relationship between melanin in the stalk and the development of the retinofugal pathway in three strains of rat: the Wild type, Long Evans Hooded, and the Albino. The Albino rat, which lacks melanin-bearing cells entirely, was shown to have the smallest uncrossed projection, approximately 1,340 ipsilaterally projecting cells (ipc), whereas the Long Evans (2,760 ipc) and the Wild-type strain (2425 ipc) were found to have a larger uncrossed retinal component. In both pigmented strains, melanin was restricted to the eye cup and absent from the optic stalk throughout all stages of development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Albino gene dosage and retinal decussation patterns in the pigmented ferret.

We have examined the retinal decussation patterns in pigmented ferrets that were either wild-type sable or heterozygous with one albino gene. Unilateral injections of horseradish peroxidase were made into the optic tract and labeled ganglion cells visualized in retinal wholemounts. In both wild-type and heterozygous ferrets, those ganglion cells in the temporal retina with the largest cell bodies projected only to the contralateral side of the brain. The total number of ipsilaterally projecting ganglion cells did not differ with the genotype of the animal. The numbers ranged from 5471-6759 cells. Unlike the cat, there is no difference in retinal decussation patterns in wild-type sable ferrets and heterozygous ferrets carrying one albino gene.

Albinism↗