Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “OPTIC PATHWAY”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1982

Posttranslational modification of a neurofilament protein during axoplasmic transport: implications for regional specialization of CNS axons.

The possibility that proteins are modified during axoplasmic transport in central nervous system axons was examined by analyzing neurofilament proteins (200,000, 140,000, and 70,000 mol wt) along the mouse primary optic pathway (optic nerve and optic tract). The major neurofilament proteins (NFPs) exhibited considerable microheterogeneity. At least three forms of the " 140,000" neurofilament protein differing in molecular weight by SDS PAGE (140,000-145,000 mol wt) were identified. The "140,000" proteins, and their counterparts in purified neurofilament preparations, displayed similar isoelectric points and the same peptide maps. The "140,000" NFPs exhibited regional heterogeneity when consecutive segments of the optic pathway were separately examined on polyacrylamide gels. Two major species (145,000 and 140,000 mol wt) were present along the entire length of the optic pathway. The third protein (143,000 mol wt) was absent proximally but became increasingly prominent in distal segments. After intravitreal injection of [(3)H]proline, newly synthesized radiolabeled proteins in the "140,000" mol wt region entered proximal mouse retinal ganglion cell (RGC) axons as two major species corresponding to the 145,000 and 14,000 mol wt NFPs observed on stained gels. When transported NFPs reached more distal axonal regions (30 d postinjection or longer), a 143,000 mol wt protein appeared that was similar in isoelectric point and peptide map to the 145,000 and 140,000 mol wt species. The results suggest that (a) the composition of CNS neurofilaments, particularly the "140,000" component, is more complex than previously recognized, that (b) retinal ganglion cell axons display regional differentiation with respect to these cytoskeletal proteins, and that (c) structural heterogeneity of "140,000" NFPs arises, at least in part, from posttranslational modification during axoplasmic transport. When excised but intact optic pathways were incubated in vitro at pH 7.4, a 143,000 NFP was rapidly formed by a calcium-dependent enzymatic process active at endogenous calcium levels. Changes in major proteins other than those in the 145,000-140,000 mol wt region were minimal. In optic pathways from mice injected intravitreally with L-[(3)H]proline, tritiated 143,000 mol wt NFP formed rapidly in vitro if radioactively labeled NFPs were present in distal RGC axonal regions (31 d postinjection). By contrast, no 143,000 mol wt NFP was generated if radioactively labeled NFPs were present proximally in RGC axons (6 d postinjection). The enzymatic process that generates 143,000 mol wt NFP in vitro, therefore, appears to have a nonuniform distribution along the RGC axons. The foregoing results and other observations, including the accompanying report (J. Cell Biol., 1982, 94:159-164), imply that CNS axons may be regionally specialized with respect to structure and function.

Animals↗
PubMed1982

Posttranslational processing of alpha-tubulin during axoplasmic transport in CNS axons.

Tubulin proteins in mouse retinal ganglion cell (RGC) neurons were analyzed to determine whether they undergo posttranslational processing during axoplasmic transport. Alpha- and beta-tubulin comprised heterogeneous proteins in the primary optic pathway (optic nerve and optic tract) when examined by two-dimensional (2D) PAGE. In addition, however, alpha-tubulin exhibited regional heterogeneity when consecutive 1.1-mm segments of the optic pathway were analyzed separately. In proximal segments, alpha-tubulin consisted of two predominant proteins separable by isoelectric point and several less abundant species. In more distal segments, these predominant proteins decreased progressively and the alpha-tubulin region of the gel was represented by less abundant multiple forms only; beta-tubulin region of the gel was represented by less abundant multiple forms only; beta-tubulin was the same in all segments. After intravitreal injection of [3H]proline to mice, radiolabeled alpha- and beta-tubulin heteroproteins were conveyed together at a rate of 0.1-0.2 mm/d in the slowest phase of axoplasmic transport. At 45 d postinjection, the distribution of radiolabeled heterogeneous forms a alpha- and beta-tubulin in consecutive segments of optic pathway resembled the distribution of unlabeled proteins by 2D PAGE, indicating that regional heterogeneity of tubulin arises during axonal transport. Peptide mapping studies demonstrated that the progressive alteration of alpha-tubulin revealed by PAGE analysis cannot be explained by contamination of the alpha-tubulin region by other proteins on gels. The results are consistent with the posttranslational processing of alpha-tubulin during axoplasmic transport. These observations, along with the accompanying report (J. Cell Biol., 1982, 94:150-158), provide additional evidence that CNS axons may be regionally specialized.

Animals↗
PubMed1979

The central pathways of optic fibres in Xenopus tadpoles.

A cobalt chloride impregnation technique was applied to the optic nerve in Xenopus tadpoles and the central optic pathways were examined in cleared, whole-mounted preparations, and in thick sections. The overall plan of the optic input was visualized in relation to the outlines of the parts of the brain and details of the structure of the tectal optic neuropil, the neuropil of Bellonci and the basal optic neuropil were seen. The fibres in the main retinotectal tract maintained an orderly disposition with respect to each other, in contrast to the fibres of the basal optic tract, in which no order was apparent. Optic fibres were seen passing caudally from the region of the basal optic neuropil.

Animals↗
PubMed1980

Protein degradation in the mouse visual system. I. Degradation of axonally transported and retinal proteins.

The analysis of proteolysis in the nervous system is complicated by the heterogeneity of cell types, extensive reutilization of liberated amino acids, and artifacts that may arise when the integrity of the tissue is disrupted during experimentation. For these reasons, changes in proteolytic activity that are observed during brain development and in neuropathological states may often be difficult to interpret. To minimize these problems, we have developed a technique that permits protein degradation to be investigated specifically within axons of the mouse retinal ganglion cells (RGC). In the present study, the method has been used to examine the degradation of proteins conveyed in the slow phases of axoplasmic transport. When adult C57Bl/6J mice were injected intravitreally with L-[3H]proline, labeled proteins within the primary optic pathway (optic nerve and tract) after 5 days were almost exclusively the slow phase axonal proteins. The rate of degradation of these proteins was then determined within the excised, but otherwise intact, optic pathway by measuring the release of acid soluble radioactivity at 37 degrees C in vitro. At physiological pH, the amino acids released by proteolysis were extensively reutilized. Unless amino acid reutilization was prevented, protein degradative rates were artifactually lowered 3-fold. At least two proteolytic systems within RGC axons actively degraded the slowly transported axonal proteins. A 'neutral' system, stimulated by exogenous calcium ions, was optimally active within the physiological pH range (pH 7.0--7.8). The rate of protein degradation at pH 7.4 was uniform along the RGC axon. An 'acidic' system was optimally active with the incubation was carried out at pH 3.8. This proteolytic activity was calcium-independent and exhibited a proximodistal gradient within the RCG axon with higher activity proximally. Similar proteolytic activities were present in isolated intact retinas but in different proportions. The half-lives of axonal and retinal proteins were comparable to CNS protein half-lives estimated in vivo by methods that take amino acid reutilization into account. These and other recent findings demonstrate the utility of this neuron-specific approach in characterizing proteolytic processes within one cell type that may otherwise be obscured by proteolytic events in other cells when brain tissue is analyzed by conventional methods.

Animals↗
PubMed2005

Natural history of neurofibromatosis 1-associated optic nerve glioma in mice.

Children affected with the inherited tumor predisposition syndrome, neurofibromatosis 1 (NF1), are prone to the development of low-grade astrocytic optic pathway tumors (optic pathway glioma [OPG]). Previously, we developed a model of NF1-associated astrocytoma (GFAPCre; Nf1(flox/mut) mice) in which mice develop optic nerve and chiasm glioma. To define the molecular pathogenesis of OPG, we used this mouse model to study the natural history of OPG formation using immunohistological and radiographic approaches. We observed that whereas astrocyte hyperplasia is present in the optic nerves associated with gross optic nerve thickening at 3 weeks of age, overt neoplastic changes were not seen until 2 months of age. Astrocyte proliferation was maximal between 3 weeks and 2 months of age, suggesting that the most rapid period of growth occurs early. Mouse OPG tumors were detected by magnetic resonance imaging at 2 months of age and exhibited contrast enhancement, as seen in human OPG. In addition, the mouse OPG tumors exhibited expression of proteins associated with astroglial progenitors, including nestin and brain lipid binding protein. Last, we observed neovascularization and microglial cell infiltration by 3 weeks of age before overt neoplastic transformation, suggesting that these cellular changes participate in the early stages of tumor formation.

Age Factors↗
PubMed1981

Axonal transport of the mitochondria-specific lipid, diphosphatidylglycerol, in the rat visual system.

Rats 24 d old were injected intraocularly with [2-3H]glycerol and [35S]methionine and killed 1 h-60 d later. 35S label in protein and 3H label in total phospholipid and a mitochondria-specific lipid, diphosphatidylglycerol(DPG), were determined in optic pathway structures (retinas, optic nerves, optic tracts, lateral geniculate bodies, and superior colliculi). Incorporation of label into retinal protein and phospholipid was nearly maximal 1 h postinjection, after which the label appeared in successive optic pathway structures. Based on the time difference between the arrival of label in the optic tract and superior colliculus, it was calculated that protein and phospholipid were transported at a rate of about 400 mm/d, and DPG at about half this rate. Transported labeled phospholipid and DPG, which initially comprised 3-5% of the lipid label, continued to accumulate in the visual structures for 6-8 d postinjection. The distribution of transported material among the optic pathway structures as a function of time differed markedly for different labeled macromolecules. Rapidly transported proteins distributed preferentially to the nerve endings (superior colliculus and lateral geniculate). Total phospholipid quickly established a pattern of comparable labeling of axon (optic nerve and tract) and nerve endings. In contrast, the distribution of transported labeled DPG gradually shifted toward the nerve ending and stabilized by 2-4 d. A model is proposed in which apparent "transport" of mitochondria is actually the result of random bidirectional saltatory movements of individual mitochondria which equilibrate them among cell body, axon, and nerve ending pools.

Animals↗
PubMed1977

Specific patterns of neuronal connexions involved in the control of the rabbit's vestibulo-ocular reflexes by the cerebellar flocculus.

1. In anaesthetized albino rabbits, the occurrence of Purkinje cell inhibition on canal-ocular reflexes was surveyed with a reflex testing method. 2. Test reflexes were elicited by electrical stimulation of the semicircular canals. The results were appaised by recording potentials and tension from extraocular muscles. Twelve reflexes were defined in terms of the receptor canal and the effector muscle. 3. Conditioning electrical stimuli were applied to the flocculus, the inferior olive, and optic pathways at the retinae, optic chiasm, pretectal area and upper medulla. 4. The conditioning stimulation at the ipsilateral flocculus induced depression in six of the twelve canal-ocular reflexes; four of the six arose from the anterior canal and the remaining two from the horizontal canal. 5. The effect of stimulation of the contralateral inferior olive was similar to that of the ipsilateral flocculus, though less clear in two of the four reflexes from the anterior canal because of a contaminating effect. 6. The two reflexes from the horizontal canal were depressed by stimulation of the ipsilateral optic pathway which reached the ipsilateral flocculus via the contralateral pretectal area and inferior olive. 7. The four reflexes from the anterior canal were affected by stimulation of optic pathways in a different manner from each other. One was depressed from the contralateral retina via the ipsilateral pretectal area, while another was depressed from the ipsilateral retina via the contralateral pretectal area, though only occasionally. The third reflex was depressed from the ipsilateral pretectal area but not from the retina. The fourth was affected from neither the retina nor the pretectal area. 8. On the basis of latency measurements, it was concluded that the depression of canal-ocular reflexes was due to inhibition of relay neurones of the testing reflexes by flocculus Purkinje cells which were activated either directly, or indirectly through olivocerebellar climbing fibre afferents. 9. The above conclusion was supported by the observation that the depression induced by stimulation of the inferior olive and optic pathways was abolished by acute destruction of the ipsilateral flocculus. 10. The possible functional significance of the specific patterns of connexions from flocculus Purkinje cells to canal-ocular reflex pathways is discussed, and specialization among flocculus Purkinje cells in relationship with vestibulo-ocular reflexes is postulated.

Action Potentials↗
PubMed2005

A technique for producing demyelination of the rat optic nerves.

Demyelination is a major cause of neurological disability within the human population, and the end product of a number of pathological processes, though the most common is the disease multiple sclerosis. This disease commonly affects the optic pathway, particularly the optic nerve and chiasm. This paper reports a novel technique of producing chemical glial toxin induced demyelination in the rat optic nerves and chiasm by the direct instillation of the glial toxin ethidium bromide into the rat cranial subarachnoid space causing demyelination of the optic nerves and chiasm. This model, because of its involvement of the optic pathways, will allow both histological and functional assessments of the processes of demyelination and remyelination in the rat animal model.

Animals↗
PubMed2001

Visual-evoked potentials in the assessment of optic gliomas.

The most effective method for the screening and monitoring of optic pathway gliomas in children with neurofibromatosis type 1 remains a dilemma. Children less than 6 years of age are the group at highest risk for the development of optic pathway gliomas. Although an annual ophthalmologic examination currently is recommended as the most efficient method to screen for optic pathway gliomas, this method is often unreliable and inaccurate in young children. Magnetic resonance imaging remains the most sensitive test; however, cost and the need for sedation or general anaesthetic preclude its use as a routine screening test. We previously have recommended visual-evoked potentials (VEPs) as a possible alternative or aid in the assessment of optic pathway gliomas in this group of patients. The aims of this study were to ascertain the sensitivity of VEPs in detecting optic pathway gliomas and to determine whether VEPs are useful in monitoring the progress of optic pathway gliomas. This study provides further evidence of the sensitivity of VEPs in detecting optic pathway gliomas. In addition, VEPs may provide additional useful information concerning the progression of optic pathway gliomas once they have been detected.

Adolescent↗
PubMed1999

"Uncaging" using optical fibers to deliver UV light directly to the sample.

Photolysis or "uncaging" of caged compounds represents a significant tool in cell biology and chemistry. It provides a means for quantitative control of compound delivery with temporal and spatial resolution while observing their consequences for cellular signaling. We discuss the use of ultraviolet-transmitting optical fibers to directly deliver UV energy to the sample, combined with a nitrogen pulsed laser as a source of UV light. In this approach the size of the photolysis area is regulated by the exit aperture of the fiber tip which is controlled by pulling the optical fibers to desirable diameters. A diode (red) laser that is also coupled to the optical fiber aids the location of UV energy delivery through the fiber. We used this method to quantitatively uncage norepinephrine and calcium. The major advantage of this photolysis approach is its independence of microscope objectives and traditional optical pathways. Because the optical pathway of the microscope needs no modification to accommodate this photolysis system, integration with other experimental methods, such as electrochemistry, electrophysiology, confocal microscopy, and wide-field epifluorescence microscopy, is relatively simple.

Adrenergic Agonists↗
PubMed1993

Moyamoya phenomenon after radiation for optic glioma.

The role of radiotherapy in the management of patients with optic pathway glioma is controversial. In a series of patients with optic pathway glioma treated at The Hospital for Sick Children in Toronto, five children were encountered who developed moyamoya phenomenon after radiotherapy. A retrospective review of the medical records was undertaken in order to assess the relationship between optic pathway glioma, neurofibromatosis type 1 (NF1), radiation therapy, and moyamoya disease. Forty-seven patients with optic pathway glioma were operated on at The Hospital for Sick Children between 1971 and 1990. The moyamoya phenomenon did not occur in any of the 19 patients not receiving radiotherapy. Among the 28 patients who received radiotherapy, five developed moyamoya disease (two of 23 without NF1 and three of five with NF1). There was a statistically significant relationship between radiotherapy and moyamoya disease when the analysis was stratified according to the presence of NF1 (Mantel-Haensel chi-squared test 15.23, p < 0.01). The high incidence of moyamoya disease (three of five cases, or 60%) in patients with NF1 who have undergone radiotherapy suggests a synergistic relationship that should be considered when formulating a treatment plan for NF1 patients with optic pathway glioma.

Cerebral Angiography↗