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PubMed1993

Distinct subsets of neuropeptide Y-negative principal neurons receive basket-like innervation from enkephalinergic and gabaergic axons in the superior cervical ganglion of adult rats.

The distributions of axons immunoreactive for [Leu]- or [Met]enkephalin and GABA were studied in the superior cervical ganglion of adult rats. The antigens were visualized separately and in combination with neuropeptide Y by the immunoperoxidase technique, using reaction end-products of different colors. Similarities and differences were found in the light-microscopic innervation patterns of enkephalin- and GABA-immunoreactive nerve fibers. Both fiber systems were heterogeneously distributed within the superior cervical ganglion, forming denser networks in its rostral part than elsewhere in the ganglion. The appearance of labeled nerve fibers differed in the two systems. Enkephalin-immunoreactive axons exhibited dotted profiles due to a strong immunoreaction in the axonal varicosities as compared with that in the intervaricose segments, whereas GABA-positive fibers were evenly labeled in both parts of the axons. The most marked difference between the innervation patterns from enkephalin- and GABA-immunoreactive axons was the presence of bundles of varicose axons in conjunction with the basket-like aggregation of enkephalin-immunoreactive nerve terminals. The possibility that enkephalins and GABA are co-localized in certain axons was excluded in double-labeling studies, silver intensification being used for the first antigen and the nickel-enhanced diaminobenzidine reaction for the second antigen. Different subsets of principal neurons were richly innervated in a basket-like manner by axons immunoreactive for enkephalins and GABA. Additionally, combined staining with antisera against either enkephalin and neuropeptide Y or GABA and neuropeptide Y revealed that both subsets of principal neurons richly innervated either by enkephalin-immunoreactive or by GABA-immunoreactive axons were devoid of neuropeptide Y immunoreactivity. Thus, the enkephalinergic and GABAergic axons have different subpopulations of neuropeptide Y-negative principal neurons as targets in the superior cervical ganglion. These results provide further evidence that sympathetic ganglion cells can be classified on the basis of their receiving input from different sources.

Animals↗
PubMed1991

Molecular mechanisms separating two axonal pathways during embryonic development of the avian optic tectum.

During embryonic development of the avian optic tectum, retinal and tectobulbar axons form an orthogonal array of nerve processes. Growing axons of both tracts are transiently very closely apposed to each other. Despite this spatial proximity, axons from the two pathways do not intermix, but instead restrict their growth to defined areas, thus forming two separate plexiform layers, the stratum opticum and the stratum album centrale. In this study we present experimental evidence indicating that the following three mechanisms might play a role in segregating both axonal populations: Retinal and tectobulbar axons differ in their ability to use the extracellular matrix protein laminin as a substrate for axonal elongation; the environment in the optic tectum is generally permissive for retinal axons, but is specifically nonpermissive for tectobulbar axons, resulting in a strong fasciculation of the latter; and growth cones of temporal retinal axons are reversibly inhibited in their motility by direct contact with the tectobulbar axon's membrane.

Animals↗
PubMed1993

Time-lapse video analysis of retinal ganglion cell axon pathfinding at the mammalian optic chiasm: growth cone guidance using intrinsic chiasm cues.

The specific routing of retinal ganglion cell axons at the mammalian optic chiasm into the ipsilateral or contralateral optic tracts results from axon pathfinding. Using time-lapse microscopy, we show that encounters between axons from opposite eyes at the chiasm induce axon turning, but do not always aim retinal axons into the optic tracts. Following removal of one eye before retinal axons have invaded the chiasm, axons from the remaining eye are still routed into the correct optic tracts. Ipsilaterally projecting axons make turning decisions without pausing over 10-20 min, whereas contralaterally projecting axons occasionally pause before crossing the midline. Thus, initial pathfinding at the chiasm does not depend on binocular axon interactions, but on local cues that trigger differential growth cone responses.

Animals↗
PubMed1994

Polysialic acid regulates growth cone behavior during sorting of motor axons in the plexus region.

Removal of polysialic acid (PSA) from N-CAM during the time when chick motoneuron axons are segregating into target-specific fascicles at the base of the limb was previously shown to result in motoneuron projection errors. Here, it is established that these errors are associated with altered growth cone behavior in the plexus. In contrast to control embryos, in which individual axons were observed to exhibit dramatic changes in direction and extensive divergence, axonal trajectories following the removal of PSA were relatively straight. To determine whether enhanced axon-axon fasciculation following PSA removal had prevented growth cones from responding appropriately to guidance cues at the base of the limb, we also examined the role of L1, a major mediator of axon-axon fasciculation in this system. Anti-L1 reversed the effects of PSA removal on both growth cone trajectories and projection errors. These results indicate that PSA plays a permissive role, attenuating axon-axon interactions in the plexus and thereby allowing the axonal reorganization that is essential for the formation of specific motoneuron projections.

Animals↗
PubMed2003

Time-lapse analysis of ethanol's effects on axon growth in vitro.

The cortical abnormalities found in animal models of fetal alcohol syndrome (FAS) suggest a disruption of axon growth. After emerging from the cell body, axons exhibit saltatory growth, cycling between periods of extension and periods of retraction. The timing of neuronal process outgrowth an the balance between extension and retraction together determine the net rate of axon elongation, and may be independently regulated. In this study, we used time-lapse digital microscopy and custom-designed analytic software to assess the effects of ethanol on the growth of axons from embryonic rat hippocampal pyramidal neurons in culture during 24 h of development, beginning approximately 7 h after plating. We recorded the amount of time elapsed before axons emerged, the relative amount of time spent in periods of growth and nongrowth, and the rate and direction of change in axon length during both periods of growth and nongrowth. The initiation of axonal outgrowth was significantly delayed by ethanol in a dose-dependent fashion at concentrations in the medium at or above 100 mg/dl. However, once established, axons exhibited accelerated growth in the presence of ethanol. This increase in overall growth rate was primarily due to a significant decrease in axon retraction during nongrowth periods. Ethanol did not affect the duration or frequency of growth and nongrowth periods. We propose, therefore, that mechanisms underlying ethanol-mediated changes in axon growth are linked to signaling events that differentially regulate outgrowth and retraction.

Animals↗
PubMed2005

Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation.

Regeneration of axons in the peripheral nervous system is enhanced by the removal of glycosaminoglycan side chains (GAGs) of chondroitin sulfate proteoglycans. However, some axons regenerate poorly despite such treatment, suggesting the existence of additional inhibitors. We compared the effects of enzymatic removal of GAGs from chondroitin sulfate proteoglycans versus two other proteoglycan species, heparan sulfate and keratan sulfate proteoglycans, on the regeneration of peripheral axons. Common fibular (CF) nerves of thy-1-YFP-H mice were cut and repaired using short segments of CF nerves harvested from wild-type littermates and pre-treated with a GAG-degrading enzyme for 1 h prior to nerve repair. Axonal regeneration was assayed by measuring the lengths of profiles of YFP+ axons in optical sections of the grafted nerves 1 week later. Except for grafts treated with keratanase, more and longer axon profiles were encountered in enzyme-treated grafts than in control grafts. Heparinase III treatments induced the greatest number of axons to enter into the graft. The proportions of axon profiles longer than 1000 microm were greater in grafts treated with chondroitinase ABC or heparinase I, but not with either keratanase or heparinase III. More regenerative sprouts were observed after treatment with heparinase I than any other enzymes. Treatment with a mixture of all four enzymes resulted in an enhancement of axon regeneration which was greater than that observed after treatment with any of the enzymes individually. The effects of chondroitinase ABC and heparinase III were correlated with specific GAG degradation. We believe that enzymatic removal of GAGs is especially effective in promoting the ability of regenerating axons to select their pathway in the distal stump (or nerve graft) and, in the case of chondroitinase ABC or heparinase I, it may also promote growth within that pathway.

Analysis of Variance↗
PubMed2005

Axon loss is responsible for chronic neurological deficit following inflammatory demyelination in the rat.

Axonal loss is now considered a consistent feature of MS pathology and evidence suggests that its accumulation may be the pathological correlate for the development of irreversible disability. In this study, we investigated the features of axonal loss in myelin autoimmunity and tested the hypothesis that loss of axons determines permanent neurological impairment in a model of inflammatory demyelination that closely mimics the pathology and course of MS. EAE was induced in DA rats by injection of recombinant mouse MOG with IFA. Animals that developed progressive EAE were killed at several time points after disease onset and animals that followed a chronic relapsing-remitting course of EAE were killed at approximately 4 months, exhibiting varying degrees of residual disability. Toluidine blue staining of semithin sections and immunohistochemistry for OX-42 were used to quantify demyelination, remyelination, inflammation and axonal loss in the spinal cord of MOG-EAE rats. In progressive EAE, the degree of axon loss, demyelination and inflammation all correlated significantly with clinical severity scores and a causative role for macrophages in the pathogenesis of axonal injury is suggested. However, in the chronic stage of relapsing-remitting EAE, in rats having suffered a variable number of relapses, only axonal loss correlated significantly with clinical severity scores. In addition, both axonal loss and clinical severity scores correlated with the number of relapses. These findings imply that secondary, or 'bystander', axonal loss is the main determinant of irreversible neurological disability in MOG-EAE and make the model a useful tool for the investigation of mechanisms of axonal loss and the evaluation of the benefits of neuroprotective therapies under conditions of antibody-mediated inflammatory demyelination.

Animals↗
PubMed2005

The experimental toxicology of metallic mercury on the murine peripheral motor system: a novel method of assessing axon calibre spectra using the phrenic nerve.

The toxicology of metallic mercury on motor neurons and their processes requires further work to resolve controversial implications in the aetiology of human motor neuron disease (MND). The assessment of experimental neurotoxicity in the peripheral motor system is, however, technically problematic and difficult to interpret. The mean number of axons in a nerve can vary considerably due to a high degree of biological variation. Atrophy of large axons can appear as loss when, in fact, their numbers appear in smaller diameter axonal categories. We addressed these quantitative problems using the murine phrenic nerve (MPN), a mono-fascicular, predominantly motor nerve as a model system. One micrometer transverse sections of gluteraldehyde/osmium tetroxide fixed MPNs were stained for myelin using a silver technique. Axon areas were measured from digital images of the nerve in cross-section (ImagePro Plus software) and transformed to circular diameter equivalents, then displayed as frequency distributions. We found a high biological variation in the mean axon number between paired nerves within experimental groups. Therefore, axon diameter data within individuals group was pooled. Theoretical simulation of axonal degeneration, atrophy and hypertrophy of larger myelinated axons (also affected in MND) were modelled by manipulating the original data set. With this model, by comparing normal distributions, it is possible to distinguish axonal atrophy, degenerative loss, and hypertrophy as distinct pathological processes in the large calibre axon subgroup that are selectively vulnerable to metallic toxins such as mercury.

Animals↗
PubMed2005

Regulation of Wallerian degeneration and nerve growth factor withdrawal-induced pruning of axons of sympathetic neurons by the proteasome and the MEK/Erk pathway.

Treatment of transected distal axons of rat sympathetic neurons in compartmented cultures with MG132 (5 microM) and other inhibitors of proteasome activity, preserved axonal mitochondrial function, assessed by Mitotracker-Orange and MTT staining, for at least 24 h. MG132 similarly protected axons from undergoing branch elimination (pruning) in response to local NGF deprivation. Axons protected by MG132 displayed persistent phosphorylation of Erk1/2, and pharmacological inhibition of MEK activity with U0126 (50 microM) restored rapid axonal degeneration. Therefore, the proteasome does not appear to be necessary as a general effector of protein degradation during axonal degeneration. Rather, the proteasome functions in the regulation of signaling pathways that control axonal survival and degeneration. Specifically, the down-regulation of the MEK/Erk pathway by the proteasome plays roles in Wallerian degeneration of severed axons and axonal pruning in response to local NGF deprivation. Identification of the pathways that regulate axonal survival and degeneration will provide possible target sites for pharmacological treatments of neurodegenerative diseases and traumatic injury.

Animals↗
PubMed2005

AMPA/kainate receptors mediate axonal morphological disruption in hypoxic white matter.

We used acute brain slices to investigate the hypothesis that oxygen-glucose deprivation (OGD) induced loss of axon function and neurofilament labeling are correlated to axonal morphological disruption in the corpus callosum of adult brain. Coronal brain slices including corpus callosum were prepared from adult mice. White matter immunohistochemical properties and conduction along axons remained stable over 12 h after preparation. White matter injury was assessed by recording compound action potentials (CAPs) across corpus callosum, combined with immunofluorescence for axonal neurofilaments and by bright field microscopy of myelin profiles in semi-thin sections. OGD for 30 min resulted in irreversible loss of the CAPs, formation of axon heads and bulbs, and swelling of myelin profiles in slices examined 1h after OGD. In slices followed for 9 h after OGD, there was complete loss of neurofilament labeling and myelin profiles. Because overactivation of AMPA/kainate receptors mediates axon structural and functional disruption in hypoxic corpus callosum slices, we tested whether blockade of AMPA/kainate receptors reduced OGD-induced axonal morphological disruption. NBQX (30 microM), an AMPA/kainate receptor antagonist, prevented OGD-induced formation of axon heads and bulbs, swelling of myelin profiles, loss of neurofilament staining and preserved axonal morphology. These results expand our previous findings that the AMPA/kainate receptor activation contributes to axonal morphological disruption, as well as loss of electrical function.

Action Potentials↗
PubMed2006

Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning.

Axon pruning by degeneration remodels exuberant axonal connections and is widely required for the development of proper circuitry in the nervous system from insects to mammals. Developmental axon degeneration morphologically resembles injury-induced Wallerian degeneration, suggesting similar underlying mechanisms. As previously reported for mice, we show that Wlds protein substantially delays Wallerian degeneration in flies. Surprisingly, Wlds has no effect on naturally occurring developmental axon degeneration in flies or mice, although it protects against injury-induced degeneration of the same axons at the same developmental age. By contrast, the ubiquitin-proteasome system is intrinsically required for both developmental and injury-induced axon degeneration. We also show that the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration, similar to its function in injury-induced degeneration. Thus, mechanistically, naturally occurring developmental axon pruning by degeneration and injury-induced axon degeneration differ significantly in early steps, but may converge onto a common execution pathway.

Animals↗
PubMed2003

gamma-diketone central neuropathy: quantitative morphometric analysis of axons in rat spinal cord white matter regions and nerve roots.

A quantitative analytical method was used to measure myelinated axon morphometric parameters (e.g., axon area, ratio of axon area/fiber area, and index of circularity) in rat nervous tissue during intoxication with 2,5-hexanedione (HD). Parameters were assessed in nerve roots (dorsal and ventral) and in ascending (gracile fasciculus and spinocerebellar tract) and descending (corticospinal and rubrospinal tracts) spinal cord white matter tracts (L4-L5) of rats intoxicated with HD at two different daily dose-rates (175 or 400 mg HD/kg/day, gavage). For each dose-rate, tissue was sampled at four neurological endpoints: unaffected, slight, moderate, and severe toxicity, as determined by gait analysis and measurements of grip strength. Results indicate that, regardless of the HD dose-rate, axon atrophy (reduced axon area) was a widespread, abundant effect that developed in concert with neurological deficits. The atrophy response occurred contemporaneously in both ascending and descending spinal tracts, which suggests that loss of caliber developed simultaneously along the proximodistal axon axis. In contrast, swollen axons were a numerically small component and were present in nerve roots and spinal tracts only during subchronic intoxication at the lower HD dose-rate (i.e., 175 mg/kg/day). Intoxication at the higher dose-rate (400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. These observations in conjunction with our previous studies of HD-induced peripheral neuropathy (Toxicol. Appl. Pharmacol. 135 (1995) 58; and Toxicol. Appl. Pharmacol. 165 (2000) 127) indicate that axon atrophy, and not axonal swelling, is a primary neuropathic phenomenon.

Animals↗
PubMed2004

Role of cell adhesion molecule DM-GRASP in growth and orientation of retinal ganglion cell axons.

The cell adhesion molecule (CAM) DM-GRASP was investigated with respect to a role for axonal growth and navigation in the developing visual system. Expression analysis reveals that DM-GRASP's presence is highly spatiotemporally regulated in the chick embryo retina. It is restricted to the optic fiber layer (OFL) and shows an expression maximum in a phase when the highest number of retinal ganglion cell (RGC) axons extend. In the developing retina, axons grow between the DM-GRASP-displaying OFL and the Laminin-rich basal lamina. We show that DM-GRASP enhances RGC axon extension and growth cone size on Laminin substrate in vitro. Preference assays reveal that DM-GRASP-containing lanes guide RGC axons, partially depending on NgCAM in the axonal membrane. Inhibition of DM-GRASP in organ-cultured eyes perturbs orientation of RGC axons at the optic fissure. Instead of leaving the retina, RGC axons cross the optic fissure and grow onto the opposite side of the retina. RGC axon extension per se and navigation from the peripheral retina towards the optic fissure, however, is not affected. Our results demonstrate a role of DM-GRASP for axonal pathfinding in an early phase of the formation of the higher vertebrate central nervous system.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2000

Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions.

Recent magnetic resonance (MR) studies of multiple sclerosis lesions indicate that axonal injury is a major correlate of permanent clinical deficit. In the present study we systematically quantified acute axonal injury, defined by immunoreactivity for beta-amyloid-precursor-protein in dystrophic neurites, in the central nervous system of 22 multiple sclerosis patients and 18 rats with myelin-oligodendrocyte glycoprotein (MOG)-induced chronic autoimmune encephalomyelitis (EAE). The highest incidence of acute axonal injury was found during active demyelination, which was associated with axonal damage in periplaque and in the normal appearing white matter of actively demyelinating cases. In addition, low but significant axonal injury was also observed in inactive demyelinated plaques. In contrast, no significant axonal damage was found in remyelinated shadow plaques. The patterns of axonal pathology in chronic active EAE were qualitatively and quantitatively similar to those found in multiple sclerosis. Our studies confirm previous observations of axonal destruction in multiple sclerosis lesions during active demyelination, but also indicate that ongoing axonal damage in inactive lesions may significantly contribute to the clinical progression of the disease. The results further emphasize that MOG-induced EAE may serve as a suitable model for testing axon-protective therapies in inflammatory demyelinating conditions.

Acute Disease↗
PubMed1968

Surface charge of giant axons of squid and lobster.

A method is described for the determination of the electrophoretic mobility of single, isolated, intact, giant axons of squid and lobster. In normal physiological solutions, the surface of hydrodynamic shear of these axons is negatively charged. The lower limit of the estimated surface charge density is -1.9 x 10(-8) coul cm(-2) for squid axons, -4.2 x 10(-8) coul cm(-2) for lobster axons. The electrophoretic mobility of squid axons decreases greatly when the applied transaxial electric field is made sufficiently intense; action potential propagation is blocked irreversibly by transaxial electric fields of the same intensity. The squid axon recovers its mobility hours later and is then less affected by transaxial fields. Eventually, a state is reached in which the transaxial field irreversibly reverses the sign of the surface charge. In contrast, there is no obvious effect of electric field on the mobility of lobster axons. The mobility of lobster axons becomes undetectable in the presence of Th(4+) at a concentration which blocks the action potential, and in the presence of La(3+) at a concentration which does not affect propagation. Quinine does not alter lobster axon mobility at a concentration which blocks action potential conduction. Replacement of extracellular Na(+) by K(+) is without effect upon lobster axon mobility. The electrophysiological implications of the results are discussed.

Action Potentials↗
PubMed1996

Differential sprouting responses in axonal fiber systems in the dentate gyrus following lesions of the perforant path in WLDs mutant mice.

Axons in both peripheral nerves and central fiber pathways undergo very slow Wallerian degeneration in Wlds mutant mice. It has recently been shown that in Wlds mutant mice there is a delay in the intensification of acetylcholinesterase histochemical staining in the molecular layer of the dentate gyrus following lesions of the entorhinal cortex. Thus, it appears that delayed post-lesion reactive sprouting is associated with the delayed degeneration of cut central axons in this mutant. We have studied the time course of changes in the septohippocampal and the hippocampal commissural projections following interruption of perforant path in Wlds mutant mice and in normal (C57BL/6J) mice using the anterograde tracer, wheat germ agglutinin conjugated horseradish peroxidase. In normal mice, changes in the distribution of labeled septal and commissural axons indicative of sprouting are seen in the dentate molecular layer as early as 3 days post-lesion. The earliest survival time at which similar changes are found in Wlds mutant mice is seven days post-lesion, when an increase in the density of labeled septal axons begins in the outer molecular layer. The delay in the sprouting of commissural axons in the mutant is even longer. Changes in the distribution of labeled commissural axons in the dentate gyrus of Wlds mutant mice are first seen 12 days post-lesion. These results confirm that post-lesion reactive axonal sprouting can be delayed in the central nervous system of Wlds mutant mice. In addition, our results indicate that the extent of this delay may differ among axonal fiber systems. These findings are consistent with the notion that various central axonal systems may respond differentially to sprouting cues and are reminiscent of differences found in the regenerating response exhibited by sensory and motor axons in the Wlds mutant after peripheral nerve cuts.

Animals↗
PubMed1998

p75-deficient sensory axons are immunoreactive for the glycoprotein L1 in mice overexpressing nerve growth factor.

Nerve growth factor (NGF) regulates the expression of the glycoprotein L1 among neural cell populations. The purpose of this investigation was to determine whether NGF equally affects the immunolocalization of L1 on both sympathetic and sensory axons, and whether the functional expression of the p75 neurotrophin receptor (p75NTR) is required for the immunodetection of this glycoprotein on peripheral axons. Two lines of transgenic mice overexpressing NGF among glial cells were used in this study: (1) one line of mice possessing two normal alleles for p75NTR, and (2) another line of mice possessing two mutated alleles for p75NTR. In both types of animals, sensory axons stained immunohistochemically for calcitonin gene-related peptide and sympathetic axons stained immunohistochemically for tyrosine hydroxylase invaded the deep white matter portions of the cerebellum (a central structure containing high levels of transgene expression and synthesis); the cerebella of wild type (C57Bl/6) and p75NTR-deficient mice lacked these sensory and sympathetic fibers. Both lines of transgenic animals also possessed a dense plexus of L1-immunoreactive axons in their cerebella; the spatial distribution of these L1-immunostained axons paralleled that seen for the sensory and sympathetic axons. A unilateral removal of the superior cervical ganglion in both lines of transgenic animals caused a complete reduction of tyrosine hydroxylase-immunopositive axons in the cerebellum but did not affect the density of L1-immunopositive axons. From these in vivo data, we conclude that collateral branches of sensory axons which invade a NGF-rich target area display L1 immunoreactivity, and that such immunodetection does not require the functional expression of p75NTR.

Animals↗
PubMed1987

Optic nerve head axonal transport in rabbits with hereditary glaucoma.

Rabbits with hereditary glaucoma develop ocular changes that resemble human congenital glaucoma and buphthalmia. The inheritance is autosomal recessive (bu). Previous research was performed primarily on albino bu/bu rabbits that were unhealthy and bred poorly. We have bred pigmented bu/bu rabbits to determine if this would improve hardiness and provide a better model for the disease in humans. First-generation offspring from matings of bu/bu albino with bu/bu pigmented rabbits were all affected, indicating that the bu gene is found at the same locus in both strains. The pigmented bu/bu offspring had a high degree of mortality, as reported previously for albino bu/bu rabbits. Newborn bu/bu rabbits initially had normal intraocular pressure (IOP; 15-23 mmHg); after 1- to 3 months, the IOP increased to 26-48 mmHg. The eyes became buphthalmic and the IOP returned to normal or sub-normal levels after 6-10 months. Since the lamina cribrosa is absent or poorly formed in the rabbit optic nerve head (ONH), this model was used to test the role of mechanical factors in the etiology of ONH pathology caused by increased IOP. Orthograde axonal transport was evaluated in both eyes from eight normal and 24 bu/bu rabbits of different ages, using intravitreal injections of [3H]leucine to mark orthograde axonal transport, followed by light- and electron-microscopic radioautography of the ONHs and superior colliculi. Normal rabbits of all ages showed no blockage of axonal transport in the ONH. All optic axons from young bu/bu rabbits with normal IOP and most axons from older buphthalmic rabbits that previously had elevated IOP were normal morphologically. Small zones of transport blockage occurred in bu/bu eyes while IOP was elevated; most affected axons lay immediately adjacent to ONH connective tissue beams that radiate outward from the central retinal vessels to the optic-nerve sheath. Thus, the rabbit, which lacks a true lamina cribrosa, does not show marked blockage of axonal transport as occurs in the LS of the monkey and cat ONH when IOP is elevated acutely. This anatomic difference appears to be protective against axonal damage, since bu/bu rabbits with chronic IOP elevation did not show significant loss of optic axons. These results are consistent with the proposed 'mechanical' theory of ONH damage resulting from increased IOP. Electron-microscopic radioautography revealed that chronically elevated IOP in bu/bu rabbits, which caused small foci of blocked ONH axonal transport against ONH beams, also caused degeneration of a few optic nerve terminals in the superior colliculi as the disease progressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗