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Glial domains and nerve fiber patterns in the fish retinotectal pathway.

Optic nerve fibers run parallel from the retina as far as the optic tract in fish, then suddenly criss-cross into a new pattern matching the tectal map. This change coincides with a unique demarcation between two astroglial territories in the retinotectal pathway, located where the optic chiasm occurs in other vertebrates, which we defined using antibodies directed against intermediate filaments (IF). We found that astroglia in optic nerve territory express an Mr 56,000 IF polypeptide, band 3, which we identify as the fish equivalent of vimentin in mammals. These astrocytic cells lack glial fibrillary acidic protein (GFAP; cf. Dahl and Bignami, 1973). Conversely, glia in brain territory, that is, in the optic tract and elsewhere in the CNS, lack the fish vimentin, but express GFAP. By electron microscopy, we obtained evidence that new retinal axons extend swiftly through the growing optic nerve, where they are tightly shepherded into a narrow track by newly differentiating glial cells, positive for the fish vimentin. In the GFAP-positive glial territory of the optic tract, by contrast, growing axons are slowed down and probably branch. We suggest that this allows them to fasciculate accurately with older fibers and thereby propagate a tectotopic pattern established by pioneer axons in the embryo.

Animals↗

Malignant gliomas of the optic nerve pathways.

We compared the clinical course and histopathologic findings in five patients with malignant gliomas originating from the optic nerve pathways with those in previously reported cases to elucidate further the clinical features of this tumor and facilitate future diagnoses. Patients with malignant optic nerve pathway gliomas had unilateral or bilateral visual dysfunction, which was often accompanied by periorbital discomfort in an otherwise asymptomatic adult. Regardless of origin, the clinical course invariably was bilateral blindness rapidly followed by death. Occasionally, the diagnosis was made preoperatively and was confirmed by surgical exploration and biopsy.

Aged↗

Optic-nerve gliomas, chiasmal gliomas and neurofibromatosis type 1.

PURPOSE OF REVIEW: To review the most recent literature describing the natural history and disease progression patterns of optic-pathway gliomas in neurofibromatosis type 1 (NF1) patients. To aid in clarifying the current treatment patterns and follow-up recommendations. RECENT FINDINGS: Contrary to prior documentation, current literature reveals that optic-pathway gliomas in NF1 can be diagnosed after the age of 6, and may progress until the age of 12. The disease progression occurs most frequently in the first two years following diagnosis. SUMMARY: Optic-pathway gliomas in NF1 can display a variety of manifestations and exhibit an unpredictable disease course. No specific characteristics have been found thus far to predict an aggressive compared with indolent disease course. Recently primary diagnoses of optic-pathway gliomas have been made in children aged six or older, and have been shown to progress until the age of 12. Although large-scale studies are required to change current follow-up recommendations, the data suggest that NF1 patients should be vigilantly evaluated for optic-pathway gliomas past the age of 12.

Humans↗

Optic tract edema: a highly specific magnetic resonance imaging finding for the diagnosis of craniopharyngiomas.

PURPOSE: To clarify the accuracy, sensitivity, and specificity of optic tract edema in the diagnosis of craniopharyngiomas. MATERIAL AND METHODS: Preoperative magnetic resonance images (MRIs) of 49 patients (between May 1996 and March 2003) who had a diagnosis of parasellar masses were blindly reviewed by two radiologists. The spread of edema surrounding the tumor on the coronal TSE T2-weighted images was analyzed. Sensitivity and specificity were calculated based on the numbers in this series and also pooled numbers from previous known reported series. RESULTS: Edema along the optic tracts was detected in 7 of 11 craniopharyngiomas, giving a sensitivity of 63.6% (95% CI = 30.8-89.1) for our series and 66.7% (95% CI = 47.2-82.7) for the pooled numbers. The specificity was 100% (95% CI = 90.7-100.0) for our series and 93.9% (95% CI = 87.1-97.7) for the pooled numbers. None of the 28 pituitary macroadenomas, 4 meningiomas, 2 hypothalamic astrocytomas, 2 germinomas, 1 mixed-germ cell tumor and 1 arachnoid cyst in our study showed edema of the optic pathways. CONCLUSION: Optic tract edema, commonly seen in craniopharyngiomas, is a useful MR finding for distinguishing craniopharyngiomas from other parasellar tumors with considerable sensitivity and high specificity.

Adolescent↗

MRI findings in children with neurofibromatosis type 1: a prospective study.

To determine the frequency and nature of MRI lesions in children with neurofibromatosis type I (NF1), 50 patients aged 8 to 16 years were evaluated prospectively with cranial MRI. Forty-one children were asymptomatic with respect to central nervous system pathology, and 50% were macrocephalic. Sixteen patients (32%) had normal MRI examinations. Thirty-two patients (64%) had high intensity lesions on T2-weighted images and 16 patients (32%) had hyperintense lesions on T1-weighted images. Seven patients (14%) had ventricular dilatation (associated with increased intracranial pressure in 2) and 11 patients (22%) had optic pathway lesions (optic glioma in 7). MRI was superior to CT in differentiating optic sheath thickening and optic nerve tortuosity from optic glioma in four patients. An intracranial tumour (ependymoma) and sphenoid wing dysplasia were evident in individual patients. Findings previously unreported in NF1 included an aqueductal web resulting in hydrocephalus, intraocular neurofibroma resulting in retinal detachment, and asymptomatic enlargement of the septum pellucidum. T1 and T2 signal abnormalities in isolation were not associated with neurological deficits or the occurrence of macrocephaly, and all lesions that required intervention were suspected clinically. Macrocephaly in the absence of increased intracranial pressure or accelerated head growth is not an indication for neuroimaging in children with NF1. However, the majority of children (68%) had disease-specific abnormalities and thus MRI may provide a useful adjunct to clinical evaluation in the diagnosis of equivocal cases.

Brain↗

A breakdown of the blood-brain barrier is associated with optic nerve regeneration in the frog.

We have examined the integrity of the blood-brain barrier during optic nerve regeneration in the frog Litoria (Hyla) moorei using rhodamine B-labeled bovine serum albumin (RBA). A transient localized breakdown of the blood-brain barrier was observed between 1 and 5 weeks after extracranial optic nerve crush. The zone of breakdown progressed along the experimental optic nerve, ascended the opposite optic tract, and swept rostro-caudally across the tectum contralateral to the crushed nerve. By 7 weeks, the blood-brain barrier was once again intact along the length of the optic pathway. In a concurrent series of frogs, regenerating optic axons were visualized by anterograde transport of horseradish peroxidase (HRP). At each stage examined, the region reached by the front of regenerating axons corresponded to that in which the blood-brain barrier had been shown to break down. In contrast to the results after nerve crush, the blood-brain barrier remained intact along the length of the optic pathway following optic nerve ligation to prevent regeneration. We conclude that the breakdown of the blood-brain barrier which occurs during optic nerve regeneration in the frog is triggered by the regenerating axons.

Animals↗

Sudden infant death due to neurofibromatosis type I.

Sudden infant death syndrome (SIDS) is the unexpected death of an infant under the age of 1 year, where a complete autopsy, including scene investigation, fails to reveal a cause of death. Although the frequency of SIDS has decreased almost 50% over the past 10 years, it remains the leading cause of death in infants aged 1 to 6 months. SIDS is a diagnosis of exclusion and requires the elimination of a wide range of possible causes, including asphyxia, poisoning, abuse, occult heart disease, and other natural disease processes. In this report, we describe the case of an infant death initially suspected to be a SIDS death in which autopsy revealed an optic pathway glioma (optic glioma or hypothalamic glioma) and other stigmata of neurofibromatosis type I.

Autopsy↗

A single-cell analysis of early retinal ganglion cell differentiation in Xenopus: from soma to axon tip.

Intracellular injections of Lucifer yellow (LY) were made into the cell bodies of Xenopus retinal ganglion cells from the earliest stages of axonogenesis to the beginning of target innervation. Embryos were intact during the injection so that the entire cell (cell body, dendrites, axon, and growth cone) could be visualized. The purpose of the study was 3-fold: (1) to characterize the early steps in retinal ganglion cell differentiation before the axon reaches its target; (2) to determine whether guidepost cells exist as possible navigation cues in the vertebrate optic pathway; and (3) to investigate whether the morphology of early retinal ganglion cell growth cones varies in a position-dependent manner along the primordial optic pathway. Axons were generally initiated before dendrites and followed a well-defined course along the primordial optic pathway without branching. Surprisingly, at least 5% of the retinal ganglion cells sent more than one axon into the optic pathway. Sister axons from the same parent cell traveled separately in the pathway, indicating that their growth cones navigated independently. Examination of dendrite genesis showed that dendrites usually begin to emerge from the cell body well before the axon tip reaches the target. This observation argues against the possibility that target contact influences dendrite initiation. Nascent dendrites were commonly tipped with pronounced varicosities that did not resemble axon growth cones. Their number and branching correlated well with axon length, indicating that the age of the retinal ganglion cell itself, rather than the age of its presynaptic cells or local environment, is the strongest influence on dendrite genesis. Examination of LY-filled growth cones at varying points in the pathway showed no evidence of dye transfer to adjacent cells. This indicates that gap junctional contacts probably do not form during axonal pathfinding and suggests that direct intercellular communication between growing axons and other cells in the pathway does not play a major role in axon guidance. Growth cone morphology was analyzed quantitatively and found to vary at different positions along the pathway. Growth cones entering the optic nerve head were the largest and most complex; those on the retinal surface were the smallest and showed a simple morphology. Growth cones in the chiasm and optic tract showed a degree of complexity similar to those in the optic nerve head but were smaller.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

CT in homonymous hemianopia.

Computed tomography (CT) is useful for demonstrating a lesion of the optic pathway, because a slice of the brain almost parallel to the optic pathway can be viewed and the relationship between the optic pathway and the extent of the lesion can be demonstrated. We studied 53 cases of homonymous hemianopia by CT. In 85% of our cases, positive CT findings were obtained. When the lesion was in the occipital lobe, correlation between the size of the lesion and the type of visual field defect was observed.

Brain Neoplasms↗

Tenascin-R as a repellent guidance molecule for newly growing and regenerating optic axons in adult zebrafish.

In adult fish, in contrast to mammals, new optic axons are continuously added to the optic projection, and optic axons regrow after injury. Thus, pathfinding of optic axons during development, adult growth, and adult regeneration may rely on the same guidance cues. We have shown that tenascin-R, a component of the extracellular matrix, borders the optic pathway in developing zebrafish and acts as a repellent guidance molecule for optic axons. Here we analyze tenascin-R expression patterns along the unlesioned and lesioned optic pathway of adult zebrafish and test the influence of tenascin-R on growing optic axons of adult fish in vitro. Within intraretinal fascicles of optic axons and in the optic nerve, newly added optic axons grow in a tenascin-R immunonegative pathway, which is bordered by tenascin-R immunoreactivity. In the brain, tenascin-R expression domains in the ventral diencephalon, in non-retinorecipient pretectal nuclei and in some tectal layers closely border the optic pathway in unlesioned animals and during axon regrowth. We mimicked these boundary situations with a sharp substrate border of tenascin-R in vitro. Optic axons emanating from adult retinal explants were repelled by tenascin-R substrate borders. This is consistent with a function of tenascin-R as a repellent guidance molecule in boundaries for adult optic axons. Thus, tenascin-R may guide newly added and regenerating optic axons by a contact-repellent mechanism in the optic pathway of adult fish.

Animals↗

Phased-array surface coil MR of the orbits and optic nerves.

PURPOSE: To devise a practical technique for high-resolution evaluation of the anterior optic apparatus using a phased-array surface coil system, and to evaluate this system in patients with suspected optic pathway abnormalities. METHODS: A four-element phased-array coil pair was placed on each side of the head, and signal-to-noise measurements were obtained using a head phantom. Comparison between the phased-array coil, the quadrature coil, and a single-turn 12.7-cm (5-in) surface coil was done. T1 spin-echo and T2 fast spin-echo sequences were obtained in the oblique axial and oblique sagittal planes, to approximate the long axis of the optic nerves and the nonoblique coronal plane. RESULTS: The phantom signal-to-noise measurements at simulated locations of the optic nerve head, optic canal, and optic chiasm revealed an improvement of at least 30% using the phased-array system. Of 24 imaged cases, 9 had trauma, 5 had suspected neoplasms, and 2 had optic neuritis. In 3 patients, an unexpected diagnosis of optic pathway contusion or infarction was made. The remaining 8 patients had various suspected visual pathway lesions. CONCLUSION: Phased-array surface coils allow rapid, thin-section imaging of the entire anterior optic pathway, with improved signal-to-noise ratio. This may improve evaluation of optic pathway lesions over conventional techniques.

Adolescent↗

Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway.

Optic neuritis is one of the most common clinical manifestations of multiple sclerosis (MS), a chronic inflammatory disease of the CNS. High-dosage methylprednisolone treatment has been established as the standard therapy of acute inflammation of the optic nerve (ON). The rationale for corticosteroid treatment lies in the antiinflammatory and immunosuppressive properties of these drugs, as shown in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Optic neuritis was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE. By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase (MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. The methylprednisolone-induced inhibition of MAPK phosphorylation was calcium dependent. Hence, we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen.

Animals↗

Complete penetration of the optic chiasm by an unruptured aneurysm of the ophthalmic segment: case report.

BACKGROUND: It is well known that aneurysms of the ophthalmic segment sometimes elevate the optic nerve or chiasm, and in case of large or giant aneurysms, the optic apparatus can be dramatically thinned. Nonetheless, they rarely penetrate the optic pathway completely. To our knowledge, no previous reports have dealt with the complete penetration of the optic chiasm by unruptured aneurysms of the ophthalmic segment. CASE DESCRIPTION: A 70-year-old woman presented with visual dysfunction in her left eye that she had experienced for several months. Her left visual acuity had rapidly deteriorated to the level of finger counting and visual field testing demonstrated nasal hemianopsia in the left eye and upper temporal quadrant hemianopsia in the right eye. Left internal carotid angiograms and three-dimensional digital subtraction angiograms showed an aneurysm of the ophthalmic segment projecting superomedially. Intraoperative findings revealed complete penetration of the optic chiasm by the fundus of the aneurysm. The optic pathway adjacent to the dome had become remarkably thin and dark yellow. After clipping was completed, the fundus of the aneurysm was punctured to decompress the optic chiasm. Postoperatively, patient's visual acuity in the left eye gradually recovered, but the visual field deficit persisted after the operation. CONCLUSION: This rare case demonstrates the potentially aggressive behavior of unruptured aneurysms of the ophthalmic segment. Patients with unruptured aneurysms of the ophthalmic segment who present with visual symptoms should be treated with surgical clipping to decompress the optic pathway as soon as possible.

Aged↗

Selective release of N-acetylaspartylglutamate from rat optic nerve terminals in vivo.

Glutamate (Glu) and aspartate (Asp) are considered to be the neurotransmitters of the optic pathway in submammalian species, but their roles in mammals is uncertain. Recently, N-acetylaspartylglutamate (NAAG) has been proposed as a neurotransmitter in mammalian optic pathway; however, the release of endogenous NAAG on stimulation of the optic pathway has not been demonstrated. Using an in vivo microdialysis technique, we now report that electrical stimulation of rat optic nerve markedly increased the extracellular concentration of NAAG but not Glu/Asp in superficial superior colliculus where retinal afferents terminate, whereas non-specific stimulation of neurotransmitter release by high potassium or veratridine increased both extracellular Glu/Asp and NAAG concentration in the perfusate. The release of NAAG was dependent on Ca2+ and the presence of optic terminals. We conclude that NAAG is a better candidate as a neurotransmitter of rat optic nerve terminals than Glu/Asp.

Animals↗

Regeneration of the frog optic nerve. Comparisons with development.

Developing and regenerating frog optic axons grow within optic pathways and form connections only with optic targets. However, unlike normal development, many regenerating optic axons in the adult frog are misrouted within optic pathways, including axons that grow into the opposite retina. Many of the axons misrouted during regeneration appear to be collaterals of axons that grow in normal directions. Ganglion cell loss of up to 60% occurs after optic nerve damage, beginning prior to reinnervation of optic targets. Massive axonal collateralization also takes place near the point of nerve damage, causing the normal order found within the nerve to be lost. Collaterals are eliminated as selective reinnervation is completed, and the smaller complement of optic cell axons remaining after regeneration form an expanded projection within optic targets. Evidence is reviewed that suggests that factors involved in axonal guidance and target recognition during development remain intact in the adult frog brain. Additional conditions resulting from nerve injury causes axonal guidance to be less successful during regeneration.

Animals↗

Laminin alpha 2 chain (M chain) is found within the pathway of avian and murine retinal projections.

Laminin-1 is found at the end-feet of neuroepithelial cells along the outer margin of the optic pathway during early stages of development. Prior to the establishment of most retinal projections in vivo, laminin-1 expression becomes restricted to basement membranes associated with the eye and optic pathway. We report that, in contrast to the alpha 1, beta 1, and gamma 1 chains of laminin-1, laminin alpha 2 chain (formerly laminin M chain) is expressed within the pathway of avian and murine retinal ganglion cell (RGC) growth cones as they extend into the optic nerve, across the optic chiasm and into the brain. Expression of laminin alpha 2 chain is reduced soon after formation of the visual projections but nevertheless maintained at non-basal lamina sites within the adult optic nerve. Laminin alpha 2 chain, in contrast to laminin-1 chains, is also highly expressed in the developing avian tectobulbar pathway. Chick optic nerve derived type-1 astrocytes in culture express laminin alpha 2 chains as extracellular fibrils on their surface. Laminin alpha 2 chain was also detected on the surface of cultured embryonic retinal neurons and developing RGCs. These results suggest that astrocytes and/or RGCS may synthesize laminin alpha 2 chain along the developing optic pathway, and imply that laminin alpha2--in a complex with non-beta1 and non-gamma1 laminin chains-may serve as an adhesive substrate and possibly as a guidance cue for elongating RGC growth cones in vivo.

Aging↗

Transient expression of somatostatin receptors in the rat visual system during development.

The ontogeny of somatostatin receptors in the rat visual system was studied by auto-radiography, using [125I-Tyr0,DTrp8]S14 as a radioligand. The binding sites showed high affinity for somatostatin and somatostatin analogues, and were regulated by GTP as early as day 16 of fetal life (E16), indicating that they represent functional somatostatin receptors. The density of somatostatin receptors was quantified by computerized image-analysis of film autoradiograms, and by grain counting on emulsion-coated slides. During fetal life, somatostatin receptors were observed in the retina, optic nerve, optic chiasma, optic tract, and lateral geniculate nucleus. The highest densities of somatostatin receptors were measured from E16 to E18 in the retina and primary optic pathways. During the first postnatal days, the density of somatostatin receptors decreased dramatically in the retina. In both the optic pathways and dorsal lateral geniculate nucleus, somatostatin receptors gradually disappeared, and the levels of somatostatin receptors were almost undetectable at postnatal day 21 (P21). Conversely, the density of somatostatin receptors remained stable in the ventral lateral geniculate nucleus during the early postnatal life (P0-P7). The timing of expression and the localization of somatostatin receptors in the developing visual system suggest that the immature ganglion cells are responsible for the expression of these evanescent somatostatin receptors. After eye opening, the distribution patterns of somatostatin receptors in the retina and the lateral geniculate nucleus were similar to those observed in adults. In particular, from P14 onwards, somatostatin receptors were concentrated in the inner plexiform layer and, to a lesser extent, in the ganglion cell and photoreceptor layers. In the ventral lateral geniculate nucleus, a heterogeneous distribution of somatostatin receptors was noted, the highest densities being found in the intergeniculate leaflet and the medial zone limiting the parvo-magnocellular interface. The distribution of somatostatin receptors in the retina and the ventral lateral geniculate nucleus after the second postnatal week, together with the presence of somatostatin-like immunoreactive elements in these structures, provide support for the involvement of somatostatin as a neurotransmitter or neuromodulator in the visual system of the adult rat. Conversely, the transient expression of somatostatin receptors observed before maturation and complete organization of the optic pathways suggests that somatostatin plays a trophic role during development of the visual system.

Aging↗

Electrophysiology of the optic nerve: recent insights.

The introduction of automated recording and processing systems, the development of electro-optical technologies, and the numerous findings deriving from experimental electrophysiology have intensified the interest in electrofunctional non-invasive tests for optic pathways studies. Pattern ERG was demonstrated as the most efficacious stimulus to investigate the ganglion cell activity. The contrast sensitivity measurement by means of electrofunctional methods, contribute to obtain more information about the retinal and optic pathways functionality. The utility of electrofunctional and psychophysic methods in some pathologies of optic pathways (diabetes opticopathy, endocular hypertension, retrobulbar neuritis) is discussed.

Animals↗