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Anterior ischaemic optic neuropathy and intraocular pressure.

Anterior ischaemic optic neuropathy is a stroke syndrome of the distal optic nerve, characterised by disc oedema and optic nerve dysfunction--loss of central vision, loss of colour vision, a relative afferent pupillary defect, and nerve fibre layer field loss. We prospectively evaluated the changes of intraocular pressure throughout the day in 16 patients with non-arteritic anterior ischaemic optic neuropathy and 15 normal control subjects of similar age and race. The peak intraocular pressure exceeded 21 mm Hg in five of the ischaemic optic neuropathy patients but none of the controls. The mean peak intraocular pressure was 19.9 mm Hg for the ischaemic optic neuropathy group versus 17.6 mm Hg for controls (p = 0.034). The range of intraocular pressure was also greater for the ischaemic optic neuropathy group (p = 0.030). Eight of 16 ischaemic optic neuropathy patients had a range of intraocular pressure of 6 mm Hg or more, compared with three of 15 control subjects. The intraocular pressure exceeded 21 mm Hg during a subsequent visit in two additional patients in whom the hourly determined intraocular pressure peaked at less than 21 mm Hg. Thus, seven of 16 of our ischaemic optic neuropathy group had an intraocular pressure exceeding 21 mm Hg during the study period. Raised intraocular pressure may be a predisposing factor in some patients who develop anterior ischaemic optic neuropathy.

Aged↗

Serum methanol levels in subjects with or without optic nerve head disease.

We evaluated serum methanol levels in subjects with or without optic nerve head disease. Serum methanol levels were determined using gas chromatography in 71 patients with optic nerve head disease and in 127 subjects without optic nerve head disease. Their ages ranged from 17 to 89 years. Serum methanol levels in 127 subjects without optic nerve head disease ranged from 0.12 to 3.86 microg/ml (mean +/- standard deviation, 1.72 +/- 0.86 microg/ml). In the subjects without optic nerve head disease, the differences in the levels between those with cataract versus retinal detachment, men versus women, and between each age-group (50-80 years) were not significant. The methanol levels in patients with optic neuritis (n = 2), Wolfram syndrome (n = 1), Leber hereditary optic neuropathy at the late stage (n = 2), retinitis pigmentosa (n = 23), and primary open-angle glaucoma (n = 16) were less than 3.86 microg/ml. Methanol levels in 1 patient with Leber hereditary optic neuropathy at the acute stage was 5.28 microg/ml. Of 10 patients with primary angle-closure glaucoma, 1 had a slightly elevated level and 9 had levels less than 3.86 microg/ml. Of 17 patients with normal tension glaucoma, 5 had methanol levels higher than 3.86 microg/ml, and 12 patients had levels less than 3.86 microg/ml. The present study shows that serum methanol levels in subjects without optic nerve head disease ranged from 0.12 to 3.86 microg/ml and were much lower than the levels that produce acute ocular symptoms of methanol intoxication. It is possible that high serum methanol levels may play a part in the acute stage of Leber hereditary optic neuropathy and normal tension glaucoma in certain patients. It is unlikely that increased serum methanol levels participate in primary angle-closure glaucoma.

Adolescent↗

Association of retinal vessel caliber to optic disc and cup diameters.

PURPOSE: To investigate whether optic disc size is related to retinal venule and arteriole diameters. METHODS: The population of Beaver Dam, Wisconsin, aged 43 to 86 years were invited to participate in a baseline examination from 1988 to 1990. During this examination, photographs, centered on the optic discs, were taken after pupil dilation. Optic discs and cups were measured from stereoscopic photographs, whereas retinal vessel measurements were taken from a single digitized photograph. Central retinal vein and central retinal arterial equivalents were subsequently calculated. Data for 3887 right eyes are included in the analyses. RESULTS: Narrower retinal venules and arterioles were found in the smaller optic discs controlling for optic cup diameter as well as age, systolic and diastolic blood pressure, refraction, and sex. Central retinal artery equivalents ranged from 156.04 +/- 16.82 microm in the smallest optic disc category to 165.93 +/- 15.17 microm in the larger disc category (P < 0.001). Central retinal vein equivalents ranged from 228.93 +/- 21.26 microm in the smallest to 243.18 +/- 22.32 microm in the larger disc categories (P < 0.001). The significant reduction in retinal vessel diameters was only apparent for the smallest optic disc sizes. A reduction in retinal vessel diameters was less consistent and not significant for small optic cup sizes. CONCLUSIONS: Smallest optic discs were associated with smaller central retinal artery and central retinal vein diameters. This anatomic relationship may be useful as an additional associated indicator for nonarteritic anterior ischemic optic neuropathy as well as for retinal vascular events.

Adult↗

Determination of optic cup depth by confocal scanning laser tomography.

PURPOSE: To assess whether confocal scanning laser tomography of the optic disc and clinical ophthalmoscopy using stereoscopic optic disc photographs, agree in the evaluation of the deepest part of the optic cup. PATIENTS AND METHODS: The study included 33 eyes of patients with focal normal-pressure glaucoma. Using 15 degrees color stereoscopic optic disc photographs and dividing the optic disc into an upper and a lower half, two trained observers independently established the location of the deepest part of the cup. By selection, the two observers had made congruent judgements for all eyes in the study. All patients also underwent confocal scanning laser tomography of the optic disc using the Heidelberg Retina Tomograph (HRT). The location of the deepest "mean cup depth" was noted. RESULTS: The deepest optic cup region based on stereoscopic evaluation of photographs and on scanning laser tomography did not correlate significantly with each other (p=0.18; chi-square test, linear-by-linear association). According to the scanning laser tomography data, the maximal optic cup depths were not correlated with the corresponding locations of maximal visual field defect (p=0.80). Using the stereo photographic data, the locations of maximal optic cup depth and maximal visual field defect were correlated (p=0.006). CONCLUSIONS: In some glaucomatous eyes, confocal scanning laser tomographic assessment of the location of the deepest optic cup region does not agree with clinical judgement and, in contrast to clinical examination, does not correlate with the location of the maximal visual field defect.

Adult↗

The pattern electroretinogram: a long-term study in acute optic neuropathy.

We report a 2-year prospective study of the electroretinographic response to reversal of checkerboard patterns (P-ERG) obtained in 63 eyes with acute optic nerve lesions. The aim of the study was to document the value of P-ERG regarding diagnosis and prognosis of four types of optic neuropathy: optic neuritis, compressive or hereditary optic atrophy, and traumatic optic neuropathy. We documented visual loss by neuro-ophthalmologic examination and recorded pattern-reversal visual evoked potentials (P-VEP). The initial P-ERG was normal to large- and medium-sized checks in 89% and the P-VEP abnormal in 94% of eyes with acute optic nerve lesions. Forty-six eyes were followed for up to 2 years. Two groups emerged. Group A (n = 17) gradually and permanently had significant reduction of the P-ERG to three separate check sizes. All 17 had no improvement in acuity better than 20/100, retained centrocecal scotomas, and developed optic atrophy. In group B (n = 29) the P-ERG remained within normal limits to one or more check sizes. Twenty-two of these eyes recovered acuity to 20/25 or better and had resolution of the field defect. The data showed that P-VEP was superior to P-ERG in diagnosis of acute and chronic optic nerve lesions. However, significant reduction of the b-wave of the P-ERG to three separate check sizes correlated closely with failure of visual recovery and the eventual development of severe optic atrophy, suggesting a prognostic value for P-ERG in optic neuropathy.

Adolescent↗

[Structural analysis of the optic nerve head in healthy eyes and in eyes with glaucoma].

PURPOSE: Assess the possibilities of structural analysis of the optic nerve head by Heidelberg Retina Tomograph (HRT) and its use in detection of glaucomatous changes of the optic nerve in particular. Indicate the topographical parameters that are most influenced by glaucoma and are therefore vital in early diagnosis of glaucomatous changes of the optic nerve. PATIENTS AND METHODS: Laser scanning tomography (HRT II) was used to examine 68 healthy eyes (control group) and 42 eyes with open angle glaucoma (study group). All the examined subjects were older than 35 years of age. The analysis concerned the following topographical parameters of the optic nerve head: disc area, cup area and rim area, cup volume, rim volume, cup/disc area ratio, mean cup depth, maximum cup depth, mean retinal nerve fiber layer thickness (RNFL), RNFL cross sectional area, height variation contour and cup shape measure and discriminant functions used for classification of the optic nerve head finding according to F. S. Mikelberg and R. Burk. Statistical analysis was employed to ascertain the significant difference in these topographical parameters for the healthy eyes and the eyes with glaucoma. This method was used for both the whole optic disc and the 6 sectors of the optic nerve head. Another aim of the analysis was also to find out the correlation between the topographical parameters and age. RESULTS: Significant difference in the topographical parameters for the whole optic disc was spotted in the following parameters: rim volume, mean RNFL thickness, RNFL cross sectional area and discriminant function FSM. Significant differences were also found in between individual sectors of the optic nerve head, except for the upper temporal and upper nasal sector. The parameter, which varied most frequently between the groups, was rim volume. Significant correlations between age and topographical parameters were found for the following parameters: rim area, cup shape measure and mean RNFL thickness. CONCLUSION: Results of our study showed, that HRT is able to distinguish between normal and the pathological findings of optic nerve head according to topographical parameters significantly different between the two examined groups. These parameters are important in the diagnosis of glaucoma and also in the follow-up of patients with open angle glaucoma.

Adult↗

Orthograde axonal transport of optic nerve and injury--morphological study.

To investigate the effects of injury to the orthograde axonal transport in the optic nerve, horseradish peroxidase (HRP) was injected into the vitreous of the cat eye after various types of optic nerve injury, and the retina and optic nerve were examined with light and electron microscopes 8 hours after the injection. The optic nerve was sectioned in one eye at about 6 mm behind the eyeball and the optic nerve of the contralateral eye was used as the control. HRP reaction products were frequently observed within the retinal ganglion cells and their axons of the nerve fiber layer as well as in the retrolaminar optic nerve on the experimental side, and the findings were similar to those on the control side. The optic nerve was injured by cryocoagulation for 10 seconds or 30 seconds, and ischemic changes of various degrees were induced. Intracellular and intra-axonal HRP reaction products were markedly reduced at the retrolaminar portion, and the degree of reduction depended on the duration of cryocoagulation. The section of the optic nerve had, at least in the early stage, only minimal effects on the orthograde axonal transport, but the optic nerve injury accompanied by ischemic changes markedly blocked the axonal transport in both the inner part of the retina and the optic nerve.

Animals↗

Optic nerve damage in head trauma: clinical and experimental studies.

A total of 33 cases with optic nerve damage due to blunt head trauma were followed for 6 months to one year with the average follow-up period of 9 months. Eleven cases were treated by surgical decompression of the optic canal and 22 cases were followed by medical treatment. The optic canal fracture was documented in 51% of the cases, and the incidence was not significantly different between both groups. When the visual acuity was zero at the time of the first examination, no visual improvement could be obtained. Omitting these cases, visual improvement was seen in 42.8% of patients treated by surgery and in 58.8% of patients with medical treatment, which consisted of a combined use of prednisolone, mannitol, urokinase and vitamin B12. The percentage of visual improvement did not differ between cases with and without optic canal fracture. In the Japanese monkey, the optic nerve was exposed and various insults were given, including traction, ligation and small optic sheath resection. After traction and ligation, the visually evoked response (VEP) became extinguished or reduced, but after release from the insult, a tendency of recovery was found in the VEP. The threshold to elicit the VEP by localized light stimulus was increased by optic nerve ligation, but after its release the threshold tended to decrease. The effects of the optic nerve sheath resection were slight, and the increase in the threshold recovered after 4 weeks. It was thought that the optic nerve is resistant to indirect insults. From the clinical and experimental studies, it was concluded that the mechanism of the optic nerve damage due to blunt head trauma is multiple, and that the cases should be treated by intensive medical treatment rather than by surgical intervention.

Adolescent↗

Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve.

OBJECTIVE: To determine the foci and duration of protein expression following virus-mediated gene transfer to the optic nerve. METHODS: A cytomegalovirus (CMV) promoter was linked to a lacZ-SV40 polyA reporter gene or a humanized green fluorescent protein (hgfp) reporter gene, then inserted into a bacterial plasmid containing adeno-associated virus (AAV) terminal repeat sequences. The CMV-lacZ or the CMV-hgfp construct were injected into the vitreous cavity of strain-13 guinea pigs. Controls consisted of eyes injected with AAV without the promoter and reporter elements or eyes that received no injections. The eyes and optic nerves were processed for beta-galactosidase immunohistochemistry and hgfp fluorescence analyses. Cellular transduction at the messenger RNA (mRNA) level was evaluated by in situ reverse transcription-polymerase chain reaction. RESULTS: Weekly fundus photography, done for 1 month, documented the absence of any ocular abnormality due to the viral injections. No in vivo hgfp fluorescence of the retina was visualized. Beta-galactosidase histochemical analysis of eye cups that received the lacZ gene construct showed blue lacZ staining of the optic nerve head at 2 weeks. Light microscopy revealed the blue beta-galactosidase reaction product in fibers, glial cells, and blood vessels of the optic nerve head and retrobulbar nerve. Histochemistry showed absence of beta-galactosidase in the optic nerve at 3 to 12 months, but immunochemistry showed the persistence of beta-galactosidase in fibers, glial cells, and blood vessels as late as 1 year after a single ocular injection. In the retina, histochemical staining showed evidence of lacZ at 3 months, but not later. In situ reverse transcription-polymerase chain reaction revealed brown lacZ mRNA reaction product in ganglion cells of the retina. Control eyes that received AAV without the promoter and reporter elements and the eyes that received no viral injections and were processed for beta-galactosidase showed no reporter gene expression in any ocular tissue or cell type. CONCLUSIONS: Viral-mediated gene transfer can be successfully accomplished in the optic nerve. Further evaluation is needed to determine whether the level of protein expression at 1 year after injection, which is clearly reduced relative to shorter postinjection time, is sufficient for therapeutic purposes. CLINICAL RELEVANCE: We have previously shown that gene therapy with catalase suppressed experimental optic neuritis at 1 month after injection. Viral-mediated gene transfer may be a powerful technique for the treatment of optic neuropathies, particularly for recurrences of optic neuritis, if long-term expression of transduced protein can be demonstrated in the optic nerve.

Animals↗

Race-, age-, gender-, and refractive error-related differences in the normal optic disc.

OBJECTIVE: To determine race-, age-, gender-, and refractive error-related differences in the size and topography of the optic disc in healthy Americans. DESIGN: Population-based study. SETTING: Eastern and southeastern health districts of Baltimore, Md. PARTICIPANTS: A population-based sample of 4877 non-institutionalized black and white individuals aged 40 years or older without evidence of optic nerve disease. MAIN OUTCOME MEASURE: Race-, age-, gender-, and refractive error-related differences in optic disc measurements: disc area, neural rim area, cup area, cup-to-disc ratio, and neural rim area-to-disc area ratio. RESULTS: We analyzed simultaneous stereoscopic optic disc photographs from 3387 (1534 black and 1853 white) of the 4877 healthy individuals using an image analyzer (Topcon Image Analyzer, Topcon Instrument Corporation, Paramus, NJ). A total of 1490 individuals were excluded owing to the absence of good-quality images from either eye. The image analyzer defined the cup margin 150 microns below the surface of the disc margin. On average, blacks had significantly larger disc areas (blacks, 2.94 mm2; whites, 2.63 mm2), larger cup areas (blacks, 1.04 mm2; whites, 0.71 mm2), larger cup-to-disc ratios (blacks, 0.56; whites, 0.49), similar neural rim areas (blacks, 1.90 mm2; whites, 1.92 mm2), and smaller neural rim area-to-disc area ratios (blacks, 0.66; whites, 0.74) compared with whites. There were no age-related differences in any of the disc measurements. Male subjects had 2% to 3% larger optic discs compared with female subjects. No association between refractive error and any of the optic disc measurements studied was detected. CONCLUSIONS: Racial differences in the normal optic disc are present among urban Americans, and these differences must be considered in evaluation of the optic disc for glaucoma and other optic neuropathies. Among the individuals in our study, all of whom were 40 years of age or older, no progressive age-related decline in neural rim area was detectable. Neither gender nor refractive error were associated with any significant differences in the size and topography of the normal optic disc.

Adult↗

Retinotopy of the human retinal nerve fibre layer and optic nerve head.

The organisation of the primate nerve fibre layer and optic nerve head with respect to eccentricity or the positioning of central and peripheral axons remains controversial. Crystals of the carbocyanine dyes DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), or DiA (4-[4-didecylaminostryryl]-N-methylpridiniumiodide) were used to trace retinal ganglion cell axons within the nerve fibre layer, optic nerve head, and optic nerve. The present study demonstrated that peripheral retinal axons were scattered throughout the vitreal-scleral depth of the nerve fibre layer. This scattered distribution was maintained as the fibres passed through the optic nerve head and into the optic nerve. Axons of the arcuate bundles showed a bias towards the scleral portions of the nerve fibre layer and a variable degree of fibre scatter across the nerve fibre layer which was not as evident in labelling from other retinal regions. There was a rough topographic representation within the optic nerve head according to retinal circumference such that both peripheral and central fibres were mixed within a wedge extending from the periphery to the centre of the nerve. Foveal fibres occupied a large proportion of the temporal aspect of the optic nerve head and nerve, whereas fibres from areas temporal to the fovea appeared to be displaced to more superior and inferior regions. Consistent with the scleral bias seen in the retina, arcuate fibres maintained a peripheral position as they passed through the optic nerve head and occupied a more peripheral position in the nerve. The present results suggest that any degree of order present within the optic nerve is not an active process; optic axons are not instructed to establish a retinotopic order within the initial portions of the visual pathway.

Adult↗

Prenatal development of central optic pathways in albino rats.

The development of the central optic projections in albino rat fetuses has been studied using light and electron microscopic degeneration techniques and the horseradish peroxidase method for demonstrating axonal projections of neurons. The first optic axons to reach the region of the optic chiasm arrive at day 15. By day 16, a substantial optic chiasm is seen and the optic tract can be traced into the epithalamus, having first passed through the ventral lateral geniculate nucleus and a thin lamina of cells which is thought to correspond to part of the future dorsal geniculate nucleus. A growth rate of 80-100 mum per hour is estimated for the fastest growing axons. By day 16-1/3 the first axons have entered the anterior border of the superior colliculus and in the next day have grown across the entire rostrocaudal extent with the exception of the medial and lateral edges. The optic axons are recognized at day 17 as bundles lying just below the surface, but in older animals they come to lie deeper, as the whole layer of optic innervation broadens. The first synapses to be formed in the superior colliculus (some of them of optic origin) appear on day 17. Subsequently, there is a gradual increase in the number of contacts, the great majority being formed by optic axons. Compared with previous studies on Xenopus and chick, one of the most striking features of the development of the central visual connections in the rat is the relatively long time before the first optic axons reach the brain and the speed with which they innervate the central structures once they have arrived.

Animals↗

Long-term survival of centrally projecting axons in the optic nerve of the frog following destruction of the retina.

A significant number of unmyelinated axons and their synaptic endings in the frog, Rana pipiens, were found to retain a normal morphology long after separation from their cell bodies. At the end of various survival periods following unilateral removal of the retina, horseradish peroxidase (HRP) was administered to the optic nerve stump by a fiber-filling method. In frogs maintained at 20 degrees C, unmyelinated optic nerve axons conducted HRP from the site of application in the orbit to layers A, C, and E of the contralateral optic tectum, even though their retinas had been removed up to 69 days earlier. Such fiber-filling was absent beyond 19 days in other frogs surviving at 35 degrees C. No labeled fibers were continuous with any intracerebral neurons. The HRP was always localized intraaxonally, and the marked axons and terminals were ultrastructurally normal. Counts of surviving axons from electron micrographs of the optic nerves showed that, at 20 degrees C, more than half of the normal complement of unmyelinated axons disappeared in the first 10 days. All the myelinated axons degenerated during the first 6 weeks survival. However, approximately 55,000 normal-appearing unmyelinated axons (12% of the unmyelinated fiber population) persisted in the optic nerve at 10 weeks following removal of the retina. The survival rate was lower at 35 degrees C. In other frogs, one eye was injected with 3H-leucine to initiate axonal transport into the retinal ganglion cell axons. That eye was removed 48 hours later. Autoradiographic analysis of brain sections of frog surviving an additional 31 to 61 days at 20 degrees C showed strong labeling of the optic tract and layers A, C, and E of the contralateral optic tectum. The absence of displaced ganglion cells that might exist within the optic nerve was verified by other observations. It is hypothesized that the potential shown by frog optic axons for long-term survival in the absence of the cell-body expresses a general property of vertebrate (and invertebrate) axons, rather than a special property of the frog optic nerve.

Animals↗

Connections of the octopus optic lobe: an HRP study.

The major visual centers of the octopus central nervous system are the paired optic lobes. Bidirectional transport of horseradish peroxidase (HRP) was used to determine connections of the optic lobe. Cells afferent to the optic lobe were identified by retrograde HRP transport in the following lobes of the central ganglia: anterior basal, median basal, dorsal basal, interbasal, subvertical, precommissural, brachial, and magnocellular. Labeled cells were also observed within the contralateral optic lobe, various optic tract lobes bilaterally, and in photoreceptors of the ipsilateral retina. Additionally, individual fibers, in part originating from cells in the posterior subvertical lobe, were labeled within the central neuropil core of various vertical lobules. Differences in results between superficial and deep optic lobe medulla injections indicate that some afferent projections from central sources may terminate on cell populations at specific depths within the lobe. Efferent optic lobe fibers into the superior frontal and lateral basal lobes were labeled by anterograde transport. Other possible optic lobe efferent projections terminated in supraesophageal lobes and the magnocellular lobe. The many inputs to the optic lobe from higher motor and associative centers in the central ganglia emphasize that the medulla region of the optic lobe is an exceptionally complex integrative area.

Animals↗

Retinotopic and chronotopic organization of goldfish retinal ganglion cell axons throughout the optic nerve.

The organization of the retinal ganglion cell (RGC) axons within the goldfish optic nerve head and optic nerve was established by labeling select groups of axons either autoradiographically or with cobaltous lysine. In the optic nerve head, the axons are organized eccentrically with respect to their time of development. Axons of older RGCs are located dorsally and those of younger RGCs are located ventrally. The retinal sectors map across the rostrocaudal axis of the optic nerve head, resulting in four dorsoventrally oriented columns that contain, from rostral to caudal, the axons of ventronasal, dorsonasal, dorsotemporal, and ventrotemporal RGCs. Thus, the optic nerve head is organized into orthogonally oriented laminae. One dimension maps the age of the axons and the other maps the retinal sector of the axons' origin. The optic nerve is organized virtually in the same fashion as the optic nerve head. However, glial septa that invade the optic nerve severely distort, but do not eliminate, the columnar organization of the retinal sectors. These septa deflect many RGC axons and disrupt nearest-neighbor relationships. The distortions produced by the glial septa include folding of the columns and distortion of the chronological lamination. However, the glial septa do not extend into the optic foramen. Therefore, a virtually undistorted columnar organization reappears in the optic foramen. Several roles for the glial septa are discussed.

Animals↗

Course of retinogeniculate projection fibers in the cat optic nerve.

The fiber courses of the cat optic nerve were studied by using wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), which was iontophoretically applied to electrophysiologically defined positions in the lateral geniculate nucleus (LGN). Grossly, there were two distinct bends along the length of the optic nerve. The ventrally flexing anterior bend was located approximately 2 mm from the eyeball, while the dorsally flexing posterior bend was found at some 6 mm distant. The optic nerve fibers showed a tendency to scatter toward the chiasm. At the optic nerve head, the fibers from the different retinal areas maintained the retinal topography in a simplified form according to the trajectory of optic fibers surrounding the optic disc. Between the anterior and posterior bends, the fibers from the pericentral, middle-temporal, and most upper areas of the dorsal retina migrated ventrally and were arranged in the middle of the lateral, middle, and medial parts of the optic nerve, respectively, while fibers from the middle-temporal area of the ventral retina migrated dorsally and scattered into the lateral half. The fibers from the temporal and nasal horizontal meridian areas tended to hold their respective positions in the lateral and medial halves of the optic nerve. As a result, in this level they displayed a complex retinotopy in that the fibers from each part of the retina were mixed. Passing the posterior bend, as the optic nerve proceeded toward the chiasm, the characteristic pattern became less defined. Near the chiasm, the retinotopy became very scattered, showing a partial dorsoventral inversion of the retinal topography with substantial overlapping. It was noted from the present findings that the fibers from ventral retina scattered more quickly than the fibers from the dorsal retina, which tended to hold their grouping until the anterior bend, but the central or pericentral retinal fibers proceeded without significant scatter as far as the posterior bend. The analysis of labelled ganglion cells suggested that even if fibers that arise from one certain "mode" of ganglion cells are selected, it is unlikely that they maintain their initial fiber topography along the entire length of the optic nerve.

Animals↗

Abnormal pigmentation and unusual morphogenesis of the optic stalk may be correlated with retinal axon misguidance in embryonic Siamese cats.

Studies of albino rodents have shown that an absence of pigment in the developing optic stalk may alter the position of the first retinal fibers that grow toward the brain, thereby disrupting the gross topographic relationship of fibers in the nerve (Silver and Sapiro: J. Comp. Neurol. 202:521-538, '81). The abnormalities associated with albinism are more extensive in the Siamese cat than-in previously studied species. Therefore, any abnormalities in differentiation of the stalk and axon guidance may be more readily detected. To investigate the guidance and/or misguidance of optic axons, light and electron microscope analyses were made of serial sections through the optic stalk in normally pigmented and Siamese fetal cats. On E20, before axons enter the optic stalk, the only clear morphological distinction between Siamese and normal cats is the distribution of pigment in the stalk. Pigment is found in the dorsal stalk cells of the normal cat for 200 microns from the optic disc. Although the retinal pigment epithelium of the Siamese optic stalk. By E23 axons invade the ventral optic stalk in both strains. Concurrent with the early stages of axonal exit from the retina, there is complete separation of the stalk's dorsal and ventral tiers. As the cleavage occurs, basal lamina invaginates into the zone of separation following along the plane of the old lumen. The ventral stalk fills with axons while the dorsal tier is shed gradually. In contrast, in the Siamese cat, dorsal stalk cells are not sloughed off properly and instead are incorporated ectopically into the nerve. Basal lamina invagination is irregular. Axons do not fill the Siamese stalk symmetrically but enter the region of ectopic cells, which in turn disrupts gross fiber position. Usually, in the mutant, axons originating from the retina temporal to the optic fissure are those that invade the dorsal tier of ectopic cells. The altered position of optic axons in the mutant stalk may provide an explanation for the chiasmatic misrouting of optic axons in this species.

Albinism↗

Further study of the outward displacement of retinal ganglion cells during optic nerve regeneration, with a note on the normal cells of Dogiel in the adult frog.

In a previous study we observed massive retinal ganglion cell death in adult Rana pipiens after periods of optic nerve regeneration, and reported that large numbers of the surviving cells had become displaced bodily into the inner plexiform layer of the affected eye (Scalia et al.: Brain Research 344:267-280, 1985). The outwardly displaced cells could be identified as retinal ganglion cells because they could be back-filled with horseradish peroxidase (HRP) injected into the regenerated optic nerve. Quantitative observations on the abnormal outward displacement of ganglion cells are reported here. Parallel observations on normally displaced ganglion cells (cells of Dogiel) are also reported to clarify the distinctions between these two classes of cells. For the present work, injections of HRP of varying size were placed in the optic tectum bilaterally in 3 normal frogs and 9 frogs sustaining unilateral optic nerve regeneration. Most injections were centered at loci mapping the middle region of the nasal retina. The retinas were examined as flat-mounts and in-section. In 8 other frogs sustaining optic nerve regeneration, the HRP was administered bilaterally directly to the optic nerves in the orbit. Ganglion cells were labeled by retrograde transport of the HRP in the retinal ganglion cell layer in both the normal and affected eyes in areas topographically isomorphic with the tectal areas subtended by the injections. In the normal eyes, the orthotopic ganglion cells formed a strict monolayer, and virtually no cells existed in the inner plexiform layer. In the retinas sustaining optic nerve regeneration, the retinal ganglion cells abnormally displaced into the inner plexiform layer were also labeled topographically in correspondence with the injection sites. The abnormally displaced cells comprised 5.5% of the total population of surviving neurons in the retinal ganglion cell and inner plexiform layers. The mean outward dislocation of the displaced cells, as measured in one frog surviving optic nerve crush for 8 weeks, was 69.9 +/- 2.4% of the distance across the inner plexiform layer, which itself was uniformly 14.3 +/- 0.39 microns thick. Cells of Dogiel, which were embedded within the inner nuclear layer, were also labeled when the injections of HRP spread to include the area of representation of the optic disc. The labeled cells were restricted to a dorsal, peripapillary locus capping the optic disc. Therefore, some cells of Dogiel project to the tectum normally, but only from the central retina.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Ocular↗