Ganglion Cells In Central Retina Research Articles

Assessment of objective visual function following idebenone administration in patients with leber hereditary optic neuropathy.

To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage. A descriptive study involving four confirmed LHON patients. Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms. Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends. fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation.

Contribution of parasol-magnocellular pathway ganglion cells to foveal retina in macaque monkey

Parasol-magnocellular pathway ganglion cells form an important output stream of the primate retina and make a major contribution to visual motion detection. They are known to comprise ON and OFF type response polarities but the relative numbers of ON and OFF parasol cells, and the overall contribution of parasol cells to high-acuity foveal vision are not well understood. Here we use antibodies against carbonic anhydrase 8 (CA8) and intracellular injections of the liphilic dye DiI to show that CA8 selectively labels OFF parasol cells in macaque retina. By combined labeling with CA8 antibodies and a previously-described marker for parasol cells (GABAA receptor antibodies), we show that ON and OFF parasol cells each comprise ∼ 6% of all ganglion cells in central retina (each peak density ∼ 3000 cells/mm2 at 5 deg.), and each population comprises ∼ 10% of all ganglion cells in peripheral temporal retina. Thus, the spatial density of parasol cells in central retina is greater than reported by previous anatomical studies, and the central-peripheral gradient in parasol cell density is shallower than previously reported. The data nevertheless predict decline in spatial acuity with visual field eccentricity for both midget-parvocellular pathway and parasol-magnocellular pathway mediated visual functions. The spatial resolving power of the OFF parasol array (peak ∼ 7 cpd) falls short of macaque behavioral grating acuity by at least a factor of three throughout the retina.

Optic nerve thinning and neurosensory retinal degeneration in the rTg4510 mouse model of frontotemporal dementia

Visual impairments, such as difficulties in reading and finding objects, perceiving depth and structure from motion, and impaired stereopsis, have been reported in tauopathy disorders, such as frontotemporal dementia (FTD). These impairments however have been previously attributed to cortical pathologies rather than changes in the neurosensory retina or the optic nerve. Here, we examined tau pathology in the neurosensory retina of the rTg(tauP301L)4510 mouse model of FTD. Optic nerve pathology in mice was also assessed using MRI, and corresponding measurements taken in a cohort of five FTD sufferers and five healthy controls. rTg(tauP301L)4510 mice were imaged (T2-weighted MRI) prior to being terminally anesthetized and eyes and brains removed for immunohistochemical and histological analysis. Central and peripheral retinal labelling of tau and phosphorylated tau (pTau) was quantified and retinal layer thicknesses and cell numbers assessed. MR volumetric changes of specific brain regions and the optic nerve were compared to tau accumulation and cell loss in the visual pathway. In addition, the optic nerves of a cohort of healthy controls and behavioural variant FTD patients, were segmented from T1- and T2-weighted images for volumetric study. Accumulation of tau and pTau were observed in both the central and peripheral retinal ganglion cell (RGC), inner plexiform and inner nuclear layers of the neurosensory retina of rTg(tauP301L)4510 mice. This pathology was associated with reduced nuclear density (− 24.9 ± 3.4%) of the central RGC layer, and a reduced volume (− 19.3 ± 4.6%) and elevated T2 signal (+ 27.1 ± 1.8%) in the optic nerve of the transgenic mice. Significant atrophy of the cortex (containing the visual cortex) was observed but not in other area associated with visual processing, e.g. the lateral geniculate nucleus or superior colliculus. Atrophic changes in optic nerve volume were similarly observed in FTD patients (− 36.6 ± 2.6%). The association between tau-induced changes in the neurosensory retina and reduced optic nerve volume in mice, combined with the observation of optic nerve atrophy in clinical FTD suggests that ophthalmic tau pathology may also exist in the eyes of FTD patients. If tau pathology and neurodegeneration in the retina were to reflect the degree of cortical tau burden, then cost-effective and non-invasive imaging of the neurosensory retina could provide valuable biomarkers in tauopathy. Further work should aim to validate whether these observations are fully translatable to a clinical scenario, which would recommend follow-up retinal and optic nerve examination in FTD.

Approche « point par point » de la corrélation structure–fonction du glaucome sur le complexe cellulaire ganglionnaire du pôle postérieur

To try to establish a "point by point" relationship between the local thickness of the retinal ganglion cell complex and its sensitivity. In total, 104glaucomatous eyes of 89patients with a confirmed 24-2 visual field, were measured by superimposing the visual field, using imaging software, with the Wide 40° by 30° measurements of retinal ganglion cell complex obtained from the Topcon© 3D 2000 OCT, after upward adjustment, inversion and scaling. Visual fields were classified into two groups according to the extent of the disease: 58mild to moderate (MD up to -12dB), and 46severe (MD beyond -12dB). The 6mm by 6mm central region, equipped with a normative database, was studied, corresponding to 16points in the visual field. These points were individually matched one by one to the local ganglion cell complex, which was classified into 2groups depending on whether it was greater or less than 70microns. The normative database confirmed the pathological nature of the thin areas, with a significance of 95 to 99%. Displacement of central retinal ganglion cells was compensated for. Of 1664points (16central points for 104eyes), 283points were found to be "borderline" and excluded. Of the 1381 analyzed points, 727points were classified as "over 70microns" and 654 points "under 70 microns". (1) For all stages combined, 85.8% of the 727points which were greater than 70microns had a deviation between -3 and +3dB: areas above 70microns had no observable loss of light sensitivity. (2) In total, 92.5% of the 428points having a gap ranging from -6 to -35dB were located on ganglion cell complex areas below 70microns: functional visual loss was identified in thin areas, which were less than 70microns. (3) Areas which were less than 70microns, that is 654points, had quite variable sensitivity and can be divided into three groups: the first with preserved sensitivity, another with obliterated sensitivity, and an intermediate group connecting the two previous ones. In pathologically thin areas, the distribution of these three functional groups seems to correspond to the progression of glaucomatous visual degradation, including a period of resistance, a period of rapid decline, finally leading to complete functional loss. In the studied area, the analysis of retinal ganglion cell complex is relevant to identify areas which are still functional when they exceed 70microns. Scotomas correspond to the thin areas less than 70microns. The functionality of areas which are pathologically thinned by glaucomatous degeneration is not correlated to their thickness. In the future, the correlation between structure and function, currently "regional" may be realized "point by point" once automation of the visual field superimposition is made available for the ganglion cell complex.

Steroid-Induced Ocular Hypertension Model in the Mice

Purpose: To determine whether rat eyes develop increases in intraocular pressure (IOP) in response to a topically applied corticosteroid and to investigate the relationship between ocular hypertension and apoptosis of retinal ganglion cells. Methods: IOP was monitored by rebound tonometry in a group of 10 rats that received topically administered dexamethasone in both eyes (experimental) and in another group of 5 rats that received artificial tears (control) three times daily for 4 weeks after the establishment of baseline IOP values. Only eyes that increased by more than 50% compared with the basal IOP were administered once per day for 5 weeks. After 8 weeks, selective immunofluorescence stain for retinal ganglion cells and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stain were conducted. Results: Among 20 experimental eyes, 11 eyes (55%) showed a greater than 50% increase in IOP compared with basal IOP. After 8 weeks, the mean IOPs for the experimental and control groups were 11.8 ± 1.4 mm Hg and 18.5 ± 1.0 mm Hg, respectively (p < 0.01). The counts of central retinal ganglion cells (RGCs) were 2718 ± 240 and 2612 ± 443, respectively (p = 0.294). The results of the TUNEL stain also showed no differences. Conclusions: Rat eyes exhibit a steroid-induced ocular hypertensive response with no local complications. However, maintaining ocular hypertension increased by 50% for two months was not enough to detect changes in RGCs. J Korean Ophthalmol Soc 2014;55(8):1202-1207

Contrast sensitivity, ocular blood flow and their potential role in assessing ischaemic retinal disease

To examine the definition, evaluation methodology, association to ocular blood flow and potential clinical value of contrast sensitivity (CS) testing in clinical and research settings, focusing in patients with ischemic retinal disease. A review of the medical literature focusing on CS and ocular blood flow in ischemic retinal disease. CS may be more sensitive than other methods at detecting subtle defects or improvements in primarily central retinal ganglion cell function early on in a disease process. CS testing attempts to provide spatial detection differences which are not directly assessed with standard visual acuity chart testing. Analyzing all studies that have assessed both CS change and ocular blood flow, it is apparent that both choroidal circulation and retinal circulation may have an important role in influencing CS. The concept that CS is directly influenced by ocular blood flow is supported by reviewing the studies involving both. Although the studies in the literature have not established a direct cause and effect relationship per se, the literature review makes it logical to assume that changes in retinal and choroidal blood flow influence CS. This raises the possibility that a subjective visual characteristic, specifically CS, may be able to be evaluated more objectively by studying blood flow. It appears appropriate to study the relationship between blood flow and CS more extensively to develop improved ways of measuring various aspects of blood flow to the eye and to best quantify early changes in visual function.

Retinotopy of visual projections to the optic tectum and pretectum in larval sea lamprey

The sea lamprey has a complex life cycle with very different larval and adult stages. The eyes of larvae are subcutaneous, lack a differentiated lens and probably work only as an ocellus-like photoreceptor organ, while the well-developed adult eyes are capable of forming images. The larval retina differs greatly from the adult retina and presents a central region with differentiated photoreceptors and a lateral, largely undifferentiated part that grows in the second half of larval life. In the present study, we examined the retinotopy of projections from larval ganglion cells to the optic tectum and pretectum in sea lamprey by using retrograde tract-tracing techniques. In most regions of the tectum, application of the tracer neurobiotin (NB) resulted in labelled ganglion cells in the lateral retina, mostly in the contralateral eye. Ganglion cells of the lateral retina showed a very simple dendritic tree, possibly because of the lack of differentiation of most retinal layers in this region. The retinotectal projection is already retinotopically organized in larvae and follows a pattern similar to that observed in adult lampreys and other vertebrates. Application of NB to the central region of the tectum also led to labelling of a few ganglion cells in the central retina, which were clearly more complex than those in the lateral region, as they had dendrites that branched both in the outer and inner plexiform layers. Application of NB to the medial pretectum led to labelling of ganglion cells in the contralateral central retina. Occasional cells were also labelled in the lateral retina. The differential organization of larval retinal projections to the pretectum and tectum suggests a different role for these projections, which is consistent with the different involvement of these centres in visual behaviour, as determined in adult lampreys. The observations in larvae also reveal very different developmental timetables for these putative functions.

VEGF expression by ganglion cells in central retina before formation of the foveal depression in monkey retina: Evidence of developmental hypoxia

In macaque monkeys the foveal depression forms between fetal day (Fd) 105 and birth (Fd 172 of gestation). Before this, the incipient fovea is identified by a photoreceptor layer comprising cones almost exclusively, a multilayered ganglion cell layer (GCL), and a "domed" profile. Vessels are absent from the central retina until late in development, leading to the suggestion that the GCL in the incipient fovea may be transitorily hypoxic. Vascular endothelial growth factor (VEGF), expressed by both glial and neuronal cells and mediated by the hypoxia-inducible transcription factor (HIF)-1, is the principal factor involved in blood vessel growth in the retina. We examined VEGF expression in macaque retinas between Fd 85 and 4 months postnatal. Digoxygenin-labeled riboprobes were generated from a partial-length human cDNA polymerase chain reaction fragment, detected using fluorescence confocal microscopy, and quantified using Scion Image. High levels of VEGF mRNA were detected in astrocytes associated with developing vessels. We also detected strong expression of VEGF mRNA in the GCL at the incipient fovea prior to Fd 105, with peak labeling in the incipient fovea that declined with distance in nasal and temporal directions. By Fd 152 peak labeling was in two bands associated with development of the inner nuclear layer (INL) capillary plexus: in the inner INL where Müller and amacrine cell somas are located, and in the outer INL where horizontal cells are found. The findings suggest that at the incipient fovea the GCL is hypoxic, supporting the hypothesis that the adaptive significance of the fovea centralis is in ensuring adequate oxygen supply to neuronal elements initially located within the avascular region.

Uneven mapping of magnocellular and parvocellular projections from the lateral geniculate nucleus to the striate cortex in the macaque monkey.

Central vision is substantially over represented in the lateral geniculate nucleus (dLGN) and striate cortex. The over representation could be accompanied by a selective expansion of central vision in parvocellular dLGN, in which case the ratio of parvocellular to magnocellular inputs to striate cortex should change with retinal eccentricity. To test this, sample ratios were determined from counts of neurons in dLGN labelled retrogradely with WGA-HRP from striate cortex at the cortical representations of various eccentricities. Parvocellular to magnocellular ratios decreased from a mean of 35:1 at the fovea to 5:1 at 15 degrees eccentricity. Furthermore, they exceeded the ratio of P beta to P alpha ganglion cells in central retina, but not in peripheral retina, showing that the uneven P to M ratio in the LGN does not merely mirror the distribution of ganglion cells in the retina. This provides direct evidence for selective over representation of central vision in parvocellular dLGN.

Study of Central Retinal Ganglion Cell Loss in Experimental Glaucoma in Monkey Eyes

The objective of this research was to compare the loss of retinal ganglion cells subserving the fovea to that of the ganglion cells in the surrounding perifoveal region in eyes with experimental glaucoma. Ganglion cell nucleoli were counted using light microscopy from vertically oriented retinal, strips and the cell density was calculated using the modified Abercombie formula. Percent ganglion cell loss in glaucomatous eyes from five monkeys was determined for each of up to five contiguous areas within the central 12 degrees of the retina by comparison to normal fellow eyes. Loss of central ganglion cells was present even in eyes with mild glaucomatous damage. The percent ganglion cell loss in glaucomatous eyes at five adjacent areas within the central 12 degrees of the retina did not differ significantly (ANOVA, p = 0.77, n = 8). Cell loss in areas nearest to the fovea was indistinguishable from that in more peripheral perifoveal areas. Foveal ganglion cells appear to be susceptible to experimental glaucoma injury. Psychophysical testing of foveal functions may deserve renewed attention in glaucoma diagnosis and follow-up.

Changing Patterns of the Retinoic Acid System in the Developing Retina

In retinas of embryonic rat and chick, as in the mouse, synthesis of retinoic acid is mediated by different dehydrogenases in dorsal and ventral portions, with the ventral pathways generating higher retinoic acid levels. In the mouse, the dorsal enzyme was previously found to be the aldehyde dehydrogenase class-1 isoform AHD-2 and the ventral enzyme an unknown acidic dehydrogenase activity. This acidic dehydrogenase activity is now shown to consist of an early and a later expressed form, with the early form being indistinguishable from the activity in the early embryonic trunk and heart regions. Expression of the acidic dehydrogenase in the eye is first detected at the optic pit stage (E8.0), a day before the appearance of AHD-2 in the optic vesicle. The acidic dehydrogenase accounts for most of the retinoic acid synthesis in the retina during embryonic and early postnatal stages; during later postnatal stages it disappears and in the adult retina all retinoic acid synthesis is mediated by AHD-2. HPLC measurements in mice show high levels of all-trans- and 13-cis-retinoic acid: at E14 the retina contains a total of about 0.5 μM retinoic acid, and levels in the adult retina are about fourfold lower. The dorso-ventral asymmetry extends also to the cellular retinoic acid binding protein CRABP I, which first appears in the early differentiating ganglion cells in central retina and in the later embryo shows transiently a ventro-dorsally receding pattern of expression.

Atrophy and Degeneration of Ganglion Cells in Central Retina Following Loss of Postsynaptic Target Neurons in the Dorsal Lateral Geniculate Nucleus of the Adult Cat

Selective degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN) of the adult cat was produced by in situ injection of kainic acid. This rapid degeneration mimics the loss of lateral geniculate neurons seen after neonatal visual cortex ablation. Following survivals of 2, 4, or 6 months, the geniculate was injected with horseradish peroxidase (HRP) and the retinas were examined for the presence of retrogradely labeled, as well as unlabeled, cells. Total ganglion cell density in central nasal retina was not different from that of controls at 2 or 4 months, but by 6 months had decreased to 68% of control values. The proportion of cells labeled with HRP did not change at 2 months, but decreased from 84% in controls to less than 1% by 4 months, and none were labeled at 6 months. Surviving ganglion cells in central retina showed atrophy of the cell body, a finding not apparent in data from the retinal periphery. Shrinkage occurred in the few cells labeled with HRP surviving at 4 months, as well as among the unlabeled cells surviving at 4 and 6 months. These results show that the survival of central retinal ganglion cells in the cat continues to depend on intact target neurons beyond the period of development. Mature ganglion cells in central retina respond to loss of appropriate targets first by axon terminal retraction and then by atrophy and cell death. However, when compared to the response of cells located in far peripheral retina following dLGN neuron loss, central ganglion cells take longer to undergo axonal retraction and a greater proportion of the central ganglion cells, although atrophied, survive after 6 months.

Spatial density and immunoreactivity of bipolar cells in the macaque monkey retina.

The anatomical substrates of spatial and color vision in the primate retina are investigated by measuring the immunoreactivity and spatial density of bipolar, amacrine and horizontal cells in the inner nuclear layer of the macaque monkey retina. Bipolar cells can be distinguished from amacrine and horizontal cells by their differential immunoreactivity to antisera against glutamate, glycine, GABA, parvalbumin, calbindin (CaBP D-28K), and the L7 protein from mouse cerebellum. The spatial density of bipolar cells is compared to the densities of photoreceptors and ganglion cells at different retinal eccentricities. In the centralmost 2 mm, cone bipolar cells outnumber ganglion cells by about 1.4:1. The density of cone bipolar cells is thus high enough to allow for input to different (parasol and midget) ganglion cell classes by different (diffuse and midget) bipolar cell classes. The density gradient of cone bipolar cells follows closely that of ganglion cells in central retina but falls less steeply in peripheral retina. This suggests that the convergence of cone signals to the receptive fields of ganglion cells in the peripheral retina occurs in the inner plexiform layer. The density of cone bipolar cells is 2.5-4 times that of cones at all eccentricities studied, implying that cone connectivity to bipolar cells remains constant throughout the retina. Different subgroups of bipolar cells are distinguished by their relative immunoreactivity to the different antisera. All rod and cone bipolar cells show moderate to strong glutamate-like immunoreactivity. The bipolar cells that show weak to moderate GABA-like immunoreactivity are also labeled with the antiserum to the L7 protein and are thus identified as rod bipolar cells. Nearly half of all cone bipolar cells showed glycine-like immunoreactivity. The results suggest that the inhibitory neurotransmitter candidates GABA and glycine are segregated respectively in rod and cone bipolar cell pathways. A diffuse, cone bipolar cell type can be identified by the anti-parvalbumin and the anti-calbindin antisera. All horizontal cells show parvalbumin-like immunoreactivity. Nearly all amacrine cells show GABA-like or glycine-like immunoreactivity; a variety of subpopulations also show immunoreactivity to one or more of the other markers used.

Dendritic arbors of large-field ganglion cells show scaled growth during expansion of the goldfish retina: a study of morphometric and electrotonic properties

The retina of the goldfish grows by a balloon-like expansion and by the addition of new neurons at the margin. It has been proposed that as a consequence of this expansion the dendritic arbors of ganglion cells in central retina grow in a uniform manner without the addition of new branches. In the present study, we have examined this proposal by comparing the geometries of individual dendritic arbors of large-field ganglion cells from the retinas of small/young and large/old fish. These comparisons were based on measurements of several parameters of dendritic morphology, including number of segments and branches, branch angles, changes in diameter at branch points, and proximal versus distal distribution of arbor length. In addition, we used passive, steady-state cable modeling as an independent method of estimating the functional architectures of small and large dendritic arbors. Our morphometric data indicate that, though they are very different in absolute size, dendritic arbors of small and large ganglion cells have remarkably similar architectures. Analysis with steady-state cable equations indicates that the arbors from small and large cells have equivalent electrotonic lengths and show comparable propagation of synaptic currents. These data are consistent with the hypothesis that dendritic arbors of small and large ganglion cells are scaled versions of one another. We conclude that the growth of these cells during the expansion of the retina is the result of the addition of dendritic mass to an arbor whose basic geometry remains unchanged.

Organization of retinopetal axons in the optic nerve of the cichlid fish, Herotilapia multispinosa

We have studied the position and numbers of retinopetal axons in the rainbow cichlid fish, Herotilapia multispinosa, to determine the response of related parts of the brain of fish to the continual addition of new neurons in the retina. The retinopetal axons were traced by using the retrograde tracers HRP and cobaltous lysine and an immunocytochemical probe, antibodies to FMRF amide, the molluscan cardioexcitatory peptide. One population of cells with retinopetal axons was found in the telencephalon (in the nucleus olfactoretinalis) and the other was scattered in the diencephalon. Some of the cells in the nucleus olfactoetinalis with retinopetal axons were FMRF amide positive; antibodies were used to trace the axons of these cells into the retina. All the retinopetal axons, from the nucleus olfactoretinalis and the diencephalon, were confined to the portion of the optic nerve that contains axons from the central retinal ganglion cells, that is, the oldest ganglion cells. This result suggests that the retinopetal axons grow into the optic nerve and retina early in the life of the fish, and no new ones are added later in life despite the extensive addition of cells in the retina. Counts of the cells in the nucleus olfactoretinalis that project to the retina in 3-month-old and adult fish support this interpretation. We conclude that retinopetal axons grow into the retina early in the life of the fish and respond to the formation of new retina by extending their arbors toward the new retina.

Studies of the early stages of optic axon regeneration in the goldfish

We have studied the early stages (4-14 days) of axonal regeneration following intraorbital optic nerve crush in the goldfish. We used 3H-proline autoradiography to anterogradely label and visualize the growing axons and wheat germ agglutinin-conjugated horseradish peroxidase (WGA:HRP) for retrograde labeling to determine the cells of origin of the earliest projections. The first retinal ganglion cells (RGCs) that could be retrogradely filled from the optic tract, following optic nerve crush, were in the central retina and were seen at 8 days postoperative. More peripheral cells were only labeled with longer postcrush survival periods. Thus, the first axons to regenerate past the lesion were from central RGCs. The axons of these cells extended into the cranial nerve stump between 4 and 5 days postcrush and entered the nerve as a fascicle, which travelled just beneath its surface. Studies of nerve cross sections from animals at 5-8 days postoperative demonstrated that initial outgrowth was not confined to any particular locale within the nerve although the early fibers appeared to avoid its temporal aspect. When the regenerating axons reached the optic tract they remained in fascicles but left the surface to run along the medial, deep portion of the tract, immediately adjacent to the diencephalon and pretectum. The positions occupied by the earliest-regenerating axons in the optic nerve were variable and not always appropriate for their central retinal origin. However, the abrupt change in growth trajectory as the fibers entered the optic tract brought them into the areas of the visual paths that are occupied by central axons in intact animals. We suggest that this change in position is related to both changes in the structural organization of the intracranial visual paths and to possible axon guidance signals in the region of the nerve-tract juncture.

Evidence for shifting connections during development of the chick retinotectal projection

The pattern in which optic axons invade the tectum and begin synaptogenesis was studied in the chick. The anterogradely transported marker, horseradish peroxidase, was injected into one eye of embryos between 5 and 16 days of development (E5 to E16). This labeled the optic axons in the brain. The first retinal axons arrived in the most superficial lamina of the tectum on E6. They entered the tectum at the rostroventral margin. During the next 6 days of development the axons grew over the tectal surface. First they filled the rostral tectum, the oldest portion of the tectum, and then they spread to the caudal pole. Shortly after the first axons entered the tectum on E6, labeled retinal axons were found penetrating from the surface into deeper tectal layers. In any given area of the tectum, optic axons were seen penetrating deeper layers shortly after arriving in that area. Electron microscopic examination showed that at least some of the labeled axons in rostral tectum formed synapses with tectal cells by E7. These results show two things which contrast with results from previous studies. First, there is no delay between the time the retinal axons enter the tectum and the time they penetrate into synaptic layers of the tectum. Second, the first retinotectal connections are formed in rostral tectum and not central tectum. Retrograde tracing showed the first optic axons that arrived in the tectum were from ganglion cells in central retina. Previous studies have shown that the ganglion cells of central retina project to the central tectum in the mature chick. This opens the possibility that the optic axons from central retina, which connect to rostral tectum in the young embryo, shift their connections to central tectum during subsequent development. As they enter the tectum the growth cones of retinal axons appear to be associated with the external limiting membrane. During the time that connections would begin to shift in the tectum a second population of axons appears at the bottom of stratum opticum, some with characteristics of growth cones. This late-appearing population may represent axons shifting their connections. These results have implications for theories on how the retinotopic pattern of retinotectal connections develops.

Topography of the goldfish optic tracts: Implications for the chronological clustering model

Both the dorsal and ventral optic tracts of goldfish have similar shapes when they are sectioned perpendicularly to their longitudinal axes. Each tract is pear-shaped, consisting of a narrow and a deep apex, a wide midspan, and a progressively curved and tapered superficial base. The tracts differ in that the apex of the dorsal optic tract points caudally, while the apex of the ventral optic tract points medially. In addition, upon segregating from the main optic tract, the dorsal optic tract courses dorsally while the ventral optic tract courses caudally. Thus, the two optic tracts have similar shapes and are orthongonal to one another. The topography of the retinal fibers within the optic tracts was determined either by ablating part of the retina and subsequently filling the axons from the intact hemiretina with cobaltous-lysine or by applying cobaltous-lysine to a slit in the retina. Both optic tracts contain a similar arrangement of optic fibers. Axons of central retinal ganglion cells (RGCs) are in the apex of each tract and optic fibers of peripheral RGCs are located along the base of each tract. Axons of temporal RGCs are located dorsally in the ventral optic tract and laterally in the dorsal optic tract, while axons of nasal RGCs are located ventrally in the ventral optic tract and medially in the dorsal optic tract. These findings indicate that the optic axons are organized as laminae. Deeper laminae contain the axons of older annuli of RGCs and superficial laminae contain the axons of younger annuli of RGCs. This type of chronological organization appears to be consistent across vertebrates.(ABSTRACT TRUNCATED AT 250 WORDS)

The development of retinal ganglion cells in a tetraploid strain of Xenopus laevis: A morphological study utilizing intracellular dye injection

The morphological development of retinal ganglion cells was examined in a tetraploid strain of Xenopus frogs. The enlarged cells of the tetraploid strain facilitate the application of intracellular techniques. Using an in vitro retinal preparation and Nomarski optics, intracellular recording and dye injection were carried out under visual control on ganglion cells in central retina from 2 days of development (stage 24) to metamorphosis (stage 64). We identified three phases in the morphological differentiation of ganglion cells. During the first phase (stages 24-30), all cells were neuroepitheliallike in form and possessed robust resting potentials in the range of -35 to -60 mV, and dye-coupling was occasionally observed between neighboring cells. During the second phase of ganglion cell development (stages 31-45) the neurons had begun to elaborate axons and dendrites. These cells possessing neurites had resting potentials between -15 and -30 mV, and no dye-coupling was observed between neighbors. During the third and final phase of maturation, from stage 46 onward, three distinct morphological types of ganglion cells could be identified. Type I cells had the smallest somata and the smallest-diameter dendritic arborizations. The profusely branched dendrites of these cells ramify extensively throughout the inner plexiform layer. Type II cells had large somata, intermediate-diameter dendritic fields, and a highly elaborate dendritic branching pattern. These cells were seen to arborize within two sublamina in the inner plexiform layer. Type III cells had large somata, the largest-diameter dendritic fields, and a dendritic arbor with long primary branches but little higher-order branching. These large dendritic fields were confined to a single sublamina of the inner plexiform layer, abutting the inner nuclear layer. While most phase 3 cells showed radial axon trajectories from the soma to the optic disc, a minority of cells (1-5%) with erratic and nonradial axon trajectories were also observed. Our data provide a morphological description of ganglion cell maturation in the central retina of Xenopus. We show that very early in development (as early as stage 46) three distinct morphological types of retinal ganglion cells are present, which correspond to the three classes of ganglion cells previously described in adult Xenopus (Chung et al., '75).

Amblyopia occurs in retinal ganglion cells in cats reared with convergent squint without alternating fixation

The spatial resolving power, contrast sensitivity, and receptive field properties of retinal ganglion cells were studied in cats reared with either convergent or divergent squint in one eye. Sustained-X cells in the area centralis of the squinting eye of the cats with esotropia without alternating fixation showed significantly poorer spatial resolution, and reduced contrast sensitivity compared with cells in the area centralis of the normal eye. These amblyopic sustained-X cells in the area centralis of the squinting eye had receptive field characteristics similar to those found in immature cells of young kittens. They had a shallow sensitivity gradient within a relatively widespread centre zone and a weak and widespread inhibitory surround. In contrast, the sustained cells in the area centralis of the normal eye revealed a typical, well defined, small centre zone with its sensitivity gradient extremely steep and its inhibitory surround strong and confined. A minor degree of amblyopia was also found in transient Y-cells in the area centralis of the squinting eye of these cats. However, no loss of resolving power was found in the cells in the area centralis of the squinting eye of the cats with esotropia or exotropia which showed alternating fixation. Thus, amblyopia occurs in those eyes which have lost the use of the area centralis as the normal visual axis during early postnatal development, and its organic lesion is already apparent in the retinal ganglion cells--the third order neurone in the afferent visual system. It is suggested that the loss of the ability to fixate results in inadequate stimulation of the central retinal ganglion cells due to the habitual presence of blurred images at the area centralis which prevents their full development during the critical period.