Evidence for degeneration of retinal W cells following early visual cortical removal in cats

Size and distribution of ganglion cells surviving unilateral visual cortical removal at 5-7 days of age were examined in domestic cats. Such lesions were expected to result in a substantial loss of X cells in ipsilateral temporal and contralateral nasal retina, leaving ipsilateral nasal and contralateral temporal retina to serve as intact controls. A computer model of normal retinal ganglion cell topography was used to make qualitative predictions of the distribution of surviving ganglion cells. Contrary to expectations, a visual streak was no more prominent in the distribution of surviving cells than in the distribution of the normal ganglion cell population. The magnitude of ganglion cell loss, furthermore, was at least twice as great in nasal retina as in temporal retina. In nasal retina, the cell loss extended well into the small-medium size range, while in temporal retina, cell loss was restricted to the large-medium size range. Taken together, the differential magnitude of cell loss in nasal and temporal retina and the greater loss of small-medium cells in nasal retina cannot be explained by the exclusive degeneration of X cells and suggest that many of the degenerated ganglion cells were medium-sized W or gamma cells. These cells, therefore, share the susceptibility of retinal X cells to early cortical ablation. Surviving gamma cells in both nasal and temporal retina appeared to increase in soma size which may explain why their decreased numbers were not detected in previous physiological studies. Alpha cells, at least in nasal retina, decreased in some size.     

Gap junction protein connexin43 (GJA1) in the human glaucomatous optic nerve head and retina

Primary open angle glaucoma is characterised by the progressive and irreversible death of retinal ganglion cells. Experimental evidence suggests that the initial site of injury to the retinal ganglion cell is at or near the lamina cribrosa or in the peripapillary retina. However, the mediators of axonal injury remain poorly understood. The purpose of this study was to investigate the expression of the gap junction protein connexin43 (GJA1) in the human glaucomatous optic nerve head and retina as a potential mediator of axonal injury. Using affinity isolated polyclonal antibodies to the C-terminal segment of human connexin43, the expression of connexin43 was determined in post-mortem human eyes with primary open angle glaucoma and age-matched controls. In normal eyes, connexin43 was present on glial fibrillary acidic protein (GFAP)-positive astrocytes in the retinal ganglion cell layer and optic nerve head. In glaucomatous eyes, increased connexin43 immunoreactivity was observed at the level of the lamina cribrosa and in the peripapillary and mid-peripheral retina in association with glial activation. This novel finding may suggest that gap junction communication is a potential mediator of retinal ganglion cell injury in glaucoma.     

Glutamate Receptor Subunit GluR2 and NMDAR1 Immunoreactivity in the Retina of Macaque Monkeys with Experimental Glaucoma Does Not Identify Vulnerable Neurons

Excitatory amino acid neurotoxicity has been proposed as a mechanism underlying selective neuronal death in glaucoma. The relationships between the cellular distribution of glutamate receptor subunit proteins GluR2 and NMDAR1 and the vulnerability of restricted retinal neuron subpopulations was explored in experimental glaucoma in macaque monkeys, produced by treating the trabecular meshwork in one eye with argon or diode laser burns. Immunostaining of retinal segments was performed using specific monoclonal antibodies to the GluR2 and NMDAR1 subunit proteins as well as neurofilament protein. The distribution of immunoreactivity was qualitatively assessed in the retina, and ganglion cells were counted in the paracentral and peripheral regions of each retinal segment. Immunoreactivity for both of these glutamate receptor subunit proteins was widely distributed in most retinal neuron types in control eyes and was colocalized with neurofilament protein in ganglion cells. In the glaucomatous eyes, densities of GluR2- and NMDAR1-immunoreactive ganglion cells were dramatically reduced compared to unaffected fellow eyes, but GluR2- and NMDAR1-immunoreactive populations of horizontal, bipolar, and amacrine cells were not affected. These data parallel previous observations on the selective vulnerability of ganglion cells in this experimental model of glaucoma. However, GluR2 and NMDAR1 subunits do not constitute cell type-specific markers of vulnerability in glaucoma as they are present in neurons prone to degeneration as well as in resistant ones. While retinal pathology in glaucoma involves excitotoxic mechanisms that may be related to glutamate receptor subunits regulating calcium fluxes, the specific pattern of neuronal vulnerability clearly depends on other cellular characteristics such as morphology, connectivity, and other aspects of the neurochemical phenotype.     

Selective innervation of the goldfish suprachiasmatic nucleus by ventral retinal ganglion cell axons

The contribution of central, peripheral, dorsal, ventral, nasal and temporal retinal ganglion cells to the innervation of the suprachiasmatic nucleus of goldfish was examined with cobaltous-lysine. The nucleus is innervated by axons from central, peripheral, temporal and nasal retina. However, this innervation originates only from ventral retinal ganglion cell axons. The retinal origin of the innervation may be related to being in an aquatic environment.     

The topography of ganglion cell production in the cat's retina

The ganglion cells of the cat's retina form several classes distinguishable in terms of soma size, axon diameter, dendritic morphology, physiological properties, and central connections. Labeling with [3H]thymidine shows that the ganglion cells which survive in the adult are produced as several temporally shifted, overlapping waves: medium-sized cells are produced before large cells, whereas the smallest ganglion cells are produced throughout the period of ganglion cell generation (Walsh, C., E. H. Polley, T. L. Hickey, and R. W. Guillery (1983) Nature 302: 611-614). Large cells and medium-sized cells show the same distinctive pattern of production, forming rough spirals around the area centralis. The oldest cells tend to lie superior and nasal to the area centralis, whereas cells in the inferior nasal retina and inferior temporal retina are, in general, progressively younger. Within each retinal quadrant, cells nearer the area centralis tend to be older than cells in the periphery, but there is substantial overlap. The retinal raphe divides the superior temporal quadrant into two zones with different patterns of cell addition. Superior temporal retina near the vertical meridian adds cells only slightly later than superior nasal retina, whereas superior temporal retina near the horizontal meridian adds cells very late, contemporaneously with inferior temporal retina. The broader wave of production of smaller ganglion cells seems to follow this same spiral pattern at its beginning and end. The presence of the area centralis as a nodal point about which ganglion cell production in the retinal quadrants pivots suggests that the area centralis is already an important retinal landmark even at the earliest stages of retinal development. This sequence of ganglion cell production differs markedly from that seen in the retinae of nonmammalian vertebrates, where new ganglion cells are added as concentric rings to the retinal periphery, and also bears no simple relationship to the cat's retinal decussation line. However, it can be related in a straightforward manner to the organization of axons in the cat's optic tract, suggesting that the fiber order in the tract represents a grouping of fibers by age.     

Neurofilament immunoreactivity in developing rat autonomic and sensory ganglia

Immunoreactivity to neurofilament (NF) antiserum appears early in the development of both the central and peripheral nervous systems of the rat fetus. In 10 somite embryos, positive cell bodies are present in the ventromedial part of anterior rhombencephalic and mesencephalic neural tube. From there the appearance of immunoreactivity spreads cranially to the prosencephalic anlage before closure of the anterior neuropore and caudally following the sequence of neural tube closure. Immunoreactivity increases rapidly in axon bundles of central and peripheral systems, but in immature cell bodies of sensory ganglia the NF material only forms a ring around the nucleus. At 16 days of gestation, some cell bodies are progressively loaded with NF-immunoreactive material as a thick perinuclear network first and then in more excentrically located aggregates. This category of neurons is mainly observed in the distal part of the trigeminal ganglion, in petrous and nodose ganglia and in cervical dorsal root ganglia. In adult ganglia large cell bodies and some small ones present high NF immunoreactivity. In autonomic cell bodies (in superior cervical ganglion and in parasympathetic cranial ganglia) the immunoreactive material only forms a perinuclear ring slowly transformed into a loose perinuciear meshwork at the end of gestation. Intensely reactive nerve fibers are observed in cranial sensory as well as in sympathetic and parasympathetic ganglia and nerves. No positive cell bodies and only a few NF-immunoreactive nerves are observed in the carotid bodies. The NF immunoreactivity is better visualized on sections of fresh frozen material, treated with acetone, than in fixed specimens.These results are compared to previous observations reported for other species and for developing dorsal root ganglia. This immunostaining may be used to detect differentiation of peripheral sensory and autonomic neurons under experimental conditions. The uneven distribution of NF immunoreactivity in sensory neurons from stage 16 days of gestation as specific for precise subpopulations of neurons is discussed.     

Spatial organization of the retinal projection to the avian lentiform nucleus of the mesencephalon

Utilizing the horseradish peroxidase retrograde tracing technique and the 2-deoxy-D-glucose metabolic mapping technique, we have demonstrated in chickens the distribution of retinal ganglion cells that project to the lentiform nucleus of the mesencephalon (LM) and the retinotopic organization of the projection in the LM. Retinal ganglion cells labeled after a nearly complete injection into the LM were found in the four quadrants, distributed in a wide horizontal belt lying along both sides of the retinal equator and stretching from the temporal to the nasal retina. The HRP-labeled cells, which appeared round or oval, ranged from 25 to 840 micron 2 in size with most in the smaller size range. Results of partial HRP injections into the LM and metabolic mapping patterns in the LM produced by stimulation of half the retina with horizontal visual motion suggest that there is an orderly mapping of the retina onto the LM. The inferior temporal quadrant projects to the rostrodorsal LM; the inferior nasal quadrant projects to the caudodorsal LM. The superior temporal quadrant projects to the middle and ventral LM, extending from the rostral to the caudal pole, whereas the superior nasal quadrant projects to a small zone in the caudal LM. The mapping of the retinal quadrants in the LM is remarkably similar to that reported in the optic tectum of birds. We suggest that a common embryological anlage with the optic tectum and the arrangement of retinal axons in the optic tract are important factors in establishing the retinotopic organization of the LM.     

The retinal projection to the superior colliculus in the cat: A quantitative study with HRP

The projections of cat retinal ganglion cells to the superior colliculus (SC) were examined using the method of retrograde axonal transport of horseradish peroxidase (HRP). Several injections of HRP were made in a single SC after the visual projection to the injection sites had been established physiologically. The HRP injections resulted in a homogeneous distribution of labelled ganglion cells in whole mount preparations of the retinae of both eyes. In the eye contralateral to the injected colliculus, ganglion cells with a crossed projection were labelled in both nasal and temporal retina; in the ipsilateral eye, ganglion cells with uncrossed projection were labelled only in the temporal retina. Analysis of the counterstained retinal whole mounts indicated that at least 50% of all ganglion cells in the nasal retina and 26% in the temporal retina have a crossed projection to SC, and that 24% of all ganglion cells of the temporal retina have an uncrossed projection to the SC. The morphological classes of retinal ganglion cells have different patterns of crossed/uncrossed decussation and they participate in varying proportions in the retino-tectal projection. Almost all Alpha cells in the retina send axon collaterals to the SC. Probably only about 10% of the Beta cells project to the SC and at least 80% of all Gamma cells send axons to the SC.     

Gradients between nasal and temporal areas of the cat retina in the properties of retinal ganglion cells

Evidence is presented of gradients between nasal and temporal areas of the cat's retina in the properties of their ganglion cell populations. Mean ganglion cell size is greater in temporal retina than in nasal retina, partly because the α- and β-cells of temporal retina are distinctly bigger than their counterparts in nasal retina, and partly because more medium-sized cells, and fewer small cells, are to be found in temporal retina. This high proportion of medium-sized ganglion cells may reflect a high proportion of β-cells or of the medium sized γ-cells described by Stone and Clarke ('80). Several of these differences can be related to prior morphological, electrophysiological, and behavioural observations in the cat, and similar differnces have been reported in several other mammalian species. Evidence is presented that, in the cat, at least some of these differences are less marked near the vertical meridian of the retina than more temporally or nasally. The present results may therefore, be evidence of a nasal-temporal gradient in retinal structure and function common to many mammals, and distinct from previously recognised gradients in ganglion cell properties related to the area centralis and visual streak specialisations.     

Retinal ganglion cell degeneration following loss of postsynaptic target neurons in the dorsal lateral geniculate nucleus of the adult cat.

Kainic acid was used to produce selective degeneration of neurons in the dorsal lateral geniculate nucleus of the adult cat. This degeneration mimics the rapid loss of geniculate neurons seen after visual cortex ablation in the neonate. Following survivals of 2, 4, or 6 months, the geniculate was injected with horseradish peroxidase and the retinae were examined for the presence of retrogradely labeled cells. Analysis of ganglion cell density in peripheral nasal retina revealed a 58% loss of cells overall at 6 months. The proportion of cells labeled with horseradish peroxidase decreased more rapidly, until none were labeled at 6 months. Separate analysis of small, medium, and large ganglion cell populations revealed that only medium-sized cells were lost at 2 months whereas both medium and large cells were lost at 4 and 6 months. By 6 months, 92% of medium cells and 65% of large cells had degenerated. These results show that mature retinal ganglion cells in the cat maintain a dependence on target integrity for their continued survival. When the appropriate target is lost, the ganglion cells respond first by axon terminal retraction and then by cell death.     

The retinal ganglion cell layer and visual acuity of the camel.

We examined the retinal ganglion cell layer of the dromedary camel, Camelus dromedarius. We have estimated that there are 8 million neurons in the ganglion cell layer of this large retina (mean area of 2,300 mm(-2)). However, only approximately 1 million are considered to be ganglion cells. The ganglion cells are arranged as two areas of high cell density, one in the temporal and one in the nasal retina. Densities of ganglion cells between these two high density regions is much lower, often less than 100 per mm(-2). In between these two high density regions, on the nasal side of the optic nerve head, is a unique and dense vertical streak of mostly non-ganglion cells; the function of this specialization is unknown. On the basis of ganglion cell density we estimate that the peak acuity in the dromedary camel is about 10 and 9.5 cycles per degree in the temporal and nasal high density regions respectively and falls to 2-3 cycles per degree in the central retina. Behavioral acuity was estimated for one bactrian camel and was found to be approximately 10 cyc deg(-1). The camel has a retina with a mean thickness of 104 microm, less than the 143 microm thickness that has previously been thought to be necessary for a retinal vasculature. Nevertheless, there is an extensive vitreal vasculature that does not appear to spare any retinal region.     

Temporal retinal growth cones collapse on contact with nasal retinal axons

The behavior of retinal ganglion cell growth cones was examined as they met retinal ganglion cell axons in culture. All possible pairings of growth cones and axons from the ventral-nasal, ventral-temporal, and dorsal-temporal quadrants of the chick retina were examined. Growth cones grow across axons with little difficulty in all those combinations in which nasal growth cones meet either nasal or temporal axons or temporal growth cones meet temporal axons. However, temporal growth cones generally collapse on contact with nasal axons and thereby experience great difficulty in crossing them. These results are consistent with the hypothesis that nasal axons have associated with them a cue that (i) interferes with temporal growth cone motility, (ii) is absent on temporal axons, and (iii) is not recognized by nasal growth cones. This finding may explain why temporal growth cones prefer to grow on temporal as opposed to nasal axons, while nasal growth cones display no such preference.     

Transneuronal retrograde degeneration of retinal ganglion cells following cerebral hemispherectomy in cats

We have assessed the extent of transneuronal retrograde degeneration of retinal ganglion cells (RGCs) following the removal of a whole cerebral hemisphere at postnatal age 16 and 25 days. In the P16 animal, the nasal retina contralateral to the lesion suffered a 41% cell loss, whereas cell loss in the temporal retina ipsilateral to the lesion was 33%. Cell loss was greater in nasal retina and mainly included medium sized cells (200–600 μm²). In the P25 animal overall there was no evidence for ganglion cell loss.     

Immunochemical localization of calretinin in the retina of the turbot (Psetta maxima) during development

The expression of the calcium-binding protein calretinin was analysed by immunohistochemistry techniques in the retina of turbot (Psetta maxima) from embryonic to juvenile stages. Calretinin immunoreactivity was first detected in retinae from newly hatched larvae, in which the anlage of the inner plexiform layer and a subset of amacrine and ganglion cells displayed a faint immunolabelling. First appearance of photoreceptors during larval life coincided with an increase in the intensity of the labelling. During subsequent larval development, the expression of calretinin affected distinctive retinal components. The inner plexiform layer, optic fiber layer, and a population of amacrine and ganglion cells were invariably labelled. Occasional bipolar cells were labelled at the end of the larval period. By metamorphosis, calretinin is sequentially expressed in horizontal cells, and bipolar immunoreactive cells become numerous. The pattern of calretinin immunoreactivity of the inner plexiform layer changes from the larval to juvenile period. In all cases, calretinin immunoreactivity exhibited variations between the peripheral retina, which contains the most recently differentiated retinal components, and the remainder of the differentiated retina. Our results suggest that the progressive expression of calretinin in the turbot retina appears associated with some degree of neuronal differentiation. Once the definitive pattern of calretinin immunoreactivity is established in the turbot retina, both similarities and differences with the calretinin location in the retina of other vertebrates can be demonstrated.     

Effects of intraocular tetrodotoxin on the development of the retinocollicular pathway in the Syrian hamster

The developing uncrossed retinocollicular projection in the Syrian hamster undergoes a characteristic set of changes during the first 2 postnatal weeks. The retinal fibres, which initially project across the whole superior colliculus, withdraw from the caudal part and their terminals become clustered into deep, discrete clumps rostrally. Coincident with these afferent changes, there is substantial retinal ganglion cell death. To examine whether neuronal activity plays a role in these changes, we made daily injections of the sodium channel blocker tetrodotoxin (TTX) into one or both eyes from postnatal day 2 or 4 up to day 12. Following TTX treatment, the uncrossed terminals retracted on schedule from the caudal and superficial parts of the superior colliculus and came to lie, as normal, in the deep layers rostrally. Within the rostral superior colliculus, however, the uncrossed terminals from TTX-injected eyes lost their characteristic patchy distribution and were arranged diffusely. When only one eye received TTX injections, this inhibiting effect on terminal segregation was seen only in the projections from the TTX-treated eye. The effect of TTX treatment on terminal segregation was much less severe than that of unilateral enucleation, after which uncrossed terminals persis throughout the entire superior colliculus. TTX injections appeared to have little effect on overall ganglion cell death since the total number of ganglion cells in the crossed projection from TTX-treated eyes was similar to that in normal eyes. However, the relative distribution of uncrossed cells in temporal and nasal retina was altered. In eyes that received TTX injections, the proportion of uncrossed cells in nasal retina was about 1.6 times that in normal animals and was close to the proportion seen in unilaterally enucleated animals. This increase in the treated eye occurred whether one or both eyes were injected with TTX. We conclude that neuronal activity plays a role in the segregation of uncrossed terminals into discrete clumps in rostral colliculus and in the preferential elimination of uncrossed cells from the nasal retina. The inactive uncrossed projections from TTX-treated eyes showed the greatest degree of disruption. The extent of the disruption was similar whether the crossed input from the other eye was active or inactive. This suggests that the activity-drive interactions between ganglion cells within one eye are more significant than those between the two eyes in shaping the final form of the uncrossed retinocollicular projection.     

An investigation into the role of ganglion cells in the regulation of division and death of other retinal cells

The patterns of cell death and division are described in the normal postnatal rat retina and following transection of the optic nerve on the day of birth. Optic nerve transection on the day of birth results in the rapid degeneration of the ganglion cells. Mitosis at the outer retinal surface ceases first in the temporal retina, then in the nasal retina and becomes progressively more restricted to peripheral regions. Mitotic activity was not affected by the loss of ganglion cells. Cell death takes place in a wave passing from the ganglion cell to the inner nuclear to the outer nuclear layer. The time course of cell death is not affected by the loss of ganglion cells following optic nerve transection, and there is no significant increase in the number of cells which degenerate in the inner nuclear layer. The effects of removing a major postsynaptic target of local circuit neurones appears to be less pronounced than has been reported for relay neurones.     

Distribution of substance P-like immunoreactive retinal ganglion cells and their pattern of termination in the optic tectum of chick (Gallus gallus)

Substance P-like immunoreactive (SP-LI) neurons were identified within the inner nuclear layer and ganglion cell layer of the chick retina. The SP-LI cells in the inner nuclear layer consisted of several subtypes of neurons, differing in soma size and dendritic arborization. In the ganglion cell layer a population of moderately labelled SP-LI neurons was also present. About 6-9 microns in diameter and spaced 50-80 microns apart, they formed a regular array across the entire retina, with a density of about 400 cells/mm2 in the superior temporal retina, declining to less than 100 cells/mm2 in the peripheral retina. The total number of SP-LI cells in the ganglion cell layer was approximately 75,000. Individual axons could be followed toward the optic nerve head. Lesions near the optic nerve head resulted in axotomy of ganglion cells within a limited portion of the retina. Two days of postaxotomy there were numerous SP-LI swellings in the proximal segments of axotomized axons. SP-LI neurons in the axotomized zone were larger, more numerous, and showed increased staining of their processes. Fourteen days following a retinal lesion, there was depletion of all SP-LI cells in the ganglion cell layer within the axotomized zone, but the SP-LI neurons in the inner nuclear layer were not noticeably affected. Following a localized injection of rhodamine-coupled latex beads into the optic tectum, a population of retinal ganglion cells (RGCs) in the contralateral retina was retrogradely labelled. Many of these cells also exhibited SP-like immunoreactivity. Examination of the optic tectum indicated the presence of SP-LI fibres in laminae 2-13 (nomenclature of Cajal: Histologie du Systeme Nerveux. Vol. 2. Paris: Maloine, '11), with immunoreactive terminal regions present mainly in laminae 2-4, 7, and 9-13. SP-LI cell bodies were found predominantly in laminae 10-12 and 13. Fourteen days following a retinal lesion, SP-LI processes and terminals were depleted from laminae 2 and 3. Immunoreactive cells and processes in the remaining laminae of the optic tectum were not noticeably altered. The present report confirms the existence of SP-LI retinal ganglion cells in the chick retina and demonstrates their contribution to lamina specific SP-LI arborization in the optic tectum.     

Activated retinal glia mediated axon regeneration in experimental glaucoma

Glaucoma, a leading cause of blindness, is a neurodegenerative disease characterized by progressive loss of retinal ganglion cell axons in the optic nerve and their cell bodies in the retina. Reactive retinal glial changes have been observed in glaucoma but the role of such glial changes in the pathogenesis of the condition remains unclear.In the present study we found that retinal ganglion cells in an experimental animal model of glaucoma have an increased axon regenerative potential. Regeneration of adult rat retinal ganglion cell axons after optic nerve crush was significantly increased in vivo when combined with intraocular pressure-induced experimental glaucoma. This enhanced axon regeneration response was correlated with a significant increase in activation of glial fibrillary acidic protein + retinal glia. Using a dissociated retinal ganglion cell culture model we showed that reducing the number of activated retinal glia with a glial specific toxin, α-Aminoadipic acid, significantly reduced the growth potential of retinal ganglion cells from glaucomatous rat eyes, suggesting that activated retinal glia mediate, at least in part, the growth promoting effect. This was shown to be mediated by both membrane-bound and soluble glial-derived factors. Neurotrophin and ciliary neurotrophic/leukemia inhibitory factor blockers did not affect the regenerative potential, excluding these growth factors as principal mediators of the enhanced growth response occurring in glaucomatous retinal cultures.These observations are the first to reveal that retinal ganglion cells from glaucomatous rat eyes have an enhanced regenerative capacity. Furthermore, our results suggest that activated retinal glia mediate at least part of this response. Further work to understand and enhance the regeneration-promoting effect of activated retinal glia is required to determine if this approach could be useful as part of a therapeutic strategy to encourage optic nerve regeneration in glaucoma.     

Retinal ganglion cell size groups projecting to the superior colliculus and the dorsal lateral geniculate nucleus in the North American opossum

The retinal ganglion cells projecting to the superior colliculus (SC) and dorsal lateral geniculate nucleus (LGNd) of the North American opossum (Didelphis virginiana) were studied by using the retrograde transport of horseradish peroxidase (HRP). The four ganglion cell size groups recognized previously were found to project in systematically different ways. After injections of HRP into the superior colliculus, labeled cells were seen in nasal retina contralateral to the injection and in temporal retina both ipsilateral and contralateral to the injection. In contralateral nasal retina cells of all size classes were labeled, while in contralateral temporal retina small (8-14 micrometers diameter), small-medium (15-19 micrometers diameter), and large (greater than 24 micrometers diameter) cells were labeled but few, if any, large-medium (20-24 micrometers diameter) cells were labeled. In ipsilateral temporal retina, soma size groups labeled included small-medium, large-medium, and large cells, but very few small cells. A nasal-temporal difference in the soma size of ganglion cells projecting to the SC was found: Labeled cells in temporal retina were 1.7-4.2 micrometers larger than their counterparts in nasal retina. Following injection of HRP into the LGNd, label was seen in contralateral nasal and ipsilateral temporal retina with no label seen in contralateral temporal retina. The labeled cells were small-medium, large-medium, and large. No small ganglion cells were labeled from the LGNd. A small nasal-temporal soma size difference in retinal ganglion cells projecting to the LGNd was seen: labeled cells in temporal retina were 1.0-2.1 micrometers larger than in nasal. It is concluded that all four ganglion cell size groups in the opossum project to the SC, but that only the three largest project to the LGNd.     

Time of ganglion cell genesis in relation to the chiasmatic pathway choice of retinofugal axons.

The time of generation of retinal ganglion cells in fetal cats has been related to the course taken later by their axons in the optic chiasm. The ganglion cells were labelled with tritiated thymidine either on embryonic day (E) 26 or on E-30. When the cats were mature, ganglion cells were retrogradely labelled with horseradish peroxidase injected into one optic tract. The distribution of double-labelled cells showed that cells in the temporal retina generated on E-26 all have axons that take an uncrossed course in the chiasm, whereas, of the cells generated on E-30 in the temporal retina, some take a crossed course and others take an uncrossed course. The uncrossed axons of the E-26 cohort come from cells having a central distribution on the retina. For the E-30 cohort, the uncrossed axons come from cells having a relatively peripheral distribution, whereas the crossed axons come from more central cells. The present results suggest that the mechanism which serves to direct temporal retinal axons into the ipsilateral optic tract weakens as development proceeds. In principle, the change may occur in either a chiasmatic signal, read by temporal but not nasal optic axons, or in a retinal label, carried by temporal but not nasal cells and their processes. Since temporal retinal cells born concurrently at different places can project to opposite optic tracts, a retinal signal that deteriorates with time in a centroperipheral fashion is favored by the present results.