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Visual latency of ganglion X- and Y-cells: a comparison with geniculate X- and Y-cells.

Visual response latencies and rise times of X and Y ganglion cells recorded in the optic tract of anaesthetized, paralyzed cats were measured during repeated stimulation with sinusoidal gratings. These measures were compared with visual latencies and rise times of X- and Y-cells in the dorsal lateral geniculate nucleus. Measurements were restricted to individual trials on which the instantaneous discharge rate exceeded a criterion amplitude defined in terms of the statistics of the baseline activity of each cell in order to screen out false alarm responses. The onset and peak latencies of ganglion Y-cells are about 10-15 msec shorter than those of ganglion X-cells at low spatial frequencies (less than 0.25 c/deg) but about 10-20 msec longer at higher spatial frequencies (greater than 0.75 c/deg/). The onset latencies of geniculate X- and Y-cells lag their ganglion counterparts by 10-20 msec. Despite a delay in onsets of geniculate responses, the peak latencies of geniculate and ganglion X-cells are similar, and peak latencies of geniculate Y-cells are even shorter than those of their ganglion inputs. The short latencies of the peak responses of geniculate Y-cells are related to their short response rise times. A functional consequence of the bursty, but fast responses of geniculate Y-cells may be to accelerate the processing of lower spatial frequencies by the retino-geniculate Y-cell pathway.

Action Potentials↗

Intracellular recording of light responses from visually identified ganglion cells in the rabbit retina.

In this report electrophysiological recordings were made from fluorescently labeled ganglion cells in the rabbit retina. Using a retinal strip preparation, cells in the ganglion cell layer were stained following a brief application of the fluorescent dye acridine orange to the bathing solution. Through an epifluorescence microscope the tip of a recording microelectrode could be positioned near a cell of interest. Extracellular recordings from ganglion cells showed that good recovery of light responses was obtained following a brief exposure of the retina to fluorescent light (400-440 nm excitation). The rate of recovery, however, depended upon the prevailing background light level. Large acridine orange-stained cell bodies in the peripheral retina were impaled under visual control by micropipette electrodes filled with either Lucifer Yellow or the fluorescent dye pyranine. When stained intracellularly, all possessed an axon identifying them as ganglion cells. The majority (approximately 80%) of the cells recorded intracellularly were identified physiologically as either ON-center or OFF-center brisk ganglion cells. The other cells encountered were ON-OFF directionally selective ganglion cells.

Action Potentials↗

A quantitative comparison of the reactions of retinal ganglion cells to optic nerve crush in neonatal and adult mice.

The response of neurons and glia of the ganglion cell layer of the retina to optic nerve crush was studied in adult and neonatal albino mice between 10-85 days post-lesion (dpl). The numbers of ganglion cells and glia surviving optic nerve transection were quantified using Nissl-stained retinal whole mounts. Large- and intermediate-sized ganglion cells were more sensitive to axotomy in the optic nerve than small-sized cells. About 80% of the former cells degenerated by 10 dpl in adult mice whilst 90-100% were affected in neonates. 40-60% of the small-sized ganglion cells survived in adults whilst in neonates, although a similar number escaped the effects of axotomy at 10 dpl, by 30 dpl only less than 10% remained. These aspects were reflected in the changes in the relative frequency distribution with time of ganglion cells in normal and lesioned mice. No significant alterations in glial cells in the ganglion cell and fibre layers of the retina were recorded at any time of lesioning the optic nerve.

Age Factors↗

Effect of proteoglycan purified from rat superior colliculus on the survival of murine retinal ganglion cells.

Recently, Schulz and coworkers purified a chondroitin sulfate proteoglycan from the superior colliculus of the neonatal rat which promoted survival of neonatal rat retinal ganglion cells in vitro. The present work tests whether this factor supports the survival of axotomised retinal ganglion cells in vivo. To this effect, murine retinae 15 and 20 days after conception were explanted to the chorioallantoic membrane of live chicken embryos. The explants, which were left in the egg for 1, 2 or 7 days, differentiated and grew according to a normal timetable. Purified proteoglycan from neonatal rat superior colliculus was applied daily to one group of retinae while a control group received Ham's F-10 medium. Results indicated that application of proteoglycan resulted in the preferential survival of large cells in the ganglion cell layer, namely ganglion cells, for up to 7 days post-explantation. In addition, the proteoglycan had a significant short-term anti-traumatic effect on the ganglion cell layer of explants by causing a 72% decrease in the number of dead cells relative to controls 1 day post-explantation. It was concluded that the chondroitin sulfate proteoglycan purified from the superior colliculus of the neonatal rat promotes the survival of fetal and neonatal murine retinal ganglion cells in retinae explanted to the chorioallantoic membrane of the chick.

Animals↗

Effects of aging on the densities, numbers, and sizes of retinal ganglion cells in rhesus monkey.

We used sterological procedures that yield unbiased estimates to quantify the densities, numbers, and soma sizes of retinal ganglion cells in seven young adult and six old rhesus monkeys. The retinae were flat mounted so that we could determine whether there are different aging-related losses in different retinal regions. The mean (+/-standard deviation) total number of ganglion cells was 1,529,039 +/- 115,260 in young-adult retinae and 1,556,698 +/- 165,056 in old retinae, a difference that was not statistically significant. There also were no significant differences between young and old retinae in the densities or total numbers of ganglion cells in the four retinal quadrants, in four concentric retinal zones from fovea to peripheral retina, or in smaller hemiretinal regions of the concentric zones. Ganglion-cell soma sizes also did not differ significantly between young and old animals. Moreover, counts of the largest ganglion cells, which probably correspond to P alpha ganglion cells, revealed no selective loss of these cells with aging. These results are consistent with our previous anatomical and physiological studies of the LGN. Together they suggest that the retino-geniculate pathways are relatively unaffected by aging in the rhesus monkey.

Aging↗

Retinal ganglion cells that project to the dorsal lateral geniculate nucleus in the macaque monkey.

Horseradish peroxidase was deposited in the optic nerve to retrogradely label and reveal the dendritic form of all classes of ganglion cell, or it was injected into the dorsal lateral geniculate nucleus to reveal only those classes projecting to the thalamus. The results were compared with those of the accompanying paper in which the ganglion cells projecting to the midbrain are selectively revealed. Two major classes of ganglion cells are described, the P alpha and P beta cells. For both classes dendritic field size increases with eccentricity from the fovea and there is no overlap in the two classes at any given eccentricity. Cell body size shows a similar mean difference but with a slight overlap. Both cell bodies and dendritic fields are larger along the temporal horizontal meridian than the nasal horizontal meridian, for P alpha and for P beta cells, but these differences are reduced when naso-temporal differences in ganglion cell density are taken into account, that is, size correlates closely with density. Injections restricted to the parvocellular layers of the lateral geniculate nucleus labelled almost exclusively P beta cells, whereas injections confined to the magnocellular layers labelled almost exclusively P alpha cells. As midbrain injections label no P beta cells and few P alpha cells it can be shown that about 80% of ganglion cells are P beta cells projecting to parvocellular lateral geniculate nucleus, and that about 10% are P alpha cells projecting to magnocellular layers. The coverage factor, that is the number of cells covering each point on the retina, varied from 1.9-2.3 for P beta cells, and from 2-7 for P alpha cells. Comparing the results with those of comparable investigations on cats and rabbits shows a much clearer segregation of the terminal targets of different classes of ganglion cell in monkeys, the greatest difference being the absence in the monkey of a projection to the geniculate from gamma- and epsilon-like cells. Further, axons which branch and innervate both thalamus and midbrain are rare in monkeys but common in other mammals. Comparing the results with those from physiological investigations suggests that the P beta cells correspond to colour-opponent cells, whereas P alpha cells correspond to the achromatic broad-band magnocellular cells.

Animals↗

Binocular interaction in the fetal cat regulates the size of the ganglion cell population.

During fetal development of the cat's visual system there is a marked overproliferation of optic nerve axons. In utero binocular interaction contributes to the severity of fiber loss since removal of an eye during gestation attenuates axon loss in the remaining optic nerve. The purpose of the present study was to determine whether this reduced loss of optic nerve fibers is due to a failure of retraction by supernumerary axon branches or to a reduction in ganglion cell death. To resolve this issue, we compared the number of ganglion cells and optic nerve fibers in adult cats which had one eye removed at known gestational ages. Retinal ganglion cells were backfilled with horseradish peroxidase and counts were made from retinal wholemounts. The axon complement was assessed with an electron microscopic assay. In the retinas of a normal cat we estimated 151,000 and 152,000 ganglion cells. The optic nerves of two other normal cats contained approximately 158,000 and 159,000 axons. In comparison, an animal enucleated on embryonic day 42 had 180,000 ganglion cells and 178,000 optic nerve fibers, while in an animal enucleated on embryonic day 51 the corresponding estimates were 182,000 and 190,000. The close agreement between cell and fiber counts indicates that axonal bifurcation does not contribute appreciably to the axon surplus in the optic nerve of prenatally enucleated cats. These results demonstrate that prenatal binocular interaction regulates the size of the mature retinal ganglion cell population.

Animals↗

Somatostatin-like immunoreactive material in associational ganglion cells of human retina.

The retinal ganglion cell is classically viewed as the output cell of the retina, sending a single axon via the optic nerve to synapse in visual relay nuclei of the brain. However, some ganglion cells, termed associational ganglion cells, have axons which do not leave the retina and presumably serve intraretinal communication. Using high-affinity and specific monoclonal antibodies to somatostatin-14 and the avidin-biotin-peroxidase immunohistochemical procedure, somatostatin-immunoreactive associational ganglion cells are specifically stained in human retinas obtained at necropsy. These cells are more numerous in the inferior than the superior retina; they have dendrites which ramify in the inner plexiform layer; and they have sparsely branching axons, many of which can be traced over 1 cm. These axons do not enter the optic nerve. They follow remarkably straight courses at the border of the inner plexiform layer and ganglion cell layer and thereby form a gridwork of fibers covering the entire retinal area. These observations verify the existence of associational ganglion cells in the human and establish somatostatin as a neurotransmitter or neuromodulator candidate for these neurons. The morphology of these cells suggests that they are involved in long-distance interactions within the retina.

Humans↗

Optic nerve glia secrete a low-molecular-weight factor that stimulates retinal ganglion cells to regenerate axons in goldfish.

The ability of lower vertebrates to regenerate an injured optic nerve has been widely studied as a model for understanding neural development and plasticity. We have recently shown that, in goldfish, the optic nerve contains two molecules that stimulate retinal ganglion cells to regenerate their axons in culture: a low-molecular-weight factor that is active even at low concentrations (axogenesis factor-1) and a somewhat less active polypeptide of molecular weight 10,000-15,000 (axogenesis factor-2). Both are distinct from other molecules described previously in this system. The present study pursues the biological source and functional significance of axogenesis factor-1. Earlier studies have shown that cultured goldfish glia provide a highly favorable environment for fish or rat retinal ganglion cells to extend axons. We report that the glia in these cultures secrete high levels of a factor that is identical to axogenesis factor-1 in its chromatographic properties and biological activity, along with a larger molecule that may coincide with axogenesis factor-2. Axogenesis factor-1 derived from either goldfish glial cultures or optic nerve fragments is a hydrophilic molecule with an estimated molecular weight of 700-800. Prior studies have reported that goldfish retinal fragments, when explanted in organ culture, only extend axons if the ganglion cells had been "primed" to begin regenerating in vivo for one to two weeks. However, axogenesis factor-1 caused the same degree of outgrowth irrespective of whether ganglion cells had been induced to regenerate new axons in vivo. Moreover, ganglion cells primed to begin regenerating in vivo continued to extend axons in culture only when axogenesis factor-1 was present. In summary, this study shows that glial cells of the goldfish optic nerve secrete a low-molecular-weight factor that initiates axonal regeneration from retinal ganglion cells.

Animals↗

Spiral ganglion cell density in young and old gerbils.

The Mongolian gerbil, like other mammalian species, has a decreased number of spiral ganglion cells as a function of age. This loss of cells was first seen in 24- to 30-month old animals in the basal end of the ganglion. In the oldest individuals the apical end of the ganglion was also affected. There were approximately 15-25% fewer cells in the affected areas in the 36- to 42-month old animals. In the oldest animals degeneration of the stria vascularis was seen in the apical turn and some degenerative changes in the organ of Corti were seen throughout the length of the cochlear duct. The aging pattern in the gerbil cochlea, is similar to that described for other species. Vacuoles, previously described in the gerbil cochlear nucleus, were also seen in the auditory nerve within the modiolus, but central to the Schwann-glial border in all animals. Vacuoles were not present within the spiral ganglion or the peripheral processes of the ganglion cells. Because the ganglion cell axons should be similar on either side of the Schwann-glial border, but the vacuoles were confined to the central nervous system, it is concluded that the degenerative process affects glial cells as opposed to neurons.

Aging↗

Ontogenesis of type II spiral ganglion neurons during development: peripherin immunohistochemistry.

In this study, we analysed the distribution of the intermediate filament peripherin in the developing cochlea of the rat. At gestational day 16, weak immunolabeling was observed in neuronal somas throughout the spiral ganglion. At gestational day 20, the peripherin labeling increased in intensity throughout the spiral ganglion. At gestational day 20, the peripherin labeling increased in intensity throughout the cochlea but became especially strong in some ganglion neurons of the basal turn. Homogeneous immunolabeling was observed throughout the spiral ganglion of the apical turn. Double immunofluorescence labeling of the prenatal cochlea with peripherin and neurofilament (NF) antibodies revealed colocalization on the same structures. By postnatal day 3, the peripherin labeling intensity had decreased in the majority of spiral ganglion neurons, but remained strong in some cells of the basal turn. Only a few neurons continued to be immunolabeled into adulthood that correspond to Type II spiral ganglion neurons expressing both NF protein and peripherin, two classes of intermediate filament proteins. In the organ of Corti, the first immunolabeling was observed on gestational day 20 as peripheral fibers reaching the receptor cells. Positive fibers were observed below both inner (IHCs) and outer (OHCs) hair cells. At birth and at postnatal day 3, peripherin immunolabeling was still observed below both IHCs and OHCs. By postnatal day 4, peripherin labeling became more dominant in fibers below OHCs, but some immunoreactivity was still present below IHCs. No immunoreactivity was present in the intraganglionic spiral bundle (IGSB) fibers containing the olivary complex efferent fibers before birth. A few days after birth some fibers of the IGSB started to be immunoreactive.

Animals↗

An unusual meniscal ganglion cyst that triggered recurrent hemarthrosis of the knee.

A 58-year-old woman suffered spontaneous recurrent hemarthrosis of the knee. In the clinical course, pigmented villonodular synovitis was mostly suspected, but in arthroscopic surgery the lateral meniscus appeared to be upturned and stuck into the lateral pouch with the meniscal ganglion cyst. It was suggested that meniscal tear with meniscal ganglion cyst was related with recurrent hemarthrosis. Generally, both the meniscal ganglion cysts and spontaneous recurrent hemarthrosis are highly rare conditions. In this case, we speculated that a negligible power could induce the meniscal tear with recurrent hemarthrosis in the particular situation in which the meniscal ganglion cyst existed. In other words, the meniscal ganglion cyst might basically and physically relate with hemorrhagic condition. Arthroscopically, the meniscal ganglion cyst was removed together with the anterior segment of the lateral meniscus. Recurrent hemarthrosis was treated successfully by resection of the meniscus.

Arthroscopy↗

Information transmission rate changes of retinal ganglion cells during contrast adaptation.

During adaptation to high-contrast stimulation, retinal ganglion cell's responsiveness change is characterized by decreased firing rate and declined sensitivity. In order to examine the modification of information transmission properties of the ganglion cell during this adaptation process, neural activities were recorded extracellularly from the chicken retina using a multi-electrode recording system, and the information transmission rate of the retinal ganglion cells was estimated. The results show that the response entropy and noise entropy of the ganglion cells both decreased during the adaptation process, which resulted in a modest decline of information transmission rate of ganglion cells after several seconds' adaptation. However, due to the decrease of the neuron's firing rate during the adaptation, it is revealed that the information carried by each spike was increased as compared to pre-adaptation, suggesting that retinal ganglion cells' information processing strategies during contrast adaptation may reflect economical principle by promoting each spike more informative. These results also suggest that contrast adaptation and sensitivity rescaling of the visual neurons provide an efficient manner in information transmission and save the system's metabolic cost in the meantime.

Action Potentials↗

CNTF gene transfer protects ganglion cells in rat retinae undergoing focal injury and branch vessel occlusion.

Ciliary neurotrophic factor (CNTF) has been shown to protect ganglion cells in a variety of acute ischaemia models. Here we assess the efficacy of local CNTF gene transfer in protecting retinal ganglion cells when there is focal ischaemia combined with interruption of axoplasmic flow. This dual injury may be more representative of the pathological mechanisms operating in acute retinal diseases, such as vascular events acting at the optic nerve head. Fourteen rats received an intravitreal injection of an adeno-associated viral (AAV) vector expressing a secretable form of CNTF into the right eye and a control vector into the left eye. Three weeks later, each rat underwent a symmetrical small vertical 2mm standardised retinal crush injury approximately 2mm temporal to the optic disc. The injury also occluded the temporal retinal arteriole so that the axon crush was combined with an acute retinal infarction visible on fundoscopy. Changes in the damaged sector were compared histologically four weeks after injury and ganglion cell survival was estimated by comparing cell counts on retinal flat-mounts immunostained with RT-97 antibody. This mode of injury led to a profound loss of both the inner nuclear and ganglion cell layers, but was limited to the lesioned sector. In AAV.CNTF-treated eyes approximately 12% of ganglion cells survived compared with approximately 2% in control eyes (p=0.01). The scotopic electroretinogram (ERG), however, was reduced to about 50% in AAV.CNTF-treated eyes, both before and after injury. We therefore show that CNTF gene transfer confers neuroprotection to ganglion cells undergoing an acute ischaemic injury combined with interruption of axoplasmic flow. This approach may be relevant to optic nerve trauma and a variety of retinal vascular diseases that lead to swelling of the optic nerve head, provided CNTF can be delivered in a way that does not significantly suppress retinal function.

Animals↗

Iba1-expressing microglia respond to herpes simplex virus infection in the mouse trigeminal ganglion.

Microglial response in the trigeminal ganglion of mice corneally inoculated with herpes simplex virus (HSV) was investigated. Virus-infected neurons of the trigeminal ganglion did not exhibit apoptotic signal, while those of the trigeminal sensory brainstem nucleus did. Cells expressing ionized calcium binding adapter molecule 1 (Iba1), a specific marker of microglia/macrophages, increased in number in the virally infected region of the trigeminal ganglion, with morphological transformation to an activated phenotype, frequently detected as perineural satellites. Further microglial transformation to macropahges was not evident. Iba1-immunopositive perineural satellites also appeared in the vicinity of virally infected region. Such activated microglia expressed basic fibroblast growth factor (bFGF) molecules. The reverse transcription-polymerase chain reaction (RT-PCR) detected upregulated synthesis of mRNA for bFGF in the trigeminal ganglion. In contrast, in the trigeminal sensory brainstem nucleus, a small number of bFGF-producing cells appeared only in the vicinity of virally infected area. Collectively, Iba1-bearing microglia exist in the mouse trigeminal ganglion and respond to herpes simplex virus infection, most likely conferring neuroprotective functions upon the trigeminal ganglion.

Animals↗

Retinal ganglion cell type, size, and spacing can be specified independent of homotypic dendritic contacts.

In Brn3b(-/-) mice, where 80% of retinal ganglion cells degenerate early in development, the remaining 20% include most or all ganglion cell types. Cells of the same type cover the retinal surface evenly but tile it incompletely, indicating that a regular mosaic and normal dendritic field size can be maintained in the absence of contact among homotypic cells. In Math5(-/-) mice, where only approximately 5% of ganglion cells are formed, the dendritic arbors of at least two types among the residual ganglion cells are indistinguishable from normal in shape and size, even though throughout development they are separated by millimeters from the nearest neighboring ganglion cell of the same type. It appears that the primary phenotype of retinal ganglion cells can develop without homotypic contact; dendritic repulsion may be an end-stage mechanism that fine-tunes the dendritic arbors for more efficient coverage of the retinal surface.

Animals↗

Axonal regeneration of cat retinal ganglion cells is promoted by nipradilol, an anti-glaucoma drug.

Neurons in the CNS can regenerate their axons in an environment of the peripheral nervous system, but this ability is limited. Here we show that an anti-glaucoma drug, nipradilol, at low concentration led to a four-fold increase in the number of cat retinal ganglion cells regenerating their axons into a transplanted peripheral nerve 4 and 6 weeks after axotomy. Nipradilol also increased the number of three main regenerating retinal ganglion cell types (alpha, beta, not alpha/beta), and enhanced the rate of axonal regeneration of these retinal ganglion cells. Nipradilol is a donor of nitric oxide and an antagonist of alpha-1, beta-1 and -2 adrenoreceptors, and we therefore examined whether one of these pharmacological effects might be more important in promoting axon regeneration. A nitric oxide donor increased the number of regenerating retinal ganglion cells, but not the rate of axonal regeneration. Denitro-nipradilol (nitric oxide-deprived nipradilol) or a nitric oxide scavenger injected before nipradilol increased the number of regenerating retinal ganglion cells but did not promote regeneration rate. Blockade of individual alpha- and beta-adrenoreceptors did not increase the number of regenerating retinal ganglion cells or the rate of regeneration. From these results, it is suggested that nitric oxide plays a crucial role in mediating the effects of nipradilol on axon regeneration and neuroprotection, and the metabolite of nipradilol supports the effects.

Adrenergic alpha-Antagonists↗

Effects of beta-adrenergic blockers on glutamate-induced calcium signals in adult mouse retinal ganglion cells.

Betaxolol, a selective beta(1)-adrenoceptor antagonist, is an antiglaucoma drug commonly used to lower the intraocular pressure (IOP) in treatment of glaucoma. Recent evidence has also shown that it attenuates ligand- and voltage-gated currents in retinal ganglion cells, which may lead to reduction of intracellular calcium and prevention of glutamate-induced ganglion cell damage in glaucoma. In the present study, we examined the effectiveness of betaxolol and other beta-adrenergic blockers on glutamate-induced calcium signals. Dissociated adult mouse retinal ganglion cells were immuno-labeled with antibody CD90.2 and loaded with Fura-2AM. Calcium signals were recorded with optical recording techniques. Low doses of glutamate cause an increase in intracellular calcium that may result in pathological changes in ganglion cells. The action of glutamate could be reversibly suppressed by beta-adrenergic blockers and the order of inhibitory potency is (s)(-)-propranolol>betaxolol>>timolol, with average IC(50) of 78.05, 235.7 and 2167.05, microM, respectively. Betaxolol compressed the dose-response curve of glutamate. The EC(50) of glutamate was shifted from 6.19 to 23.53 microM, indicating that betaxolol acts as a non-competitive inhibitor of glutamate response in retinal ganglion cells. Our data are consistent with previous reports that betaxolol and other beta-adrenergic blockers may exert its neuroprotective action by suppression of glutamate-induced intracellular calcium increase in retinal ganglion cells.

Adrenergic beta-Agonists↗