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At least 1,207 records · Page 67Linked to original sources
PubMed2006

Voltage-gated and two-pore-domain potassium channels in murine spiral ganglion neurons.

The systematically varied firing features of spiral ganglion neurons provide an excellent model system for the exploration of how graded ion channel distributions can be used to organize neuronal firing across a population of neurons. Elucidating the underlying mechanisms that determine neuronal response properties requires a complete understanding of the combination of ion channels, auxiliary proteins, modulators, and second messengers that form this highly organized system in the auditory periphery. Toward this goal, we built upon previous studies of voltage-gated K+-selective ion channels (Kv), and expanded our analysis to K+-selective leak channels (KCNK), which can play a major role in setting the basic firing characteristics of spiral ganglion neurons. To begin a more comprehensive analysis of Kv and KCNK channels, a screening approach was employed. RT-PCR was utilized to examine gene expression, the major results of which were confirmed with immunocytochemistry. Initial studies validated this approach by accurately detecting voltage-dependent K+ channels that were documented previously in the spiral ganglion. Furthermore, an additional channel type within the Kv3 family, Kv3.3, was identified and further characterized. The major focus of the study, however, was to systematically examine gene expression levels of the KCNK family of K+-selective leak channels. These channel types determine the resting membrane potential which has a major impact on setting the level of neuronal excitation. TWIK-1, TASK-3, TASK-1, and TREK-1 were expressed in the spiral ganglion; TWIK-1 was specifically localized with immunocytochemistry to the neuronal somata and initial processes of spiral ganglion neurons in vitro.

Animals↗
PubMed2004

Wrist joint ganglion presenting as a painless mass in the palm: report of 2 cases.

Ganglions occur commonly in the wrist and arise from the radiocarpal and intercarpal joints. Although ganglions present commonly as masses on the dorsal or volar surface of the wrist, ganglions from wrist joints appear rarely at other locations in the hand. We report 2 cases of ganglions arising from wrist joints that presented as painless masses in the center of the palm without signs or symptoms of median or ulnar nerve compression. Surgical treatment required extensile exposure to trace the proximal stalks to their joints of origin. Knowledge of the possibility that a painless mass in the palm could be a ganglion arising from a joint in the wrist allows proper presurgical planning and informed consent.

Adult↗
PubMed2004

Dissociation of retinal ganglion cells without enzymes.

We describe here methods for dissociating retinal ganglion cells from adult goldfish and rat without proteolytic enzymes, and show responses of ganglion cells isolated this way to step-wise voltage changes and fluctuating current injections. Taking advantage of the laminar organization of vertebrate retinas, photoreceptors and other cells were lifted away from the distal side of freshly isolated goldfish retinas, after contact with pieces of membrane filter. Likewise, cells were sliced away from the distal side of freshly isolated rat retinas, after these adhered to a membrane filter. The remaining portions of retina were incubated in an enzyme-free, low Ca2+ solution, and triturated. After aliquots of the resulting cell suspension were plated, ganglion cells could be identified by dye retrogradely transported via the optic nerve. These cells showed no obvious morphological degeneration for several days of culture. Perforated-patch whole-cell recordings showed that the goldfish ganglion cells spike tonically in response to depolarizing constant current injections, that these spikes are temporally precise in response to fluctuating current injections, and that the largest voltage-gated Na+ currents of these cells were larger than those of ganglion cells isolated with a neutral protease.

Action Potentials↗
PubMed2003

Rat retinal ganglion cells upregulate the pro-apoptotic BH3-only protein Bim after optic nerve transection.

Increased expression of Bim, a pro-apoptotic member of the Bcl-2 family, has been shown to be critical for neuronal apoptosis. To study the involvement of Bim in injury-induced cell death in retina, Bim expression was studied in normal rat retina and in retina after optic nerve transection using quantitative RT-PCR and immunohistochemistry. As a complement to this, the apoptotic regulators Bax, Bcl-2, caspase-3 and phosphorylated c-jun were studied. The relative levels of Bim mRNA in retina were significantly higher 4 days after optic nerve transection and below normal levels at 14 days after transection. A parallel increase in the number of Bim-immunoreactive cells in the retinal ganglion cell layer could be seen. Bim-immunoreactivity localized to retrogradely True Blue-labeled retinal ganglion cells. The relative mRNA levels for both Bax and Bcl-2 were higher at 4 days after transection when compared to normal. Immunoreactivity for Bax, Bcl-2 as well as for caspase-3 and phosphorylated c-jun, indicative of cell death, localized to True Blue-identified retinal ganglion cells 4 days after injury. Bcl-2 immunoreactivity was also seen on other cells, most likely Müller glia cells. In addition, optic nerve transection caused an increase in Bim, Bax, and Bcl-2 mRNA levels in optic nerve and superior colliculus. Our results suggest that Bim is involved in injury-induced retinal ganglion cell death and indicate that the increase in Bim and Bax expression promote cell death of axotomized retinal ganglion cells whereas the elevation in Bcl-2 in retina may contribute to the control of the extent of apoptosis after the optic nerve transection.

Animals↗
PubMed2006

Morphological properties of mouse retinal ganglion cells.

The mouse retina offers an increasingly valuable model for vision research given the possibilities for genetic manipulation. Here we assess how the structural properties of mouse retinal ganglion cells relate to the stratification pattern of the dendrites of these neurons within the inner plexiform layer. For this purpose, we used 14 morphological measures to classify mouse retinal ganglion cells parametrically into different clusters. Retinal ganglion cells were labeled in one of three ways: Lucifer Yellow injection, 'DiOlistics' or transgenic expression of yellow fluorescent protein. The resulting analysis of 182 cells revealed 10 clusters of monostratified cells, with dendrites confined to either On or Off sublaminae of the inner plexiform layer, and four clusters of bistratified cells, dendrites spanning the On and Off sublaminae. We also sought to establish how these parametrically identified retinal ganglion cell clusters relate to cell types identified previously on the basis of immunocytochemical staining and the expression of yellow fluorescent protein. Cells labeled with an antibody against melanopsin were found to be located within a single cluster, while those labeled with the SMI-32 antibody were in four different clusters. Yellow fluorescent protein expressing cells were distributed within 13 of the 14 clusters identified here, which demonstrates that yellow fluorescent protein expression is a useful method for labeling virtually the entire population of mouse retinal ganglion cells. Collectively, these findings provide a valuable baseline for future studies dealing with the effects of genetic mutations on the morphological development of these neurons.

Animals↗
PubMed2005

The cranial cervical ganglion and its branches in the yak (Bos grunniens).

The heads and necks of 10 yaks were dissected to study the shape, location, arrangement, and branches of the cranial cervical ganglion. The ganglion was a greyish fusiform structure, mean length 19.72 mm, width 7.65 mm and depth 4.55 mm, located on the rostrolateral surface of the m. longus capitis. Approximately 25% of the ganglion was covered by the tympanic bulla, the rest by the m. stylohyoideus. The branches of the cranial cervical ganglion included the internal and external carotid nerves, sympathetic trunk and the branches connecting with the glossopharyngeal, vagus and hypoglossal nerves. In one animal the right cranial cervical ganglia was a greyish pyramidal structure 10 mm long, 8 mm wide and 5 mm thick but the left ganglion was similar to those found in the other specimens examined.

Animals↗
PubMed2006

Cross-talk between ON and OFF channels in the salamander retina: indirect bipolar cell inputs to ON-OFF ganglion cells.

It has been widely accepted that ON and OFF channels in the visual system are segregated with little cross-communication, except for the mammalian rod bipolar cell-AII amacrine cell-ganglion cell pathway. Here, we show that in the tiger salamander retina the light responses of a subpopulation of ON-OFF ganglion cells are mediated by crossing the ON and OFF bipolar cell pathways. Although the majority of ON-OFF ganglion cells (type I cells) receive direct excitatory inputs from depolarizing and hyperpolarizing bipolar cells (DBCs and HBCs), about 5% (type II cells) receive indirect excitatory inputs from DBCs and 20% (type III cells) receive indirect excitatory inputs from HBCs. These indirect bipolar cell inputs are likely to be mediated by a subpopulation of amacrine cells that exhibit transient hyperpolarizing light responses (AC(H)s) and make GABAergic/glycinergic synapses on DBC or HBC axon terminals. GABA and glycine receptor antagonists enhanced the ON and OFF excitatory cation current (DeltaI(C)) in type I ganglion cells, but completely suppressed the ON DeltaI(C) mediated by DBCs in type II cells and the OFF DeltaI(C) mediated by HBCs in types III cells. Dendrites of type I cells ramify in both sublamina A and B, type II cells exclusively in sublamina A, and type III cells exclusively in sublamina B of the inner plexiform layer. These results demonstrate that indirect, amacrine cell-mediated bipolar cell-ganglion cell synaptic pathways exist in a non-mammalian retina, and that bidirectional cross-talk between ON and OFF channels is present in the vertebrate retina.

Amacrine Cells↗
PubMed1995

Comparison of ganglion cell loss and cone loss in experimental glaucoma.

PURPOSE: To compare the loss of ganglion cells to cone loss in the macular area of monkey eyes with experimental glaucoma. METHODS: Experimental glaucoma was induced in eyes of three cynomolgus monkeys by argon laser applications to the trabecular meshwork. The average duration +/- S.D. of glaucoma in the experimental animals was 3.8 +/- 0.5 months. Glaucomatous damage was estimated, before the animals were killed, by evaluating stereoscopic photographs of the optic disk and red-free photographs of the nerve fiber layer. Ganglion cell nucleoli and cone pedicles were counted by using light microscopy from slides containing strips of retinal tissue. Cell density was then calculated by using the modified Abercrombie formula. Percent loss of ganglion cells and cones was determined from three eyes of three monkeys in 300-micron segments that were 900 to 1,200 microns superior and inferior to the foveal center. RESULTS: Cone loss was not found at 4.5 to 6 degrees eccentricity above and below the fovea, whether damage was mild or severe. The average loss +/- S.D. of ganglion cells was 81.1% +/- 10.7%, whereas the average cone loss was only 3.5% +/- 6.4%. CONCLUSIONS: Marked parafoveal cone loss was not found in experimental glaucoma in which extensive damage to ganglion cells occurred.

Animals↗
PubMedDate not supplied

Quantitative and somatotopic mapping of neurones in the trigeminal mesencephalic nucleus and ganglion innervating teeth in monkey and baboon.

Neurones of the trigeminal mesencephalic nucleus (Mes V) and ganglion innervating the periodontium of incisor, canine and molar teeth in 10 monkeys and 10 baboons were counted and mapped using the horseradish peroxidase (Hrp), retrograde axonal transport method. Periodontal afferent neurones of all these teeth were well represented in the Mes V, although the incisors had a significantly higher number of labelled neurones than the canines or molars. The primary cell bodies of the periodontal afferents were located mainly in the caudal part of the ipsilateral Mes V from the level of the inferior colliculus to the floor of the fourth ventricle in the pons. The caudal periodontal Mes V neurones may be favourably located to make collateral connections with the trigeminal motor nucleus for jaw reflexes. Incisors and canines had a large and predominantly ipsilateral representation of Hrp-labelled neurones in the ganglion. In contrast, molar representation in the ganglion was sparse and all labelled neurones supplied ipsilateral teeth. The maxillary and mandibular teeth had a somatotopic distribution within the respective maxillary (middle) and mandibular (posterolateral) compartments of the trigeminal ganglion. It is suggested that the anterior teeth with greater connections to the Mes V and the ganglion may impart greater sensory perception and be involved in jaw reflexes to ensure a good occlusal relation during mastication, while the afferent connections of the molars may initiate complex jaw reflexes during the occlusal phase of mastication.

Animals↗
PubMed2000

Failure to activate NF-kappaB promotes apoptosis of retinal ganglion cells following optic nerve transection.

NF-kappaB is a transcription factor, which is activated by various stimuli. One of the well-known activators of NF-kappaB is oxidative stress, which is a cause of cell death in some tissue, or cell types. Optic nerve transection, axotomy, results in retinal cell death, because of oxidative stress, deprivation of neurotrophic factors, etc. Since it has been hypothesized that the retinal ganglion cell death after axotomy is due to the generation of reactive oxygen species, we investigated whether NF-kappaB is involved in the retinal cell death after axotomy. This study was performed to investigate the role of NF-kappaB in retinal ganglion cell death after optic nerve transection. We used double staining experiment by using anti-NF-kappaB antibody and ethidium bromide to observe the correlation of NF-kappaB activation and the cell death. NF-kappaB was observed only in the surviving cells. NF-kappaB translocation was observed 3 days after the optic nerve transection. The NF-kappaB inhibitor, sulfasalazine, was used to block the activation of NF-kappaB in the axotomized retina, and the number of ganglion cells was quantified using retrograde in the presence or absence of sulfasalazine after axotomy. Inhibition of NF-kappaB by sulfasalazine accelerated the degeneration of ganglion cells in the retina. The results suggest that the activated NF-kappaB plays a protective role from the cell death in the injured ganglion cells.

Animals↗
PubMed1997

Identification of retinal ganglion cells projecting to the lateral hypothalamic area of the rat.

The objective of the present study was to identify the retinal ganglion cells projecting to the lateral hypothalamic area of the rat. The retinohypothalamic tract has been divided into a medial and a lateral component on anatomical and developmental grounds. The medial component projects to the suprachiasmatic nucleus and adjacent structures such as the anterior hypothalamic and retrochiasmatic areas. The lateral component terminates in the lateral hypothalamic are dorsal to the supraoptic nucleus. Injections of the retrograde tracer FluoroGold were made into the retinorecipient region of the lateral hypothalamic area and retinal whole mounts were immunohistochemically processed for retrogradely labeled retinal ganglion cells. With FluoroGold injections confined to the lateral hypothalamic area, retrogradely labeled retinal ganglion cells are located almost exclusively in the superior temporal quadrant of the retina. Their size and morphology indicates that they are a homogeneous subset of type III cells, but a definitive classification would require a more complete fill of dendritic arbors than is available in our retrograde material. In contrast, injections involving fibers of passage in the optic tract, or centered in the medial terminal nucleus of the accessory optic system, label cells distributed across the entire retinal surface. Unlike the retinal ganglion cells projecting to the suprachiasmatic nucleus [Moore et al., J. Comp. Neurol., 352 (1995) 351-366], the cells labeled after restricted lateral hypothalamic injections are not distributed evenly across the retinal surface. The difference in location of the retinal ganglion cells projecting to the lateral hypothalamic area supports the view that this retinohypothalamic projection is anatomically and functionally distinct from the projection to the suprachiasmatic nucleus and adjacent medial hypothalamus.

Animals↗
PubMed2003

Evidence that ganglion cells react to retinal detachment.

Growth associated protein 43 (GAP 43) is involved in synapse formation and it is expressed in the retina in a very specific pattern. Although GAP 43 is downregulated at the time of synapse formation, it can be re-expressed following injury such as axotomy or ischemia. Because of this we sought to characterize the expression of GAP 43 after retinal detachment (RD). Immunoblot, immunocytochemical and quantitative polymerase chain reaction (QPCR) techniques were used to assess the level of GAP 43 expression after experimental RD. GAP 43 was localized to three sublaminae of the inner plexiform layer of the normal retina. GAP 43 became upregulated in a subset of retinal ganglion cells following at least 7 days of RD. By immunoblot GAP 43 could be detected by 3 days. QPCR shows the upregulation of GAP 43 message by 6hr of detachment. To further characterize changes in ganglion cells, we used an antibody to neurofilament 70 and 200kDa (NF) proteins. Anti-NF labels horizontal cells, ganglion cell dendrites in the inner plexiform layer, and ganglion cell axons (fasicles) in the normal retina. Following detachment it is upregulated in horizontal cells and ganglion cells. When detached retina was double labelled with anti-GAP 43 and anti-NF, some cells were labelled with both markers, while others labelled with only one. We have previously shown that second order neurons respond to detachment; here we show that third order neurons are responding as well. Cellular remodelling of this type in response to detachment may explain the slow recovery of vision that often occurs after reattachment, or those changes that are often assumed to be permanent.

Animals↗
PubMedDate not supplied

Apoptosis in retinal ganglion cell decrease in human glaucomatous eyes.

Hematoxylin-eosin staining, the TUNEL method for in situ detection of the intranuclear DNA fragmentation, which indicates apoptosis, and electron microscopy were used to study the morphologic changes in specimens from the eyes of 8 patients with secondary glaucoma and 2 normal control eyes to evaluate our hypothesis that apoptosis causes a decrease in retinal ganglion cells in human glaucomatous eyes. The TUNEL method permits identification of intranuclear DNA fragmentation. Apoptosis was found in the ganglion cells of 2 glaucomatous eyes with recent sight loss, and in the ganglion cells of a control eye from a 95-year-old subject, taken at autopsy. Results of our study indicate that a decrease in retinal ganglion cells in glaucomatous eyes is caused by apoptosis. In addition, apoptosis resulting from aging must be considered in order to understand the reduction of retinal ganglion cells in the glaucomatous eyes of elderly patients.

Adult↗
PubMed2003

Ganglion cysts of the shoulder: technique of arthroscopic decompression and fixation of associated type II superior labral anterior to posterior lesions.

Ganglion cysts of the shoulder and concomitant suprascapular nerve compression should be considered in the differential diagnosis of shoulder pain. They are associated commonly with labral tears, most commonly SLAP lesions. MRI has become commonplace in evaluating shoulder pain and has led to the increased awareness of shoulder cysts. MRI accurately demonstrates the size and location of ganglions, which is critical when planning surgical intervention. It also has shown the frequent association of intra-articular pathology with these cysts. Despite that MRI can detect atrophy, the diagnosis of suprascapular nerve compression can be confirmed only by EMG/NCS, because the presence of a cyst does not necessarily mean the nerve is compressed. Likewise, a positive EMG does not confirm that the compression is caused by a ganglion cyst. EMG/NCVs are necessary for confirming the diagnosis and evaluating nerve and muscle function. A trial of nonoperative management is warranted; however, this is associated with a high failure rate. Aspiration techniques are successful for decompression of the cysts and initial pain relief; however, the intra-articular pathology is not addressed and there is a higher rate of recurrence. Open resection of the ganglion cyst is successful; however, the intra-articular labral tears are not addressed, which can lead to recurrence and the morbidity of the cyst excision is not warranted. Shoulder arthroscopy has led to the identification of associated intra-articular pathology such as SLAP lesions. These were not appreciated previously with open surgery and therefore were not addressed. Arthroscopic techniques have evolved to allow decompression of the ganglion cysts and repair of the labral lesions. This should decrease the possibility of recurrence of the cyst by eliminating the cyst and the pathologic lesion that created it. Arthroscopic excision also avoids much of the morbidity of the open approach and allows intra-articular pathology to be addressed concomitantly. This point has been emphasized by other investigators also. Furthermore, because of the limited surgical dissection, rehabilitation is able to begin earlier, with less patient discomfort and more prompt return to normal activities.

Arthroscopy↗
PubMed1997

An efficient method that reveals both the dendrites and the soma mosaics of retinal ganglion cells.

A method of using neurobiotin to stain both the dendrites and the soma mosaics of retinal ganglion cells in fresh retinae is described. This method is simple to use and efficient in revealing morphological details for a large number of retinal ganglion cells. It has five advantages over currently available staining methods. (1) It stains all ganglion cells in the whole retina or in a selected retinal area, permitting ganglion cell distributions across the retina to be obtained. (2) It reveals cell dendrites in great detail, especially in regions outside the area centralis. The dendritic field mosaics and, therefore the dendritic field coverage factors, of different ganglion cell types across the whole retina can be obtained easily. (3) It works reliably, efficiently, and does not require the expensive set-up or the pains-taking work needed when staining cells through intracellular injection. (4) It works under both in vivo and in vitro settings, permitting the use of retinae from animals sacrificed for other purposes and the use of postmortem human retinae. (5) The end product of the visualization process is optically dark and electron dense, permitting specimens to be examined under both light and electron microscopes.

Animals↗
PubMed2001

Characterization of a transformed rat retinal ganglion cell line.

The purpose of the present study was to establish a rat retinal ganglion cell line by transformation of rat retinal cells. For this investigation, retinal cells were isolated from postnatal day 1 (PN1) rats and transformed with the psi2 E1A virus. In order to isolate retinal ganglion cells (RGC), single cell clones were chosen at random from the transformed cells. Expression of Thy-1 (a marker for RGC), glial fibrillary acidic protein (GFAP, a positive marker for Muller cells), HPC-1/syntaxin (a marker for amacrine cells), 8A1 (a marker for horizontal and ganglion cells) and neurotrophins was studied using reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunocytochemistry. One of the retinal cell clones, designated RGC-5, was positive for Thy-1, Brn-3C, Neuritin, NMDA receptor, GABA-B receptor, and synaptophysin expression and negative for GFAP, HPC-1, and 8A1, suggesting that it represented a putative RGC clone. The results of RT-PCR analysis were confirmed by immunocytochemistry for Thy-1 and GFAP. Upon further characterization by immunoblotting, the RGC-5 clone was positive for Thy-1, negative for GFAP, 8A1 and syntaxin. RGC 5 cells were also positive for the expression of neurotrophins and their cognate receptors. To establish the physiological relevance of RGC-5, the effects of serum/trophic factor deprivation and glutamate toxicity were analyzed to determine if these cells would undergo apoptosis. The protective effects of neurotrophins on RGC-5 after serum deprivation was also investigated. Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated fluoresceinated dUTP nick end labeling (TUNEL). Serum deprivation resulted in apoptosis and supplementation with both BDNF and NT-4 in the growth media, protected the RGC-5 cells from undergoing apoptosis. On differentiation with succinyl concanavalin A (sConA), RGC-5 cells became sensitive to glutamate toxicity, which could be reversed by inclusion of ciplizone (MK801). In conclusion, a transformed rat retinal cell line, RGC-5, has certain characteristics of retinal ganglion cells based on Thy-1 and Brn-3C expression and its sensitivity to glutamate excitotoxicity and neurotrophin withdrawal. These cells may be valuable in understanding of retinal ganglion cell biology and physiology including in vitro manipulations in experimental models of glaucoma.

Animals↗
PubMed1997

YVAD protect post-natal retinal ganglion cells against axotomy-induced but not free radical-induced axonal degeneration in vitro.

In the developing central nervous system (CNS), the differentiation of neurons is accompanied by a large amount of cell loss in the form of programmed cell death (apoptosis). On the other hand, injury in the adult CNS often results in permanent neuronal degeneration leading to the failure of axonal regeneration. This could be related to an axotomy-induced activation of an apoptotic program. The interleukin-1beta-converting enzyme family of proteases has been implicated in playing a fundamental role in apoptotic processes in both invertebrates and vertebrates. In order to determine what role, if any, inhibitors of the interleukin-1beta-converting enzyme family might play in axonal regeneration after axotomy we employed an in vitro system using retinal explants from post-natal rats at the age between 9 and 12 days [R. Lucius, P. Young, S. Tidow and J. Sievers, Growth stimulation and chemotropic attraction of retinal ganglion cell axons in vitro by co-cultured optic nerves, astrocytes and astrocyte conditioned medium, Int. J. Dev. Neurosci., Vol. 14 (1996) 387-398]. The retinal ganglion cells in this model are comparable to adult animals in their regenerative response (D. Alcutt, M. Berry and J. Sievers, A qualitative comparison of the reaction of retinal ganglion cells to optic nerve crush in neonatal and adult mice, Dev. Brain Res., Vol. 16 (1984a) 231-240; D. Allcutt, M. Berry and J. Sievers, A quantitative comparison of the reaction of retinal ganglion cells to optic nerve crush in neonatal and adult mice, Dev. Brain Res., Vol. 16 (1984b) 219-230]. The addition of the synthetic peptide inhibitor YVAD (Ac-Tyr-Val-Ala-Asp-aldehyde), which reversible inhibits interleukin-1beta-converting enzyme and subsequent apoptosis, enhances the number and length of regenerating neurites of retinal ganglion cells. However, this manipulation was not able to overcome free radical-induced axonal degeneration/neuronal apoptosis, suggesting at least two different death pathways leading to neuronal degeneration/cell death. These results provide the first evidence that inhibitors of key enzymes of the apoptotic program could play a beneficial role to overcome neurite degeneration after axotomy in the adult mammalian CNS.

Animals↗
PubMed1998

Up-regulation of fast-axonally transported proteins in retinal ganglion cells of adult rats with optic-peroneal nerve grafts.

Metabolic labeling and quantitative 2D gel fluorography were used to assess changes in the synthesis and transport of five fast-axonally transported and developmentally regulated proteins (GAP-43, SNAP-25, and proteins of 18, 22, and 23/24 kDa) after grafting of a peroneal nerve segment onto a transected optic nerve in adult rats. After optic nerve transection alone, only GAP-43 was up-regulated significantly compared to normal adult controls. The other proteins showed little change or were down-regulated following axotomy. By 4 weeks following optic nerve transection and peroneal nerve grafting, however, GAP-43, proteins 22 and 23/24 kDa showed a sustained up-regulation in synthesis and transport compared to normal controls; SNAP-25 and protein 18 kDa showed levels of expression similar to or slightly greater than normal controls. Increased expression of GAP-43 in retinal ganglion cells was also examined with immunocytochemistry. While a transient up-regulation of GAP-43 in retinal ganglion cells was observed following optic nerve transection, a sustained increase in GAP-43 immunoreactivity was present only in animals with nerve grafts. Backfilling of retinal ganglion cells from the grafts with horseradish peroxidase combined with GAP-43 immunocytochemistry revealed that all retinal ganglion cells with axons growing into the grafts were positive for GAP-43, but not all retinal ganglion cells showing GAP-43 immunoreactivity were extending axons into the grafts. We conclude that the presence of a nerve graft sustains the up-regulation of a number of proteins including GAP-43, and that this up-regulation is correlated with an increased potential for nerve growth, but other as yet unknown factors or conditions appear to play a role in determining if this growth potential will be realized.

Aging↗