Regeneration of axons in the optic nerve of the adult Browman-Wyse (BW) mutant rat

Summary We have studied the regeneration of axons in the optic nerves of the BW rat in which both oligodendrocytes and CNS myelin are absent from a variable length of the proximal (retinal) end of the nerve. In the optic nerves of some of these animals, Schwann cells are present. Axons failed to regenerate in the exclusively astrocytic environment of the unmyelinated segment of BW optic nerves but readily regrew in the presence of Schwann cells even across the junctional zone and into the myelin debris filled distal segment. In the latter animals, the essential condition for regeneration was that the lesion was sited in a region of the nerve in which Schwann cells were resident. Regenerating fibres appeared to be sequestered within Schwann cell tubes although fibres traversed the neuropil intervening between the ends of discontinuous bundles of Schwann cell tubes, in both the proximal unmyelinated and myelin debris laden distal segments of the BW optic nerve. Regenerating axons never grew beyond the distal point of termination of the tubes. These observations demonstrate that central myelin is not an absolute requirement for regenerative failure, and that important contributing factors might include inhibition of astrocytes and/or absence of trophic factors. Regeneration presumably occurs in the BW optic nerve because trophic molecules are provided by resident Schwann cells, even in the presence of central myelin, oligodendrocytes and astrocytes. All the above experimental BW animals also have Schwann cells in their retinae which myelinate retinal ganglion cell axons in the fibre layer. Control animals comprised normal Long Evans Hooded rats, BW rats in which both retina and optic nerve were normal, and BW rats with Schwann cells in the retina but with normal, i.e. CNS myelinated, optic nerves. Regeneration was not observed in any of the control groups, demonstrating that, although the presence of Schwann cells in the retina may enhance the survival of retinal ganglion cells after crush, concomitant regrowth of axons cut in the optic nerve does not take place.     

Contacts between regenerating axons and the Schwann cells of sciatic nerve segments grafted to the optic nerve of adult rats

Summary The relation between Schwann cells, basal laminae and axons during retinal ganglion cell regeneration was studied by using cellular, acellular and partially acellular sciatic nerve autografts into the optic nerve. Acellular grafts were achieved by temporary compression which eliminates living Schwann cells and axons. The compressed sciatic nerve together with the intact portion was used as a partially acellular graft. The compressed portion was anastomosed to the optic nerve and the intact portion was situated distally. After 3–21 days post-operation, the grafts were studied by thin sectioning and freeze-fracture. Axons were seen to regenerate into cellular grafts in contact with Schwann cells after one week, but not into acellular grafts for the entire period. In the partially acellular grafts, regenerating axons were first observed after two weeks and were always in contact with Schwann cells migrating from the intact portion. Moreover, membrane specializations, fuzzy materials in the space between apposed membranes, and putative tight junctions, were found between regenerated axons including growth cone and Schwann cells, and between adjoining Schwann cells. An extensive meshwork of putative tight junctions was displayed between reforming perineurial cells surrounding the groups of Schwann cells and associated axons. Gap junctions were seen between adjoining Schwann cells, and between reforming perineurial cells. These results suggest that the axonal contact with Schwann cell surfaces plays an important role in retinal ganglion cell regeneration.     

Response of axons and glia at the site of anastomosis between the optic nerve and cellular or acellular sciatic nerve grafts

Summary Axonal and glial reactions at the site of optic nerve section and at the junctional zone between optic nerve and normal or acellular peripheral nerve grafts have been studied. Following optic nerve section, no axons grew into the distal optic nerve stump. Similarly, no axons invaded the acellular peripheral nerve grafts, although in both instances fibres did regenerate into the junctional zone and a few remained there at least until 30 days post lesion (dpl, the duration of the experiments). Axons regenerated into normal peripheral nerve grafts by 3–5 dpl and by 10 dpl large numbers had penetrated deeply into the grafts. The glial response to injury appeared similar in both groups of grafted animals. Astrocytes and oligodendrocytes grew out into the junctional zone over the 5–7 day period and invaded the margins of the cellular grafts by 10 dpl. They did not penetrate the acellular nerves or distal optic nerve stumps. We were unable to determine whether Schwann cells invaded the junctional zone from the normal peripheral nerve grafts. Schwann cells are both GFAP⁺ and Vim⁺, especially when reacting after injury, and Lam^– when not associated with axons: it is therefore possible that Schwann cells from the cellular grafts contributed to the population of GFAP⁺, Vim⁺ cells in the junctional zone of the cellular grafts. Anti-laminin immuno-reactivity persisted in the basal lamina tubes of both the normal and acellular peripheral nerve grafts. Thus, the failure of axon regeneration into acellular peripheral nerve grafts can be correlated with the absence of Schwann cells and does not appear to be related to the presence of laminin.     

Electron microscopic study of the interaction of axons and glia at the site of anastomosis between the optic nerve and cellular or acellular sciatic nerve grafts

Summary The interactions between retinal ganglion cell (RGC) axons and glia at the site of optic nerve section and at the junctional zone between optic nerve and cellular or acellular peripheral nerve (PN) grafts have been studied electron microscopically. After transection, RGC axons, accompanied by processes of astrocyte cytoplasm, grew out from the proximal optic nerve stump into the scar tissue that developed between proximal and distal stumps. However, axons failed to cross the scar, and none entered the distal stump. By 3 days post lesion (DPL), bundles of RGC axons, accompanied by astrocytes and oligodendrocytes, grew out from the proximal optic nerve stump into the junctional zone between optic nerve and either type of PN graft. The bundles of RGC axons and growth cones that grew towards acellular PN grafts degenerated within 10–20 DPL; by 30 DPL a small number of axons persisted within the end of the proximal optic nerve stump. No axons were seen within the acellular PN grafts. These results suggest that reactive axonal sprouting, axon outgrowth and glial migration from the proximal optic nerve stump are events that occur during an acute response to injury, and that they are independent of the presence of Schwann cells. However, it would appear that few axons entered either scar or junctional zone unless accompanied by glia. There was little evidence that axon outgrowth was laminin-dependent.The bundles that grew towards cellular PN grafts encountered cells that we have identified as Schwann cells within the junctional zone: the axons in these bundles survived and entered the cellular grafts. Schwann cells migrated into the junctional zone from the cellular PN graft. It is probable that Schwann cells facilitated RGC axon entry into the graft directly by both cell contact and the secretion of neuronotrophic factors, and indirectly by modifying the CNS glia in the junctional zone.     

Regeneration and retrograde degeneration of axons in the rat optic nerve

Summary The retinal stump of the rat optic nerve was examined histologically 1–64 weeks after intracranial section of the nerve with or without grafting of autologous peripheral nerve segments. Single unmyelinated axons and bundles of unmyelinated axons appeared in cut optic nerves and were most abundant 2–4 weeks after section. With light and electron microscope radioautography after injection of tritiated amino acids into the globe, it was confirmed that many unmyelinated fibres arose from the optic nerve rather than from nearby peripheral nerves and it was estimated that some axons regenerated as far as 0.5 mm. At or near the end of retinofugal axons, structures resembling growth cones were seen at 2 weeks and vesicle-containing swellings similar to synapses were found at 1–2 months. Outgrowth from optic nerve axons was not obviously enhanced by peripheral nerve grafts although a few retinofugal axons became ensheathed by Schwann cells. Retrograde axonal degeneration was rapid in both cut and grafted optic nerves, the number of nerve fibres near the globe falling to less than 10% of normal after 4 weeks. A few myelinated and unmyelinated fibres were still present 64 weeks after nerve transection. In conclusion, some cut axons in the rat optic nerve display a transient regenerative response before undergoing retrograde degeneration.     

Regrowth of PNS axons through grafts of the optic nerve of the Browman-Wyse (BW) mutant rat

Summary We have examined the behaviourin vivo of regenerating PNS axons in the presence of grafts of optic nerve taken from the Browman-Wyse mutant rat. Browman-Wyse optic nerves are unusual because a 2–4 mm length of the proximal (retinal) end of the nerve lacks oligodendrocytes and CNS myelin and therefore retinal ganglion cell axons lying within the proximal segment are unmyelinated and ensheathed by processes of astrocyte cytoplasm. Schwann cells may also be present within some proximal segments. Distally, Browman-Wyse optic nerves are morphologically and immunohistochemically indistinguishable from control optic nerves.When we grafted intact Browman-Wyse optic nerves or triplets consisting of proximal, junctional and distal segments of Browman-Wyse optic nerve between the stumps of freshly transected sciatic nerves, we found that regenerating axons avoided all the grafts which did not contain Schwann cells, i.e., proximal segments which contained only astrocytes; regions of Schwann cell-bearing proximal segments which did not contain Schwann cells; junctional and distal segments (which contained astrocytes, oligodendrocytes and CNS myelin debris). However, axons did enter and grow through proximal segments which contained Schwann cells in addition to astrocytes. Schwann cells were seen within grafts even after mitomycin C pretreatment of sciatic proximal nerve stumps had delayed outgrowth of Schwann cells from the host nerves; we therefore conclude that the Schwann cells which became associated with regenerating axons within the grafts of Browman-Wyse optic nerve were derived from an endogenous population. Our findings indicate that astrocytes may be capable of supporting axonal regeneration in the presence of Schwann cells.     

Influence of peripheral nerve grafts on the expression of GAP-43 in regenerating retinal ganglion cells in adult hamsters

Summary We have examined the ability of axotomized retinal ganglion cells in adult hamsters, to regenerate axons into a peripheral nerve graft attached to the optic nerve and the expression of GAP-43 by these neurons. We also examined the effect on these events of transplanting a segment of peripheral nerve to the vitreous body. The left optic nerves in three groups of hamsters were replaced with a long segment of peripheral nerve attached to the proximal stump of the optic nerve 2 mm from the optic disc to induce regeneration of retinal ganglion cells into the peripheral nerve. An additional segment of peripheral nerve was transplanted into the vitreous of the left eye in the second group. The animals from the first and second groups were allowed to survive for 1–8 weeks and the number of regenerating retinal ganglion cells was determined by applying the retrograde tracer, Fluoro-Gold to the peripheral nerve graft and the expression of GAP-43 was studied by immunocytochemistry in the same retinas. As a control, a segment of optic nerve was transplanted into the vitreous body of the left eye in the third group of hamsters. These animals were allowed to survive for 4 weeks and the number of regenerating retinal ganglion cells was counted as in Groups 1 and 2. The percentages of the regenerating retinal ganglion cells which also expressed GAP-43 were very high at all time points in Group 1 (with no intravitreal peripheral nerve) and Group 2 (with intravitreal peripheral nerve) and at 4 weeks for the Group 3 (with intravitreal optic nerve) animals. In addition, the number of regenerating retinal ganglion cells, the number of retinal ganglion cells expressing GAP-43 and the number of regenerating retinal ganglion cells which also expressed GAP-43 were much higher in Group 2 than in Group 1 at all the time points and it was also much higher in Group 2 than in Group 3 at 4 weeks whereas there was no significant difference between the results from Groups 1 and 3 at 4 weeks. These data suggested that there was a close correlation between the number of the axotomized retinal ganglion cells regenerating axons into the peripheral nerve graft attached to the optic nerve and the expression of GAP-43. In addition, the intravitreal peripheral nerve, probably by releasing various neurotrophic factors and by acting synergistically, can enhance the expression of GAP-43 in some of the axotomized retinal ganglion cells and promote the regeneration of retinal ganglion cells into the peripheral nerve graft.     

Ganglioside 9-O-acetyl GD3 expression is upregulated in the regenerating peripheral nerve

Evidence accumulates suggesting that 9-O-acetylated gangliosides, recognized by a specific monoclonal antibody (Jones monoclonal antibody), are involved in neuronal migration and axonal growth. These molecules are expressed in rodent embryos during the period of axon extension of peripheral nerves and are absent in adulthood. We therefore aimed at verifying if these molecules are re-expressed in adult rats during peripheral nerve regeneration. In this work we studied the time course of ganglioside 9-O-acetyl GD3 expression during regeneration of the crushed sciatic nerve and correlated this expression with the time course of axonal regeneration as visualized by immunohistochemistry for neurofilament 200 in the nerve. We have found that the ganglioside 9-O-acetyl GD3 is re-expressed during the period of regeneration and this expression correlates spatio-temporally with the arrival of axons to the lesion site. Confocal analysis of double and triple labeling experiments allowed the localization of this ganglioside to Schwann cells encircling growing axons in the sciatic nerve. Explant cultures of peripheral nerves also revealed ganglioside expressing reactive Schwann cells migrating from the normal and previously crushed nerve. Ganglioside 9-O-acetyl GD3 is also upregulated in DRG neurons and motoneurons of the ventral horn of spinal cord showing that the reexpression of this molecule is not restricted to Schwann cells. These results suggest that ganglioside 9-O-acetyl GD3 may be involved in the regrowth of sciatic nerve axons after crush being upregulated in both neurons and glia.     

The role of basic fibroblast growth factor in peripheral nerve regeneration

In the peripheral nervous system regeneration and gradual functional restoration occur following peripheral nerve injury. Growth of regenerating axons depends on the presence of diffusible neurotrophic factors, in addition to the substratum. Neurotrophic factors that are involved in peripheral nerve regeneration include nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, glial cell line-derived neurotrophic factor, and interleukin-6. Recent functional and expression studies of basic fibroblast growth factor and its receptors have emphasized a physiological role of these molecules in the peripheral nervous system. Basic fibroblast growth factor and its receptors are constitutively expressed in dorsal root ganglia and the peripheral nerve. These molecules display an upregulation in dorsal root ganglia and in the proximal and distal nerve stumps following peripheral nerve injury. In the ganglia these molecules show a mainly neuronal expression, whereas at the lesion site of the nerve, Schwann cells and invading macrophages represent the main cellular sources of basic fibroblast growth factor and the receptors 1–3. Exogenously applied basic fibroblast growth factor mediates rescue effects on injured sensory neurons and supports neurite outgrowth of transectioned nerves. Regarding the expression pattern and the effects after exogenous administration of basic fibroblast growth factor, this molecule seems to play a physiological role during nerve regeneration. Thus, basic fibroblast growth factor could be a promising candidate to contribute to the development of new therapeutic strategies for the treatment of peripheral nerve injuries.     

Regrowth of retinal ganglion cell axons into a peripheral nerve graft in the adult hamster is enhanced by a concurrent optic nerve crush

Summary Transplantation of a segment of peripheral nerve to the retina of the adult hamster resulted in regrowth of damaged ganglion cell axons into the graft, with the fastest regenerating axons extending at 2 mm/day after an initial delay of 4.5 days (Cho and So 1987b). In this study, the effect of making 2 lesions on the same axon (the conditioning lesion effect) on the regrowth of ganglion cell axons into the peripheral nerve graft was examined. When a conditioning lesion (first lesion) was made by crushing the optic nerve 7 or 14 days before the peripheral nerve grafting (the second lesion) to the retina, the distance of regrowth achieved by the fastest regenerating axons in the graft, measured at the 7th post-grafting day, was lower than in animals with a peripheral nerve grafted to a normal eye. This indicated that in contrast to the situation in peripheral nerve axons (Forman et al. 1980) and goldfish optic axons (Edwards et al. 1981), the conditioning lesion was unable to enhance the regrowth of mammalian retinal ganglion cell axons. However, when crushing of the optic nerve was followed immediately by peripheral nerve grafting, an enhancement in axonal regrowth could be observed. The initial delay time before the axons extended into the peripheral nerve graft was reduced by 1 day while the rate of elongation of the fastest regrowing axons in the graft apparently remained unchanged. Moreover, the shortening of the initial delay could still be observed even when the sequence of performing the 2 lesions was reversed. From these data, it was concluded that the classical conditioning lesion effect was not responsible for the enhancement observed. Rather it was suggested that changes in the intra-retinal environment brought about by crushing of the optic nerve might account for it.     

Peripheral nerve fibres regenerate through myenteric plexus

The ability of myenteric glia and neurons to support peripheral nerve regeneration was tested by grafting pieces of muscularis externa 5 mm long from the distal colon of inbred CBA mice adjacent to the proximal stump of cut common peroneal nerves. By two weeks after operation many axons had invaded the plexus and after 3 weeks regeneration common peroneal nerve fibres could be identified in all parts of the plexus throughout the grafts. Some axonal profiles within the plexus appeared to be in the early stages of myelination by enteric glia. Axons surrounded by compact myelin were found at the periphery of ganglia, but the cells involved resembled Schwann cells and could not be positively identified as enteric glia. Profiles similar to those of regenerating axons were only very rarely seen in control experiments in which grafts were placed adjacent to intact common peroneal nerves. It is suggested that the cellular elements of the myenteric plexus can support peripheral nerve regeneration.     

Central and peripheral nerve regeneration by transplantation of Schwann cells and transdifferentiated bone marrow stromal cells

In contrast to the peripheral nervous system (PNS), little structural and functional regeneration of the central nervous system (CNS) occurs spontaneously following injury in adult mammals. The inability of the CNS to regenerate is mainly attributed to its own inhibitorial environment such as glial scar formation and the myelin sheath of oligodendrocytes. Therefore, one of the strategies to promote axonal regeneration of the CNS is to experimentally modify the environment to be similar to that of the PNS. Schwann cells are the myelinating glial cells in the PNS, and are known to play a key role in Wallerian degeneration and subsequent regeneration. Central nervous system regeneration can be elicited by Schwann cell transplantation, which provides a suitable environment for regeneration. The underlying cellular mechanism of regeneration is based upon the cooperative interactions between axons and Schwann cells involving the production of neurotrophic factors and other related molecules. Furthermore, tight and gap junctional contact between the axon and Schwann cell also mediates the molecular interaction and linking. In this review, the role of the Schwann cell during the regeneration of the sciatic (representing the PNS) and optic (representing the CNS) nerves is explained. In addition, the possibility of optic nerve reconstruction by an artificial graft of Schwann cells is also described. Finally, the application of cells not of neuronal lineage, such as bone marrow stromal cells (MSCs), in nerve regeneration is proposed. Marrow stromal cells are known as multipotential stem cells that, under specific conditions, differentiate into several kinds of cells. The strategy to transdifferentiate MSCs into the cells with a Schwann cell phenotype and the induction of sciatic and optic nerve regeneration are described.     

Morphological plasticity of axotomized retinal ganglion cells following intravitreal transplantation of a peripheral nerve segment

Summary During normal development of retinal ganglion cells when the axons are growing, transient dendritic spines have been observed. Similar dendritic spine-like processes are also exhibited by retinal ganglion cells undergoing axonal regeneration into a peripheral nerve grafted to the damaged optic axons. Here we show, using the intracellular injection of Lucifer Yellow, that when a segment of peripheral nerve is transplanted to the vitreous body, a procedure which induces ectopic sprouting of axon-like processes from the cell bodies and dendrites of some retinal ganglion cells, similar spine-like processes appear on the dendrites of cells with ectopic sprouts. Quantitative analysis indicated that there were significant changes with post-transplantation survival time in the distributions of spine-like processes and axon-like processes on these sprouting retinal ganglion cells following the intravitreal transplantation of a piece of peripheral nerve. The remodelling of the spine-like processes and axon-like processes correlated with one another suggesting that plastic changes can occur in certain dendritic subcompartments independent of the growth activity of the other dendritic subcompartments.     

睫状神经营养因子对视神经损伤的修复作用

视神经损伤后,视网膜神经节细胞进行性损害,轴突变性坏死,再生困难。睫状神经营养因子是一种非靶源性神经营养因子,在视网膜神经节细胞的生长发育中起重要调控作用,主要表现在对损伤的视网膜神经节细胞有促进存活及轴突再生的作用。     

Peripheral nerve regeneration using acellular nerve grafts

Long gap peripheral nerve injuries usually require a graft to facilitate axonal regeneration into the distal nerve stump. The use of autografts is often limited because of graft availability and donor-site morbidity. We investigated whether acellular nerve allografts would provide an appropriate channel for the promotion and induction of sciatic nerve regeneration in rats. Axons sprouted from the proximal portion and reached the distal portion in the 1 cm-long grafts by 1 month. The number of axons in the regenerated nerves was similar to that of normal nerves at 1 month. Loading the grafts with betaNGF and VEGF increased the number and mean diameter of axons and neovascularization in the regenerated nerves at 1 month. The motor conduction velocity increased over time and reached 63 +/- 10% of that of normal nerves at 6 months. The nerve injuries treated with the acellular grafts had a significant improvement in motor, nociception, and proprioception function compared to untreated nerves. The results from this study suggest that acellular nerve allografts may be a useful biomaterial for functional peripheral nerve regeneration.     

The conditioning effect of optic nerve injury upon axonal regrowth from adult rat retinal ganglion cells explanted in vitro

An in vitro assay was used to determine the effects of conditioning nerve lesions on the regeneration of adult rat retinal ganglion cell (RGC) axons from retinal explants. Following the conditioning lesion (CL) of unilateral optic nerve transection, maximal regrowth was seen from RGC explanted from ipsilateral retinae 10 days post-CL. Explants from this group initiated axonal regrowth earlier and a greater percentage regrew axons when compared with explants from normal rats. Axonal regrowth from explants of retinae contralateral to CL was also seen earlier than normal. In further experiments, the effects of both exposure of the optic nerve sheath in the orbit and the incision of the dura without injury to optic nerve axons were studied. The conditioning effect of a dural incision was found to be the same as that of optic nerve transection, whilst exposure of the optic nerve sheath had no conditioning effect on RGC axonal regrowth in vitro.     

Retrograde degeneration of myelinated axons and re-organization in the optic nerves of adult frogs (Xenopus laevis) following nerve injury or tectal ablation

Summary The optic nerve proximal to the lesion (toward the retina) was examined by light and electron microscopy in adultXenopus laevis after various types of injury to optic nerve fibres. Intraorbital resection, transection or crush of the optic nerve or ablation of the contralateral optic tectum all resulted in marked alterations in the myelinated axon population and in the overall appearance of the nerve proximal to the site of injury. Examination of the nerves from 3 days to 6 months postoperatively indicated that a progressive, retrograde degeneration of myelin and loss of large-diameter axons occurred throughout the retinal nerve stump regardless of the type of injury or distance of the injury from the retina. The retinal stump of nerves receiving resection or transection showed a nearly complete loss of myelin and large-diameter axons while the degree of degeneration was subtotal in nerves receiving crush injury or after lesions farther from the retina (i.e. tectal ablation). In addition, the entire retinal nerve stump after all types of injury was characterized by the appearance of an actively growing axon population situated circumferentially under the glia limitans. The latter fibres are believed to represent regrowing axons which are being added onto the nerve, external to the original axon population and are suspected to modify actively the glial terrain and glia limitans.     

Ultrastructural and morphometric analysis of long-term peripheral nerve regeneration through silicone tubes

Summary Light and electron microscopy were used to investigate long-term regeneration in peripheral nerves regenerating across a 10 mm gap through silicone tubes. Schwann cells and axons co-migrated behind an advancing front of fibroblasts, bridging the 10 mm gap between 28 and 35 days following nerve transection. Myelination of regenerated fibres started between 14 and 21 days after transection and occurred in a manner similar to that reported during development. Although these early events were successful in producing morphologically normal-appearing regenerated fibres, complete maturation of many of these fibres was never achieved. Axonal distortion by neurofilaments, axonal degeneration and secondary demyelination were seen at 56 days following nerve transection. These changes progressed in severity with time as more axons advanced through the distal stump towards their peripheral target. Since regeneration occurs in the absence of endoneurial tubes, and because constrictive forces act on the nerve during regeneration, we suggest that these extrinsic factors limit the successful advancement of axons through the distal stump to their target organ.     

A morphometric study of the retinal ganglion cell response to optic nerve severance in the frog Rana pipiens

Summary This study examines the cell body response to axotomy of retinal ganglion cells in the frogRana pipiens. Cell soma sizes were measured in carefully matched regions of Nissl-stained wholemounted retinae after either nerve crush, nerve cut with stump separation, nerve crush with intraocular nerve growth factor (NGF) or nerve cut with NGF applied to the proximal stump. The state of axonal regeneration was also assessed in each case by anterograde transport of HRP.Following nerve crush axons crossed the lesion by 7 days, reached the chiasma by 14 days and entered the tectum around 20–30 days. The normally evenly stained ganglion cells exhibited granular Nissl staining at 7 and 10 days but very little change in soma size. From 10 to 28 days the mean retinal ganglion cell area increased by 102% and maintained this size until at least 75 days. By 102 days soma size had nearly returned to normal. A population of displaced amacrine cells retained a normal appearance and soma size throughout regeneration.Following nerve cut and stump separation the retinal ganglion cells were slightly more reactive in appearance at 7 days after crush but otherwise the soma reaction developed in a similar manner. Axon tracing revealed no extension beyond the lesion site in these animals and therefore the state of axonal growth did not affect the early soma response.NGF applied at the time of the lesion had no detectable effect on the soma reaction.Although many retinal ganglion cells re-establish contact with visual centres after axotomy in the frog, a considerable proportion die. This contrasts with both the goldfish, where all cells regenerate successfully, and various mammals, where none do so and all retinal ganglion cells die. All retinal ganglion cells in the frog undergo reactive changes similar to those of goldfish and there is no sign of the cell shrinkage seen in mammals. Therefore the cell death in frog would appear to be different from that in mammalian retina but similar to that of mammalian peripheral nerve in which chromatolysis generally preceeds death.     

Defective myelination in the optic nerve of the Browman-Wyse (BW) mutant rat

Summary The Browman-Wyse (BW) rat displays a spectrum of ocular abnormalities which include myelination by Schwann cells of retinal ganglion cell (RGC) axons within the retina. Immunohistochemical and ultrastructural studies of the optic nerves of adult BW rats (30–60 days of age) with myelinated intraretinal axons were performed. Although individual nerves displayed considerable morphological variability, all were characterized by an initial dysmyelinated proximal segment which was separated from a normally myelinated distal segment by a transitional junctional zone. The proximal segment contained axons which were predominantly unmyelinated: where myelination occurred, almost all sheaths were P_o-positive, proteolipid protein-negative, and the myelinating cell was a Schwann cell. In the distal segment the distribution of myelinated axons appeared to be normal, sheaths were PLP⁺, and the myelinating cell was an oligodendrocyte. Within the proximal segment, axons that were myelinated by Schwann cells were isolated by a basal lamina and expanded extracellular spaces from the bulk of other RGC axons within the optic nerve. Few carbonic anhydrase (CAII)⁺ or GalC⁺ oligodendrocytes were seen in proximal segments that contained Schwann cells: anti-CAII antibody stained atypical cells within the proximal segments which did not resemble CAII⁺ oligodendrocytes in the distal segment, and which were probably GalC^–. Astrocytes appeared normal throughout the length of the nerve, and there was no morphological specialization at the junctional zone similar to that at the lamina cribrosa. The possible source (s) of the intraneural Schwann cells, and the pathogenetic mechanisms underlying the aberrant myelination of RGC axons within the BW optic nerve are discussed.