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PubMed1985

Axonal transport of actin and regeneration rate in non-myelinated sensory nerve fibres.

The relationship was examined between the rate of regeneration and rate of axonal transport of actin in the sensory fibres of the rabbit vagus nerve. Regeneration rate, determined as the distance moved by [35S]methionine-radiolabelled, fast-transported proteins beyond a crush, was about 3 mm/day. The rate of transport of actin, identified by two-dimensional polyacrylamide gel electrophoresis with fluorography, and DNase affinity chromatography, was 25-30 mm/day. No slower rate of actin transport comparable with regeneration rate, could be found in either control or regenerating nerves. While the provision of actin, by slow axonal transport, to the axonal growth cone may be essential for nerve regeneration, the regeneration rate is not directly controlled by the rate of actin transport.

Actins↗
PubMed1986

Regeneration of primary afferent neurons containing substance P-like immunoreactivity.

We compared changes in levels of substance P-like immunoreactivity (SPLI) in L4-6 dorsal root ganglia (DRG), L4-6 dorsal roots, sciatic nerve, tibial nerve and hind foot skin in rats following resection or crush injury of the sciatic nerve. The initial depletion of SPLI, which occurred in all areas sampled, was similar after either type of lesion. In DRG and dorsal roots, recovery to control values occurred in SPLI levels 35-45 days after sciatic crush, but not after resection. In sciatic nerve proximal to the injury, a partial recovery in SPLI content to about 60% of control occurred following crush injury, but not following resection. Distal to the injury, tibial nerve levels recovered rapidly following crush injury, consistent with the previously observed rapid regeneration of SPLI-containing axons. After resection, no recovery was observed until after 35 days, when it appeared that some axons succeeded in crossing the resection zone and regaining the distal nerve stump. Delayed and poor recovery of SPLI levels was observed in foot skin, even after crush injury. This correlated with the poor recovery of the plasma extravasation reaction, a functional index of SP-innervation of skin. In contrast, reinnervation by high-threshold mechanoreceptors was more rapid and complete, in agreement with a previous study. We conclude that although SPLI-containing axons regenerate rapidly, they appear to reinnervate skin less successfully than other afferents. Axon regeneration is associated with a recovery of SPLI levels which fell after axotomy: no recovery occurs if regeneration is prevented. Recovery was almost complete in DRG and roots, but incomplete in sciatic nerve. This peptide transmitter in afferent neurons thus behaves in a similar fashion to previously studied low-molecular weight transmitters and related materials in efferent neurons. Since recovery of SPLI levels begins before there is evidence for target reinnervation, it seems that axon regeneration is a sufficient condition for reversal of some axotomy-induced changes in these neurons. Further studies on substance P synthesis and on the response of individual DRG neurons to axotomy and regeneration will be required to explain fully the discrepancy between partial recovery of SPLI levels in sciatic nerve and full recovery in DRG and dorsal roots.

Animals↗
PubMed1986

The effects of an autologous transplant on patterns of regeneration in rat sciatic nerve.

Autologous transplants are often used in repair of peripheral nerve injury. Quantitative evaluation of the results of such a transplant is obviously desirable. In previous study, we determined numerical and cytologic parameters of the regeneration that followed transection of rat sciatic nerve, but no transplant was used. This work now serves as a basis for evaluating the use of an autologous transplant in the same transection paradigm. Our procedure is to remove 8 mm of sciatic nerve in the thigh. The removed segment is then put into the center of a silicone tube and the proximal and distal stumps of the severed nerve are placed into the ends of the tube. The data show: (1) a high percentage of successful regenerations; (2) a relatively large nerve in the gap; (3) a typical outer perineurium underlying the epineurium; (4) a well-developed fascicular perineurium; and (5) approximately equal numbers of myelinated and unmyelinated axons in the gap and distal stump. If a transplant is not used there are: (1) a greater number of failures of regeneration; (2) a smaller nerve in the gap; (3) a less well-developed fascicular perineurium; (4) unequal numbers of axons in the gap as compared to the distal stump; and (5) no outer perineurium forms. The presence of a typical outer perineurium after a transplant and its absence if a transplant is not used is probably the most striking cytologic difference between the two paradigms. The equal numbers of axons in the gap and distal stump following regeneration after transplantation presumably indicate that all axons in the gap enter the distal stump without branching or ending blindly, a situation that is presumably beneficial and contrasts with the findings when a transplant is not used. Both paradigms show a remarkable increase in the density of blood vessels in the regenerated nerve in the gap between the two stumps. These findings will serve as a basis for further studies on the mechanisms of peripheral nerve regeneration.

Animals↗
PubMed1987

Voltage-clamp analysis of nodes of Ranvier in regenerated rat sciatic nerve.

Crush-lesioned adult rat sciatic nerves were allowed to regenerate during 70-181 days. Single large regenerated nerve fibres were isolated from levels distal to the crush site, and mounted in a feedback system for potential recordings and voltage clamp. After the experiment, each isolated fibre was fixed and embedded for morphological evaluation. Internodal lengths and fibre diameters were obtained form teased preparations of regenerated and normal sciatic nerves. The isolated regenerated fibres were excitable and had action potentials of large amplitude. TEA and 4-AP had negligible effects on the action potential and excitability properties. The time constant of the nodal segment was larger than in normal fibres. The nodal Na and K permeabilities (PNa and PK) were calculated both in absolute values and relative to the leak conductance (gL). Regenerated fibres had normal PNa/gL and PK/gL ratios. The potential dependence of PNa activation and inactivation was also normal. The isolated physiologically examined fibres had internodal lengths (L) of about 300 micron and diameters (D) of about 7-11 micron. In the teased fibre preparations L was about 300 micron (range 150-600 micron) and D was 3-11 micron. In addition, all teased regenerated nerve preparations exhibited a few scattered unusually short internodes (L less than 150 micron). In control nerves L ranged from 150 micron in the lower fibre size range (D = 2-3 micron) to 1.6 mm in the upper size range (D = 15 micron).

Action Potentials↗
PubMed1988

Conditioning lesions of peripheral nerves change regenerated axon numbers.

The present study investigates the effects of conditioning lesions on regenerated axon numbers in tributary nerves after a test lesion. If a rat sciatic nerve is crushed 7 and 14 days prior to a test crush, the numbers of regenerated myelinated axons 8 weeks later in the sural nerve (SN) and nerve to the medial gastrocnemius (NMG) are increased, both over normal and over numbers after a single crush. If the lesions are only separated by 2 days, however, the numbers are similar to the numbers after a single crush. Thus conditioning occurs, but a minimum time between crushes is necessary for the effects of conditioning to be manifest. If the intervals between lesions are 14 days, the numbers are similar to those after the 7-day intervals. Moving each successive crush proximally or distally does not change regenerated myelinated axon numbers. Thus increasing the time between lesions after conditioning occurs, at least within the constraints of our paradigm, does not change regenerated axon numbers and the location of the lesion has relatively little bearing on the numbers of axons that regenerate. These findings allow us to change axonal numbers in these tributary nerves in a predictable way, and they are also compatible with the hypothesis that conditioning results from priming of the cell body rather than changes in the environment of the regenerating axons.

Animals↗
PubMed1988

Effects of growth hormone treatment on the regeneration of rat sciatic nerve.

The effect of human growth hormone (hGH) on regeneration of neuronal tissue have been studied in rats. A crush lesion was made on the sciatic nerve at the thigh level in intact or hypophysectomized rats. The hGH was administered systemically via subcutaneously implanted miniosmotic pumps. Regeneration was evaluated by the 'pinch-test' after 3, 4 and 6 days. Regeneration was significantly (P less than 0.05) impaired in hypophysectomized rats, but restored to normal after treatment with hGH (200 mIU/day). In intact rats treatment with 400 mIU/day hGH significantly (P less than 0.05) stimulated regeneration, whereas no effect was observed at 200 mIU/day. Immunoreactive insulin-like growth factor 1 (IGF-1) decreased in hypophysectomized rats, but rose again after hGH treatment. However, no consistent correlation between circulating IGF-1 and the rate of regeneration was found. Our results show that hGH can increase the rate of regeneration in peripheral nerves after injury. This can be due either to direct effects of hGH or to indirect effects via locally produced growth factors (e.g. somatomedins).

Animals↗
PubMed1988

Blind-ended semipermeable guidance channels support peripheral nerve regeneration in the absence of a distal nerve stump.

The presence of a distal nerve segment is considered to be essential for peripheral nerve regeneration through impermeable synthetic guidance channels. The use of a perm-selective material may provide a more appropriate regenerating environment by allowing solute exchange across the wall of the channel. We compared perm-selective acrylic copolymer (AC) channels with impermeable silicone elastomer (SE) channels in terms of regeneration in the absence of a distal nerve stump. Cohorts of 6 animals received AC and SE channels for either 4 or 8 weeks, with the distal end of the polymer tube left open in half of the animals, and plugged with the same polymer ('capped') in the other half. Capped and uncapped AC channels contained regenerated nerve cables which extended fully to the distal end of the channel, whereas capped SE channels contained only 1 mm long granulomatous tissue cables, and uncapped SE channels showed small cables with only a few myelinated axons. The nerve cables regenerated in uncapped AC channels were smaller and contained fewer myelinated axons than those observed in capped AC channels. Capped AC channels sleeved with a tight-fitting silicone tube to render them impermeable, showed no regenerated tissue within their lumen. The use of a perm-selective channel may have allowed the influx of nutrients and growth factors from the external environment while concentrating factors released by the proximal nerve stump.

Acrylic Resins↗
PubMed1988

Electrophysiological study of conditioning lesion effects on rat sciatic nerve regeneration following either prior section or freeze. II. Blocking by prior tenotomy.

The conditioning lesion effects refer to the earlier formation and the accelerated regeneration of axonal sprouts following two successive axotomies. In a previous study, we observed that a prior freeze or a prior cut of rat sciatic nerve resulted in differences in the enhancement of the regeneration rate and the reduction of the initial delay. These differences were interpreted as a possible non-neuronal cells influence on the intrinsic regulation of the conditioning lesion phenomenon. In the present study, we attempted to modify the status of the muscles using tenotomy before the prior nerve injury to determine the respective influence of the muscular cells on conditioning lesion effects. Thus, the conditioning lesion, which was either a cut or a freeze of the tibial nerve at the ankle, was performed 14 days after foot sole muscles were tenotomized, close to their insertion into the calcaneus bone. The test lesion was always a freeze of the sciatic nerve at midthigh performed 7 days following the prior lesion. The elongation of the regenerating sprouts was electrophysiologically evaluated and the regeneration rate as well as the initial delay were calculated by means of regression analysis. Tenotomy did not influence the regeneration as was demonstrated in a group with a single sciatic nerve lesion. In contrast, when prior lesion was performed, the tenotomy prevented both the enhancement of the rate of regeneration and the reduction of the initial delay, whatever was the type of the conditioning lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A new method for studies of the effects of locally applied drugs on peripheral nerve regeneration in vivo.

An in vivo technique which allows local application of drugs to the regenerating rat sciatic nerve for several days is presented. The sciatic nerve was transected at the knee level and a crush lesion was made proximal to the transection. The crush lesion and the nerve segment distal to it was enclosed in a chamber made of silicone tubing (STC). The STC was perfused via a catheter connected to a miniosmotic pump. Regeneration was evaluated with the 'pinch-test' at 3, 4 and 6 days after the enclosure of the nerve. The rate of regeneration in the STC-surrounded nerve segment was 3.5 mm/day after an initial delay of 1.6 days which are values similar to those in uncovered nerves with crush lesions. Perfusion of the STC with either vinblastine, cycloheximide, actinomycin D or mitomycin C inhibited regeneration. The effects were confined to the STC-covered region. Leakage of drugs was too small to affect the nerve outside the chamber. The results suggest that regeneration requires proliferation and protein synthesis in the cells surrounding the growing axons. This technique could be useful for studies of the local effects of various drugs, specific antibodies, potential growth factors etc. on regeneration of peripheral nerves.

Animals↗
PubMed1994

Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period.

In the present study we tested how nerve grafts with different pre-degeneration periods (1-28 days) influenced the early regenerative response in the rat sciatic nerve. The sciatic nerve on the right side was crushed and after 1-28 days of pre-degeneration, a 10 mm segment was used as an autologous nerve graft and transposed to a freshly made 10 mm long nerve defect on the left side. The regeneration distance was measured by the sensory pinch test 2-10 days after nerve repair. A newly developed mathematical model was used to calculate regeneration rates and initial delay periods from the measured regeneration distances. Pre-degenerated nerve grafts improved nerve regeneration by decreasing the initial delay period as compared to fresh nerve grafts without affecting the regeneration rate. Only one day of pre-degeneration was sufficient to reduce the initial delay period from 3.6 days to 1.7 days. The maximal effect on the initial delay period was achieved after 3 days of pre-degeneration. The initial delay period at later pre-degeneration intervals (7-14 days) was about 1 day. The effect persisted for at least 28 days of pre-degeneration. The regeneration rate was 1.5 mm/day for fresh nerve grafts and between 1.8-2.1 mm/day for pre-degenerated grafts. The results suggest that the effects of pre-degeneration are not only due to the increased cell proliferation in the graft, but that also trophic and/or inflammatory mechanisms may be of importance. Grafts pre-degenerated by crush may have clinical implications since they are easy to perform if an elective nerve grafting procedure is planned.

Animals↗
PubMed1994

Regeneration of lesioned rat optic nerve fibers is improved after neutralization of myelin-associated neurite growth inhibitors.

Optic nerve axons do not regenerate after lesions in postnatal mammals, except if peripheral nerve transplants are offered as a substrate. In the present study, regeneration was assessed after intracranial freeze-crush lesions of the optic nerve, which completely interrupted all axons. In rats lesioned at the age of 8-9 days and surviving for additional 5-6 days, regenerating retinal fibers were seen to enter and partially cross the lesion site, reaching a maximum distance of 0.8 mm (mean +/- S.E.M. = 0.62 +/- 0.07 mm) in the presence of brain-derived neurotrophic factor (BDNF). Without BDNF, almost all the axons were lost due to axonal die-back. This regeneration distance could be significantly enhanced, up to 1.9 mm, by application of a monoclonal antibody (mAB-IN-1) directed against oligodendrocyte- and myelin-associated neurite growth inhibitory proteins. Similar results were obtained in rats lesioned at 16-18 days and surviving for 2 weeks: whereas fibroblast growth factor (FGF) stimulated sprouting did not exceed distances of 0.5 mm (mean = 0.38 +/- 0.07 mm), FGF and IN-1 antibody treated rats showed regenerations up to 2.3 mm (mean = 1.53 +/- 0.15 mm). The specificity of this effect was confirmed by lesions of myelin- and oligodendrocyte-free optic nerves: optic nerves were locally X-irradiated at birth, day 2, 4 and 6, a procedure which kills the dividing oligodendrocyte precursor cells. When these myelin-free nerves were lesioned at 3 weeks of age, regeneration distances between 2.5 and 3.2 mm were observed 3 weeks later.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Impaired myelinated fiber regeneration following freeze-injury in rats with streptozotocin-induced diabetes: involvement of the polyol pathway.

This study examined the effects of streptozotocin-induced diabetes mellitus and aldose reductase inhibitor (ZD5522) treatment on myelinated fiber regeneration in rats. After 2 months of diabetes, with or without ZD5522 treatment (10 mg.kg-1.day-1) from induction, sciatic nerve degeneration was initiated by a punctate lesion using a liquid N2 cooled probe. Regeneration was studied over a subsequent 14-day period using in vitro electrophysiological techniques. There was a 21.4% (P < 0.001) deficit in the maximum fiber regeneration distance in diabetic rats, 14 days postlesion. This was partially (64.9%, P < 0.01) prevented by aldose reductase inhibitor treatment, the resultant regeneration distance being not significantly different from that of age-matched nondiabetic control rats. The regeneration rate, assessed from data collected 4, 9 and 14 days postlesion, was 23.7% (P < 0.001) reduced by diabetes and ZD5522 treatment provided 73.1% protection (P < 0.01). We conclude that polyol pathway activity is involved in impaired regeneration in experimental diabetes, potential pathophysiological mechanisms involving a reduction in neurotrophic support and impaired endoneurial blood supply.

Acetanilides↗
PubMed1996

Regenerated hair cells exhibit a transient resistance to aminoglycoside toxicity.

Recent studies have demonstrated that sensory hair cells in the avian inner ear are reproduced by cell proliferation in response to the death of the original hair cell population. The regenerated hair cells appear to construct functional synaptic contacts, thereby transmitting acoustic signals to the peripheral nervous system. One of the most extraordinary, but overlooked characteristics of these regenerated hair cells, is their ability to survive in a highly ototoxic environment. Here, we report that hair cells regenerated after kanamycin induced hair cell loss can survive for a substantially longer time period than their predecessors during prolonged exposure to aminoglycoside antibiotics. The prolonged survival, however, belongs solely to the immature status of regenerated hair cells. Once the regenerated hair cells reach morphological maturation, they become vulnerable to aminoglycoside toxicity. Immunohistochemical evaluation of kanamycin suggested that kanamycin may be taken up into hair cells via a receptor-mediated endocytosis at their apical surfaces. By contrast, kanamycin was rarely incorporated into the cytoplasm of the regenerated hair cells. These results suggest that the process of a receptor-mediated transmembrane transport at the apical surface of hair cells is developmentally regulated, and that the lack of some of the assembly involved in the transmembrane transport could be responsible for the inhibition of aminoglycoside uptake, leading immature hair cells to be aminoglycoside resistant.

Animals↗
PubMed1988

Benzo[a]pyrene metabolism and induction of enzyme-altered foci in regenerating rat liver.

The metabolism of benzo[a]pyrene (BP) in regenerating rat liver and the induction of enzyme-altered foci (EAF) in the liver of partially hepatectomized rats, treated with BP and promoted with 2-acetylaminofluorene (2-AAF)/CCl4 was investigated. The aim was to examine factors that might be of importance for the tumorigenicity of BP in the regenerating rat liver, such as cytochrome P-450 activity and glutathione levels. In regenerating rat liver, obtained 18 h after partial hepatectomy (PH), the amount of microsomal cytochrome P-450 was reduced by 20% whereas the level of glutathione was elevated by 15% and the cytosolic glutathione transferase activity towards chlorodinitrobenzene and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydro-BP (BPDE) was unaffected. Microsomes from these animals had a reduced capacity to activate (-)-trans-7,8-dihydroxy-7,8-dihydro-BP (BPD) to DNA-binding products but the pattern of BP metabolites was similar to that observed with control rat liver microsomes. Treatment of rats with 3-methylcholanthrene (MC, 50 mg/kg body wt.) increased cytochrome P-450 levels and glutathione transferase activity towards both substrates. Regenerating livers from these animals retained their cytochrome P-450 level and enzymatic activity towards BP and BPD. Regenerating rat liver microsomes from MC-treated animals were about 35 times more efficient in activating BPD than microsomes from uninduced, partially hepatectomized animals. Intraperitoneal administration of BP (50 mg/kg body wt.) 18 h after PH induced EAF in rats subsequently promoted with 2-AAF/CCl4. Pretreatment of rats with MC 66 h before PH and 84 h before BP administration, increased the number of EAF. In accordance with results by Tsuda et al. (Cancer Res., 40 (1980) 1157-1164), these studies demonstrate that BP is tumorigenic in regenerating rat liver, despite a reduced ability of the liver to activate this compound. Furthermore, MC, an inducer of certain cytochrome P-450 species ("aryl hydrocarbon hydroxylase"), potentiates the effect of BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1983

Regenerating adult chicken skeletal muscle and satellite cell cultures express embryonic patterns of myosin and tropomyosin isoforms.

Regenerating areas of adult chicken fast muscle (pectoralis major) and slow muscle (anterior latissimus dorsi) were examined in order to determine synthesis patterns of myosin light chains, heavy chains and tropomyosin. In addition, these patterns were also examined in muscle cultures derived from satellite cells of adult fast and slow muscle. One week after cold-injury the regenerating fast muscle showed a pattern of synthesis that was predominately embryonic. These muscles synthesized the embryonic myosin heavy chain, beta-tropomyosin and reduced amounts of myosin fast light chain-3 which are characteristic of embryonic fast muscle but synthesized very little myosin slow light chains. The regenerating slow muscle, however, showed a nearly complete array of embryonic peptides including embryonic myosin heavy chain, fast and slow myosin light chains and both alpha-fast and slow tropomyosins. Peptide map analysis of the embryonic myosin heavy chains synthesized by regenerating fast and slow muscles showed them to be identical. Thus, in both muscles there is a return to embryonic patterns during regeneration but this return appears to be incomplete in the pectoralis major. By 4 weeks postinjury both regenerating fast and slow muscles had stopped synthesizing embryonic isoforms of myosin and tropomyosin and had returned to a normal adult pattern of synthesis. Adult fast and slow muscles yielded a satellite cell population that formed muscle fibers in culture. Fibers derived from either population synthesized the embryonic myosin heavy chain in addition to alpha-fast and beta-tropomyosin. Thus, muscle fibers derived in culture from satellite cells of fast and slow muscles synthesized a predominately embryonic pattern of myosin heavy chains and tropomyosin. In addition, however, the satellite cell-derived myotubes from fast muscle synthesized only fast myosin light chains while the myotubes derived from slow muscle satellite cells synthesized both fast and slow myosin light chains. Thus, while both kinds of satellite cells produced embryonic type myotubes in culture the overall patterns were not identical. Satellite cells of fast and slow muscle appear therefore to have diverged from each other in their commitment during maturation in vivo.

Animals↗
PubMed1991

Characterization of a newt tenascin cDNA and localization of tenascin mRNA during newt limb regeneration by in situ hybridization.

We previously showed that tenascin, a large, extracellular matrix glycoprotein, exhibits a temporally and spatially restricted distribution during urodele limb regeneration. To further investigate the role of tenascin in regeneration, we cloned a newt tenascin cDNA, NvTN.1, that has 70% homology to the chicken tenascin sequence. A deduced amino acid sequence of NvTN.1 showed a modular structure unique to tenascin characterized by epidermal growth factor-like and fibronectin type III repeats. To determine the cellular origin of tenascin protein during limb regeneration, we localized tenascin transcripts by in situ hybridization using a riboprobe synthesized from NvTN.1. Transcripts could not be detected in normal limb tissues but first became detectable in the wound epithelium at 2 days and in the distal mesoderm at 5 days after amputation. These wound epithelial cells are probably the source of tenascin protein found within and immediately underneath the wound epithelium. At preblastema stages, hybridization was seen in cells associated with most of the distal mesodermal tissues but not in dermis. At blastema stages, essentially every mesenchymal cell contained tenascin transcripts. Thus, regardless of origin, blastemal mesenchymal cells may share a common regulatory mechanism that results in tenascin gene transcription. Finally, during redifferentiation stages of regeneration, tenascin gene transcription was associated with both differentiation and growth. The results show that initiation of tenascin gene expression is an early event in regeneration and continued tenascin gene transcription is associated with some of the important processes of regeneration, namely wound epithelial-mesenchymal interactions, dedifferentiation, initiation of cell cycling, blastema outgrowth, and cellular differentiation.

Amino Acid Sequence↗
PubMed1991

Fiber regeneration is not persistent in dystrophic (MDX) mouse skeletal muscle.

Fiber replacement has been measured in adult mdx mouse limb skeletal muscles. During the first 10 days after birth all fibers appear normal; between Week 3 and 4 there is massive fiber degeneration followed by regeneration in which close to 100% of the fibers are repaired or replaced. New fibers arising in adult mice are characterized by expression of fetal myosin mRNAs in whole muscle extracts, and by staining of individual fibers with an embryonic myosin heavy chain-specific antibody. By 10 weeks of age new fiber replacement rate, indicated by frequency of fibers reacting with antibody, is reduced to about 10%, and by 1 year of age less than 1% of the fibers are being replaced at rates above control. Total fiber number also remains fairly constant. We conclude that the fibers regenerating up to 10 weeks of age become stabilized and do not undergo further rounds of degeneration and regeneration. This is consistent with the observed benign phenotype of adult mdx animals and with the idea that once-regenerated fibers escape the catastrophic dystrophic phenotype by acquiring a function that compensates for their mdx mutation. The mechanism by which regenerated mdx fibers restore adequate function in the absence of dystrophin may, when understood, provide clues to effective nongenetic interventions for muscular dystrophy in humans where regenerated fibers continue to degenerate and where the disease is often fatal.

Animals↗
PubMed1991

Induction of retinal regeneration in vivo by growth factors.

We have previously reported that basic fibroblast growth factor (bFGF) can induce retinal regeneration in the stage 22-24 chicken embryo. The present study was undertaken to identify the cellular source of the regenerate and to determine whether other growth factors also elicit regeneration in this animal model. Polymer implants containing bFGF were inserted into eyes of chicken embryos immediately after extirpation of the neural retina. The retinal pigment epithelium (RPE) was left intact. Evaluation by light microscopy revealed that in bFGF-treated eyes the new neural retina arose by transdifferentiation of the entire RPE layer. Differentiation of the new neural retina occurred in a sequence similar to that of normal development but proceeded in a reverse (vitread) direction. All retinal laminae had differentiated by Day 15. However, the regenerate displayed reversed polarity, with photoreceptors closest to the lens. The RPE, pecten, and optic nerve were absent. Focal areas of degeneration in the retinal regenerate became evident for the first time on Day 10. Retinal regeneration was also observed after treatment with higher doses of acidic fibroblast growth factor, but not with nerve growth factor-beta, transforming growth factor-beta 1, insulin, or insulin-like growth factors I or II. These results raise the possibility that FGFs may play a role in retinal differentiation during development.

Animals↗