Showing papers on "Transdifferentiation published in 1988"

An ultrastructural study of rabbit ocular surface transdifferentiation.

Abstract: When debridement of the rabbit cornea is followed by re-epithelialization from the conjunctiva, a process of transdifferentiation of the endothelium occurs. Goblet cells appear peripherally 1 week after healing of the epithelial defect, are widespread at 2 weeks, and disappear centrally at 3 to 4 weeks. Six weeks after closure of the defect, the epithelium has reverted to the customary corneal appearance. The morphology of the regenerating epithelium was studied by light, transmission and scanning electron microscopy. The precursor cells for the goblet cells were identified in stage 1, before PAS-positive cells were present, as pairs of cells with dark cytoplasm and prominent Golgi. Subsequently, goblet cells were present in pairs, indicating that goblet cells are derived from non-goblet epithelial cells, and that they do not simply migrate onto the cornea. At the time of transdifferentiation, loss of goblet cells was shown to occur both by desquamation from the surface and by in situ cell death.

Reversal of conjunctival transdifferentiation by topical retinoic acid.

Abstract: After resurfacing a total corneal epithelial defect extending 2-3 mm beyond the limbus, conjunctival epithelium gradually loses goblet cells and transforms into a corneal-like epithelium. We examined the effect of topical retinoic acid on the reversal of transdifferentiation on nonvascularized corneas. Four months after total denudation of corneal epithelium using n-heptanol, rabbit corneas without vascularization received topical drops of 0.1% (wt/vol) all-trans retinoic acid in corn oil 3 times a day. Before treatment, the transdifferentiation was complete, as evidenced by the absence of goblet cells on the corneal surface using a topographical assay and routine histology. After treatment for 15 days, goblet cells reappeared 3 mm into the peripheral cornea, and extended in a centripetal density to 4.5 mm after 32 days. To prove that retinoic acid was not angiogenic, retinoid-bearing Elvax-40 pellets were implanted into normal corneal stroma. Taken together, these data indicate that vitamin A or retinoids may be an important factor in the modulation of conjunctival epithelial transdifferentiation.

[The effect of methionine enkephalin, leucine enkephalin and the hexapeptide, dalargin on the morphology of cultured neurons].

Abstract: Cell cultures derived from brain, ganglion trigeminale or retina of 5- and 9-day-old chick embryos and from brain stem or hippocampus of 16-18 day-old fetal rats were treated with Met5-, Leu5-enkephalin, or Dalargin--a synthetic hexapeptide structurally related to Leu5-enkephalin--and evaluated morphologically. The treatment of the nervous tissue cultures with the peptides markedly affected their growth pattern. Aggregates of glial and neuronal cells were surrounded by flat cells forming monolayer network structures. In cultures of brain from 5 day-old chick embryos the proliferation of the cells was significantly stimulated. No growth of neurites was observed. It is discussed that the tested Enkephalins and in the same way the Dalargin may play an important role in the early neuronal development. Their activity in phase 0 and phase 1 of the life history of nerve cells indicates aspects of temporary peptide influences. Excess of glial cells caused by the tested peptides did not enhance neuronal differentiation. The transdifferentiation of developing receptor cells into ependymal cells during the adaptation process in retina cultures as a special effect of Dalargin is discussed. The present findings suggest that the influence of (opioid) peptides in vitro may be detected morphologically and that nervous tissue culture is a valuable tool for differentiating neuronotrophic neurite-promoting and neurotoxic drug effects.

Cellular src Gene Expression Associated with Lentoidogenesis in Transdifferentiating Cultures.

Abstract: We have shown (9) that elevated pp60c–src kinase activity accompanies the transdifferentiation of chick embryo neuroretinal (NR) cells into lens in vitro; moreover, most immunologically-detectable pp60c–src protein is confined to lentoid bodies in permissive cultures (FH; 6). By contrast, pp60c–src expression is low in non-permissive cultures where lentoid formation is blocked by high glucose (FHG; 6) or medium 199 (11). We now extend these findings in several respects. Firstly, glial-enriched cultures in both FH and FHG media form small but sparse lentoid bodies at around 20 days, accompanied by increases in both δ crystallin and pp60c–src expression. In later FHG cultures, these lentoids increase neither in number/size nor in δ/pp60c–src expression, in contrast to permissive (FH) cultures. Thus the high glucose block on transdifferentiation is only partly mediated by neuronal influences (19). Secondly, transdifferentiating cultures of tapetal cells show higher levels of pp60c–src relative to redifferentiated or dedifferentiated (16, 17) cultures of these cells. Thirdly, we find no evidence that c-src oncogene expression directly signals transdifferentiation. Thus v-src expression in RSV-transformed NR cells inhibits δ crystallin accumulation (29; this study), while a c-src-substituted RSV variant has little effect on NR transdifferentiation. Late cultures of NR cells in medium 199 fail to accumulate pp60c–src protein or c-src transcripts, even though previous studies (2) showed that δ crystallin transcripts are localised within the nuclei of many cells in such cultures.