Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1993 May 2;121(4):899–908. doi: 10.1083/jcb.121.4.899

Control of lens epithelial cell survival

PMCID: PMC2119790  PMID: 8491781

Abstract

We have studied the survival requirements of developing lens epithelial cells to test the hypothesis that most cells are programmed to kill themselves unless they are continuously signaled by other cells not to do so. The lens cells survived for weeks in both explant cultures and high-density dissociated cell cultures in the absence of other cells or added serum or protein, suggesting that they do not require signals from other cell types to survive. When cultured at low density, however, they died by apoptosis, suggesting that they depend on other lens epithelial cells for their survival. Lens epithelial cells cultured at high density in agarose gels also survived for weeks, even though they were not in direct contact with one another, suggesting that they can promote one another's survival in the absence of cell- cell contact. Conditioned medium from high density cultures promoted the survival of cells cultured at low density, suggesting that lens epithelial cells support one another's survival by secreting survival factors. We show for the first time that normal cell death occurs within the anterior epithelium in the mature lens, but this death is strictly confined to the region of the anterior suture.

Full Text

The Full Text of this article is available as a PDF (2.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Appleby D. W., Modak S. P. DNA degradation in terminally differentiating lens fiber cells from chick embryos. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5579–5583. doi: 10.1073/pnas.74.12.5579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barde Y. A. Trophic factors and neuronal survival. Neuron. 1989 Jun;2(6):1525–1534. doi: 10.1016/0896-6273(89)90040-8. [DOI] [PubMed] [Google Scholar]
  3. Barres B. A., Hart I. K., Coles H. S., Burne J. F., Voyvodic J. T., Richardson W. D., Raff M. C. Cell death and control of cell survival in the oligodendrocyte lineage. Cell. 1992 Jul 10;70(1):31–46. doi: 10.1016/0092-8674(92)90531-g. [DOI] [PubMed] [Google Scholar]
  4. Batistatou A., Greene L. A. Aurintricarboxylic acid rescues PC12 cells and sympathetic neurons from cell death caused by nerve growth factor deprivation: correlation with suppression of endonuclease activity. J Cell Biol. 1991 Oct;115(2):461–471. doi: 10.1083/jcb.115.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benya P. D., Shaffer J. D. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. 1982 Aug;30(1):215–224. doi: 10.1016/0092-8674(82)90027-7. [DOI] [PubMed] [Google Scholar]
  6. Bruckner P., Hörler I., Mendler M., Houze Y., Winterhalter K. H., Eich-Bender S. G., Spycher M. A. Induction and prevention of chondrocyte hypertrophy in culture. J Cell Biol. 1989 Nov;109(5):2537–2545. doi: 10.1083/jcb.109.5.2537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cowan W. M., Fawcett J. W., O'Leary D. D., Stanfield B. B. Regressive events in neurogenesis. Science. 1984 Sep 21;225(4668):1258–1265. doi: 10.1126/science.6474175. [DOI] [PubMed] [Google Scholar]
  8. Crompton T. IL3-dependent cells die by apoptosis on removal of their growth factor. Growth Factors. 1991;4(2):109–116. doi: 10.3109/08977199109000262. [DOI] [PubMed] [Google Scholar]
  9. Garcia I., Martinou I., Tsujimoto Y., Martinou J. C. Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. Science. 1992 Oct 9;258(5080):302–304. doi: 10.1126/science.1411528. [DOI] [PubMed] [Google Scholar]
  10. HAMBURGER V., LEVI-MONTALCINI R. Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J Exp Zool. 1949 Aug;111(3):457–501. doi: 10.1002/jez.1401110308. [DOI] [PubMed] [Google Scholar]
  11. HOWARD A. Whole mounts of rabbit lens epithelium for cytological study. Stain Technol. 1952 Nov;27(6):313–315. doi: 10.3109/10520295209105094. [DOI] [PubMed] [Google Scholar]
  12. Hamburger V., Brunso-Bechtold J. K., Yip J. W. Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor. J Neurosci. 1981 Jan;1(1):60–71. doi: 10.1523/JNEUROSCI.01-01-00060.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hofer M. M., Barde Y. A. Brain-derived neurotrophic factor prevents neuronal death in vivo. Nature. 1988 Jan 21;331(6153):261–262. doi: 10.1038/331261a0. [DOI] [PubMed] [Google Scholar]
  14. Jacobson M. D., Burne J. F., King M. P., Miyashita T., Reed J. C., Raff M. C. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature. 1993 Jan 28;361(6410):365–369. doi: 10.1038/361365a0. [DOI] [PubMed] [Google Scholar]
  15. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Korsching S., Thoenen H. Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3513–3516. doi: 10.1073/pnas.80.11.3513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koury M. J., Bondurant M. C. Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science. 1990 Apr 20;248(4953):378–381. doi: 10.1126/science.2326648. [DOI] [PubMed] [Google Scholar]
  18. Kyprianou N., Isaacs J. T. Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology. 1988 Feb;122(2):552–562. doi: 10.1210/endo-122-2-552. [DOI] [PubMed] [Google Scholar]
  19. Levi-Montalcini R. The nerve growth factor: thirty-five years later. EMBO J. 1987 May;6(5):1145–1154. doi: 10.1002/j.1460-2075.1987.tb02347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McAvoy J. W. Cell division, cell elongation and distribution of alpha-, beta- and gamma-crystallins in the rat lens. J Embryol Exp Morphol. 1978 Apr;44:149–165. [PubMed] [Google Scholar]
  21. McAvoy J. W., Chamberlain C. G. Growth factors in the eye. Prog Growth Factor Res. 1990;2(1):29–43. doi: 10.1016/0955-2235(90)90008-8. [DOI] [PubMed] [Google Scholar]
  22. McAvoy J. W., Fernon V. T. Neural retinas promote cell division and fibre differentiation in lens epithelial explants. Curr Eye Res. 1984 Jun;3(6):827–834. doi: 10.3109/02713688409000795. [DOI] [PubMed] [Google Scholar]
  23. McAvoy J. W. Induction of the eye lens. Differentiation. 1980;17(3):137–149. doi: 10.1111/j.1432-0436.1980.tb01091.x. [DOI] [PubMed] [Google Scholar]
  24. McConkey D. J., Hartzell P., Nicotera P., Orrenius S. Calcium-activated DNA fragmentation kills immature thymocytes. FASEB J. 1989 May;3(7):1843–1849. doi: 10.1096/fasebj.3.7.2497041. [DOI] [PubMed] [Google Scholar]
  25. Metcalf D. The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature. 1989 May 4;339(6219):27–30. doi: 10.1038/339027a0. [DOI] [PubMed] [Google Scholar]
  26. Nuñez G., London L., Hockenbery D., Alexander M., McKearn J. P., Korsmeyer S. J. Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol. 1990 May 1;144(9):3602–3610. [PubMed] [Google Scholar]
  27. Oppenheim R. W. Cell death during development of the nervous system. Annu Rev Neurosci. 1991;14:453–501. doi: 10.1146/annurev.ne.14.030191.002321. [DOI] [PubMed] [Google Scholar]
  28. Oppenheim R. W., Haverkamp L. J., Prevette D., McManaman J. L., Appel S. H. Reduction of naturally occurring motoneuron death in vivo by a target-derived neurotrophic factor. Science. 1988 May 13;240(4854):919–922. doi: 10.1126/science.3363373. [DOI] [PubMed] [Google Scholar]
  29. Parmigiani C. M., McAvoy J. W. The roles of laminin and fibronectin in the development of the lens capsule. Curr Eye Res. 1991 Jun;10(6):501–511. doi: 10.3109/02713689109001758. [DOI] [PubMed] [Google Scholar]
  30. Rodriguez-Tarduchy G., Collins M., López-Rivas A. Regulation of apoptosis in interleukin-3-dependent hemopoietic cells by interleukin-3 and calcium ionophores. EMBO J. 1990 Sep;9(9):2997–3002. doi: 10.1002/j.1460-2075.1990.tb07492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Roederer M., Staal F. J., Raju P. A., Ela S. W., Herzenberg L. A., Herzenberg L. A. Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4884–4888. doi: 10.1073/pnas.87.12.4884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Searle J., Kerr J. F., Bishop C. J. Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance. Pathol Annu. 1982;17(Pt 2):229–259. [PubMed] [Google Scholar]
  33. Shi Y. F., Szalay M. G., Paskar L., Sahai B. M., Boyer M., Singh B., Green D. R. Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation. J Immunol. 1990 May 1;144(9):3326–3333. [PubMed] [Google Scholar]
  34. Strasser A., Harris A. W., Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991 Nov 29;67(5):889–899. doi: 10.1016/0092-8674(91)90362-3. [DOI] [PubMed] [Google Scholar]
  35. Tschan T., Höerler I., Houze Y., Winterhalter K. H., Richter C., Bruckner P. Resting chondrocytes in culture survive without growth factors, but are sensitive to toxic oxygen metabolites. J Cell Biol. 1990 Jul;111(1):257–260. doi: 10.1083/jcb.111.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vaux D. L., Cory S., Adams J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988 Sep 29;335(6189):440–442. doi: 10.1038/335440a0. [DOI] [PubMed] [Google Scholar]
  37. Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]
  38. Wyllie A. H., Kerr J. F., Macaskill I. A., Currie A. R. Adrenocortical cell deletion: the role of ACTH. J Pathol. 1973 Oct;111(2):85–94. doi: 10.1002/path.1711110203. [DOI] [PubMed] [Google Scholar]
  39. Zimmerman R. J., Marafino B. J., Jr, Chan A., Landre P., Winkelhake J. L. The role of oxidant injury in tumor cell sensitivity to recombinant human tumor necrosis factor in vivo. Implications for mechanisms of action. J Immunol. 1989 Feb 15;142(4):1405–1409. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES