Skip to main content
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 2000 Feb;84(2):212–216. doi: 10.1136/bjo.84.2.212

Apoptosis and apoptosis related gene expression in normal conjunctiva and pterygium

D Tan 1, W Y Tang 1, Y P Liu 1, H Goh 1, D Smith 1
PMCID: PMC1723383  PMID: 10655200

Abstract

BACKGROUND—Pterygium is a relatively common eye disease in the tropics whose aetiology and pathogenesis remain uncertain. As such, interest has focused on understanding the underlying mechanism of pterygia development.
METHODS—15 specimens of pterygia from 15 eyes were examined, together with normal conjunctival tissue from the same eyes for the pattern of gene expression of genes associated with the induction or repression of apoptosis (p53, bcl-2, and bax). In addition, the samples directly for apoptotic cells were examined by the terminal deoxynucleotide transferase (TdT) mediated nick end labelling (TUNEL) methodology.
RESULTS—In pterygia specimens apoptotic cells were found mainly confined to the basal layer of cells of the epithelial layer, situated immediately adjacent to the fibrovascular support layer. These cells were shown to express significant levels of p53 and bax, as well as the apoptosis inhibiting protein bcl-2. In contrast, normal conjunctival specimens displayed no bcl-2 expression and apoptotic cells were seen throughout the entire width of the epithelial layer, coupled with high levels of bax expression.
CONCLUSION—These results support a model whereby pterygia development is a result of disruption of the normal process of apoptosis occurring in the conjunctiva.



Full Text

The Full Text of this article is available as a PDF (574.8 KB).

Figure 1  .

Figure 1  

Immunohistochemical analysis of normal conjunctiva and pterygium. Specimens of normal conjunctiva and pterygium were stained with antibodies directed against p53 (a, b); bcl-2 (c, d); bax (e, f), and DNA breaks (TUNEL) (g, h). Normal conjunctiva (a, c, e, g) and pterygium (b, d, f, h) shown here are from one patient. Positive cells stain brown. Original magnification ×100.

Selected References

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

  1. Clear A. S., Chirambo M. C., Hutt M. S. Solar keratosis, pterygium, and squamous cell carcinoma of the conjunctiva in Malawi. Br J Ophthalmol. 1979 Feb;63(2):102–109. doi: 10.1136/bjo.63.2.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DeLong M. J. Apoptosis: a modulator of cellular homeostasis and disease states. Ann N Y Acad Sci. 1998 Apr 15;842:82–90. doi: 10.1111/j.1749-6632.1998.tb09635.x. [DOI] [PubMed] [Google Scholar]
  3. Detorakis E. T., Sourvinos G., Tsamparlakis J., Spandidos D. A. Evaluation of loss of heterozygosity and microsatellite instability in human pterygium: clinical correlations. Br J Ophthalmol. 1998 Nov;82(11):1324–1328. doi: 10.1136/bjo.82.11.1324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dushku N., Reid T. W. P53 expression in altered limbal basal cells of pingueculae, pterygia, and limbal tumors. Curr Eye Res. 1997 Dec;16(12):1179–1192. doi: 10.1076/ceyr.16.12.1179.5036. [DOI] [PubMed] [Google Scholar]
  5. Eastman A. Survival factors, intracellular signal transduction, and the activation of endonucleases in apoptosis. Semin Cancer Biol. 1995 Feb;6(1):45–52. doi: 10.1006/scbi.1995.0006. [DOI] [PubMed] [Google Scholar]
  6. Gannon J. V., Greaves R., Iggo R., Lane D. P. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J. 1990 May;9(5):1595–1602. doi: 10.1002/j.1460-2075.1990.tb08279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hill J. C., Maske R. Pathogenesis of pterygium. Eye (Lond) 1989;3(Pt 2):218–226. doi: 10.1038/eye.1989.31. [DOI] [PubMed] [Google Scholar]
  9. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  10. Jap A., Chan C., Lim L., Tan D. T. Conjunctival rotation autograft for pterygium. An alternative to conjunctival autografting. Ophthalmology. 1999 Jan;106(1):67–71. doi: 10.1016/S0161-6420(99)90006-4. [DOI] [PubMed] [Google Scholar]
  11. Karukonda S. R., Thompson H. W., Beuerman R. W., Lam D. S., Wilson R., Chew S. J., Steinemann T. L. Cell cycle kinetics in pterygium at three latitudes. Br J Ophthalmol. 1995 Apr;79(4):313–317. doi: 10.1136/bjo.79.4.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Mackenzie F. D., Hirst L. W., Battistutta D., Green A. Risk analysis in the development of pterygia. Ophthalmology. 1992 Jul;99(7):1056–1061. doi: 10.1016/s0161-6420(92)31850-0. [DOI] [PubMed] [Google Scholar]
  14. Milner J., Medcalf E. A. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell. 1991 May 31;65(5):765–774. doi: 10.1016/0092-8674(91)90384-b. [DOI] [PubMed] [Google Scholar]
  15. Miyashita T., Harigai M., Hanada M., Reed J. C. Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res. 1994 Jun 15;54(12):3131–3135. [PubMed] [Google Scholar]
  16. Miyashita T., Reed J. C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995 Jan 27;80(2):293–299. doi: 10.1016/0092-8674(95)90412-3. [DOI] [PubMed] [Google Scholar]
  17. Moran D. J., Hollows F. C. Pterygium and ultraviolet radiation: a positive correlation. Br J Ophthalmol. 1984 May;68(5):343–346. doi: 10.1136/bjo.68.5.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oltvai Z. N., Milliman C. L., Korsmeyer S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609–619. doi: 10.1016/0092-8674(93)90509-o. [DOI] [PubMed] [Google Scholar]
  19. Onur C., Orhan D., Orhan M., Dizbay Sak S., Tulunay O., Irkeç M. Expression of p53 protein in pterygium. Eur J Ophthalmol. 1998 Jul-Sep;8(3):157–161. doi: 10.1177/112067219800800307. [DOI] [PubMed] [Google Scholar]
  20. Rodrigues N. R., Rowan A., Smith M. E., Kerr I. B., Bodmer W. F., Gannon J. V., Lane D. P. p53 mutations in colorectal cancer. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7555–7559. doi: 10.1073/pnas.87.19.7555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Savitz S. I., Rosenbaum D. M. Apoptosis in neurological disease. Neurosurgery. 1998 Mar;42(3):555–574. doi: 10.1097/00006123-199803000-00026. [DOI] [PubMed] [Google Scholar]
  22. Selkirk J. K., He C., Patterson R. M., Merrick B. A. Tumor suppressor p53 gene forms multiple isoforms: evidence for single locus origin and cytoplasmic complex formation with heat shock proteins. Electrophoresis. 1996 Nov;17(11):1764–1771. doi: 10.1002/elps.1150171114. [DOI] [PubMed] [Google Scholar]
  23. Spandidos D. A., Sourvinos G., Kiaris H., Tsamparlakis J. Microsatellite instability and loss of heterozygosity in human pterygia. Br J Ophthalmol. 1997 Jun;81(6):493–496. doi: 10.1136/bjo.81.6.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Spraul C. W., Grossniklaus H. E. Tumors of the cornea and conjunctiva. Curr Opin Ophthalmol. 1996 Aug;7(4):28–34. doi: 10.1097/00055735-199608000-00006. [DOI] [PubMed] [Google Scholar]
  25. Tan D. T., Chee S. P., Dear K. B., Lim A. S. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol. 1997 Oct;115(10):1235–1240. doi: 10.1001/archopht.1997.01100160405001. [DOI] [PubMed] [Google Scholar]
  26. Tan D. T., Lim A. S., Goh H. S., Smith D. R. Abnormal expression of the p53 tumor suppressor gene in the conjunctiva of patients with pterygium. Am J Ophthalmol. 1997 Mar;123(3):404–405. doi: 10.1016/s0002-9394(14)70141-2. [DOI] [PubMed] [Google Scholar]
  27. Taylor H. R. Ultraviolet radiation and the eye: an epidemiologic study. Trans Am Ophthalmol Soc. 1989;87:802–853. [PMC free article] [PubMed] [Google Scholar]
  28. Vogelstein B., Kinzler K. W. p53 function and dysfunction. Cell. 1992 Aug 21;70(4):523–526. doi: 10.1016/0092-8674(92)90421-8. [DOI] [PubMed] [Google Scholar]
  29. Yang E., Zha J., Jockel J., Boise L. H., Thompson C. B., Korsmeyer S. J. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 1995 Jan 27;80(2):285–291. doi: 10.1016/0092-8674(95)90411-5. [DOI] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES