Skip to main content
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 1997 Oct;81(10):814–817. doi: 10.1136/bjo.81.10.814

Aging and the cornea

R FARAGHER 1, B MULHOLLAND 1, S TUFT 1, S SANDEMAN 1, P KHAW 1
PMCID: PMC1722015  PMID: 9486017

Full Text

The Full Text of this article is available as a PDF (84.6 KB).

Selected References

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

  1. Allsopp R. C., Vaziri H., Patterson C., Goldstein S., Younglai E. V., Futcher A. B., Greider C. W., Harley C. B. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114–10118. doi: 10.1073/pnas.89.21.10114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baroody R. A., Bito L. Z., DeRousseau C. J., Kaufman P. L. Ocular development and aging. 1. Corneal endothelial changes in cats and in free-ranging and caged rhesus monkeys. Exp Eye Res. 1987 Oct;45(4):607–622. doi: 10.1016/s0014-4835(87)80070-2. [DOI] [PubMed] [Google Scholar]
  3. Bell E., Ivarsson B., Merrill C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1274–1278. doi: 10.1073/pnas.76.3.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blake D. A., Yu H., Young D. L., Caldwell D. R. Matrix stimulates the proliferation of human corneal endothelial cells in culture. Invest Ophthalmol Vis Sci. 1997 May;38(6):1119–1129. [PubMed] [Google Scholar]
  5. Blatt H. L., Rao G. N., Aquavella J. V. Endothelial cell density in relation to morphology. Invest Ophthalmol Vis Sci. 1979 Aug;18(8):856–859. [PubMed] [Google Scholar]
  6. Bourne W. M., Nelson L. R., Hodge D. O. Central corneal endothelial cell changes over a ten-year period. Invest Ophthalmol Vis Sci. 1997 Mar;38(3):779–782. [PubMed] [Google Scholar]
  7. Campisi J. The biology of replicative senescence. Eur J Cancer. 1997 Apr;33(5):703–709. doi: 10.1016/S0959-8049(96)00058-5. [DOI] [PubMed] [Google Scholar]
  8. Chang E., Harley C. B. Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11190–11194. doi: 10.1073/pnas.92.24.11190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang S. W., Hu F. R. Changes in corneal autofluorescence and corneal epithelial barrier function with aging. Cornea. 1993 Nov;12(6):493–499. doi: 10.1097/00003226-199311000-00006. [DOI] [PubMed] [Google Scholar]
  10. Cristofalo V. J., Sharf B. B. Cellular senescence and DNA synthesis. Thymidine incorporation as a measure of population age in human diploid cells. Exp Cell Res. 1973 Feb;76(2):419–427. doi: 10.1016/0014-4827(73)90394-7. [DOI] [PubMed] [Google Scholar]
  11. Dutt S., Steinert R. F., Raizman M. B., Puliafito C. A. One-year results of excimer laser photorefractive keratectomy for low to moderate myopia. Arch Ophthalmol. 1994 Nov;112(11):1427–1436. doi: 10.1001/archopht.1994.01090230041018. [DOI] [PubMed] [Google Scholar]
  12. Ehlers N. Graft thickness after penetrating keratoplasty. Acta Ophthalmol (Copenh) 1974;52(6):893–903. doi: 10.1111/j.1755-3768.1974.tb01127.x. [DOI] [PubMed] [Google Scholar]
  13. Fitch K. L., Nadakavukaren M. J., Richardson A. Age-related changes in the corneal endothelium of the rat. Exp Gerontol. 1982;17(3):179–183. doi: 10.1016/0531-5565(82)90023-7. [DOI] [PubMed] [Google Scholar]
  14. Gorman S. D., Cristofalo V. J. Analysis of the G1 arrest position of senescent WI38 cells by quinacrine dihydrochloride nuclear fluorescence. Evidence for a late G1 arrest. Exp Cell Res. 1986 Nov;167(1):87–94. doi: 10.1016/0014-4827(86)90206-5. [DOI] [PubMed] [Google Scholar]
  15. Green K. Free radicals and aging of anterior segment tissues of the eye: a hypothesis. Ophthalmic Res. 1995;27 (Suppl 1):143–149. doi: 10.1159/000267860. [DOI] [PubMed] [Google Scholar]
  16. Gwin R. M., Lerner I., Warren J. K., Gum G. Decrease in canine corneal endothelial cell density and increase in corneal thickness as functions of age. Invest Ophthalmol Vis Sci. 1982 Feb;22(2):267–271. [PubMed] [Google Scholar]
  17. Hayashi K., Hayashi H., Hayashi F. Topographic analysis of the changes in corneal shape due to aging. Cornea. 1995 Sep;14(5):527–532. [PubMed] [Google Scholar]
  18. Hayashi K., Masumoto M., Fujino S., Hayashi F. [Changes in corneal astigmatism with aging]. Nippon Ganka Gakkai Zasshi. 1993 Oct;97(10):1193–1196. [PubMed] [Google Scholar]
  19. Hayflick L. The cell biology of aging. J Invest Dermatol. 1979 Jul;73(1):8–14. doi: 10.1111/1523-1747.ep12532752. [DOI] [PubMed] [Google Scholar]
  20. Hazlett L. D., Kreindler F. B., Berk R. S., Barrett R. Aging alters the phagocytic capability of inflammatory cells induced into cornea. Curr Eye Res. 1990 Feb;9(2):129–138. doi: 10.3109/02713689008995199. [DOI] [PubMed] [Google Scholar]
  21. Hobden J. A., Masinick S. A., Barrett R. P., Hazlett L. D. Aged mice fail to upregulate ICAM-1 after Pseudomonas aeruginosa corneal infection. Invest Ophthalmol Vis Sci. 1995 May;36(6):1107–1114. [PubMed] [Google Scholar]
  22. Hoppenreijs V. P., Pels E., Vrensen G. F., Treffers W. F. Effects of platelet-derived growth factor on endothelial wound healing of human corneas. Invest Ophthalmol Vis Sci. 1994 Jan;35(1):150–161. [PubMed] [Google Scholar]
  23. Jonas J. B., Ruprecht K. W., Schmitz-Valckenberg P., Brambring D., Platt D., Gebhart E., Schachtschabel D. O., Naumann G. O. Ophthalmic surgical complications in Werner's syndrome: report on 18 eyes of nine patients. Ophthalmic Surg. 1987 Oct;18(10):760–764. [PubMed] [Google Scholar]
  24. Kanai A., Kaufman H. E. Electron microscopic studies of corneal stroma: aging changes of collagen fibers. Ann Ophthalmol. 1973 Mar;5(3):285–passim. [PubMed] [Google Scholar]
  25. Khaw P. T., Doyle J. W., Sherwood M. B., Grierson I., Schultz G., McGorray S. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol. 1993 Feb;111(2):263–267. doi: 10.1001/archopht.1993.01090020117035. [DOI] [PubMed] [Google Scholar]
  26. Khaw P. T., Sherwood M. B., MacKay S. L., Rossi M. J., Schultz G. Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon's capsule fibroblasts. Arch Ophthalmol. 1992 Aug;110(8):1150–1154. doi: 10.1001/archopht.1992.01080200130040. [DOI] [PubMed] [Google Scholar]
  27. Kondo M., Araie M. Concentration change of fluorouracil in the external segment of the eye after subconjunctival injection. Arch Ophthalmol. 1988 Dec;106(12):1718–1721. doi: 10.1001/archopht.1988.01060140890035. [DOI] [PubMed] [Google Scholar]
  28. LEBLOND C. P. CLASSIFICATION OF CELL POPULATIONS ON THE BASIS OF THEIR PROLIFERATIVE BEHAVIOR. Natl Cancer Inst Monogr. 1964 May;14:119–150. [PubMed] [Google Scholar]
  29. Laing R. A., Sanstrom M. M., Berrospi A. R., Leibowitz H. M. Changes in the corneal endothelium as a function of age. Exp Eye Res. 1976 Jun;22(6):587–594. doi: 10.1016/0014-4835(76)90003-8. [DOI] [PubMed] [Google Scholar]
  30. Lass J. H., Greiner J. V., Merchant T. E., Glonek T. The effects of age on phosphatic metabolites of the human cornea. Cornea. 1995 Jan;14(1):89–94. [PubMed] [Google Scholar]
  31. Laule A., Cable M. K., Hoffman C. E., Hanna C. Endothelial cell population changes of human cornea during life. Arch Ophthalmol. 1978 Nov;96(11):2031–2035. doi: 10.1001/archopht.1978.03910060419003. [DOI] [PubMed] [Google Scholar]
  32. Liu S., Thweatt R., Lumpkin C. K., Jr, Goldstein S. Suppression of calcium-dependent membrane currents in human fibroblasts by replicative senescence and forced expression of a gene sequence encoding a putative calcium-binding protein. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2186–2190. doi: 10.1073/pnas.91.6.2186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. MacCallum D. K., Bahn C. F., Lillie J. H., Meyer R. F., Martonyi C. L. Evidence for corneal endothelial cell hypertrophy during postnatal growth of the cat cornea. Invest Ophthalmol Vis Sci. 1983 Feb;24(2):247–250. [PubMed] [Google Scholar]
  34. Macieira-Coelho A. Changes in membrane properties associated with cellular aging. Int Rev Cytol. 1983;83:183–220. doi: 10.1016/s0074-7696(08)61688-5. [DOI] [PubMed] [Google Scholar]
  35. Macieira-Coelho A., Pontén J., Philipson L. The division cycle and RNA-synthesis in diploid human cells at different passage levels in vitro. Exp Cell Res. 1966 Jun;42(3):673–684. doi: 10.1016/0014-4827(66)90280-1. [DOI] [PubMed] [Google Scholar]
  36. Malik N. S., Meek K. M. Vitamins and analgesics in the prevention of collagen ageing. Age Ageing. 1996 Jul;25(4):279–284. doi: 10.1093/ageing/25.4.279. [DOI] [PubMed] [Google Scholar]
  37. Malik N. S., Moss S. J., Ahmed N., Furth A. J., Wall R. S., Meek K. M. Ageing of the human corneal stroma: structural and biochemical changes. Biochim Biophys Acta. 1992 Mar 20;1138(3):222–228. doi: 10.1016/0925-4439(92)90041-k. [DOI] [PubMed] [Google Scholar]
  38. Millis A. J., Hoyle M., McCue H. M., Martini H. Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp Cell Res. 1992 Aug;201(2):373–379. doi: 10.1016/0014-4827(92)90286-h. [DOI] [PubMed] [Google Scholar]
  39. Millis A. J., Sottile J., Hoyle M., Mann D. M., Diemer V. Collagenase production by early and late passage cultures of human fibroblasts. Exp Gerontol. 1989;24(5-6):559–575. doi: 10.1016/0531-5565(89)90060-0. [DOI] [PubMed] [Google Scholar]
  40. Mishima S. Clinical investigations on the corneal endothelium-XXXVIII Edward Jackson Memorial Lecture. Am J Ophthalmol. 1982 Jan;93(1):1–29. doi: 10.1016/0002-9394(82)90693-6. [DOI] [PubMed] [Google Scholar]
  41. Murphy C., Alvarado J., Juster R., Maglio M. Prenatal and postnatal cellularity of the human corneal endothelium. A quantitative histologic study. Invest Ophthalmol Vis Sci. 1984 Mar;25(3):312–322. [PubMed] [Google Scholar]
  42. Murphy C., Alvarado J., Juster R., Maglio M. Prenatal and postnatal cellularity of the human corneal endothelium. A quantitative histologic study. Invest Ophthalmol Vis Sci. 1984 Mar;25(3):312–322. [PubMed] [Google Scholar]
  43. Møller-Pedersen T. A comparative study of human corneal keratocyte and endothelial cell density during aging. Cornea. 1997 May;16(3):333–338. [PubMed] [Google Scholar]
  44. Nzekwe E. U., Maurice D. M. The effect of age on the penetration of fluorescein into the human eye. J Ocul Pharmacol. 1994 Fall;10(3):521–523. doi: 10.1089/jop.1994.10.521. [DOI] [PubMed] [Google Scholar]
  45. O'Neal M. R., Polse K. A. Decreased endothelial pump function with aging. Invest Ophthalmol Vis Sci. 1986 Apr;27(4):457–463. [PubMed] [Google Scholar]
  46. Pawelec G., Sansom D., Rehbein A., Adibzadeh M., Beckman I. Decreased proliferative capacity and increased susceptibility to activation-induced cell death in late-passage human CD4+ TCR2+ cultured T cell clones. Exp Gerontol. 1996 Nov-Dec;31(6):655–668. doi: 10.1016/s0531-5565(96)00097-6. [DOI] [PubMed] [Google Scholar]
  47. Polse K. A., Brand R., Mandell R., Vastine D., Demartini D., Flom R. Age differences in corneal hydration control. Invest Ophthalmol Vis Sci. 1989 Mar;30(3):392–399. [PubMed] [Google Scholar]
  48. Pontén J., Stein W. D., Shall S. A quantitative analysis of the aging of human glial cells in culture. J Cell Physiol. 1983 Dec;117(3):342–352. doi: 10.1002/jcp.1041170309. [DOI] [PubMed] [Google Scholar]
  49. Poot M., Visser W. J., Verkerk A., Jongkind J. F. Autofluorescence of human skin fibroblasts during growth inhibition and in vitro ageing. Gerontology. 1985;31(3):158–165. doi: 10.1159/000212697. [DOI] [PubMed] [Google Scholar]
  50. Schneider E. L., Mitsui Y. The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3584–3588. doi: 10.1073/pnas.73.10.3584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Schultz G., Cipolla L., Whitehouse A., Eiferman R., Woost P., Jumblatt M. Growth factors and corneal endothelial cells: III. Stimulation of adult human corneal endothelial cell mitosis in vitro by defined mitogenic agents. Cornea. 1992 Jan;11(1):20–27. doi: 10.1097/00003226-199201000-00003. [DOI] [PubMed] [Google Scholar]
  52. Serrano M., Lin A. W., McCurrach M. E., Beach D., Lowe S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997 Mar 7;88(5):593–602. doi: 10.1016/s0092-8674(00)81902-9. [DOI] [PubMed] [Google Scholar]
  53. Seshadri T., Campisi J. Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. Science. 1990 Jan 12;247(4939):205–209. doi: 10.1126/science.2104680. [DOI] [PubMed] [Google Scholar]
  54. Smith J. R., Pereira-Smith O. M. Replicative senescence: implications for in vivo aging and tumor suppression. Science. 1996 Jul 5;273(5271):63–67. doi: 10.1126/science.273.5271.63. [DOI] [PubMed] [Google Scholar]
  55. Smith J. R., Whitney R. G. Intraclonal variation in proliferative potential of human diploid fibroblasts: stochastic mechanism for cellular aging. Science. 1980 Jan 4;207(4426):82–84. doi: 10.1126/science.7350644. [DOI] [PubMed] [Google Scholar]
  56. Sorrentino J. A., Millis A. J. Structural comparisons of fibronectins isolated from early and late passage cells. Mech Ageing Dev. 1984 Nov;28(1):83–97. doi: 10.1016/0047-6374(84)90155-6. [DOI] [PubMed] [Google Scholar]
  57. Staatz W. D., Van Horn D. L. The effects of aging and inflammation on corneal endothelial wound healing in rabbits. Invest Ophthalmol Vis Sci. 1980 Aug;19(8):983–986. [PubMed] [Google Scholar]
  58. Treffers W. F. Human corneal endothelial wound repair. In vitro and in vivo. Ophthalmology. 1982 Jun;89(6):605–613. doi: 10.1016/s0161-6420(82)34757-0. [DOI] [PubMed] [Google Scholar]
  59. Trinkaus-Randall V., Tong M., Thomas P., Cornell-Bell A. Confocal imaging of the alpha 6 and beta 4 integrin subunits in the human cornea with aging. Invest Ophthalmol Vis Sci. 1993 Oct;34(11):3103–3109. [PubMed] [Google Scholar]
  60. Tuft S. J., Gartry D. S., Rawe I. M., Meek K. M. Photorefractive keratectomy: implications of corneal wound healing. Br J Ophthalmol. 1993 Apr;77(4):243–247. doi: 10.1136/bjo.77.4.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Van Horn D. L., Hyndiuk R. A. Endothelial wound repair in primate cornea. Exp Eye Res. 1975 Aug;21(2):113–124. doi: 10.1016/0014-4835(75)90076-7. [DOI] [PubMed] [Google Scholar]
  62. Venable M. E., Lee J. Y., Smyth M. J., Bielawska A., Obeid L. M. Role of ceramide in cellular senescence. J Biol Chem. 1995 Dec 22;270(51):30701–30708. doi: 10.1074/jbc.270.51.30701. [DOI] [PubMed] [Google Scholar]
  63. Waring G. O., 3rd, Lynn M. J., Nizam A., Kutner M. H., Cowden J. W., Culbertson W., Laibson P. R., McDonald M. B., Nelson J. D., Obstbaum S. A. Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study five years after surgery. The Perk Study Group. Ophthalmology. 1991 Aug;98(8):1164–1176. doi: 10.1016/s0161-6420(91)32156-0. [DOI] [PubMed] [Google Scholar]
  64. Wilson S. E., He Y. G., Weng J., Li Q., McDowall A. W., Vital M., Chwang E. L. Epithelial injury induces keratocyte apoptosis: hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing. Exp Eye Res. 1996 Apr;62(4):325–327. doi: 10.1006/exer.1996.0038. [DOI] [PubMed] [Google Scholar]
  65. Wilson S. E. Molecular cell biology for the refractive corneal surgeon: programmed cell death and wound healing. J Refract Surg. 1997 Mar-Apr;13(2):171–175. doi: 10.3928/1081-597X-19970301-15. [DOI] [PubMed] [Google Scholar]
  66. Wistrom C., Villeponteau B. Cloning and expression of SAG: a novel marker of cellular senescence. Exp Cell Res. 1992 Apr;199(2):355–362. doi: 10.1016/0014-4827(92)90445-e. [DOI] [PubMed] [Google Scholar]
  67. Zeng G., Millis A. J. Differential regulation of collagenase and stromelysin mRNA in late passage cultures of human fibroblasts. Exp Cell Res. 1996 Jan 10;222(1):150–156. doi: 10.1006/excr.1996.0019. [DOI] [PubMed] [Google Scholar]
  68. van den Berg T. J., Tan K. E. Light transmittance of the human cornea from 320 to 700 nm for different ages. Vision Res. 1994 Jun;34(11):1453–1456. doi: 10.1016/0042-6989(94)90146-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES