Long-term treatment of photoaged human skin with topical retinoic acid improves epidermal cell atypia and thickens the collagen band in papillary dermis

J Am Acad Dermatol. 2005 Nov;53(5):769-74. doi: 10.1016/j.jaad.2005.06.052.


Background: Risk of photocarcinogenesis and the relevance of collagen in wrinkle effacement are two issues related to prolonged use of retinoic acid (RA) that have not been fully addressed.

Objective: Our purpose was to investigate the degree of epidermal cellular atypia and the thickness of papillary dermal collagen in photoaging after long-term use of RA.

Methods: Thirty-four subjects with photoaged skin were treated daily with 0.05% RA for at least 6 months. Epidermal cellular atypia was graded by means of a semiquantitative scale. Thickness of collagen band was measured by using image-analysis software.

Results: Compared with pretreatment findings, melanocytic and keratinocytic atypia was significantly reduced and the collagen band thickness doubled.

Limitations: This was an open-label study.

Conclusion: Improvement in epidermal cellular atypia is consistent with the ability of RA to act as a chemopreventive agent in epithelial carcinogenesis. Prolonged use also significantly increased collagen matrix deposition in dermal repair zones, which most likely contributes to wrinkle effacement by RA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Topical
  • Collagen / drug effects*
  • Epidermal Cells*
  • Epidermis / drug effects*
  • Female
  • Humans
  • Middle Aged
  • Skin Aging / drug effects*
  • Skin Aging / pathology*
  • Time Factors
  • Tretinoin / administration & dosage*


  • Tretinoin
  • Collagen