Retinoids and photodamage.

Extensive well-controlled clinical studies performed over the past 5 years have demonstrated a consistent, dose-dependent, statistically significant improvement in the appearance of photodamaged skin after 3-6 months of daily treatment with topical 0.001-0.1% tretinoin cream. Clinical changes included decreases in surface roughness, irregular pigmentation, fine and coarse wrinkling, and sallowness. Actinic keratoses have also been reported to decrease in size and number. Blinded analysis of biopsies from more than 500 subjects showed that there was compaction of the stratum corneum, an increase in the number of granular layers, thickening of the epidermis and a decrease in epidermal melanin. There were no detectable histological changes in any dermal parameters. The specific cellular mechanisms by which retinoic acid (RA) exerts its beneficial effect on photodamaged skin are currently the subject of intensive investigation. It is well established that RA enters the nucleus where it binds to an RA receptor (RAR), and that the RA-RAR complex then binds to specific RA response elements in the DNA, modulating the expression of target genes. It is thus likely that RA improves at least some aspects of photoageing by modifying cellular differentiation programmes, as retinoids have been shown to do during embryogenesis, in malignantly transformed cells and in skin affected by certain dermatoses.