Since trans-RA is the active form of vitamin A in skin, the abundant published literature on the former is applicable to this discussion. Trans-RA interacts with nuclear receptor proteins described as RA receptors and retinoid X receptors, which can form heterodimer complexes. These complexes then interact with specific DNA sequences to affect transcription, to either increase or decrease expression of specific proteins/enzymes (1). Using genomic methodology, we have observed that the expression of over 1200 genes is
significantly affected by topical retinoid treatment of photoaged human skin (unpublished observations). Many of these changes can be ascribed, at least on some level, as being normalization of the altered skin conditions that occur with aging (induced by both chronological and environmental influences such as chronic sun exposure). Some specific changes induced by retinoid that are likely relevant to skin anti-wrinkle benefits are those that result in thicker skin to diminish the appearance of fine lines and wrinkles, e. g., increased epidermal proliferation and differentiation (increased epidermal thickness), increased production of epidermal ground substance [glycosaminoglycans (GAGs) which bind water, increasing epidermal hydration and thickness], and increased dermal production of extracellular matrix components such as collagen (increase dermal thickness) (2).
In addition to stimulation of events in skin such as those mentioned above, retinoids can also have an inhibitory effect on other tissue components. For example, retinoids are reported to inhibit production of collagenase (3). And while retinoid will stimulate production of ground substance (GAGs) in epidermis, it will inhibit production of excess ground substance in photoaged dermis (Fig. 1). While a low level of GAGs are required in the dermis for normal collagen structure and function, excess dermal GAGs are associated with altered dermal collagen structure and wrinkled skin appearance in photoaged skin (4) and in the Shar Pei dog (5). Reduction in this excess is associated with reduced skin wrinkling (6,7).
Since at least some of the epidermal effects of topical retinoid (e. g., epidermal thickening) (8) occur relatively rapidly (days) after initiation of treatment, some skin benefits (e. g., diminution of fine lines) can be realized quickly. The dermal effects likely occur on a much longer time frame (weeks to months) such that reduction in skin problems like wrinkles require much longer time frames (weeks to months) (2).