Cosmetic retinoid use in photoaged skin: A review of the compounds, their use and mechanisms of action

Abstract

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging.

Keywords: cosmeceuticals; formulation/stability; skin barrier; skin physiology/structure; topical retinoids.

FIGURE 1

Characteristics of photo‐protected and photoaged skin. Histologically, young photo‐protected skin (a) has a thick epidermis and highly convoluted dermal–epidermal junction with interdigitations into the dermis called rete ridges (white arrows). Dermally, there are fibrillin‐rich microfibrils (black arrows) within the papillary dermis. In contrast, photoaged skin (b) exhibits a thinner epidermis, flattened dermal–epidermal junction (with marked loss of rete ridges) and loss of fibrillin‐rich microfibrils.

FIGURE 2

Categorization of retinoid compounds. Characterization of the retinoid family of compounds is based on structure and time of introduction. These are categorized as: Non‐aromatic (a), mono‐aromatic with an N‐terminal benzene ring (b), poly‐aromatic (c) and pyranone‐derived (d). Compounds that have been used in cosmeceutical formulations indicated with an asterisk (*).

FIGURE 3

The retinoid signalling pathway. Systemic and topical retinol enters the cell via different pathways but are processed intracellularly in the same way. Processing of retinol to retinoic acid leads to activation of the RAR/RXR or PPARβ/δ/RXR pathways via translocation by CRABP2 or FABP5, respectively. The CRABP2/FABP5 ratio determines which of the nuclear receptors is activated. A higher CRABP2/FABP5 ratio drives RAR/RXR receptor heterodimerization and activation of cell growth arrest and apoptosis. Conversely, a lower CRABP2/FABP5 ratio drives activation of proliferation and differentiation by activating the PPARβ/δ‐RXR pathway.

FIGURE 4

Retinol‐induced increase in epidermal thickness and dermal fibrillin deposition. Retinol induces remodelling by increasing epidermal thickness and the dermal deposition of fibrillin‐rich microfibrils (FRM) in photoaged skin following 12‐day patch test under occlusion. (a) Representative images showing immunostaining for fibrillin‐rich microfibrils. (b) Quantification of FRM deposition by ordinal scoring. (c) Quantification of epidermal thickness. Statistical significance for differences between the treatments compared to the baseline control was assessed by repeated‐measures one‐way ANOVA followed by a Dunnett's multiple comparison test (*p < 0.05). (Extracted from Mellody et al. [86]).