RESUMEN
Acne vulgaris is a nearly universal cutaneous inflammatory disease. Excess sebum production is an integral part of disease pathogenesis. Medical therapies that reduce sebum excretion result in clinical improvement of acne. Given the preferential susceptibility of lipid-containing cells to cold, we investigated the hypothesis that controlled local skin cooling causes preferential injury to sebaceous glands, in murine and swine models using a range of temperatures as low as -10 °C, and then on the backs of human subjects. In mouse ears, peak histologic damage occurred 72 hours after treatment; eosinophilic necrotic plugs formed within sebaceous glands, and the number of glands was significantly reduced up to 1 week post treatment. Cooling disrupted sebocyte cell membranes, alkaline phosphatase activity, and significantly reduced sebocyte lipid content. In human volunteers, cooling damaged sebaceous glands and reduced sebum output for 2 weeks, with minimal injury to surrounding tissues. Selective cryolysis of sebaceous glands is achievable through brief, non-invasive skin cooling, suggesting that controlled cooling could be developed as an effective treatment for acne vulgaris.
Asunto(s)
Acné Vulgar/patología , Acné Vulgar/terapia , Frío , Crioterapia/métodos , Glándulas Sebáceas/patología , Animales , Biopsia con Aguja , Modelos Animales de Enfermedad , Estudios de Factibilidad , Humanos , Inmunohistoquímica , Masculino , Ratones , Proyectos Piloto , Glándulas Sebáceas/metabolismo , Especificidad de la Especie , Porcinos , Adulto JovenRESUMEN
Sebaceous glands perform complex functions, and they are centrally involved in the pathogenesis of acne vulgaris. Current techniques for studying sebaceous glands are mostly static in nature, whereas the gland's main function-excretion of sebum via the holocrine mechanism-can only be evaluated over time. We present a longitudinal, real-time alternative-the in vivo, label-free imaging of sebaceous glands using Coherent Anti-Stokes Raman Scattering (CARS) microscopy, which is used to selectively visualize lipids. In mouse ears, CARS microscopy revealed dynamic changes in sebaceous glands during the holocrine secretion process, as well as in response to damage to the glands caused by cooling. Detailed gland structure, plus the active migration of individual sebocytes and cohorts of sebocytes, were measured. Cooling produced characteristic changes in sebocyte structure and migration. This study demonstrates that CARS microscopy is a promising tool for studying the sebaceous gland and its associated disorders in three dimensions in vivo.
