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S.Y. Lee et al. / Journal of Photochemistry and Photobiology B: Biology 88 (2007) 51–67 65 bodies of evidence of increased collagen and elastic fibers as well as clinical photographs and double-blinded assess- ment of the investigators and the subjects. A notable increase of TIMP-1 and 2 was observed in the immunohis- tochemical staining, which suggested that altered enzy- matic activity related to the dermal matrix remodeling may play a role in the mechanism of action of LED photo- therapy. Particularly, it is notable that LED phototherapy, which does not cause any thermal or chemical damaging, induced proinflammatory cytokines just as in photother- mally-mediated nonablative skin rejuvenation, which we consider consequently led to the biosynthesis of new colla- gen within the dermis. More importantly, these histological changes occurred deeper than 100-500 lm below the DEJ, the actively responding area to most nonablative laser treatments, and hence their target zone, and in addition deeper than the classically-accepted optical penetration depth of at least the visible red wavelength. We hypothesize that this result might be caused by an extensive cellular response to the photobiomodulative effect of LED therapy through enhanced gap junctional intercellular communica- tion, even though the sample size was too small to draw a clear conclusion. Further studies with larger sample sizes and repeated follow-up biopsies are merited to investigate the exact changes and roles of these biologic effectors in the dermal remodeling process after LED phototherapy. We concluded that 830 nm and 633 nm LED photother- apy is an effective, safe, well-tolerated and painless treat- ment for skin rejuvenation. From the clinical aspect, the non-thermal feature of LED phototherapy may be a signif- icant advantage, because we could achieve effective rejuve- nation of aging skin without inducing any thermal damage or wound in normal skin. We recommend the use of the combination of these two wavelengths of light to maximize the effect through utilizing the advantages specific to each wavelength. 6. Abbreviations CO2 carbon dioxide Cx43 connexin-43 DEJ dermoepidermal junction Er:YAG erbium: yttrium-aluminum-garnet GJIC gap junctional intercellular communication H&E hematoxylin and eosin ICAM-1 intercellular adhesion molecule-1 IL-1b interleukin-1b IL-6 interleukin-6 IPL intense pulsed light KTP potassium-titanyl-phosphate LED light-emitting diode MMP matrix metalloproteinase mRNA messenger ribonucleic acid Nd:YAG neodymium: yttrium-aluminum-garnet PBS phosphate buffered saline PDL pulsed dye lasers RM-ANOVA repeated measures of analysis of variance RT-PCR reverse transcriptase-polymerase chain reaction TBS tris-buffered saline TEM transmission electromicroscopy TIMP tissue inhibitor of matrix metalloproteinase TNF-a tumor necrosis factor- a 7. Disclosure of conflicts of interest Photo Therapeutics Ltd. supported the costs of only the electromicroscopic examination, immunohistochemical staining and real time RT-PCR processes. The authors have not received any funds toward the plan or conduction of this study. We certify that we have no affiliation with or financial involvement in any organization or entity with a direct or indirect financial interest in the subject matter or materials discussed in the manuscript. Acknowledgement We wish to thank Photo Therapeutics Ltd., Fazely, Tamworth, UK, for generously making available the LED-based OmniluxTM devices used in this study at no cost. We are also deeply grateful to Antonius R. Soelistyo, B. Tech (hons), for his kindness to help us with performing this study and to R. Glen Calderhead, MSc, PhD(MedSci), FRSM, for the English proofreading of this paper. References [1] J.L. Bolognia, Aging skin, Am. J. Med. 98 (suppl 1A) (1995) S99– S103. [2] C.E.M. Griffiths, The clinical identification and quantification of photodamage, Br. J. Dermatol. 127 (suppl 41) (1992) S37–S42. [3] L.H. Kligman, Photoaging. Manifestations, prevention, and treat- ment, Clin. Geriatr. Med. 5 (1989) 235–251. [4] Y. Takema, Y. Yorimoto, M. Kawai, G. Imokawa, Age related changes in the elastic properties and thickness of human facial skin, Br. J. Dermatol. 131 (1994) 641–648. [5] G.H. Branham, J.R. Thomas, Rejuvenation of the skin surface: chemical peel and dermabrasion, Facial. Plast. Surg. 12 (1996) 125– 133. [6] L.E. Airan, G.J. Hruza, Current lasers in skin resurfacing, Facial. Plast. Surg. Clin. North. Am. 13 (2005) 127–139. [7] J.S. Orringer, S. Kang, T.M. Johnson, D.J. Karimipour, T. Hamilton, C. Hammerberg, J.J. Voorhees, G.J. Fisher, Connective tissue remodeling induced by carbon dioxide laser resurfacing of photo- damaged human skin, Arch. Dermatol. 140 (2004) 1326–1332. [8] C.A. Nanni, T.S. Alster, Complications of carbon dioxide laser resurfacing: an evaluation of 500 patients, Dermatol. Surg. 24 (1998) 315–320. [9] S. Sriprachya-Anunt, R.E. Fitzpatrick, M.P. Goldman, S.R. Smith, Infections complicating pulsed carbon dioxide laser resurfacing for photoaged skin, Dermatol. Surg. 23 (1997) 527–535. [10] C.A. Hardaway, E.V. Ross, Nonablative laser skin remodeling, Dermatol. Clin. 20 (2002) 97–111. [11] R.A. Weiss, D.H. McDaniel, R.G. Geronemus, Review of nonabla- tive photorejuvenation: reversal of the aging effects of the sun and environmental damage using laser and light sources, Semin. Cutan. Med. Surg. 22 (2003) 93–106. [12] C.C. Dierickx, R.R. Anderson, Visible light treatment of photoaging, Dermatol. Ther. 18 (2005) 191–208.PDF Image | LED phototherapy for skin rejuvenation
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