{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:12:21Z","timestamp":1784866341582,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Apollo Medical Optics, Ltd.","award":["108426DM"],"award-info":[{"award-number":["108426DM"]}]},{"name":"Apollo Medical Optics, Ltd.","award":["DMR-110-167"],"award-info":[{"award-number":["DMR-110-167"]}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["108426DM"],"award-info":[{"award-number":["108426DM"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR-110-167"],"award-info":[{"award-number":["DMR-110-167"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although nude mice are an ideal photoaging research model, skin biopsies result in inflammation and are rarely performed at baseline. Meanwhile, studies on antiphotoaging antioxidants or rejuvenation techniques often neglect the spontaneous reversal capacity. Full-field optical coherence tomography (FFOCT) can acquire cellular details noninvasively. This study aimed to establish a photoaging and sequential function reversal nude mice model assisted by an in vivo cellular resolution FFOCT system. We investigated whether a picosecond alexandrite laser (PAL) with a diffractive lens array (DLA) accelerated the reversal. In the sequential noninvasive assessment using FFOCT, a spectrophotometer, and DermaLab Combo\u00ae, the photodamage percentage recovery plot demonstrated the spontaneous recovery capacity of the affected skin by UVB-induced transepidermal water loss and UVA-induced epidermis thickening. A PAL with DLA not only accelerated skin barrier regeneration with epidermal polarity, but also increased dermal neocollagenesis, whereas the nonlasered group still had &gt;60% collagen intensity loss and 40% erythema from photodamage. Our study demonstrated that FFOCT images accurately resemble the living tissue. The photoaging and sequential function reversal model provides a reference to assess the spontaneous recovery capacity of nude mice from photodamage. This model can be utilized to evaluate the sequential noninvasive photodamage and reversal effects after other interventions.<\/jats:p>","DOI":"10.3390\/ijms23137009","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T21:25:00Z","timestamp":1656019500000},"page":"7009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Photoaging and Sequential Function Reversal with Cellular-Resolution Optical Coherence Tomography in a Nude Mice Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0425-9154","authenticated-orcid":false,"given":"Yen-Jen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Cosmetic Applications and Management, MacKay Junior College of Medicine, Nursing, and Management, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0463-7346","authenticated-orcid":false,"given":"Chang-Cheng","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cosmeceutics, China Medical University, Taichung 40433, Taiwan"},{"name":"Institute of Imaging and Biomedical Photonics, National Yang Ming Chiao Tung University, Tainan 71150, Taiwan"},{"name":"School of Medicine, College of Medicine, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan"},{"name":"Aesthetic Medical Center, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-En","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cosmeceutics, China Medical University, Taichung 40433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-2197","authenticated-orcid":false,"given":"Yu-Hung","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Wei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cosmeceutics, China Medical University, Taichung 40433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1586-910X","authenticated-orcid":false,"given":"Hsiu-Mei","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Cosmeceutics, China Medical University, Taichung 40433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bor-Shyh","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Imaging and Biomedical Photonics, National Yang Ming Chiao Tung University, Tainan 71150, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/1523-1747.ep12542169","article-title":"Sunscreens promote repair of ultraviolet radiation-induced dermal damage","volume":"81","author":"Kligman","year":"1983","journal-title":"J. Investig. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"G\u0119gotek, A., \u0141uczaj, W., and Skrzydlewska, E. (2021). Effects of Natural Antioxidants on Phospholipid and Ceramide Profiles of 3D-Cultured Skin Fibroblasts Exposed to UVA or UVB Radiation. Antioxidants, 10.","DOI":"10.3390\/antiox10040578"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wu, P.Y., Lyu, J.L., Liu, Y.J., Chien, T.Y., Hsu, H.C., Wen, K.C., and Chiang, H.M. (2017). Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102118"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1097\/DSS.0000000000002405","article-title":"Photoaging Reversibility in Asian Patients With Melasma Treated Using Picosecond Lasers With Diffractive Lens Array: A 1-Year Prospective Observational Cohort Study","volume":"47","author":"Lin","year":"2020","journal-title":"Dermatol. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/lsm.23244","article-title":"A Systematic Review of Picosecond Laser in Dermatology: Evidence and Recommendations","volume":"53","author":"Wu","year":"2021","journal-title":"Lasers Surg. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/jbio.201100083","article-title":"Minimally invasive non-thermal laser technology using laser-induced optical breakdown for skin rejuvenation","volume":"5","author":"Habbema","year":"2012","journal-title":"J. Biophotonics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0738-081X(95)00154-8","article-title":"The hairless mouse model for photoaging","volume":"14","author":"Kligman","year":"1996","journal-title":"Clin. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/1523-1747.ep12506359","article-title":"Prevention of ultraviolet damage to the dermis of hairless mice by sunscreens","volume":"78","author":"Kligman","year":"1982","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1159\/000146996","article-title":"Nude mice are not hairless. A morphological study","volume":"139","author":"Mboneko","year":"1990","journal-title":"Acta Anat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/asj\/sjz066","article-title":"Conventional Nanofat and SVF\/ADSC-Concentrated Nanofat: A Comparative Study on Improving Photoaging of Nude Mice Skin","volume":"39","author":"Zheng","year":"2019","journal-title":"Aesthet. Surg. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e467","DOI":"10.1097\/SCS.0000000000001902","article-title":"An Experimental Model Design for Photoaging","volume":"26","author":"Fan","year":"2015","journal-title":"J. Craniofac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1038\/sj.onc.1209384","article-title":"Chronic UVA irradiation of human HaCaT keratinocytes induces malignant transformation associated with acquired apoptotic resistance","volume":"25","author":"He","year":"2006","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1159\/000514686","article-title":"Application of Cellular Resolution Full-Field Optical Coherence Tomography in vivo for the Diagnosis of Skin Tumours and Inflammatory Skin Diseases: A Pilot Study","volume":"238","author":"Wang","year":"2021","journal-title":"Dermatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s10103-018-2696-1","article-title":"Optical coherence tomography imaging of melanoma skin cancer","volume":"34","author":"Bittar","year":"2019","journal-title":"Lasers Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/srt.12914","article-title":"In vivo characterization of extramammary Paget\u2019s disease by ultra-high cellular resolution optical coherence tomography","volume":"27","author":"Wang","year":"2021","journal-title":"Skin Res. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1046\/j.1523-1747.1998.00212.x","article-title":"Expression of neuropsin in the keratinizing epithelial tissue-immunohistochemical analysis of wild-type and nude mice","volume":"110","author":"Inoue","year":"1998","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2005.05.010","article-title":"Photoaging: Mechanisms and repair","volume":"55","author":"Rabe","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Graindorge, S., Cognat, V., Johann To Berens, P., Mutterer, J., and Molinier, J. (2019). Photodamage repair pathways contribute to the accurate maintenance of the DNA methylome landscape upon UV exposure. PLoS Genet., 15.","DOI":"10.1101\/673780"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/lsm.22934","article-title":"A preclinical model to investigate the role of surgically-induced inflammation in tumor responses to intraoperative photodynamic therapy","volume":"50","author":"Davis","year":"2018","journal-title":"Lasers Surg. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/srt.12782","article-title":"In vivo reflectance confocal microscopy for evaluating common facial hyperpigmentation","volume":"26","author":"Zeng","year":"2020","journal-title":"Skin Res. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s10103-013-1498-8","article-title":"Melasma and low-energy Q-switched laser: Treatment assessment by means of in vivo confocal microscopy","volume":"29","author":"Longo","year":"2014","journal-title":"Lasers Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/lsm.23025","article-title":"Using reflectance confocal microscopy to observe in vivo melanolysis after treatment with the picosecond alexandrite laser and Q-switched Nd:YAG laser in melasma","volume":"51","author":"Jo","year":"2018","journal-title":"Lasers Surg. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/lsm.22788","article-title":"Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions","volume":"50","author":"Deegan","year":"2018","journal-title":"Lasers Surg. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/lsm.22540","article-title":"The histology of skin treated with a picosecond alexandrite laser and a fractional lens array","volume":"48","author":"Tanghetti","year":"2016","journal-title":"Lasers Surg. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/phpp.12505","article-title":"Serial change in laser-induced optical breakdown by 1064-nm Nd:YAG picosecond laser","volume":"36","author":"Hwang","year":"2020","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7286","DOI":"10.1364\/BOE.410991","article-title":"Laser-induced optical breakdown effects of micro-lens arrays and diffractive optical elements on ex vivo porcine skin after 1064\u2005nm picosecond laser irradiation","volume":"11","author":"Kim","year":"2020","journal-title":"Biomed. Opt. Express"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1364\/BOE.6.001234","article-title":"Influence of absorption induced thermal initiation pathway on irradiance threshold for laser induced breakdown","volume":"6","author":"Varghese","year":"2015","journal-title":"Biomed. Opt. Express"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"125004","DOI":"10.1117\/1.JBO.20.12.125004","article-title":"Finesse of transparent tissue cutting by ultrafast lasers at various wavelengths","volume":"20","author":"Wang","year":"2015","journal-title":"J. Biomed. optics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e202100129","DOI":"10.1002\/jbio.202100129","article-title":"Dependence of laser-induced optical breakdown on skin type during 1064\u2009nm picosecond laser treatment","volume":"14","author":"Kim","year":"2021","journal-title":"J. Biophotonics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/sj.jid.5700786","article-title":"Keratinocyte-fibroblast interactions in wound healing","volume":"127","author":"Werner","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jdermsci.2009.01.005","article-title":"Keratinocyte growth factor down-regulates intracellular ROS production induced by UVB","volume":"54","author":"Kovacs","year":"2009","journal-title":"J. Dermatol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"655281","DOI":"10.3389\/fphar.2021.655281","article-title":"Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin Damage via Activating the AhR\/Nrf2 Signaling Pathway","volume":"12","author":"Gao","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1016\/j.bbrc.2017.12.078","article-title":"Activation of KGFR-Akt-mTOR-Nrf2 signaling protects human retinal pigment epithelium cells from Ultra-violet","volume":"495","author":"Hu","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chu, Y., Wu, P.Y., Chen, C.W., Lyu, J.L., Liu, Y.J., Wen, K.C., Lin, C.Y., Kuo, Y.H., and Chiang, H.M. (2019). Protective Effects and Mechanisms of N-Phenethyl Caffeamide from UVA-Induced Skin Damage in Human Epidermal Keratinocytes through Nrf2\/HO-1 Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010164"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/jid.2013.26","article-title":"Autophagy Is Induced by UVA and Promotes Removal of Oxidized Phospholipids and Protein Aggregates in Epidermal Keratinocytes","volume":"133","author":"Zhao","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Moreiras, H., Seabra, M.C., and Barral, D.C. (2021). Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202104.0441.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1111\/php.12752","article-title":"Skin Erythema, Pigmentation and Hydration Kinetics after Ultraviolet Radiation-induced Photodamage in Southern Chinese Women","volume":"93","author":"Wan","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/exd.12388","article-title":"New insights in photoaging, UVA induced damage and skin types","volume":"23","author":"Battie","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/phpp.12493","article-title":"Cyanidin-3-o-glucoside inhibits UVA-induced human dermal fibroblast injury by upregulating autophagy","volume":"35","author":"Wu","year":"2019","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2576823","DOI":"10.1155\/2020\/2576823","article-title":"The Antiaging Activity of Ergothioneine in UVA-Irradiated Human Dermal Fibroblasts via the Inhibition of the AP-1 Pathway and the Activation of Nrf2-Mediated Antioxidant Genes","volume":"2020","author":"Hseu","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, Q., Bai, D., Qin, L., Shao, M., Liu, X., Zhang, S., Yan, C., Yu, G., and Hao, J. (2020). Protective Effect of L-Hexaguluroic Acid Hexasodium Salt on UVA-Induced Photo-Aging in HaCaT Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041201"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Oh, J.H., Joo, Y.H., Karadeniz, F., Ko, J., and Kong, C.S. (2020). Syringaresinol Inhibits UVA-Induced MMP-1 Expression by Suppression of MAPK\/AP-1 Signaling in HaCaT Keratinocytes and Human Dermal Fibroblasts. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113981"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jdermsci.2019.03.005","article-title":"Effects of irradiance on UVA-induced skin aging","volume":"94","author":"Lan","year":"2019","journal-title":"J. Dermatol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/srt.12718","article-title":"The inter-rater and test-retest reliability of skin thickness and skin elasticity measurements by the DermaLab Combo in healthy participants","volume":"25","author":"Peperkamp","year":"2019","journal-title":"Skin Res. Technol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7009\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:00Z","timestamp":1760139540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,23]]},"references-count":44,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137009"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137009","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,23]]}}}