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In Vivo Imaging of Human and Mouse Skin with a Handheld Dual-Axis Confocal Fluorescence Microscope
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Document Title
In Vivo Imaging of Human and Mouse Skin with a Handheld Dual-Axis Confocal Fluorescence Microscope
Author
Ra H, Piyawattanametha W, Gonzalez-Gonzalez E, Mandella MJ, Kino GS, Solgaard O, Leake D, Kaspar RL, Oro A, Contag CH
Name from Authors Collection
Affiliations
Stanford University; Stanford University; Stanford University; National Science & Technology Development Agency - Thailand; National Electronics & Computer Technology Center (NECTEC); Chulalongkorn University; Thermo Fisher Scientific; Stanford University; Stanford University; Stanford University
Type
Article
Source Title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Year
2011
Volume
131
Issue
5
Page
1061-1066
Open Access
Green Accepted, Bronze
Publisher
NATURE PUBLISHING GROUP
DOI
10.1038/jid.2010.401
Format
Abstract
Advancing molecular therapies for the treatment of skin diseases will require the development of new tools that can reveal spatiotemporal changes in the microanatomy of the skin and associate these changes with the presence of the therapeutic agent. For this purpose, we evaluated a handheld dual-axis confocal (DAC) microscope that is capable of in vivo fluorescence imaging of skin, using both mouse models and human skin. Individual keratinocytes in the epidermis were observed in three-dimensional image stacks after topical administration of near-infrared (NIR) dyes as contrast agents. This suggested that the DAC microscope may have utility in assessing the clinical effects of a small interfering RNA (siRNA)-based therapeutic (TD101) that targets the causative mutation in pachyonychia congenita (PC) patients. The data indicated that (1) formulated indocyanine green (ICG) readily penetrated hyperkeratotic PC skin and normal callused regions compared with nonaffected areas, and (2) TD101-treated PC skin revealed changes in tissue morphology, consistent with reversion to nonaffected skin compared with vehicle-treated skin. In addition, siRNA was conjugated to NIR dye and shown to penetrate through the stratum corneum barrier when topically applied to mouse skin. These results suggest that in vivo confocal microscopy may provide an informative clinical end point to evaluate the efficacy of experimental molecular therapeutics.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
OBTI; NIH [R44AR055881-02, U54 CA105296]; Pachyonychia Congenita Project; NATIONAL CANCER INSTITUTE [U54CA105296] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR052785, R01AR054780, R44AR055881] Funding Source: NIH RePORTER
License
Copyright
Rights
The Society for Investigative Dermatology
Publication Source
WOS