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High-resolution, noninvasive longitudinal live imaging of immune responses
Edited* by Michael D. Cahalan, University of California, Irvine, CA, and approved June 15, 2011 (received for review March 30, 2011)

Abstract
Intravital imaging emerged as an indispensible tool in biological research, and a variety of imaging techniques have been developed to noninvasively monitor tissues in vivo. However, most of the current techniques lack the resolution to study events at the single-cell level. Although intravital multiphoton microscopy has addressed this limitation, the need for repeated noninvasive access to the same tissue in longitudinal in vivo studies remains largely unmet. We now report on a previously unexplored approach to study immune responses after transplantation of pancreatic islets into the anterior chamber of the mouse eye. This approach enabled (i) longitudinal, noninvasive imaging of transplanted tissues in vivo; (ii) in vivo cytolabeling to assess cellular phenotype and viability in situ; (iii) local intervention by topical application or intraocular injection; and (iv) real-time tracking of infiltrating immune cells in the target tissue.
Footnotes
↵1M.H.A. and G.F. contributed equally to this work.
↵2A.C., A.P., and P.-O.B. contributed equally to this work.
- 3To whom correspondence may be addressed. E-mail: acaicedo{at}med.miami.edu, apileggi{at}med.miami.edu, or per-olof.berggren{at}ki.se.
Author contributions: M.H.A., R.D.M., V.P., C.R., A.C., A.P., and P.-O.B. designed research; M.H.A., G.F., M.L.-C., J.M., Y.T., E.Z.-A., R.R.-D., and A.C. performed research; M.H.A., R.D.M., P.K.E., I.L., A.L.B., and A.P. contributed new reagents/analytic tools; M.H.A., G.F., and O.A.R.E. analyzed data; and M.H.A., G.F., R.D.M., A.C., A.P., and P.-O.B. wrote the paper.
Conflict of interest statement: P.-O.B. is one of the founders of the biotech company Biocrine, which is going to use the anterior chamber of the eye as a commercial servicing platform. A.C. and I.L. are also involved in the commercialization of this servicing platform.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1105002108/-/DCSupplemental.
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