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This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-096891v1 22/6/1973    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Miyahara, S. Articles by Hafezi-Moghadam, A. PubMed PubMed Citation Articles by Miyahara, S. Articles by Hafezi-Moghadam, A.

In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis

Shinsuke Miyahara^*,, Lama Almulki^*,, Kousuke Noda^*,, Toru Nakazawa^*,, Toshio Hisatomi^*,, Shintaro Nakao^*,, Kennard L. Thomas^*,, Alexander Schering^*,, Souska Zandi^*,, Sonja Frimmel^*,, Faryan Tayyari^*,, Rebecca C. Garland^*,, Joan W. Miller^*,, Evangelos S. Gragoudas^*,, Sharmila Masli^, and Ali Hafezi-Moghadam^*,,1

^* Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, and

Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and

Schepens Eye Research Institute, Boston, Massachusetts, USA

¹Correspondence: Angiogenesis Laboratory, 325 Cambridge St., 3rd Floor, Boston, MA 02114 USA. E-mail: ahm{at}meei.harvard.edu

Early detection of ocular inflammation may prevent the occurrence of structural damage or vision loss. Here, we introduce a novel noninvasive technique for molecular imaging and quantitative evaluation of endothelial injury in the choriocapillaris of live animals, which detects disease earlier than currently possible. Using an established model of ocular inflammation, endotoxin-induced uveitis (EIU), we visualized the rolling and adhesive interaction of fluorescent microspheres conjugated to recombinant P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in choriocapillaris using a scanning laser ophthalmoscope (SLO). The number of rolling microspheres in the choriocapillaris peaked 4–10 h after LPS injection. The number of the accumulated microspheres peaked 4 h after LPS injection in the temporal choriocapillaris and 4 and 36 h after LPS injection in the central areas around the optic disk. Furthermore, we semiquantified the levels of P-selectin mRNA expression in the choroidal vessels by reverse transcription-PCR and found its pattern to match the functional microsphere interactions, with a peak at 4 h after LPS injection. These results indicate that PSGL-1-conjugated fluorescent microspheres allow specific detection of endothelial P-selectin expression in vivo and noninvasive assessment of endothelial injury. This technique may help to diagnose subclinical signs of ocular inflammatory diseases.—Miyahara, S., Almulki, L., Noda, K., Nakazawa, T., Hisatomi, T., Nakao, S., Thomas, K. L., Schering, A., Zandi, S., Frimmel, S., Tayyari, F., Garland, R. C., Miller, J. W., Gragoudas, E. S., Masli, S., Hafezi-Moghadam, A. In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis.

Key Words: inflammation • adhesion molecules • subclinical diagnosis • noninvasive molecular imaging • vascular diseases