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 1 Correspondence: Angiogenesis Laboratory, 325 Cambridge St., 3rd Floor, Boston, MA 02114 USA. E-mail: ahm@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
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In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis
Miyahara, Shinsuke; Almulki, Lama; Noda, Kousuke; Nakazawa, Toru; Hisatomi, Toshio; Nakao, Shintaro; Thomas, Kennard L.; Schering, Alexander; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Garland, Rebecca C.; Miller, Joan W.; Gragoudas, Evangelos S.; Masli, Sharmila; Hafezi-Moghadam, Ali
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, Volume 22 (6): 1973
Fed of American Socs for Experimental Biology – Jun 1, 2008
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