title: In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis.
abstract: 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.
authors.affiliation: Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA 02114 USA.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Miyahara
authors.forename: Lama
authors.initials: L
authors.lastname: Almulki
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Hisatomi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.forename: Kennard L
authors.initials: KL
authors.lastname: Thomas
authors.forename: Alexander
authors.initials: A
authors.lastname: Schering
authors.forename: Souska
authors.initials: S
authors.lastname: Zandi
authors.forename: Sonja
authors.initials: S
authors.lastname: Frimmel
authors.forename: Faryan
authors.initials: F
authors.lastname: Tayyari
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Garland
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.forename: Evangelos S
authors.initials: ES
authors.lastname: Gragoudas
authors.forename: Sharmila
authors.initials: S
authors.lastname: Masli
authors.forename: Ali
authors.initials: A
authors.lastname: Hafezi-Moghadam
mesh_terms: D000818:Animals; D002829:Choroid / Q000098:blood supply*; D015862:Choroid Diseases / Q000473:pathology*; D003952:Diagnostic Imaging / Q000379:methods; D004727:Endothelium / Q000293:injuries*; D004731:Endotoxins / Q000009:adverse effects*; D008562:Membrane Glycoproteins; D008863:Microspheres; D009887:Ophthalmoscopy / Q000379:methods*; D019007:P-Selectin / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014605:Uveitis / Q000139:chemically induced*
chemical_list: D004731:Endotoxins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012333:RNA, Messenger