In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis.
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
Shinsuke
S
Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA 02114 USA.
Almulki
Lama
L
Noda
Kousuke
K
Nakazawa
Toru
T
Hisatomi
Toshio
T
Nakao
Shintaro
S
Thomas
Kennard L
KL
Schering
Alexander
A
Zandi
Souska
S
Frimmel
Sonja
S
Tayyari
Faryan
F
Garland
Rebecca C
RC
Miller
Joan W
JW
Gragoudas
Evangelos S
ES
Masli
Sharmila
S
Hafezi-Moghadam
Ali
A
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*
D004731:Endotoxins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012333:RNA, Messenger